Hypertension Holistic Treatment

High Blood Pressure Exercise Program

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Platelet Vegf Contents In Patients With Pulmonary Hypertension Or With Chronic Hypoxemic Lung Disease

VEGF released from platelets and acting specifically on endothelial cells may play a pivotal role. In systemic vessels, increasing VEGF bioavailability at sites of endothelial denudation has been shown to accelerate endothelial repair and to limit neointima formation 34 . Moreover, VEGF overexpression within the vascular wall has been shown to restore endothelium-dependent relaxation and to protect against vasoconstriction and platelet activation. The overall balance between VEGF and other platelet-derived non-specific mitogens such as PDGF may, therefore, be of importance in pulmonary vascular diseases and pulmonary hypertension. In recent studies, we investigated serum and platelet VEGF and PDGF in a large population of patients with pulmonary arterial hypertension, either idi-opathic or associated with various diseases, as well as in patients with chronic hypoxemic lung disease. We found that platelet VEGF content was markedly elevated in patients with idiopathic or associated PH,...

Effects of Exogenous VEGF on Development of Experimental Pulmonary Hypertension and Endotheliumdependent Relaxation

In addition to its well-known angiogenic properties, VEGF has been shown to protect against endothelial vascular injury and to improve endothelial function. Our previous finding of impaired endothelium-dependent relaxation in chronic hypoxic pulmonary hypertension 1 invited an investigation of whether lung VEGF overexpression can protect against hypoxic pulmonary hypertension and alter the development of pulmonary vascular remodeling. Gene therapy may be a valuable therapeutic approach in pulmonary hypertension. Several studies using intratracheal administration of adeno-virus vectors have shown that transgene expression is mainly located in epithelial cells 15 . Using this route of administration, previous studies demonstrated that adenoviral-mediated gene transfer of human endothelial nitric oxide synthase (eNOS) in rats was associated with a reduction in acute pulmonary vasoconstriction 17 . We therefore reasoned that overexpression of a secreted and diffusible form of VEGF...

Effects of Inhibition of Lung Overexpression of Angiostatin on Development of Experimental Pulmonary Hypertension in

Whereas lung VEGF overexpression by adenovirus mediated gene transfer attenuates development of hypoxic pulmonary hypertension 28 . However, VEGF is only one among various angiogenic molecules that are upregu-lated during chronic hypoxia. Moreover, VEGF receptors are present not only on endothelial cells but also on lung epithelial cells and monocytes 2,4 . Finally, the regulation of angiogenesis is a complex process, which depends upon the local balance between proangiogenic and antiangiogenic molecules. In recent studies, we questioned whether changing the angiogenic set point by inducing lung overexpression of an endogenous angiogenesis inhibitor would alter development of hypoxic pulmonary hypertension. Indeed, physiological angiogenesis is a highly regulated process under the control of both angiogenic and antiangiogenic factors. A number of endogenous angiogenesis inhibitors have been identified that antagonize the effects of VEGF, FGFs and other angiogenic factors. Among those...

Tetrahydrobiopterin in Pulmonary Hypertension Nitric Oxide in Pulmonary Hypertension

Loss of NO is implicated in pulmonary hypertension. Administration of NOS inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME), increases pulmonary vascular resistance and augments pulmonary vasoconstrictor responses to hypoxia 1 . Mice deficient in eNOS are more sensitive to hypoxia-induced pulmonary hypertension 19,73 , whereas overexpression of eNOS in the lung is partially protective 63,13 . Patients with pulmonary hypertension have lower NO levels in their exhaled breath, a lower plasma L-citrulline L-arginine ratio, lower urinary NO metabolites, and impaired endothelial-dependent vasorelaxation 42,50,56,26 . Furthermore, both inhaled NO and phosphodiesterase type 5 inhibitors, which act to increase NO-mediated cGMP signalling, have emerged as therapeutic options for pulmonary hypertension 23,38,89 . Reduced eNOS protein in lung tissues from patients with pulmonary hypertension has been described, which may again account for the low NO levels 24 . However, others have...

High altitude and hypertension during pregnancy

The first published report indicating that residence at high altitude may be associated with an increased risk for pre-eclampsia was by Colorado researchers in 1982. Pregnancy-induced hypertension, noted as a diagnosis within medical records, occurred in 12 , 4 and 3 of pregnancies at 3100 m, 2410 m and 1600 m, respectively. Proteinuria greater than 1+ was noted in 28 and 9 of pregnancies at 3100 m and 1600 m, respectively. Blood pressure was generally higher in all pregnant women at high altitude based on medical records review. Further, in a small group of prospectively studied women with pregnancy-induced hypertension (PIH, hypertension without proteinuria or other organ system involvement), arterial oxygen saturation (which is largely determined by maternal arterial PO2) was inversely correlated with blood pressure. Thus women with the lowest saturations had the highest mean arterial pressures (Moore et al., 1982). Support for the idea that lowered maternal arterial oxygen...

Hypertensive disorders in pregnancy and hypertension in later life

There is more information about the risk of hypertension in later life and previous pre-eclampsia than any other long-term outcome. This is probably because hypertension is relatively common in younger women. Relatively young women remain the focus for most of these studies for the pragmatic reason that computerized databases of pregnancy outcome are relatively recent and represent the most convenient way for initiating large-scale longitudinal studies, due to the expense of dedicated prospective observational studies. Wilson et al. described the long-term outcome for a cohort of women delivering in Aberdeen, Scotland between 1951 and 1970 (Wilson et al., 2003). Women were classified into normotensive, gestational hypertension (i.e. hypertension without proteinuria) and pre-eclampsia (i.e. hypertension with proteinuria). Hypertension in later life was ascertained by questionnaire and physical examination of respondents within the cohort. While this is open to recall bias and...

Preexistingchronic hypertension

Women with pre-existing hypertension have an increased risk of superimposed pre-eclampsia. A Canadian study found an incidence of preeclampsia of 21.2 in 337 women with chronic hypertension compared to an incidence of 2.3 in the control population (P 170 110) and those requiring more than one agent should be converted directly to one of the first-line drugs. If hypertension is noted for the first time in the first trimester or early second trimester, it is likely that it is a chronic, pre-existing problem, since pregnancy-induced hypertension (including pre-eclampsia) usually, but not invariably, appears in the second half of pregnancy. Hypertension in any young person should not be attributed to essential hypertension (particularly in the absence of a family history) before secondary causes such as renal or cardiac disease (coarctation of the aorta), and rarely Cushing's syndrome, Conn's syndrome (and other causes of hyperaldosteronism) or phaeochromocytoma have been excluded. Of...

Gestational hypertension

Gestational hypertension is usually characterized by the onset of hypertension, after 20 weeks gestation, in the absence of signs or symptoms suggesting pre-eclampsia or chronic hypertension. It may be the pre-protein phase of pre-eclampsia, the return to the high blood pressure levels of essential hypertension after the normal physiological nadir of the second trimester, or the heralding of a latent hypertensive problem that will develop in later life. No matter what the underlying pathology, any woman who develops a blood pressure above 140 90 mmHg should be seen to be at risk of progression to pre-eclampsia and assessed accordingly (Walker, 2000, 2003).

Use of antihypertensive therapy

In women who have an elevated blood pressure but do not have true pre-eclampsia and do not require admission to hospital, antihypertensive therapy can be introduced. In the United Kingdom during the past 20 years, the use of antihypertensive drugs has increased (Walker, 2000). This has been associated with a reduction in the incidence of cerebral vascular accident as a cause of maternal mortality, although other factors may be involved. If blood pressure is above 160 100 mmHg, treatment is started in an effort to reduce the risk of hypertensive crisis, the need for further antihyper-tensive therapy and the need for a hospital admission. Methyldopa and labetalol are the most common antihypertensive therapies used in pregnancy (Magee et al., 1999). Methyldopa has proven safety in terms of long-term follow up of delivered babies (Ounsted et al., 1980). Labetalol would appear to be at least equally safe (Magee and Duley, 2000) but atenalol is associated with an increase in fetal growth...

Are women with preeclampsiaeclampsia at risk of chronic hypertension in later life

In women with a history of pre-eclampsia eclamp-sia, the reported risk for the development of chronic hypertension ranges from 0 to 78 (average 23.8 ) (Chesley et al., 1976 Sibai et al., 1986b, 1991, 1992).The risk appears to be increased in that subgroup of women who have subsequent hypertensive pregnancies as well as in those with eclampsia remote from term (Chesley et al., 1976 Sibai et al., 1986b, 1992). The wide range in reported risk is due to the influence of variables such as maternal age and duration of follow-up (the increased risk of subsequent hypertension only becomes apparent after an average follow-up of 10 years) (Sibai etal., 1986b). In addition to hypertension, women with a history of pre-eclampsia eclampsia are also at risk of developing diabetes. In one report, the incidence of diabetes in this cohort at an average follow-up of 25years was 8.3 , which is 2.5-fold higher than expected (Chesley et al., 1976). This is similar to the 5.6 incidence of subsequent...

Lung Vegf Expression During Pulmonary Hypertension Or During Exposure To Chronic Hypoxia

In recent studies, we examined the effects of exposure to chronic hypoxia (CH) and treatment with monocrotaline (MCT) on VEGF gene expression in heart and lung tissues of rats (Figure 1). The main finding of our study is that an angiogenic process is associated with right ventricular hypertrophy in hypoxia-induced pulmonary hypertension and that this process may be related to upregulation of VEGF expression in right ventricular tissue 27 . In contrast, monocrotaline-induced pulmonary hypertension caused right ventricular hypertrophy without cardiac angiogenesis, a finding consistent with down-regulation of VEGF gene expression in the right ventricular myocardium 27 . Taken together, these findings strongly suggest that VEGF plays an important role in controlling right ventricular perfusion during hypertrophy secondary to pulmonary hypertension. Moreover, lung VEGF mRNA levels were also strikingly decreased in rats given MCT, but remained unchanged after exposure to hypoxia. Since...

