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Bardet-Biedl syndrome is an autosomal recessive disorder. It is characterized by cardinal anomalies including retinal dystrophy, digital malformations, mental retardation, obesity, and hypogonadism. Recently, renal anomalies also are mentioned among the cardinal signs. Although association of genital anomalies among affected boys are well known, the association of vaginal atresia and other structural genital anomalies are not mentioned among the less-common manifestations of Bardet-Biedl syndrome in girls. Two girls with Bardet-Biedl syndrome presented with hematometrocolpos in the preadolescent period and vaginal atresia was diagnosed. After surgical treatment and extended hospitalization, uncontrolled sepsis resulted in progressive renal failure and death of both patients. Vaginal atresia is often delayed or missed in the early childhood period. In girls with Bardet-Biedl syndrome, vaginal atresia or other structural genital anomalies should be evaluated more systematically during the initial diagnosis of the syndrome. In infancy, the evaluation of a child with vaginal atresia also should include the differential diagnosis of Bardet-Biedl syndrome. Vaginal atresia may either form a component of the syndrome, or girls who present with vaginal atresia in addition to other components of Bardet-Biedl syndrome might form a distinct entity.
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PMID:Vaginal atresia and Bardet-Biedl syndrome association: a component or a distinct entity? 1021 69

Hyperlipidemia accelerates the progression of human renal disease, and its control is becoming an important component of therapy for patients with renal failure. The biologic basis for these observations remains poorly understood. This review summarizes recent data from animal models which show how lipoproteins interact with cells directly to cause renal injury. Data are presented from recent studies on the obese Zucker rat, a metabolic model of hyperlipidemia, obesity, and glomerular sclerosis, showing that triglyceride-containing lipoproteins may mediate glomerular injury. The biochemical basis for therapy is also discussed, including actions of lipid-lowering agents apart from their effect on serum lipids, and the use of polyunsaturated fatty acids as dietary therapy. Animal models are a crucial tool for the further elucidation of mechanisms of lipoprotein-mediated glomerular injury.
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PMID:Hyperlipidemia and renal disease: the use of animal models in understanding pathophysiology and approaches to treatment. 1037 11

1. Predictors of natural and cardiovascular death were examined in a cohort from a remote Australian Aboriginal community with high mortality rates. The cohort was marked by high prevalences of diabetes (17%), hypertension (19% diastolic blood pressure (BP) > 90 mmHg), obesity (16% body mass index (BMI) > 30), albuminuria (26% albumin/creatinine ratio (ACR) > or = 34 g/mol) and renal failure (26% calculated glomerular filtration rate < 80 mL/min). 2. Relationships between baseline characteristics and subsequent mortality were examined using multivariate techniques. 3. Albuminuria, diabetes and hypertension (but not smoking dyslipidaemia or obesity) were all markers for increased risk of natural and especially of cardiovascular death. Age- and sex-adjusted relative risk [95% CI] of natural deaths were 4.3 [1.9-9.5] for overt albuminuria (ACR > or = 34, 3.2 (range 1.6-6.5) for diastolic BP > or = 100 and 3.7 (range 1.5-8.9) for diabetes. 4. The relative risk associated with albuminuria was independent of diabetes and hypertension. Albuminuria was more common than either diabetes or hypertension and represents a target for intervention to reduce not only progression to renal disease, but also overall mortality.
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PMID:Physical and biochemical predictors of death in an Australian aboriginal cohort. 1047 76

Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion. Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition. FSGS is characterized by increased urinary protein excretion and decreasing kidney function. Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref. 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS. In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4. Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients. Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage.
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PMID:Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. 1070 Jan 77

