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Adrenocortical tumors are very rare in children. The records of seven patients (four boys and three girls) who attended Srinagarind Hospital between January 1986 and September 2000 were retrospectively reviewed. Virilization and hypertension were found in four patients, two of whom had untreated congenital adrenal hyperplasia. Hypertension or virilization was the single manifestation found in two other patients. Only one patient showed clinical symptoms of Cushing's syndrome and another nonfunctioning tumor in Down's syndrome. Abdominal ultrasonography was helpful in locating the tumors. Unilateral tumors were found in all of the patients and surgical exploration was done in six of them. Pathological examination revealed four adrenocortical carcinomas, one adrenal gland hyperplasia and one lipoma. The two patients in which the cancer metastasized to the liver and lungs died 1 and 1 1/2 months after diagnosis, respectively. The authors concluded that virilization and hypertension remain the primary diagnostic symptoms of adrenocortical tumors in children. Early detection and adrenalectomies prolonged the survival time in these patients.
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PMID:Adrenocortical tumors in children. 1133 77

While a complete understanding of the pathogenesis of Alzheimer's disease (AD) remains elusive, many conclusions can be drawn from the numerous epidemiological studies undertaken to date. Prevalence and incidence estimates show consistency, following a roughly exponential pattern with a doubling of both parameters roughly every five years after age 65. Roughly 7% of the population aged 65 and over has AD. The clinical course of the disease is reasonably well established and mortality rates rise with increasing levels of cognitive deficit. Four risk factors for AD are firmly established: increasing age, the presence of the apolipoproteinE-epsilon4 allele, familial aggregation of cases, and Down's syndrome. Numerous other associations have been shown in some studies, but not in others. For example, women generally appear at higher risk than men, as do people with lower levels of education; depression is probably prodromal; head injury is an established risk factor, and may interact with the apoE gene; several occupational exposures appear hazardous, and exposure to aluminum in the water supply confers excess risk. Hypertension and other vascular symptoms appear to predispose to AD, which is now seen as nosologically closer to vascular dementia than was previously believed. Several apparently protective factors have been identified, although preventive trials based on these have so far shown minimal effectiveness. The use of non-steroidal anti-inflammatory drugs to treat arthritis is associated with a reduced risk of AD, as is estrogen use by post-menopausal women. Physical activity appears beneficial, as does a diet with high levels of vitamins B6, B12 and folate. while red wine in moderate quantities appears protective. This review concludes with a discussion of the strengths and limitations of current epidemiological methods for studying Alzheimer's disease.
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PMID:Alzheimer's disease: insights from epidemiology. 1144 98

Inhibin-related proteins are involved in the control of the feto-maternal communication required to maintain pregnancy. Human placenta, decidua, and fetal membranes are the major sites of production and secretion of activin A, inhibin A and inhibin B in maternal serum, amniotic fluid, and cord blood. The availability of suitable assays developed in the last years has enabled the measurement of inhibins and activin A in their dimeric forms, in order to investigate their role in physiological conditions of pregnancy. The studies conducted on inhibin-related proteins and human pregnancy suggested the possibility of an involvement of inhibin A and activin A in the pathogenesis of gestational diseases. In fact, several lines of evidence underline the potential role and the clinical usefulness of inhibin-related proteins measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as early pregnancy viability, Down's syndrome, fetal demise, pre-eclampsia, pregnancy-induced hypertension, preterm delivery and intrauterine growth restriction. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future, further possibilities in the early diagnosis, prediction, and monitoring diseases of pregnancy.
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PMID:Changes in inhibins and activin secretion in healthy and pathological pregnancies. 1145 81

Until recently, infectious diseases and malnutrition-related disorders constituted the major cause of ill health and mortality in the world population. However, advances in treatment of such disorders and increased understanding of the molecular basis of heredity have led to genetically transmitted conditions becoming a major cause of morbidity and mortality. Several disorders, including chromosomal (Down syndrome, Turner syndrome), single-gene (sickle-cell disease, thalassaemia, glucose-6-phosphate dehydrogenase deficiency, haemophilia, inborn errors of metabolism) and multifactorial disorders (coronary artery disease, arteriosclerosis, diabetes mellitus, hypertension, obesity) are common and becoming increasingly important. As there is no agreed-upon definitive cure with acceptable risk, these disorders are a significant burden on the health care delivery system. This is because the chronic nature of genetic diseases requires lifelong medical attention, expensive supportive and symptomatic therapy and specialist care. This review outlines the genetic disorders, their impact on health care delivery systems and the general framework required to prevent and control these disorders.
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PMID:Spectrum of genetic disorders and the impact on health care delivery: an introduction. 1192 97