Cirrhosis and portal hypertension

Hepatocellular Adenoma Mri

The commonest cause of portal hypertension is cirrhosis secondary to alcoholic liver disease or chronic hepatitis B or C (see Fig. 6.24), further causes are listed in Table 6.3. Imaging features of cirrhosis and portal hypertension include liver nodularity, reversal of portal blood flow (demonstrated on ultrasound), porto-systemic colateral vessels, splenomegaly, ascites and complications such as hepatoma. Porto-systemic colateral vessels occur at many sites (see Table 6.4) as a consequence of portal hypertension (see Fig. 6.25). Table 6.3 Causes of Portal Hypertension

White coat hypertension

The anxiety caused by the measurement itself or the environment in which it is taken can influence blood pressure by what is known as a defense reaction (Mancia et al., 1983, 1987). When the blood pressure of the patient is constantly higher when measured in the clinical environment than at home, it is known as white coat hypertension, i.e. patients who have white coat hypertension have a blood pressure that is within the normal range outside the clinic setting (Pickering et al., 2002). This phenomenon was first described more than 60 years ago (Ayman and Golshine, 1940). The mechanism of white coat hypertension is still being investigated. It is thought that it may be due to an exaggerated learning or orientating response to stressful stimuli. However, studies have failed to demonstrate an increase in laboratory stressors when comparing individuals with white coat and sustained hypertension (Floras et al., 1981 Siegel et al., 1990). There is also no difference in the variability of...

Hypertension as a predisposing factor for preeclampsia

In humans, the risk factors of essential hypertension and pre-eclampsia overlap considerably and, indeed, pre-existing hypertension increases the risk of pre-eclampsia (Eskenazi et al., 1991 Sibai et al., 1995). It is therefore not surprising that some genes that have been implicated as risk factors for pre-eclampsia, AGT (encoding angiotensinogen, a precursor of the vasoconstrictor angiotensin) (Ward et al., 1993) and NOS3 (encoding endothelial nitric oxide synthetase, eNOS) (Arngrimsson et al., 1997), are also risk factors for essential hypertension. Notably, the associations with the AGT and NOS3 genes have not been confirmed in all affected families (Lachmeijer et al., 2002 Roberts and Cooper, 2001), implying that AGT and NOS3 mutations likely do not explain all cases of pre-eclampsia. Based on these human studies alone it is difficult to say whether hypertension alone is sufficient to promote the development of pre-eclampsia. However, recent work in mice suggests that it is....

Control of severe hypertension

The objective of treating acute severe hypertension is to prevent potential cerebrovascular and cardiovascular complications such as encephalopathy, hemorrhage, and congestive heart failure (National High Blood Pressure Working Group, 2000). For obvious ethical reasons, there are no randomized trials to determine the level of hypertension to treat in order to prevent these complications. The point at which to begin antihyperten-sive drug therapy is not clear. Antihypertensive therapy is recommended by some for sustained systolic blood pressure values of 180 mmHg, and for sustained diastolic values of 110 mmHg. Some experts recommend treating systolic levels of 160 mmHg, others recommend treating diastolic levels of 105 mmHg, whereas others use a mean arterial blood pressure of 126 130 mmHg (ACOG Practice Bulletin, 2001 National High Blood Pressure Working Group, 2000). The definition of sustained hypertension is not clear and ranges from 30 min to 2 h. The most commonly used and...

Diagnosis of superimposed preeclampsia in chronic hypertension renal disease and diabetes

In contrast to gestational hypertension and preeclampsia that occur in the second half of pregnancy, hypertension that is evident before 20 weeks' gestation is diagnosed as chronic hypertension. The Australasian and American classifications are consistent in their definitions of chronic hypertension, blood pressure 140 mmHg systolic and or 90 mmHg diastolic pre-conception or in the first half of pregnancy (Anonymous, 2000 Brown et al., 2000). Rare exceptions include hydatidiform molar pregnancies, severe renal disease or antiphospholid syndrome and occasional chromosomal anomalies, where true pre-eclampsia can occur before 20 weeks. For women presenting with hypertension for the first time in early pregnancy, it is necessary to confirm that their blood pressure remains elevated at least 3 months after delivery. Chronic hypertension is subdivided into essential and secondary due to underlying causes such as renal disease (e.g. glomerulonephritis, reflux nephropathy, adult polycystic...

Sildenafil And Hypoxic Pulmonary Hypertension

Abstract We have previously demonstrated that sildenafil inhibits hypoxia-induced pulmonary vasoconstriction in healthy subjects. The aim of this study was to investigate the effects of the PDE5 inhibitor sildena-fil on pulmonary hemodynamics in patients with high altitude pulmonary hypertension (HAPH). Twenty-two patients with HAPH were randomized by age and level of mean pulmonary arterial pressure (PAP) in 3 groups a first group (n 9) treated with 25 mg of sildenafil 3 times a day a second group (n 5) - received 100 mg of sildenafil 3 times a day a third group (n 8) - treated with placebo. Pulmonary hemodynamics was measured by right heart catheterization at baseline and after 12 weeks of sildenafil therapy at, before and 1 hour after taking sildenafil or placebo. Keywords altitude pulmonary hypertension sildenafil exercise right heart failure.

Chronic Hypoxic Pulmonary Hypertension

Chronic hypoxic pulmonary hypertension is the consequence of both pulmonary vasoconstriction and remodeling. The importance of each component is still disputed. It is usually considered that proliferation (or decreased apoptosis) of cells in the intima, media and adventitia causes the vessel wall to intrude upon the lumen and pose a fixed resistance to flow through the lungs. Supporting this contention is the repeated observation that after several weeks of hypoxia, return to normoxia or to hyperoxia does not rapidly restore pulmonary vascular resistance to pre-hypoxic levels. However, it has recently been reported that the compound Y-27632, which inhibits Rho kinase and calcium sensitization, will acutely reverse chronic hypoxic pulmonary hypertension. Thus, chronic hypoxia sets in play a signaling cascade causing vasoconstriction that persists when the hypoxic stimulus is removed. This signaling cascade can be rapidly interrupted by Y-27632, (but not immediately by oxygen),...

Oxidative Stress in Pulmonary Hypertension

The association of oxidative stress with pulmonary hypertension is increasingly recognised. Markers of oxidative stress are increased in patients with pulmonary hypertension 6,16,59 . Superoxide mediates pulmonary smooth muscle cell proliferation after exposure to endothe-lin-1 85 , and pulmonary vasoconstriction after exposure to 5-HT 49 . Increased superoxide production from NADPH oxidase has been associated with pulmonary hypertension in foetal lambs after in-utero ductal ligation 8 . Superoxide produced from xanthine oxidase appears to contribute to the development of hypoxia-induced pulmonary hypertension in rodents 35 .

Proposal For Classification Of High Altitude Pulmonary Hypertension

A revised clinical classification of PH was proposed by Simonneau et al. during the Third World Symposium on Pulmonary Arterial Hypertension, and HAPH was considered in item 3.5 as Chronic exposure to high altitude 69 . For those interested in high altitude medicine, we propose a more detailed classification of HAPH with the corresponding clinical conditions, as follows High Altitude Pulmonary Hypertension.

Hypertension Relationships to Coronary Heart Disease and Stroke

Hypertension is positively correlated with CHD and stroke mortality, and is generally accepted as one of the major risk factors for eventual CHD mortality. The term 'risk factor' generally indicates an associated occurrence, but it does not automatically mean that reducing a risk factor will be beneficial, as it would be for a causal risk factor. Although hypertension has a logical causal relationship to hemorrhagic stroke, its relationship to thrombotic or ischemic events remains to be established. Both CHD and hypertension might independently be made worse by some processes initiated by some common dietary causes. By now, scientists can see that neither CHD nor hypertension is likely to be due to dietary cholesterol. However, both disorders may relate to an unbalanced dietary intake of 6 over 3 PUFAs that causes unbalanced signaling from 6 over 3 eicosanoids. A meta-analysis of 36 clinical trials involving 2,114 subjects showed that supplementing with high intakes of fish oil gave...

Severe and resistant hypertension

Hypertension beyond a mean arterial pressure of 140 mmHg is associated with a risk of cerebrovascular hemorrhage. The mean arterial pressure (MAP) exact level at which the blood-brain barrier begins to break down in pre-eclampsia eclampsia is unclear but we do know that cerebral autoregulation is affected in this condition and that brain overperfusion can occur at lower MAP levels than in non-pre-eclamptic patients (Belfort et al., 1999a, b, 2000, 2001, 2002a). In practice, any blood pressure above 160 110 mmHg is usually regarded as an indication for aggressive antihypertensive therapy. The goal of antihypertensive therapy should be to maintain systemic MAP between 100 and 126 mmHg. Patients admitted to intensive care units and managed with the benefit of invasive hemody-namic monitoring should have vasodilator therapy titrated against both systemic blood pressure and derived parameters such as systemic vascular resistance (SVR). The SVR should be restored to normal levels (1000 and...

