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Intrauterine growth retardation and fetal hypoxia are currently related to placental insufficiency. Fetal biometry assessed by echography is entirely adapted to follow the growth and integrity of the principal fetal organs. Hypoxia induces an hemodynamic adaptation which can be detected and quantified by Doppler. The objective of this article is to review the evolution of the fetal Doppler practice for the last 20 years and especially to show that isolated Doppler measurement and only from one site (umbilical or cerebral or aortic) have a moderate negative predictive value of fetal outcome, compared to the study of the fetal hemodynamic evolution (degradation) from several sites and during several days. We will insist on the fact that (a) umbilical Doppler only gives information on placental blood flow and this information does not reflect neither the adaptation to hypoxia nor the consequences of this adaptation, (b) cerebral Doppler accounts for the vascular response to the pO(2) reduction but it does not allow to predict the consequences of this response, (c) the simultaneous study of the placental hemodynamic time course degradation and the cerebral vascular response to hypoxia allows quantification of the cumulative deficit of fetal oxygenation during this period and evaluation the adverse consequences of a sustained flow redistribution toward the brain. Finally, if cerebral vasodilation in response to hypoxia can be considered as a physiological compensatory mechanism, it is associated after several days to the appearance of irreversible fonctional (abnormal fetal heart rate) or organic (cerebral lesions) abnormalities. Adverse effects of this process are illustrated during episodes of acute hypoxia (malaria crisis of several days) or during sustained exposure of the fetus to hypoxia (pregnancy-induced hypertension).
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PMID:[Doppler monitoring of fetal circulation from multiple arteries over several days to improve evaluation of fetal prognosis]. 1259 54

The last decade has witnessed an effervescence of research interest in the development of potent inhibitors of various aspartic peptidases. As an enzyme family, aspartic peptidases are relatively a small group that has received enormous interest because of their significant roles in human diseases like involvement of renin in hypertension, cathepsin D in metastasis of breast cancer, beta-Secretase in Alzheimer's Disease, plasmepsins in malaria, HIV-1 peptidase in acquired immune deficiency syndrome, and secreted aspartic peptidases in candidal infections. There have been developments on clinically active inhibitors of HIV-1 peptidase, which have been licensed for the treatment of AIDS. The inhibitors of plasmepsins and renin are considered a viable therapeutic strategy for the treatment of malaria and hypertension. Relatively few inhibitors of cathepsin D have been reported, partly because of its uncertain role as a viable target for therapeutic intervention. The beta-secretase inhibitors OM99-2 and OM003 were designed based on the substrate specificity information. The present article is a comprehensive state-of-the-art review describing the aspartic peptidase inhibitors illustrating the recent developments in the area. In addition, the homologies between the reported inhibitor sequences have been analyzed. The understanding of the structure-function relationships of aspartic peptidases and inhibitors will have a direct impact on the design of new inhibitor drugs.
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PMID:Aspartic peptidase inhibitors: implications in drug development. 1274 95