Cases where initial prenatal diagnosis was made of isolated unilateral multicystic kidney (UMCK) were reviewed to determine appropriate counselling and management strategies. For the 73 cases, chromosome abnormalities, pregnancy complications and family histories were reviewed. In addition, subsequently diagnosed birth defects, and pediatric medical and surgical outcomes were available for 54 cases. Of those with outcome information available renal/genital-urinary tract abnormalities were diagnosed subsequently in 33% and non-renal abnormalities in 16% of cases. Of the non-renal abnormalities, congenital heart defects were most frequent (7%). One chromosome abnormality, a trisomy 21, was present among 32 cases where karyotypes were known (3%). Amniotic fluid volume abnormalities were present in 11 cases but not predictive of associated anomalies, with the exception of one case where polyhydramnios accompanied multiple malformations consistent with VATER association. A family history of structural renal anomalies was reported in 11 cases (20%). There were 14 cases of partial or complete involution (25%), including two cases of complete prenatal involution of the cystic kidneys. No long-term associated morbidity such as hypertension or malignancy was present in our cohort. Based on our study and corroborating literature, amniocentesis should be offered to women when a seemingly isolated UMCK is detected on routine prenatal ultrasound. Furthermore, a detailed ultrasound with careful assessment of the fetal heart and contralateral kidney is indicated at diagnosis and during the third trimester to assess for further evidence of structural abnormalities, as well as amniotic fluid volume abnormalities. Careful assessment of the newborn is indicated with appropriate speciality referral as required.
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PMID:Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management. 1200 Nov 93

Increased fetal nuchal translucency (NT) in the first trimester is associated with adverse pregnancy outcomes. Whether the increased NT is also associated with an increased frequency of pregnancy-associated hypertension (PAH) is not known. Seven hundred and seventy-nine pregnant women who received NT-based Down syndrome screening and delivered their babies at our hospital by September 2000 were enrolled into this study. Among these women, there are 46 cases of preeclampsia, 68 cases of gestational hypertension (GH); 665 women without any adverse pregnancy outcomes served as controls. Correlation analysis demonstrated that NT MoM (multiples of median) level had a positive association with maternal diastolic blood pressure at the time of admission for delivery (r = 0.104; p < 0.01). The severity of PAH was concordant with the stepwise increase of mean NT MoM level, which was 0.88 in control, 1.07 in gestational hypertension, and 1.13 in preeclampsia (p < 0.001). Using the 95th (1.52 MoM) and 90th (1.31 MoM) percentiles of NT thickness as cut-offs, the sensitivities and odds ratios of the women at risk for developing GH after 20 weeks of gestation were 8.8%, 19.1% and 1.98, 2.15 respectively, while for preeclampsia were 10.9%, 28.3% and 2.49, 3.58 respectively. It is concluded that the pathological changes in the placenta responsible for the development of PAH may also influence the physiological decrease of NT thickness in late first trimester. However, the sensitivity of fetal NT measurement in first trimester is not sufficient as a single marker for predicting the pregnant women at risk for subsequent PAH.
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PMID:Association between fetal nuchal translucency thickness in first trimester and subsequent gestational hypertension and preeclampsia. 1222 64

A study of the risks of late pregnancy for mothers and their children indicates that there is still excess risk for mothers over age 35 but the difference is decreasing relative to the general population. National surveys of pregnancy and delivery conducted in France in 1976 and 1981 were the major source of data, supplemented by records of women giving birth in the Clinic Baudelocque, a university clinic in Paris, and by foreign data. Maternal mortality in France among women 35 and over declined from 71.7/100,000 in 1975 to 39.6/100,000 in 1983, at the same time that maternal mortality in the general population declined from 19.9 to 15.5/100,000. The risk of mortality for mothers over 34 was 3.6 times higher in 1975 and 2.6 times higher in 1983 than for the general population. In a series of 3858 pregnancies overall and 544 among women over 34, the rates of hypertension were 9.2% for all mothers and 12.3% for older mothers, while the rate for diabetes was 1.1% for all mothers and 2.4% for older mothers. Rates of proteinuria and urinary infection were about the same for the 2 groups. Rates of stillbirth in 1983 were 13.0/1000 for children of mothers 35 and over 7.6/1000 for the population at large. The frequency of trisomy 21 is very closely related to age, but the excess risk due to age is declining as result of more frequent antenatal diagnosis among older mothers. By 1976, the risk of prematurity of low birth weight was almost the same for infants of older mothers as for the population at large. Rates of prematurity were 5.6% for the general population and 5.9% for older mothers, while rates of birth weight under 2500 g were 5.2% for the general population and 5.6% for older mothers. The number of prenatal visits increased more for mothers over 34 years old than for the general population between 1976-81; in 1981, 46.4% of older mothers but only 32.3% of the general population had more than 7 prenatal consultations. The proportion of older mothers in the labor force and with university education increased considerably between 1976-81. 2 factors appear to have played a role in the improved health of older mothers and their children, improved prenatal surveillance and changes in the characteristics of the older mothers themselves. Data for England indicate that risk of prenatal mortality varies as a function of the father's occupation. The excess risk for infants of older mothers in England tends to disappear for children of the highest social classes.
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PMID:[Pregnancy after 34 years: risks and evolution of risks]. 1228 Dec 43