Hemodynamics And Pathology

In 1963, with the name of primary pulmonary hypertension in children living at high altitude , Khoury and Hawes reported their findings in 11 infants from 6 to 23 months living in Leaville, Colorado (3,100 m). Five of them were moved to Denver, Colorado (1500 m) and had cardiac catheterization with an average mPAP of 44 mm Hg and a range of 28-72 mm Hg. Post-mortem studies in two patients showed severe RVH and marked hypertrophy of the medial muscular coat and intimal proliferation, but not occlusive lesions 25 . In the following years Tibetan investigators described similar pathological findings in 57 infants who died with the diagnosis of pediatric HAHD 28 and several years later, the same authors extended their investigations to 100 infants with HAHD 27 . Lin and Wu published their clinical observations in 286 cases of pediatric HAHD 30 .

The Cellular Effects Of Hypoxia In The Pulmonary Circulation

Abstract Hypoxia causes pulmonary hypertension in nearly all species studied. The pulmonary hypertension is accompanied and augmented by pulmonary vascular remodelling. Vascular remodelling is characterised largely by fibroblast, smooth muscle cell (SMC) and endothelial cell proliferation, which results in lumen obliteration. Chronic hypoxia elicits expression of several mitogens, growth factors and cytokines by pulmonary vascular cells and the suppression of anti-proliferative factors. Although hypoxic pulmonary vascular remodelling is associated with medial hypertrophy, in vitro hypoxia does not lead directly to an increase in smooth muscle cell proliferation. It is possible that hypoxia is sensed by fibroblasts, endothelial cells, or both, and intercellular signalling by growth factors, cytokines and other mitogens to adjacent pulmonary artery SMC is the underlying mechanism for the medial hypertrophy of pulmonary vascular remodelling.

Lan Zhao Francis Bahaa Martin Wilkins

Abstract The integrity of the pulmonary vascular endothelium plays a key role in pulmonary vascular homeostasis. In particular, reduced endothelial-derived nitric oxide (NO) bioavailability is implicated in the pathogenesis of pulmonary hypertension. Recent studies in complementary murine genetic models provide clear evidence that tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase (eNOS), is a key determinant of NO production in pulmonary vasculature and that lack of BH4 leads to increased superoxide production. Congenital deficiency of BH4 in the mouse is associated with structural changes in pulmonary vessels from birth and pulmonary hypertension in the adult. Conversely, increased local production in vascular endothelium protects against hypoxia-induced pulmonary hypertension. The data suggest a possible therapeutic role for BH4 in the management of pulmonary hypertension. Keywords tretrahydrobiopterin pulmonary hypertension nitric oxide....

Pulmonary Adaptation To High Altitude In Wild Mammals

Abstract The increased pulmonary artery pressure or right ventricular hypertrophy at high altitude has been reported to vary widely among species and individuals of the same species even when they are exposed to the same altitude. Reeves et al. reported species differences in the increase in the pulmonary artery pressure resulting from chronic exposure to high altitude although pulmonary hypertension induced by exposure to high altitudes was remarkable in the cow and horse, it was minimal in the llama, dog, sheep and rabbit. It was also shown that there are two types of cow, i.e., the susceptive type, which shows marked increases in pulmonary artery pressure when exposed to high altitude and the resistant type, which is less responsive to changes in altitude. Genetic factors have been suggested to play an important role in terms of sensitivity to exposure to high altitude. Similar differences in the responsiveness to hypoxia have also been noticed in humans some individuals develop...

C838A Polymorphism of P27kip1 Gene

The balance between cell proliferation and cell quiescence is regulated by a variety of cellular mediators, in which cyclin-dependent kinases and their inhibitors play a very important role. The CDK inhibitor p27 is very important in inhibition of pulmonary artery smooth cell growth, both in vitro and in vivo. In chronically hypoxic mice lungs, hypoxia significantly inhibited p27 expression, showing a 98 decrease in p27 72 . The inhibition of hypoxic pulmonary vascular remodelling by heparin required the p27 expression 73 . In p27 null mice exposed to hypoxia, heparin did not inhibit cell proliferation in pulmonary vessels. These data strengthen the previous findings that p27 is the only CDK inhibitor involved in hypoxia-induced pulmonary hypertension 73 . Gene encoding p27 is localized on chromosome 12p 13. The known C838A polymorphism of p27 gene is associated with decreased activity of promoter region (32). The A838 allele is associated with decreased expression of p27 and...

Cardiac Limitation To Exercise Capacity At High Altitudes

Abstract Exposure to high altitude is associated with a decrease in aerobic exercise capacity. This is explained by a decrease in oxygen delivery to the tissues or the product of cardiac output by arterial oxygen content. Arterial oxygen content is decreased at altitude because of a reduced inspired partial pressure of oxygen. However, this limited by the hypoxic chemoreflex, which increases ventilation and decreases alveolar partial pressure of carbon dioxide, thereby improving alveolar partial pressure of oxygen. In addition, there is a renal synthesis and release of erythropoietin, which increases the hemoglobin content of the blood. Both adaptations bring arterial oxygen content back to its pre-hypoxic exposure sea-level value in 2 to 3 weeks at altitudes up to 5000 m, without, however, restoring exercise capacity. Altitude is also associated with a decrease in maximum cardiac output. The mechanisms of hypoxia-induced decrease in maximum cardiac output remain incompletely...

Tk Kadyraliev Nk Raiymbekov Aa Aldashev

Abstract The aim of this study was to investigate the adaptive and non-adaptive structural changes of the pulmonary vessels during the development of high-altitude pulmonary hypertension (HAPH) and their characteristics in patients with COPD at high altitude. Histological, morphometrical and electron microscopy methods were applied. In native highlanders, due to long (chronic) adaptation, regional morphofunctional changes of the pulmonary vessels develop, which are caused by strengthening of the upper and medial zones of the lungs, increase in the capacity of the capillary channel and the extent of working zones of the air haematic barrier. The following characteristics are revealed in patients with chronic obstructive pulmonary diseases (COPD) at high altitude remodeling of pulmonary arteries and arterioles, substantial expressed arterializations of the finest arterioles by diameter from 30 to 40 microns, with simultaneous increase in their quantity, reduction of terminal arteries...

Hypoxic Pulmonary Vasoconstriction

After birth, HPV may occur as a result of a localized area of alveolar hypoventilation (e.g., atelectasis). This HPV diverts the flow of relatively desaturated, mixed venous blood to better ventilated areas of the lung. If HPV is inhibited, there is a reduction in systemic arterial oxygen tension, even in normal subjects, but particularly in patients with small airways disease 7 . Thus HPV in the presence of localized hypoxia is beneficial but generalized hypoxia can lead to pulmonary hypertension and remodeling. Acute HPV predominantly affects small pulmonary arteries and veins ( 500 in diameter) 23 . The executive mechanism of HPV has three components. The first requires hypoxic inhibition of K+ channels in the cell membrane of the pulmonary artery smooth muscle cells (PASMCs), membrane depolarization and calcium entry through the L-type calcium channel, just as occurs in the carotid body type 1 cell 18 13 . The second involves release of calcium from the sarcoplasmic reticulum of...

Transgenic Gtpch Deficiency and Overexpression in Mouse

Hypertension Mouse

We first demonstrate that congenital BH4 deficiency in the hph-1 mouse results in the development of pulmonary hypertension and vascular remodelling in the adult under normoxic conditions and exacerbates the response to hypoxia 43 . Conversely, augmentation of endothelial BH4 biosynthesis in the GCH transgenic mouse (in which GCH-overexpression is target to endothelial cells) protects against the development of hypoxia-induced pulmonary hypertension and vascular remodelling during 4 weeks of hypoxia (unpublished data). Selective restoration of endothelial BH4 levels in the hph1 strain by intercross with the GCH transgenic mouse rescues the effects of systemic BH4 deficiency. A striking quantitative correlation was observed between lung BH4 levels and the development of pulmonary hypertension across the 5 genetic mouse models evaluated in our studies, suggesting that BH4 bioavailability controls both pulmonary vascular tone and structural remodelling in a dose-dependent manner 43 ....

Limitations And Expansion Of The Scoring System For Diagnosis Of Chronic Mountain Sickness

Aldashev A, Sarybaev AS, Sydkykov AS, Kalmyrzaev BB, Kim EV, Mamanova LB, Maripov R, Kojonazarov BK, Mirrakhimov MM, Wilkins MR, Morrell NW (2002) Characterization of high-altitude pulmonary hypertension in the Kyrgyz Association with angiotensin-con-verting enzyme genotype. Am J Respir Crit Care Med 166 1396-1402 5. Antezana AM, Antezana G, Aparicio O, Noriega I, Leon-Velarde F, Richalet JP (1998) Pulmonary hypertension in high-altitude chronic hypoxia response to nifedipine. Eur Respir J 12 1181-1185 7. Arias-Stella J. Morphological patterns Mechanism of pulmonary arterial hypertension. In Life at High Altitudes. Pan American Health Organization, Scientific Publication No. 140, Washington DC, 1966 9-12 11. Barst RJ, McGoon M, Torbicki A, Sitbon O, Krowka MJ, Olschewsky H, Gaine S (2004) Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 43 40S-47S 14. Cheng DS, Yang YX, Bian HP, Lu YZ, Liu PF, Zhou HL, Go BH. A study on altitude hypoxic...