The major health problems in Africa are AIDS, tuberculosis, malaria, gastroenteritis and hypertension; hypertension affects about 20% of the adult population. Renal disease, especially glomerular disease, is more prevalent in Africa and seems to be of a more severe form than that found in Western countries. The most common mode of presentation is the nephrotic syndrome, with the age of onset at five to eight years. It is estimated that 2 to 3% of medical admissions in tropical countries are due to renal-related complaints, the majority being the glomerulonephritides. There are no reliable statistics for ESRD in all African countries. Statistics of the South African Dialysis and Transplant Registry (SADTR) reflect the patients selected for renal replacement therapy (RRT) and do not accurately reflect the etiology of chronic renal failure (CRF), where public sector state facilities will offer RRT only to patients who are eligible for a transplant. In 1994, glomerulonephritis was recorded as the cause of ESRD in 1771 (52.1%) and hypertension in 1549 (45.6%) of patients by the SADTR. In a six-year study of 3632 patients with ESRD, based on SADTR statistics, hypertension was reported to be the cause of ESRD in 4.3% of whites, 34.6% of blacks, 20.9% mixed race group and 13.8% of Indians. Malignant hypertension is an important cause of morbidity and mortality among urban black South Africans, with hypertension accounting for 16% of all hospital admissions. In a ten-year study of 368 patients with chronic renal failure in Nigeria, the etiology of renal failure was undetermined in 62%. Of the remaining patients whose etiology was ascertained, hypertension accounted for 61%, diabetes mellitus for 11% and chronic glomerulonephritis for 5.9%. Patients with CRF constituted 10% of all medical admissions in this center. Chronic glomerulonephritis and hypertension are principal causes of CRF in tropical Africa and East Africa, together with diabetes mellitus and obstructive uropathy. The availability of dialysis and transplantation is quite variable in Africa: treatment rates in North Africa are 30 to 186.5 per million population (pmp) in countries with more established programs: Algeria 78.5; Egypt 129.3; Libya 30; Morocco 55.6; Tunisia 186.5 pmp. In South Africa, treatment rates of 99 pmp were reported; Dialysis and transplant programs in the rest of Africa are dependent on the availability of funding and donors. Services are still predominantly urban and therefore generally inaccessible to the poorer, less educated rural patient. There is not enough money for healthcare in the developing world, particularly for expensive and chronic treatment such as RRT. The goal should be to have a circumscribed chronic dialysis program, with as short a time on dialysis as possible, and to increase the availability of transplantation (both living donor and cadaver). Efforts should be made to optimize therapy of renal disease and renal failure globally and particularly in developing countries. Strategies should be developed to screen for and manage conditions such as hypertension and diabetes mellitus at the primary healthcare level in an effort to decrease the incidence of chronic renal failure. Increasingly, health is influenced by social and economic circumstances. Any improvements in health thus demand integrated, comprehensive action against all the determinants of ill health.
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PMID:End-stage renal disease in sub-Saharan and South Africa. 1286 89

In this cross-sectional study, 8,481 women aged 15-49 who had at least one pregnancy outcome were considered. This study aimed to examine the characteristics of Filipino women having had a pregnancy loss, and to test the association between domestic violence and pregnancy loss. To control for the confounding effect of the number of pregnancies, the sample was divided into seven groups classified by the number of pregnancies. The risk factors considered were demographic characters (age and partner's age, marital status, and place of residence), socioeconomic status (education and partner's education, having a paid helper at home, having a say in how income was spent), domestic violence (physical abuse and forced sex), sexual behavior of partner, whether the pregnancy was wanted, and disease history (tuberculosis, diabetes, hypertension, malaria, hepatitis, kidney disease, heart disease, anemia, goiter and other medical problems). The major risk factors were found to be physical abuse, region, faithfulness of partners, hypertension, hepatitis, kidney disease, anemia, and the other medical problems, respectively. The risk of pregnancy loss for the women suffering domestic violence was 1.59 (95% CI 1.28-1.97) times higher than for the women who did not. Women aged 15-19 years had a much higher risk of pregnancy loss than the other age groups (OR = 1.49, 95% CI 1.22-1.82). There were similar risk for women aged 20-24 years (OR = 1.08, 95% CI 0.94-1.25) and 35-39 years (OR = 1.05, 95% CI 0.92-1.19). No association emerged with marital status, socioeconomic status, forced sex, the number of partners, unwanted pregnancy, tuberculosis, diabetes, malaria, heart disease, and goiter. Although women's age, partner's age, residence, women's education, partner's education, and paid helper at home were significantly associated with pregnancy loss, they were likely to be confounders rather than risk factors.
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PMID:Pregnancy loss in the Philippines. 1297 77