Pediatricians are in a unique place in society by being able not only to care for the health and well-being of mothers and which, are their clinical responsibility, but also by being able to act as advocates for those patients who are often among the most vulnerable of our population. This article illustrates some of these points by referring to Australian Aboriginals from the vast desert areas of Westerns Australia. In remote areas of Western Australia, Aboriginal infants have high rates of low birth weight, failure to thrive and undernutrition. They also have high rates of respiratory, gastrointestinal and other infections. Aboriginal infant mortality has improved significantly over recent years, but Aboriginal health and mortality rates are still much worse than those of non-Aboriginal children and tend to be worst in more remote parts of the state. Overall, Aboriginal infants less than one year in age were hospitalized 9.5 times more frequently than non-Aboriginal infants for respiratory diseases (such as pneumonia, acute bronchiolitis and asthma); diarrheal diseases and skin infections were other very important causes of hospitalization for Aboriginal infants. Another poorly understood aspect of Aboriginal health is their widespread proneness to urinary tract infections. This is very important now in Australian Aboriginals in whom end-stage renal failure is becoming very prevalent. Rapid social and lifesyle changes have been very important in the poor health status of Aboriginals. They are also subject to severe socio-economic discrimination, underemployment, limited education, overcrowding, social depression and severely depressed housing conditions, relative inaccessibility to adequate and nutritious foodstuffs, and limited access to clinical services. Aboriginal people are prone to obesity, hypertension, type-2 diabetes mellitus and cardiovascular diseases. Overuse of alcohol and tobacco smoking have also become important challenges, particularly among adolescents and young adults. For the past twenty years or so, special programs have been developed to help overcome some of these problems; these include immunization programs, an extensive child health care program, special childhood screening programs, and oral rehydration therapy to reduce the high rates of mortality and morbidity associated with diarrheal diseases. These improvements have been achieved despite a set of socio-economic circumstances that face Aboriginal infants and children who live with adverse social factors. This was termed "Down and Out in 1996" in an editorial in The New Scientist (27 January 1996). A strategy that Australian Aboriginals are using now is to increase their own role through Aboriginal-controlled health and medical services including child health programs.
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PMID:A pediatrician and his mothers and infants. 1086 86

The obese ZDFxSHHF-fa/fa(cp) model was developed by crossing lean female Zucker Diabetic Fatty (ZDF +/fa) and lean male Spontaneously Hypertensive Heart Failure (SHHF/Mcc-fa(cp), +/fa) rats. The purpose of the present study was to determine renal function and morphology, hemodynamics, and metabolic status in ZDFxSHHF rats. Two sets of experiments were conducted. First, we evaluated heart and kidney function and metabolic status in aged (46 weeks old) male obese ZDFxSHHF and age matched obese SHHF rats, lean Spontaneously Hypertensive (SHR) and lean normotensive Wistar Kyoto (WKY) rats. In the second set of experiments, renal function and structure as well as metabolic and lipid status were determined in lean (LN) and obese (OB) adult (29-weeks of age) ZDFxSHHF rats. At 46 weeks of age ZDFxSHHF rats are hypertensive expressing marked cardiac hypertrophy associated with diastolic dysfunction and preserved contractile function. Fasted hyperglycemia and hyperinsulinemia are accompanied by moderate hypercholesterolemia and hypertriglyceridemia. Obese aged ZDFxSHHF have marked renal hypertrophy, a 3-8 fold decrease in creatinine clearance (compared with SHHF, SHR and WKY), a high percent of segmental + global glomerulosclerosis (59.8%+/-10.8), and severe tubulointerstitial and vascular changes. Obese ZDFxSHHF rats die at an early age (approximately 12 months) from end-stage renal failure. Studies conducted in 29-week animals showed that, although both LN and OB 29-week old animals are hypertensive, OB animals have more severely compromised renal function and structure as compared with lean litter-mates (kidney weight: 2.56+/-0.16 vs. 1.61+/-0.12 g; creatinine clearance: 0.42+/-0.04 vs. 1.24+/-0.13 L/g kid/day; renal vascular resistance 12.39+/-1.4 vs. 6.14+/-0.42 mmHg/mL/min/g kid; protein excretion: 556+/-16 vs. 159+/-9mg/day/g kid, p < 0.05, OB vs. LN, respectively). Obesity is also associated with hyperglycemia (424+/-37 vs. 115+/-11 mg/dL), hyperinsulinemia (117.2+/-8.8 vs. 42.3+/-3.5 microU/mL), hypertriglyceridemia (5200+/-702 vs. 194+/-23 mg/dL), hypercholesterolemia (632+/-39 vs. 109+/-4mg/dL), and presence of segmental + global glomerulosclerosis (20.1+/-3.2% vs. 0.1+/-0.1%) with prominent tubular and interstitial changes (p < 0.05, OB vs. LN, respectively). In summary, the present study indicates that the crossing of rat strains of nephropathy produces hybrids that carry a high risk for severe renal dysfunction. The ZDFxSHHF rats express insulin resistance, hypertension, dislipidemia and obesity and develop severe renal dysfunction. In addition, the hybrids do not develop some of the complications (hydronephrosis or congestive heart failure) common for the parental strains that may compromise studies of renal function and structure. Therefore, the ZDFxSHHF rat may be a useful model fore valuating risk factors and pharmacological interventions in chronic renal failure.
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PMID:Renal function and structure in diabetic, hypertensive, obese ZDFxSHHF-hybrid rats. 1090 Nov 78