Definition and Nomenclature

PHAHD, also named ISMS, is a syndrome, which is the occurrence of symptomatic, severe pulmonary hypertension in infants or young children who were born or brought up at high altitude above 3000 m symptoms result from an excessive increase in pulmonary artery pressure and right heart failure. These infants often died if continuously exposed to high altitude and autopsy revealed extreme medial hypertrophy of the pulmonary arteries and an increased muscularization of the pulmonary arterioles, as well as right ventricular dilatation and hypertrophy, attributed to secondary to pulmonary vascular disease. The cure for this syndrome is oxygen administration and early evacuation. Various authors use different terms to denote identical altitude illnesses. Since Wu and Liu in 1955 37 first used the term pediatric high altitude heart disease, PHAHD , it is now well accepted for this syndrome in China 44 . After that, in the year 1988, Sui GJ, a Chinese pathologist and his colleagues, in...

Tetrahydrobiopterin and Vascular Disease

Pulmonary Hypertension Vascular Changes

In vivo studies using disease models and gene-modified animals have also suggested an important role of BH4 in cardiovascular disease. BH4 deficiency due to increased oxidative stress appears to mediate chronic DOCA-salt induced hypertension in rodents 46,94 . Cardiac hypertrophy from pressure overload induced by aortic banding has been shown to trigger myocardial eNOS uncoupling, reversible by BH4 supplementation 77 . In eNOS transgenic ApoE-KO mice, enhanced superoxide production and accelerated atherosclerosis were prevented by pharmacological BH4 supplementation 64 . The GTPCH deficient (hph-1) mouse has reduced levels of BH4 and appears to have impaired NOS coupling 15 . Targeted overexpression of endothelial GTPCH, augmenting BH4 levels in the endothelium, can improve eNOS function and endothelial dysfunction in diabetic mice and also reduce atherosclerosis in ApoE-KO mice 2,3 . In humans, acute BH4 administration augments NO-dependent flow-mediated vasodilatation in smokers 32...

High Altitude Cor Pulmonale Definition And Clinical Picture

Kyrgyzian investigators do not have any publications under the name of CMS. Five decades ago they described a clinical picture named High Altitude Pulmonary Hypertension (HAPH), which may evolve to High Altitude Cor Pulmonale (HACP) and HF 36 . This clinical entity is observed in people living at the high altitudes of the Tien-Shan and Pamir Mountains (2800-4200 m) and its prevalence is 4.6 in the male population. HACP is characterized by a variable degree of PH, RVH and HF in the absence of significant hypoxemia and polycythemia 1,67 . Cardiac auscultation and the findings obtained by ECG and chest-X rays resemble those found in patients with CMS 49,55,81 and adult HAHD 62,79,80 .

Tetrahydrobiopterin as a Therapeutic Target

Given the complex pathophysiology of pulmonary hypertension, targeting of multiple pathways with combination drug therapy may be necessary. The ability of BH4 to both augment NO synthesis and decrease superoxide production addresses two pathogenic mechanisms simultaneously. The data support evaluation of pharmacological or molecular strategies that target endothelial BH4 availability in patients with pulmonary hypertension. In this context it is interesting to note that HMG-CoA inhibitors (statins), currently generating significant interest after their reversal of experimental pulmonary hypertension in rats 25 , upregulate GTPCH mRNA and BH4 levels in vascular endothelial cells 31 . A more direct approach would be to examine the clinical efficacy of oral BH4 supplementation in suitable patients. We cannot exclude the possibility that the pulmonary changes in the hph-1 mice occur at the transition from birth to neonatal life, or that BH4 has a particularly critical role in lung...

Rr Kaliev Mm Mirrakhimov

Abstract For a long time, investigations under the initiative of academician M. M. Mirrakhimov (1964 - 2004) used exogenous (hypobaric and high-altitude) hypoxia. The most attractive features of the application of hypoxia at chronic glomerulonephritis (ChGN) are its antihyperlipidemic, antihypertensive, immunomodulating and erythropoiesis-stimulating properties. Development of the new method of treatment for hyperlipidemia in nephrotic ChGN with the separate use of exogenous hypoxia and mevacor, and also their combined application and study of the effects of high-altitude climate on ChGN patients with a urinary syndrome. Two groups of patients with ChGN were studied. In the first group, 51 patients ChGN with NS ( ) were surveyed. They were divided into 4 subgroups depending on treatment (of hypobaric hypoxia training, mevacor, combination of hypoxia with mevacor and control). The second group included 17 patients with expressed urinary syndrome and was treated in a high-altitude...


Disease and B) High Altitude Pulmonary Hypertension (HAPH), which includes several entities 1) High Altitude Heart Disease (HAHD) of adult chronic type, described in China, 2) High Altitude Cor Pulmonale (HACP) described in Kyrgyzstan, and 3) Subacute Mountain Sickness (SMS), also named subacute High Altitude Heart Disease (subacute HAHD) of infantile and adult types.


In conclusion, exposure to chronic hypoxia is associated with the activation of endogenous lung angiogenic processes, which attenuate the severity of pulmonary hypertension. Recent studies also provide evidence that the angiopoietin-1 Tie2 pathway is abnormal in idiopathic PAH and contributes to PA-SMC hyperplasia through excessive release of growth factors by ECs. Since Ang1 is now considered a pericyte-derived paracrine signal for the endothelium, these findings identify dysregulation of cross-talk between endothelial and smooth muscle cells as an important component of pulmonary vascular remodeling. Further studies are needed to better understand the importance of these abnormalities in the process of hypoxia-induced smooth muscle proliferation.

Almaz A Aldashev

Abstract High altitude pulmonary hypertension (HAPH) is a genetically determined trait, associated with the diminished oxygen content at high altitudes and it usually affects native or long-term highlanders and may reflect a loss of adaptation. This paper reviews the epidemiological evidence for a genetic trait of the altitude-related illnesses, mainly HAPH, as well as the molecular evidence for the contribution of the specific candidate genes or pathways involved. We focus on our own data and experience in the research of genetics of HAPH done on the indigenous population of Pamir and Tien-Shan mountains. These data include the existence or lack of association of polymorphisms of ACE gene, P2-adrenoreceptor gene, C677T polymorphism of MTHFR gene, 838 C A polymorphism of p27kip1, polymorphisms of eNOS gene and S L polymorphism of 5-HTT gene. Keywords HAPH hypoxic pulmonary hypertension altitude sickness genetic epidemiology gene polymorphism

Hemodynamic Studies

Pulmonary hypertension was presented in all, the mean pulmonary artery pressure (MPAP) ranging from 33 2 mmHg to 47 24 mmHg, with a normal pulmonary wedge pressure (4-8 mmHg). Pulmonary vascular resistances were increased to 686-1078 dynes sec cm. The administration of 100 percent oxygen rapidly lower PAP but normal values were not reached. Exercise and induced hypoxia resulted in a marked rise in pressure.


Typical PHAHD is not difficult to diagnose. The infant presents a history of born or brought up to high altitude, the findings of a severe pulmonary hypertension (MPAP 4 kPa or 30 mmHg, via noninvasive echo-Doppler, or catheterization ), right ventricular hypertrophy and congestive heart failure support the diagnosis of PHAHD. However, PHAHD may be most readily confused with primary pulmonary hypertension (PPH) and congenital heart disease at high altitude. TABLE 2. Cardiac catheterization data in infants or children with severe pulmonary hypertension in mountainous areas of the world TABLE 2. Cardiac catheterization data in infants or children with severe pulmonary hypertension in mountainous areas of the world

Inder S Anand

High altitude pulmonary edema (HAPE) is a life threatening condition 13 characterized by pulmonary hypertension, increased pulmonary c apillary permeability, and hypoxemia 9, 12, 19 . Although the mechanisms responsible for the development of HAPE are not entirely clear, measurements of pulmonary hemodynamics in patients with HAPE or incipient HAPE suggest that edema is caused by uneven severe hypoxic pulmonary vasoconstriction and an increase in pulmonary artery pressure in the lungs without elevation of left atrial pressure. This results in leakage of large-molecular-weight proteins and erythrocytes across the alveolar capillaries in areas of the lung that are not vasoconstricted 2, 6, 11, 15 . Earlier studies of broncho alveolar lavage (BAL) fluid had suggested that inflammation may play a role in the genesis of HAPE 19 . More recent studies have, however, disproved any role of inflammation in its pathogenesis 19, 20,21 . Taken together, these studies strongly suggests that high...

Dante Penaloza

Abstract An expert consensus workshop group of the International Society for Mountain Medicine recently proposed a new classification of high altitude diseases. Chronic mountain disease or Monge's disease was defined as a separate entity on the assumption that pulmonary hypertension was not always identified in these patients. This may have to be revised. Healthy high altitude natives living above 3500 m have pulmonary hypertension and right ventricular hypertrophy associated to hypoxemia and polycythemia. There is a direct relation between the level of altitude and the degree of pulmonary hypertension, with exception of Tibetan natives who have the oldest altitude ancestry. After many years of residence at high altitude, some healthy highlanders may lose their adaptation and develop chronic mountain sickness, a clinical entity associated with marked hypoxemia, exaggerated polycythemia and increased pulmonary hypertension, evolving in some cases to heart failure. Other chronic high...


The principal findings of this study are (a) the pulmonary artery pressure (Ppa), the ratio of right to left ventricular weight (RVW LVW) and hematocrit (Ht) increased in accordance with the height of living altitude in all mammals, whereas in mammals well-adapted to high altitude, such as pika, blue-sheep and Yachi-nezumi, showed significantly lower values compared to other mammals (b) when the mammals were exposed to simulated high altitude, hypoxic pulmonary vasoconstriction (HPV) in blue-sheep was significantly attenuated compared to pig and (c) at the same altitude, a warm environment (by seasonal, latitudinal, and global warming effects) caused the decreasing RVW LVW and Ht. These findings suggest that mammals well-adapted to high altitude such as pika, blue sheep and Yachi-nezumi have a potent adaptability to high altitude environments, having a small degree of right ventricular hypertrophy, low grade pulmonary hypertension and a small degree of Ht level at high altitude....