Malaria requiring intensive care is characterized by failure of one or more organ systems and/or development of several metabolic disorders secondary to the presence of Plasmodium faliciparum in the blood. Severe imported malaria in non-immunized adults causes multiple organ failure with variable degrees of altered mental status. Acute pulmonary edema is frequent, jaundice associated with mild disturbance of liver function is consistent, arterial hypertension due to hypovolemia is usual, and acute renal insufficiency is uncommon. Coagulation disorders are generally low-grade, acidosis is an unfavorable prognostic factor, severe hypoglycemia can occur after the beginning of quinine treatment, and anemia is an consistent but discrete symptom. In endemic areas emphasis should be placed on the complications of severe malaria in pregnant women due to the high incidence of hypoglycemia and pulmonary edema. Severe malaria can develop early in children in endemic zones. Presenting signs include cerebral malaria in older children and severe anemia in young children. Quinine is the reference treatment with a bolus of 17 mg/kg followed by a daily maintenance dose of 24 mg/kg. Use of artemether should be restricted to quinine-resistant forms. Total blood exchange transfusion is not recommended. Supportive symptomatic treatment, e.g. mechanically assisted ventilation and kidney dialysis, is required. In endemic zones over 90% of deaths involve children without access to intensive care facilities. Mortality rates associated with management of severe imported malaria in intensive care range from 10 to 30%.
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PMID:[Severe malaria in intensive care units in 2003]. 1457 63

Renal failure remains a serious cause of mortality in Yemen. Our region has 1.25 million population and our hospital is the central hospital, which has a nephrology department and performs dialysis for the region. Between January 1998 and December 2002, we admitted 547 patients; including children, with acute renal failure (ARF) and chronic renal failure (CRF). CRF was observed in 400 patients, an incidence of 64 per million per year and a prevalence of 320 per million. ARF occurred in 147 persons with an incidence of 23.5 per million per year and a prevalence of 117.5 patients per million. Of all patients, 72% were adults (age range, 20-60 years) with a male preponderance. As a tropical country, malaria (27.9%), diarrhea (13.6%), and other infectious diseases were the main causes. Next most common were obstructive diseases causing CRF and ARF (26.8% and 12.9%, respectively), mainly urolithiasis, Schistosomiasis, and prostatic enlargement. However the cause of CRF in 57.5% of patients was unknown as most persons presented late with end-stage disease (64.7%), requiring immediate intervention. Other causes, such as hepatorenal syndrome, snake bite, diabetes mellitus, and hypertension, showed low occurrence rates. Patients presented to the hospital mostly in severe uremia and without a clear history of prior medications. The major findings were vomiting, acidosis, and hypertension with serum creatinine values ranging between 2.8-45 mg/dL (mean value, 13.4 mg/dL). Anemia was observed in 80.4% of CRF versus 62.6% of ARF patients. Hypertension prevalence was 65.5% among CRF patients, of whom 25% were in hypertensive crisis, whereas among ARF the prevalence was only 26.5%.
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PMID:Renal failure in Yemen. 1535 Apr 75

Although the definition of preterm birth is birth before 37 completed weeks, the major transition in terms of needing special care occurs between 34 and 37 weeks. The Homo sapiens neonate is born much more immature than other anthropoid species, perhaps because earlier birth has evolved to avoid the large head of the human fetus becoming impacted in the small pelvis of the mother, who has become adapted to a bipedal gait. The main burden of preterm birth exists in developing countries. There are no accurate recent worldwide data, but estimates of preterm birth rates range from 5% in developed countries to 25% in developing countries. The preterm delivery rate has been relatively stable at 5-10% in developed countries for many years. The North Thames database of 517,381 pregnancies demonstrates significant ethnic variation in preterm birth rates, with higher rates in black women. This is associated with an accelerated rate of maturity in the black fetus and neonate, with correspondingly lower gestation-specific neonatal mortality rates below 38 weeks, and higher at 38 weeks of gestation and beyond. Ethnic differences can explain only a very small proportion of global preterm births. The greatest aetiological factor worldwide is infection, mainly due to malaria and HIV. In developed countries, iatrogenic delivery is responsible for almost half of the births between 28 and 35 weeks; hypertension and pre-eclampsia are the major pathologies. Other factors include multiple pregnancy, intrauterine growth restriction, maternal stress and heavy physical work.
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PMID:The epidemiology of preterm labour. 1571 85