A growing number of US women are delaying childbirth until their late 30s. Pregnant women 35 years old face various risks including genetic disorders, prenatal medical and obstetric complications, intrapartum complications, and perinatal and neonatal morbidity and mortality. With each passing year, the risk of chromosomal abnormality such as Down's syndrome increases. Physicians perform chorionic villus sampling (CVS) between 9-11 weeks gestation and amniocentesis between 16-18 weeks to detect chromosomal abnormalities. CVS carries the higher risk of spontaneous abortion (1-2%). 35-year old pregnant women are more likely to suffer from hypertension and gestational diabetes than younger women. Yet their incidence remains at an acceptable level. Older pregnant women tend to also be at risk of several antepartum obstetric complications such as gestational bleeding, abruptio placentae, and placenta previa. The likelihood of cesarean section and dysfunctional labor is greater among 35-year old pregnant women. Between 1974 and 1978, older mothers were 4 times more likely to die than young mothers, but by 1982 the overall maternal mortality rate fell by 50%. The main causes of death among older mothers were hemorrhage, embolism, and hypertensive conditions. Positive effects of advanced maternal age were less worry about and better adjustment to pregnancy, cautiousness, and more likely to consult their physicians. Advanced maternal age tends not to effect neonatal outcome other than chromosomal anomalies. Physicians should not allow the pregnancy of 35-year old mothers to go beyond 42 weeks' gestation. Despite the minimal increased risks, 35-year old women should not allow their advanced age to be an absolute barrier to reproductive decisions. Obstetricians should conduct thorough and appropriate antepartum testing and surveillance, however.
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PMID:Advancing maternal age: the actual risks. 1231 79

Normal ageing and Alzheimer's disease (AD) have many features in common and, in many respects, both conditions only differ by quantitative criteria. A variety of genetic, medical and environmental factors modulate the ageing-related processes leading the brain into the devastation of AD. In accordance with the concept that AD is a metabolic disease, these risk factors deteriorate the homeostasis of the Ca(2+)-energy-redox triangle and disrupt the cerebral reserve capacity under metabolic stress. The major genetic risk factors (APP and presenilin mutations, Down's syndrome, apolipoprotein E4) are associated with a compromise of the homeostatic triangle. The pathophysiological processes leading to this vulnerability remain elusive at present, while mitochondrial mutations can be plausibly integrated into the metabolic scenario. The metabolic leitmotif is particularly evident with medical risk factors which are associated with an impaired cerebral perfusion, such as cerebrovascular diseases including stroke, cardiovascular diseases, hypo- and hypertension. Traumatic brain injury represents another example due to the persistent metabolic stress following the acute event. Thyroid diseases have detrimental sequela for cerebral metabolism as well. Furthermore, major depression and presumably chronic stress endanger susceptible brain areas mediated by a host of hormonal imbalances, particularly the HPA-axis dysregulation. Sociocultural and lifestyle factors like education, physical activity, diet and smoking may also modulate the individual risk affecting both reserve capacity and vulnerability. The pathophysiological relevance of trace metals, including aluminum and iron, is highly controversial; at any rate, they may adversely affect cellular defences, antioxidant competence in particular. The relative contribution of these factors, however, is as individual as the pattern of the factors. In familial AD, the genetic factors clearly drive the sequence of events. A strong interaction of fat metabolism and apoE polymorphism is suggested by intercultural epidemiological findings. In cultures, less plagued by the 'blessings' of the 'cafeteria diet-sedentary' Western lifestyle, apoE4 appears to be not a risk factor for AD. This intriguing evidence suggests that, analogous to cardiovascular diseases, apoE4 requires a hyperlipidaemic lifestyle to manifest as AD risk factor. Overall, the etiology of AD is a key paradigm for a gene-environment interaction. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:A unifying hypothesis of Alzheimer's disease. III. Risk factors. 1240 43

A multicentre study was carried out to determine the frequency and clinical consequences of extremely high maternal serum pregnancy-associated plasma protein (PAPP)-A. There was a total of 79 pregnancies with PAPP-A exceeding 5.0 multiples of the gestation-specific median in a series of 46 776 pregnancies tested (0.2%) at the 7 collaborating centres. Five pregnancies were lost to follow-up, one miscarried and one with Noonan's syndrome was terminated. Of the remaining 72 that ended in a live birth, one infant had gastroschisis and five pregnancies had obstetric complications: pre-eclampsia, pregnancy-induced hypertension, gestational diabetes and two with growth retardation. Among women with high PAPP-A and no complications or adverse outcomes, there was no evidence of a substantial change in the levels of other Down syndrome markers or the extent of nuchal translucency. Three analytical methods were used to assay PAPP-A and yielded different frequencies of extremely high levels (0.05%, 0.4% and 0.6%) possibly owing to cross-reaction with another substance. We conclude that women with high PAPP-A can be reassured that there is no reason to suppose that the outcome of pregnancy will differ from those with normal levels, provided other markers are normal. If, as more centres move their Down syndrome screening practice to the first trimester, additional cases emerge with Noonan's syndrome or gastroschisis and raised PAPP-A, this advice will need to be modified.
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PMID:Frequency and clinical consequences of extremely high maternal serum PAPP-A levels. 1274 35


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