The Nature of PHAHD

Transverse section of a muscular pulmonary artery from a Han male infant aged 4 months with ISMS and severe pulmonary hypertension. There is a very thick muscular media sandwich between the internal and external elastic laminae (HEx 100) (After Li and Jiao, 1983). Figure 4. Transverse section of a muscular pulmonary artery from a Han male infant aged 4 months with ISMS and severe pulmonary hypertension. There is a very thick muscular media sandwich between the internal and external elastic laminae (HEx 100) (After Li and Jiao, 1983).

Tianyi Wu

Abbreviations PHAHD pediatric high altitude heart disease ISMS subacute infantile mountain sickness SH APH symptomatic high altitude pulmonary hypertension HAHD high altitude heart disease MPAP mean pulmonary artery pressure PPH primary pulmonary hypertension CMS chronic mountain sickness. Abstract Previous studies suggest that Tibetans as the oldest mountainous population are better adapted to high altitude. We hypothesized that Tibetans have an unusually small degree of hypoxic pulmonary vasoconstriction (HPV) compared with Han newcomers from the lowlands acclimatized to high altitude. We have studied the pulmonary hemodynamics in healthy Tibetan highlanders and Han newcomers in Qinghai-Tibet. Data were collected from right cardiac catheterization. Cardiac output (CO), pulmonary artery wedge pressure and pulmonary artery pressure were measured in all volunteers at various altitudes. At a given altitude, Tibetans show a lower mean pulmonary artery pressure (MPAP) than Han subjects at...

Vascular defects in different disorders of pregnancy

In the years immediately following the discovery of failed physiological changes in pre-eclampsia, it was assumed that this histopathological defect could be considered as pathognomonic for the disease. It was thereby thought that in other hypertensive disorders, such as essential or chronic hypertension, trophoblast invasion occurred normally, as long as no pre-eclampsia was superimposed on the pre-existing hypertension (Brosens, 1977). The finding that the physiological change of spiral arteries could also be impaired in intrauterine growth restriction without hypertension, was initially somewhat of a surprise and led to animated debates between different investigators (Brosens et al., 1977 Robertson et al., 1986 Sheppard and Bonnar, 1976, 1981). Especially the occurrence of acute atherosis, another putative pathognomonic feature, in non-hypertensive cases of intrauterine growth restriction (IUGR) was under discussion. One of the difficulties was how to distinguish true foam cells...

Example from the literature

Testa et al. (1993) describe an RCT evaluating hypertensive therapy in men. Two angiotensin-converting-enzyme inhibitors, captopril and enalapril, were compared. In total, 379 active men with mild to moderate hypertension, aged 55 to 79, were randomised between the treatment arms. QoL was one of the main outcome measures. Several QoL scales were used, including an Overall QoL scale based on a mean score from 11 subscales.

Sammy SaabSteven Huy Han and Paul Martin

Ascites remains one of the most difficult management problems in the OLT candidate (Fig. 3.1.). Paracentesis should be performed on initial presentation to confirm portal hypertension as the cause of ascites. As an initial treatment, salt restriction is efficacious in less than 20 of patients, thus necessitating diuretic use. Fluid restriction is recommended only if the serum sodium is less than 120 mEq L. Rapid correction of hyponatremia should be avoided as it has been implicated in the pathogenesis of central pontine myelinolysis post-OLT. hepatocellular Failure and portal hypertension Urine sodium 10 mEq L

Increased Coronary Heart Disease Risk by Dietary Recommendations That Were Made Based on the Cholesterol Hypothesis

Subgroup with hypertension and ECG anomaly Subjects were male (35-57 years old) with high risk for CHD. Special intervention consisted of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering TC shown in table 2 . Follow-up was for 7 years on average. Conclusions and Discussion Three possible explanations for these findings are considered (1) the overall intervention program, under these circumstances, does not affect CHD mortality (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of 7years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC (usual care) group, and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI (special intervention) cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all...

Soluble fmslike tyrosine kinase 1 sFlt1

Whereas healthy maternal endothelium is crucial for the physiological adaptation to normal pregnancy, widespread endothelial dysfunction is an integral part of the multi-organ involvement of preeclampsia (Roberts and Redman, 1993). Women with pre-existing medical disorders that are characterized by endothelial dysfunction, such as hypertension and diabetes, are at increased risk of pre-eclampsia. Indeed, many of the risk factors for cardiovascular disease (all except smoking) are also risk factors for pre-eclampsia. Poor placental implantation also plays an important but not yet

Nitric oxide in preeclampsia

Chronic inhibition of NO synthesis with L-NMMA in pregnant rats results in hypertension, protein-uria and fetal growth restriction, a syndrome mimicking pre-eclampsia (Yallampali and Garfield, 1993). Simultaneous infusion of l-arginine has been shown to reverse the hypertension and growth restriction (Molnar et al., 1994 Yallampali and Garfield, 1993). It would be expected that endothelial dysfunction in pre-eclampsia would lead to impaired NOS activity. Due to methodological limitations, however, human studies have not reached a consensus on how NOS activity is altered during pre-eclampsia.

Cardiovascular Disease

Increased control of hypertension through treatment 6. The development of effective medications for treatment of hypertension and hypercholesterolemia, and an increase in coronary-care units and emergency medical services for heart disease and stroke (Chapters 3,15, and 16) (25)

Circulating angiogenic factors in preeclampsia

Soluble Flt-1 (sFlt-1), which binds VEGF, increases in the serum of women with pre-eclampsia (Koga et al., 2003 Maynard et al., 2003 Tsatsaris et al., 2003) as concentrations of circulating free PIGF and VEGF decrease, even prior to the onset of the clinical syndrome (Polliotti et al., 2003 Taylor et al., 2003). A pre-eclamptic-like state with hypertension, proteinuria and glomerular endothe-liosis was induced in pregnant rats by administering exogenous sFlt-1 (Maynard et al., 2003). Moreover, cancer patients treated with VEGF-signaling inhibitors have developed hypertension and proteinuria (Kabbinavar et al., 2003 Yang et al., 2003). Thus, excess sFlt-1 may indeed play an important role in the pathogenesis of pre-eclampsia.

Clarifying Mortality Rates

Attention to the quality of data regarding causes of death could provide insight into the mechanisms of preterm birth as well as the causes of fetal and early neonatal deaths. This approach would require clinicians to vigorously search for causes of death whenever a fetal or early neonatal death occurs. Petersson et al. (2004) found that 11.5 percent of fetal deaths that would have been characterized as unexplained were due to infections with parvovirus, cytomegalovirus, or enterovirus. Other possible causes that should be explored include thrombophilias (e.g., Factor V Leiden), fetomaternal hemorrhage, chorioamnionitis (which would include pathologic examination of the placenta and the umbilical cord), uterine anomalies, umbilical cord or placental anomalies, toxin or drug exposures, and maternal illness (e.g., diabetes, hypertension with or without preeclampsia, thyroid disease, and autoimmune diseases) (Gardosi et al., 2005). Because the most common condition associated with fetal...

Genotyping Single Nucleotide Polymorphisms

More than 99 of the genome sequence is identical across the human population. SNPs reflect the small sequence variations (often a single base change) that can occur within an individual gene. It is important to note that SNPs do not change much from generation to generation. Human genome sequencing projects have identified more than 2 million SNPs as genetic markers. Most SNPs are found outside of coding sequences, but some SNPs found within a coding sequence are of particular interest to researchers, because the change may alter the biological function of a protein. Because of the enormous potential to associate SNP maps with the development of complex diseases such as cancer, Alzheimer's, diabetes, and hypertension, researchers are feverishly working to identify thousands of useful SNP markers. For example, SNPs in the breast cancer genes 1 and 2 are associated with the development of breast cancers (Freedman et al., 2005). SNPs in the apolipoprotein E gene have been linked to a...

Carotid artery stenosis

A R Hypercholesterolemia, hypertension, DM and smoking are all strong risk factors for carotid artery disease. M Medical For asymptomatic or 70 internal carotid artery stenosis at present, recommended treatment is medical, i.e. low-dose aspirin, stopping smoking and treatment of other risk factors, hypercholesterolaemia, hypertension and diabetes. Complications from surgery Cardiac ischaemia or infarction (3 ), cranial nerve injury (2-7 , usually recurrent laryngeal nerve or hypoglossal nerves), haematoma with or without airway compromise, hypertension, hypotension, peri-operative stroke (1-5 ). The peri-operative mortality rate is 0.5-1.8 .

Answer Aortic dissection

Aortic dissection has a peak incidence in the sixth to seventh decade with a male predominance. The associated risk factors are hypertension and medial degeneration. A variety of congenital diseases are associated with dissection and these include Marfan's and Ehlers-Danlos syndrome. Pregnancy and cardiac catheterisation are further risk factors.

Altered Polyamines in the Hypertrophic Phenotype

The rise in polyamine content was accompanied by increased histone acetylation (9), and increased rates of both RNA synthesis (7,9) and protein synthesis (10). Inhibition of polyamine synthesis decreased histone acetylation and RNA transcription, and this effect was reversed by spermine (11). Later studies also implicated increased spermidine and spermine in hypertension and cardiac hypertrophy in a rat angiotensin II infusion model (12).