Acute renal failure (ARF) is a significant cause of morbidity and mortality in children. It may be pre-renal, intrinsic, or post-renal (obstructive) in aetiology. ARF was investigated in children in the south-southern part of Nigeria to determine the prevalence, aetiology, management and outcome of ARF. A retrospective review of data from all children from birth to 16 years of age admitted into the Department of Paediatrics, University of Port Harcourt Teaching Hospital (UPTH), with the diagnosis of ARF over an 18 year period (January 1985 to December 2003) was performed. Information was obtained about the age, sex, clinical features, blood pressure, laboratory and radiological investigations, aetiology, and treatment received including dialysis. Information on the outcome, factors influencing outcome, and possible causes of death were reviewed. There were 211 patients, 138 (65.4%) males and 73 (34.6%) females (M:F, 1.9:1), with a hospital prevalence of 11.7 cases/year. The patients were aged 5 days to 16 years (mean 5.6+/-4.7 years). Oliguria was the most common clinical presentation in 184 (87.2%) patients. Hypertension was seen in only 39 (18.5%) patients. The causes were age-related. The neonates had ARF from severe birth asphyxia 27 (35.5%), septicaemia 17 (22.4%), with tetanus 4 (5.3%) and congenital malformations 11 (14.5%). Sixty-one (28.9%) and 29 (13.7%) patients had ARF from gastroenteritis and malaria respectively. The patients with leukaemia were all more than 10 years old and had acute lymphoblastic leukaemia. Two patients (1.9%) had Burkitts lymphoma involving the abdomen and 3 patients had HIVAN. 112 (53%) patients had anaemia with a mean haematocrit of 20.25+/-6.9%. Dialysis was indicated in 108 patients, but only 24 patients (22.2%) had peritoneal dialysis (PD), because of financial constraints and lack of dialysis equipment. Mortality rate was 40.5%. The causes of death were uraemia 60 (70.6%), overwhelming infection 5 (5.9%), and recurrent anaemia 20 (23.5%). Hypertension (X2 15.7, P<0.001) and lack of dialysis (X2 7.96, P<0.01) significantly affected outcome. Other factors associated with demise were delayed presentation (58.8%), use of herbal treatment (35%), and unaffordability of treatment (40%). ARF is a significant cause of mortality in Nigerian children. The patients are not adequately managed because of poverty and lack of facilities for dialysis. The causes of ARF in our environment are preventable, and should be expected.
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PMID:Acute renal failure in Nigerian children: Port Harcourt experience. 1594 80

Stroke is one of the leading causes of mortality in Latin America, with variable incidence and prevalence throughout the continent reflecting regional socioeconomic differences. In Latin America, uncontrolled hypertension is one of the major causes of stroke, but other modifiable risk factors also play a role, such as heavy alcohol consumption and smoking. Intracerebral hemorrhage and lacunar stroke are more frequent in Latin America than in North America and Europe. There are multiple causes of stroke that are endemic to Latin America, including neurocysticercosis, Chagas' disease, sickle cell anemia, malaria, hemorrhagic fever, and snake bites.
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PMID:Stroke in Latin America. 1619 41

Cerebral malaria is the most common cause of non-traumatic encephalopathy in the world. The mainstay of therapy is either quinine or artemisinin, both of which are effective antimalarials. The clinical picture of cerebral malaria may persist or even become worse in spite of the clearance of parasites from blood. The death rate is unacceptably high even with effective antimalarials in tertiary care hospitals. The mortality increases in presence of multi organ failure (renal failure, jaundice, respiratory distress, severe anaemia, lactic acidosis, etc.). The pathogenesis of cerebral malaria is multifactorial and includes clogging, sequestration, rosette formation, release of cytokines, cerebral oedema, increased intracranial hypertension, etc. Attempts are made to use adjuvant therapy which will act through alternate mechanisms and address one or more of the pathogenetic processes. In this review, we have discussed the role of corticosteroids, pentoxifylline, desferrioxamine, mannitol and newer agents in the treatment of cerebral malaria. Though the literature on adjuvant therapy in cerebral malaria is large enough, there are a number of shortcomings in the clinical trials, many being open and non randomized or of very small sample size. Further research is of utmost importance through large multicentric, double-blind controlled trials to show the efficacy of any of these drugs.
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PMID:Adjuvant therapy in cerebral malaria. 1733 64


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