Benefits of Meditation

Research on the physiological effects of meditation led to the application of meditative techniques as a treatment to combat stress-related illnesses. Meditators have often experienced significant decreases in such problems as general anxiety, high blood pressure, alcoholism, drug addiction, insomnia, and other stress-related problems. Researchers have also found that the scores of meditators on various psychological tests have indicated general mental health, self-esteem, and social openness. Many psychologists argue, however, that these effects are not unique to meditation and can be produced by means of other relaxation techniques. Meditation researcher Robert Ornstein has suggested that the long-term practice of meditation may induce a relative shift in hemispheric dominance in the brain from the left hemisphere, which is associated with such linear processes as language and logical reasoning, to the right hemisphere, which is associated with nonlinear processes such as music...

The role of the placenta

Colorectal or renal cancer have shown that hypertension and proteinuria are the commonest side effects (Kabbinavar et al., 2003 Yang et al., 2003). Likewise, the infusion of sFlt-1 into rats (Maynard et al., 2003) causes these signs to appear. In the latter study the associated glomerular lesions were the same as those seen specifically in preeclampsia (Pollak and Nettles, 1960). Serum-soluble flt-1 is increased in pre-eclampsia (Maynard et al., 2003). Because it is complexed to VEGF, its high levels in pre-eclampsia can explain the variable reports of changes of plasma VEGF in this condition. If total VEGF is measured it is increased, whereas if only free VEGF is assayed it is reduced. The origin of the circulating sFlt-1 is presumed to be the placenta, although this has not yet been directly demonstrated (Clark et al., 1998 Maynard et al., 2003). The most compelling evidence is its rapid decline in concentration after delivery (Maynard et al., 2003). If soluble Flt-1 were the main...

Ai Balanced multimodal analgesia

* At the time of writing, COX-2 inhibitor drugs are subject to scrutiny by international regulatory bodies with regard to adverse outcomes when used for long-term oral prescription or for pain relief in patients with cardiovascular problems such as myocardial infarction, angina pectoris, hypertension. Rofecoxib has been withdrawn from sales and prescription of valdecoxib has been suspended pending further research into its adverse events profile for cardiovascular morbidity and the occurrence of severe muco-cutaneous side effects. The injectable COX-2 inhibitor, parecoxib remains available for short-term use in treating postoperative pain. All NSAIDs should be used with care in patients with cardiovascular disease.

Pharmaceutical Therapies

It is important to reduce cerebrovascular risk factors such as hypertension, diabetes, smoking, hyperlipidemia, and coronary artery disease in patients with vascular dementia. Dementia resulting from neurologic conditions (Parkinson's disease, normal-pressure hydrocephalus, brain lesions, carotid artery disease) requires a neurological workup. Dementia related to a hereditary condition requires referral for genetic counseling.

Toxicological Support For Phase Iiiii Studies

Non-clinical toxicology studies required to support Phase II and Phase III stages of the program depend upon a variety of factors. First, as shown in Tables 6.1 and 6.2, the ultimate clinical regimen, i.e. duration of therapy or treatment, determines the ultimate duration of the animal studies. For example, a diagnostic agent or a drug with a 3- 4 day regimen as might be the cases for disease or trauma situation that are handled in the intensive care unit may require little in the way of additional repeated-dose toxicity studies. In comparison, a new antihypertensive agent may require all of the longer-term studies.

N Diseases of Old

A list of common diseases responsible for death, compiled from hospital records in the United States (Fig. 8) and other developed countries, shows cardiovascular diseases (including hypertension and myocardial and cerebral vascular accidents) and cancer to be the diseases most related to old age (Table 12). It should be noted that when the information is secured not

Placental ischemiareperfusion and preeclampsia

Clearly demonstrated in the rhesus monkey, in which the intravenous administration of epineph-rine or norepinephrine causes a severe reduction in placental perfusion, to the point that high doses can result in fetal asphyxia and death (Adamsons and Myers, 1975 Adamsons et al., 1971). Evidence that the unconverted segment of the vessel is indeed flow-limiting is provided by the fact that despite the systemic hypertension induced the pressure in the dilated mouth of the spiral artery is decreased after administration. It has been suggested that a similar mechanism underlies the high rate of fetal loss during the second and third trimesters in women suffering from pheochromo-cytoma (Adamsons and Myers, 1975). Spontaneous changes in maternal catecholamine release, for example in response to stress, may therefore also influence the caliber of these vessels and hence perfusion of the intervillous space. Epidemiologically, there is an association between maternal anxiety and low birthweight,...

Medical Illnesses And Conditions

Indicated preterm birth appears to share a number of risk factors with spontaneous preterm birth. In a cohort of more than 2,900 pregnant women, Meis and colleagues (1998) noted a relation between indicated preterm birth and mullerian duct abnormality (OR 95 CI 7.02 1.69-29.15, proteinuria at less than 24 weeks of gestation (OR 95 CI 5.85 2.66-12.89), a history of chronic hypertension (OR 95 CI 4.06 2.29-7.55), a history of indicated preterm birth (OR 95 CI 2.79 1.45-5.40), a history of lung disease (OR 95 CI 2.52 1.32-4.80), previous spontaneous preterm birth (OR 95 CI 2.45 1.55-3.89), age greater than 30 years (OR 95 CI 2.42 1.57-3.74), being African American (OR 95 CI 1.56 1.02-2.40), and working during pregnancy (OR 95 CI 1.49 1.02-2.19). With the possibility of a significant heterogeneity of risk factors and etiologic overlap, studies of preterm birth should consider indicated and spontaneous preterm births both together and separately as outcomes of interest (Savitz et al.,...

Disease As A Tool For The Study Of Aging

Progeria syndromes do not quite duplicate all the pathophysiology of aging. Each syndrome presents an acceleration of only some of the characteristics associated with normal aging. Progeria is described as being of two main types, infantile and adult. The infantile form (Hutchinson Gilford syndrome) becomes apparent at a very early age and is associated with stunted growth, failure of sex maturation, and early signs of aging, such as skin atrophy, hypertension, and severe atherosclerosis. Death in

Policy Leading to Increased Availability of Services

Throughout the country, an increase in the number of health personnel, especially auxiliary nurses, accompanied the rise in facilities. More training was offered. The training of the clinical staff, along with community health workers (including the TBAs), focused on recognizing risks in pregnancy (extremes of age, first birth, more than four previous births, underlying medical problems) and danger signs in childbirth (including bleeding, hypertension, labor longer than 8 hours for multiparas and 10 hours for primiparas, premature rupture of membranes, fever, retained placenta, and malpresentation). Norms for the integrated care of women were published in 1995 they emphasized the identification and referral to hospitals of high-risk women and those with obstetric emergencies.

Maternal and Child Risks

Other risks associated with hormonal ovulation stimulation include ovarian hyperstimulation syndrome, in which fluid imbalances and ovary enlargement become problematic rupture of the ovaries is also a possibility (for a review of the well-being of women during the use of ARTs, see The Presidents Council on Bioethics 2004 ). Multiple pregnancies pose higher risks of mortality and morbidity to the mothers than singleton pregnancies. Mothers with multiple pregnancies are more likely to experience high blood pressure, anemia, preeclampsia, and gestational diabetes and to require delivery by cesarean (Sebire et al., 2001 Wen et al., 2004).

Polyamines in Pulmonary Vascular Biology Jack W Olson and Mark N Gillespie

Polyamines are essential for cell growth and development. They regulate many functions, including cell division, migration, ion channel regulation, apoptosis, and the cellular synthesis of DNA, RNA, and proteins. A recent review on the roles of polyamines in the lung emphasized studies on respiratory cell biology and polyamine uptake (1). The primary goal of this chapter is to review evidence that polyamines contribute to pheno-typical changes in pulmonary vascular cells that underlie the pathogenesis of pulmonary arterial hypertension. Because arginases can regulate polyamines, their potential role in the pathogenesis of pulmonary hypertension and asthma also will be reviewed. The data suggest polyamines may be future therapeutic targets for pulmonary hypertension, although clinical trials measuring polyamines and their regulation are lacking. 2. Overview of Pulmonary Hypertension Chronic pulmonary arterial hypertension is frequently a fatal disease in humans (reviewed in refs. 2-4)....

Longterm complications

The Medicare claims, 19.5 of patients identified to have had RRP by claim underwent one or more procedures for bladder neck obstruction or stricture after RRP.37 This contrasts with other studies reporting lower rates of postoperative BNC after RRP.38-40 Several studies have reported risk factors for the development of postoperative BNC, including previous prostate procedures or transurethral resections, excessive intraoperative blood loss, postoperative urinary extravasation and asymptomatic bacteriuria.39,41,42 In contrast, other studies found no relationship between development of BNC and previous transurethral resection of the prostate (TURP), or pathologic features including cancer volume, positive surgical margins, lymph node or seminal vesicle involvement.36'42 Patient comorbidities have also been implicated as risk factors for the development of BNC after RRP, including cigarette smoking, coronary artery disease, diabetes mellitus and hypertension, suggesting a microvascular...

Rodent models of preeclampsia insights into the diverse origins of the disease

In the last few years, a number of rodent models have been reported in which pregnant females develop the classic signs of pre-eclampsia including hypertension, proteinuria and renal glomerulo-sclerosis, and several others that show at least some of the associated features such as fetal growth restriction (Table 14.2). While each of the models is interesting in its own way, collectively they give us insights into what factors are and are not sufficient to initiate the pathogenesis of pre-eclampsia.

Conclusions and implications for understanding preeclampsia in humans

The results from the rodent studies suggest two important conclusions that are consistent with the human disease. First, pre-eclampsia can be initiated by several different means. These data are consistent with recent human genetic studies that rule out simple genetic mechanisms (Arngrimsson et al., 1995 Lachmeijer et al., 2001, 2002 Roberts and Cooper, 2001 Treloar et al., 2001), and actually implicate more than one locus (Lachmeijer etal., 2002 Roberts and Cooper, 2001). Collectively these studies should give pause to investigators who may be trying to find the ''one cause'' of pre-eclampsia. Second, either a strict maternal susceptibility to hypertension or a feto-placental defect is sufficient to cause pre-eclamp-sia. This idea is supported by a study of pregnancy outcomes in twin sisters that indicated that pre-eclampsia is unlikely to have a strictly maternal basis (Treloar et al., 2001). These studies highlight the need to classify the disease into different types (e.g....

Pathobiological Studies of Americans in the PDAY Study

Our comments This study clearly indicates that prevention of atherosclerosis should begin at younger ages. However, relative contributions of risk factors to raised lesions and their causal relationship need to be evaluated carefully. For example, hypertension analyzed by intimal thickness and an algorithm to estimate mean arterial pressure was characterized to be a risk factor in this study, but it may be the effect of atherosclerosis. Other studies revealed unfavorable results of antihypertensive drugs during interventions for CHD, e.g. MRFIT Study (fig. 9), J-LIT Area-Matched Control Study (fig. 11), and ALLHAT Study The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, 2002 . Another factor to be estimated is the proportion of FH high LDL HDL group in these young generations may include more than the average proportion of FH.

Principles of cDNA Microarrays as Applied in Heart Failure Research

Currently, only three classes of agents angiotensin converting enzyme inhibitors, beta blockers and aldosterone antagonists can modify the disease process and alter the natural history of heart failure 6, 7, 9 . These agents can improve survival, reduce hospitalization and enhance quality of life in HF patients. However, many challenges remain, because the one year mortality is still high in the presence of state of art therapy, and increasing numbers of patients in severe heart failure have a tremendously compromised quality of life. One such challenge is the need to find new targets for the treatment of HF. The traditional approaches have been limited to biochemical analysis of peripheral blood or myocardial biopsies. Many of the targets to date have been selected by reference to other fields of investigations, including nephrology, hypertension and cancer biology. Other targets deriv-

Conclusions And Future Directions

There are many potential pitfalls that lie in the way of researchers on the route from the discovery of a mutation in human DNA that codes for a pharmacologically important protein to the development of a clinically useful pharmacogenetic test. Very few such tests have been developed as yet, but a considerable number seem likely to be found useful over the next decade in guiding the treatment of patients with cancer, asthma, depression, hypertension, and pain.

Insulin resistanceglucose intolerance

Increased insulin resistance is seen in pregnancy and is greatest in the third trimester when hypertension typically presents. Obesity, which is a risk factor for hypertension in pregnancy (Eskenazi et al., 1991) is associated with decreased insulin sensitivity. Gestational diabetics also have an increased risk of hypertension in pregnancy (Suhonen and Teramo, 1993). A strong association has been shown between glucose intolerance and subsequent development of hypertension in pregnancy (Solomon et al., 1994). No absolute glucose level can distinguish between women who will remain normotensive and those who will develop new onset hypertension in pregnancy. However, only 9 of normotensives had glucose loading tests of 7.8 mmol or greater compared to 27 of women who develop hypertension. Fasting plasma insulin at 20 weeks gestation in African-American women who became pre-eclamptic was significantly greater than those who remain normotensive (Sowers et al., 1995). Using discriminant...

Genetic Association Studies

Disorders found to be associated with changes in the sequence of a single gene have been associated with an increased risk of preterm birth, often as a result of a predisposition to polyhydramnios in pregnancies with fetuses with changes in the sequence of that single gene. Among these conditions are myotonic dystrophy, Ehlers-Danlos syndrome, Smith-Lemli-Opitz syndrome, and neurofibromatosis. However, like many other complex human diseases, such as obesity, hypertension, diabetes, and asthma, preterm birth is a complex trait and possesses the following features non-Mendelian transmission, the involvement of multiple genes, and gene-gene and gene-environment interactions. Research on the genetics of preterm birth thus faces significant challenges. The approaches available for the identification of genes that may be associated with a particular trait include positional cloning, the identification of positional candidate genes, whole-genome association analysis, and functional candidate...

Early studies on remote prognosis of eclampsia and preeclampsia

The literature on this subject up to 1980 was reviewed in some depth by Leon Chesley, who is perhaps one of the key figures in much of the early work (Chesley, 1980). The majority of these studies employ cohorts of women who experienced some form of hypertensive disorder of pregnancy. Comparison was made either with matched control groups or population average incidences for the given outcome. The vast majority of these early studies focused on chronic hypertension as the outcome. The conclusion of these early studies was that eclampsia and pre-eclampsia were not associated with an increased risk of chronic hypertension in later life. Gestational hypertension was associated with an increased risk of chronic hypertension. The apparent paradox that the mildest form of the disease had the strongest association with long-term prognosis was explained by the fact that women diagnosed with ''gestational hypertension probably had first diagnosis of essential hypertension in pregnancy. Since...

Hypertensive disorders in pregnancy and ischemic heart disease in later life

A number of studies have demonstrated associations between a diagnosis of pre-eclampsia in pregnancy and ischemic heart disease (IHD) in later life. This association is plausible given the evidence outlined above for a relationship with hypertension, which is a well-recognized risk factor for IHD. However, IHD is relatively uncommon in young women. Consequently, the most feasible studies for addressing this question are register-based studies, since these can include a sufficient number of women to be powered to address the research question. In all but one of these studies, however, the definition of exposure is based on the coding of clinical records, which is open to misclassification. The analysis of controls for the oral contraception cohort, reported by Hannaford and described above, reported relative risks of 1.5 2.2 for a number of different IHD conditions. The association persisted when the analysis was stratified by chronic hypertension and the analysis was adjusted for age,...

Hypertensive disorders in pregnancy and cerebrovascular disease in later life

Hypertension is a major etiological factor in cerebrovascular disease. A number of studies have attempted to determine whether pre-eclampsia during pregnancy is associated with an increased risk of cerebrovascular disease in later life. The cohort study reported by Hannaford reported a non-significant trend toward an increased risk of cerebrovascular disease in relation to a history of pre-eclampsia. However, they did report that women who had no diagnosis of a hypertensive disorder of pregnancy had a lower risk of cere-brovascular disease in later life than nulliparous women (Hannaford et al., 1997). The cohort study of 600,000 women from Denmark found a fivefold risk of stroke among women delivered preterm with a diagnosis of pre-eclampsia but no excess risk of stroke among those who experienced pre-eclampsia but delivered at term (Irgens et al., 2001). These and other authors have shown that preterm birth in the absence of pre-eclampsia is associated with an increased risk of later...

Hypertensive disorders in pregnancy and venous thromboembolism in later life

Risk for venous thromboembolism of 1.6 for women with a history of pre-eclampsia (Hannaford et al., 1997). When stratified by chronic hypertension, the relationship appeared stronger among women who were normotensive. A more recent analysis of almost 300,000 pregnancies from Canada demonstrated a twofold risk of venous thromboembolism among women with a pregnancy diagnosis of pre-eclampsia (van Walraven et al., 2003). Both studies included both first and subsequent pregnancies, employed register bases definitions of pre-eclampsia and could not adjust for important potential confounders, such as obesity. While these data suggest a possible association between pre-eclampsia and venous thromboembolism, further studies are clearly required.

Possible mechanisms of association between preeclampsia and later disease

Occult cardiovascular, microvascular or hemostatic dysfunction. Since these will also make her susceptible to hypertension, atherosclerosis and throm-botic disorders, a woman's reproductive history may, therefore, also become informative in assessing her future risk of cardiovascular disease. The true nature and mechanism of these associations will only be resolved by large-scale prospective studies.

Current classification systems

Gestational hypertension Australasian (Brown et al., 2000) representative bodies have defined gestational hypertension as a blood pressure 140 90mmHg after 20weeks gestation. In a general pregnant population, blood pressure greater than 140 90 mmHg is more than two standard deviations above the mean between 20 and 34 weeks gestation, and approximately two standard deviations above the mean from 35 weeks to term (Stone et al., 1995). There are minor differences in the criteria for gestational hypertension between these consensus statements. The Canadian's elected to use only a diastolic blood pressure 90 mmHg in the definition, requiring confirmation on at least two occasions 4 h apart. The Australasian definition specifies a systolic blood pressure greater or equal to 140mmHg and or diastolic blood pressure of at least 90 mmHg, taken repeatedly over several hours and an absence of any features of multisystem disease. In the USA, the National Institutes of Health working group report...

Real And Potential Therapeutics

Inhaled NO is utilized as a therapeutic agent in pathological states in which pulmonary arterial hypertension is present. Indeed, the use of NO in patients with severe adult respiratory distress syndrome (ARDS) is now commonplace. Inhaled NO (5-80 ppm) results in improved hemodynamics and oxygenation status in a variety of pathological states. In addition, inhaled NO extends far beyond the pulmonary site and affects peripheral microvascular beds, making it a potential means of treating reperfusion injury associated with trauma. Major potential toxicities of inhaled NO, such as pulmonary edema, are related to the formation of N02 (a strong oxidizer). There is also the risk of methemoglobinemia, but this is rarely a problem as NO delivery is confined to 0.5-4 .

Objectives when defining preeclampsia

Defining pre-eclampsia by the most common early manifestations of the syndrome (hypertension and proteinuria), clusters a broad range of clinical scenarios, from mild disease posing no immediate threat to maternal or fetal health through to women with eclampsia, severe liver and renal dysfunction associated with a coagulo-pathy and or severe fetal compromise. For some these severe complications are present at the time of diagnosis, others develop them in the ensuing days or weeks. For many, pre-eclampsia never progress beyond the initial manifestations of mild disease. Thus the current definitions of pre-eclampsia function in dual capacity, as a diagnostic tool for severe maternal or fetal disease and as a screening test that identifies women at significant risk of subsequently developing severe sequelae of pre-eclampsia. Equally, if criteria are too stringent, then some women who are at risk of developing severe maternal disease will not be identified and appropriate management not...

The importance of blood pressure in pregnancy

The importance of blood pressure measurement during pregnancy has been recognized for more than a century (Seligman, 1987) and is a fundamental part of antenatal care. For many women their pregnancy will be the first point of medical contact and they may have been unaware of any pre-existing hypertension up to this point. Early diagnosis of hypertension has important implications for the management and prognosis of both the mother and the fetus. It is dependent on the accurate measurement of blood pressure, as hypertension is often the only early sign of impending pre-eclampsia. It is not, however, necessarily indicative of pre-eclampsia or indeed eclampsia. A survey of eclamptic women in the United Kingdom in 1992 demonstrated that a significant proportion of women did not have a blood pressure measurement that adequately distinguished them from the general antenatal population and fits occurred in hospital without severe hypertension (Douglas and Redman, 1994). There is also...

Blood pressure variability

Variations in blood pressure can be contributed to race, age, sex, time of day, activity, emotion, posture, etc. (MacGillivray et al., 1969). Within-patient variation can be due to systemic variation, e.g. women have a lower blood pressure than men after the age of 45 (Kannel, 1974) circadian rhythm blood pressure will be lower during sleep than wakefulness, especially during the first two hours of sleep (Coccagna et al., 1971) attenuation and reversal of the diurnal variation have been described in pre-eclampsia (Dame et al., 1977 Halligan et al., 1996 Murnaghan et al., 1980 Redman et al., 1976 Sawyer et al., 1981 Seligman, 1971) diastolic pressure will increase on standing dynamic exercise increases the systolic pressure while cessation of prolonged exercise will cause a decrease (Kenney and Seals, 1993), etc. Smoking (Cellina et al., 1975 Mann et al., 1991) or drinking coffee (Jeong and Dimsdale, 1990 Smits et al., 1985) will also cause a rise in blood pressure and many daily...

Automated blood pressure measuring devices

The need for a standardized protocol became apparent in the late 1980s after the widespread introduction of automated devices to the market. Various protocols have since been published with the aim of establishing a minimum standard of accuracy. The Association for the Advancement of Medical Instrumentation (1993), the British Hypertension Society (O'Brien et al., 1993a) and the European Society for Hypertension (O'Brien et al., 2002) all published protocols and both Germany and Australia have unpublished recommended national standards.

Selfinitiated and ambulatory monitoring

It was thought that ambulatory monitoring could have a predictive value related to the absence of a nocturnal fall ( 12 mmHg) in women destined to become pre-eclamptic (Halligan et a ., 1993 Moutquin et a ., 1992). Other studies have shown that significantly higher systolic and mean arterial pressures occur at 18 and 28 weeks gestation in those women who subsequently develop pre-eclampsia (Kyle et a ., 1993). The predictive capability of ambulatory monitoring is limited by the need to screen a large number of women with relatively intensive monitoring. It does, however, appear to be useful in evaluating hypertensive pregnancies. It is a better predictor of adverse obstetric outcome than conventional mercury sphygmomanometry (Peek et a ., 1996 Penny et a ., 1998) with regard to severe hypertension. Disappointingly, it remains a weak predictor of subsequent proteinurea, i.e. pre-eclampsia.

Identification And Evaluation Of Biomarkers

Statistical criteria have played an important role in assessing the predictive utility of biomarkers (criterion validity), but it is always hazardous to equate causation with statistical association. For that reason, increasing emphasis has been placed on establishing the biological plausibility, or construct validity, of biomarkers. Thus, clinical and epidemiological observations led to the conclusion that elevated blood pressure was associated with an increased risk of atherosclerotic cardiovascular disease, heart failure, stroke, and kidney failure (16). Subsequent pathophysiologic studies in humans and in animal models then were particularly helpful in establishing a firm linkage between hypertension and cerebral hemorrhage and infarction (17). A later epidemiologic study demonstrated that the risk of stroke and coronary heart disease is correlated with the extent of diastolic blood pressure elevation (18). In the aggregate, this considerable evidence supports the biological...

United Kingdom Prospective Diabetes Study

The findings of the United Kingdom Prospective Diabetes Study (19771999) were similar to those of the Diabetes Control and Complications Trial for persons with type 2 diabetes mellitus (36,37). In addition, it highlighted the independent role of systemic hypertension (or its control) in potentiating the development and worsening the progression of diabetic retinopathy Furthermore, like the Diabetes Control and Complications Tral, it demonstrated the negative effects of elevated cholesterol and serum lipid concentrations on the rsk for retinal complications in patients with diabetes mellitus.

Where is the critical paternal antigen and how is the female organism exposed to the paternal HLA message

However, based on his study of pregnancies after intra-uterine insemination, Smith et al. (1997) suggested that the protective factor is on the spermatozoa themselves and not in the seminal fluid. This was strongly supported by a subsequent study by Wang et al. (2002). They used a very elegant model to confirm the protective effect of previous sperm exposure and to analyse whether or not this protection is conveyed by sperm cells or seminal plasma. These authors looked at outcomes in pregnancies following Intra-Cytoplasmatic Sperm Injection (ICSI), where fertilization is achieved by injecting the sperm into the oocyte plasma. ICSI is used initially in cases where there are severe semen defects, including azoospermia. In some patients it is necessary to obtain sperm surgically. Couples in which the male partner has azoospermia and where sperm cells are obtained surgically provide an ideal ''model'' to test the protective partner-specific immune-tolerance conveyed by sperm cells. The...

Donor insemination and oocyte donation

Analogous to short periods of sperm exposure, artificial donor insemination has been reported by several investigators to result in a substantial increase in the incidence of pre-eclampsia (Schenker and Ezra, 1994). Concerning artificial donor insemination, the first major study was reported by Need et al. in 1983. They reported on 584 pregnancies following artificial donor insemination (ADI) in programs throughout Australia. The overall incidence of pre-eclampsia (proteinuric pregnancy-induced hypertension) was high (9.3 ) compared with the expected incidence of 0.5 5 . The incidence was increased in both multigravid and primigravid women. The expected pre-eclampsia incidence in Australian primigravid women was 5 , while it was 10.1 in primigravid women pregnant after ADI. This increase in the incidence of pre-eclampsia in primigravid women after ADI supports the findings of Robillard et al. (1994), who demonstrated the protective effects of a prolonged period of sperm exposure. The...

Intestinal ischaemia Acute 115

A R Atrial fibrillation, mural thrombus and endocarditis for emboli. Hypercholesterolemia, hypertension, DM and smoking for arterial thrombosis. Venous thrombosis is associated with portal hypertension, splenectomy, septic thrombophlebitis, external compression of the superior mesenteric vessels and cardiac failure. The risk of venous thrombosis is in users of OCP and in persons with thrombophilic conditions.

Consanguinity studies

Another approach to estimating heritability is to examine consanguineous families. Unfortunately, the few consanguinity studies in the literature all suffer from problems with methodology. Stevenson and coworkers conducted a 1976 study in Turkey, where a fifth of all the deliveries are consanguineous. Using clinical definitions that are probably too inclusive, they found that the incidence of ''toxemia'' was decreased when the couple was consanguineous (Stevenson et al., 1976). George et al. (1992) studied pregnancy outcomes in 814 primigravida in South India. Of these pregnancies, 26 were felt to be consanguineous. They studied pregnancy-induced hypertension rather than proteinuric pre-eclampsia specifically. Most of the marriages were either cousin cousin or uncle niece. They found the odds of pre-eclampsia were 1.12 in consanguineous couples compared to non-consanguineous couples (with a confidence interval of 0.72 1.75).

Searching For New Indications

Once a drug is approved for an indication, many years of its patent life have usually expired. Information gathered from Phase III clinical trials or from use of the drug under normal conditions (postmarketing) may suggest alternative indications that may extend the patent life. For an invention to be patented in the USA, it must be a new and useful improvement and not obvious (see also Chapter 35). Patentable categories in drug development include pharmaceutically active compounds, processes for making compounds, and compositions comprising an active compound and a pharmaceutical carrier (Hammer 1990). New formulations may satisfy these criteria and extend the patent life, e.g. minoxidil (originally used orally as an antihypertensive agent) as a topical preparation for the treatment of hair loss. New indications also help to keep up the 'noise level' for the product, enabling the marketing team to capitalize on new information that could potentially expand the market for existing...

Heterotopic Auxiliary Transplantation

Hepatic arterial flow, and hepatic venous drainage of the draft into the suprarenal vena cava of the recipient. A serious concern is whether the low portal pressure would preferentially shunt portal blood flow to the native liver and threaten the viability of the HLT graft. Thus, a constriction or ligation of the portal vein in the native liver may be mandatory for graft viability in the absence of portal hypertension. Techniques that have been described for FHF include reduced-size hetero-topic graft, with right subhepatic location (Moritz), and auxiliary partial orthot-opic liver transplantation (APOLT) (Pichlmayr).

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Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.

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