While the ethnic make up of the New Zealand population is predominantly European, the Polynesian population, consisting of indigenous New Zealand Maori and more recent immigrants from the other Pacific Islands is increasing rapidly. The prevalence of diabetes in these Polynesians is high. There is also an increasing prevalence of obesity, and obesity is a greater problem amongst Polynesian people. The number of elderly people in the population is increasing. All of these demographic changes are increasing the incidence and prevalence of Type 2 diabetes. The incidence of Type 1 diabetes is also rising, although the reasons for this are unknown. Diabetic nephropathy is the most common cause of end stage renal failure in New Zealand. Polynesian people with diabetes, and in particular Maori, have a very high rate of diabetic nephropathy and develop renal failure at a more rapid rate than European patients with nephropathy relating to Type 1 diabetes. The propensity for Maori patients with Type 2 diabetes to develop renal failure may relate to a younger age at the onset of diabetes, a genetic susceptibility to nephropathy, and socio-economic or cultural factors leading to less adequate medical care.
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PMID:Diabetes in New Zealand. 1102 86

The left ventricular hypertrophy is a risk marker of the cardiovascular morbidity and mortality in hypertensive patients--it contributes to sudden death, myocardial infarction, myocardial ischemia, heart failure, arrhythmias, left ventricular diastolic dysfunction, stroke and renal failure. The mechanisms by which the heart hypertrophy increases the risk of cardiovascular morbidity and mortality, however, is not completely clear yet. Pressure overload (resulting in the concentric hypertrophy) and volume overload (resulting in the eccentric hypertrophy) of the left ventricle play a significant role in the development of the hypertrophy of the left ventricle. Other risk factors, stimulating left ventricular hypertrophy, include growth factors, genetic predisposition, age, obesity, hyperinsulinemia and anemia. The hypertrophy of left ventricle most often occurs with hypertension, cardiomyopathy and aortic stenosis. Several clinical studies evaluated functional consequences of the reduction of the ventricular hypertrophy and found out that the function of the left ventricle to be improved in hypertensive patients who had undergone an effective and long-term antihypertensive treatment. However, these studies did not differentiate whether for the improvement in the function of left ventricle was the matter of the reduction of the left ventricular mass or whether it was because of the decrease of the arterial pressure during the period of anti-hypertensive treatment. On the basis of the literature studied we can emphasize that the reduction of myocardial hypertrophy resulting from a specific antihypertensive treatment appears to be more favourable than harmful for the heart's pump performance.
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PMID:[Hypertrophy of the left ventricle--etiopathogenesis, clinical consequences and prognosis]. 1104 62

Left ventricular hypertrophy LVH is supposed to be a useful marker of cardiovascular complications during the course of hypertension. Occurrence of other risk factors of atherosclerosis in these hypertensive patients such as hyperlipidemia and smoking deteriorate the prognosis too. The authors compared clinical findings in hypertensive patients with and without left ventricular hypertrophy defined by echocardiography. Hospital records of 185 hypertensive patients treated at our medical department during years 1996-1999 were analysed. Left ventricular hypertrophy was defined by echocardiography (Penn convention) as left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women. Presence of LVH was found in 109 patients (mean age 66.7 years), absence of LVH in 76 patients (mean age 64.7 years). Both groups of hypertensive patients were matched by demographic parameters by the presence of hyperlipidemia and by smoking habits. Hypertensive patients with diabetes mellitus and obesity were excluded. They were statistically significant in the incidence of heart failure, myocardial infarction, renal failure and mitral regurgitation, and non-significant in the incidence of left ventricular diastolic dysfunction. There were more cardiovascular complications in LVH-positive patients than in those with LVH-negative findings. The incidence of stroke was slightly higher in LVH-negative patients. Left ventricular hypertrophy in patients with hypertension brings usually a complicated course of the disease. The authors recommend to examine the patients with arterial hypertension for the presence of left ventricular hypertrophy as it complicates the course of the disease significantly. (Tab. 3, Fig. 2, Ref. 26.)
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PMID:[Left ventricular hypertrophy in hypertension]. 1115 71

Diabetic nephropathy is the most common single cause of end-stage renal failure (ESRF) in the Western world, recorded as the cause of renal failure in up to 40% to 45% of those entering renal replacement therapy (RRT) programs. However, marked differences exist between countries; the percentage of patients entering RRT in Norway because of diabetic nephropathy is 10% of the incident RRT population. The percentage in the United States is approximately 40%; therefore, the purpose of the present study was to compare data from Norway with data from the United States in an attempt to detect factors that might explain some of the differences. To make the comparisons as valid as possible, an attempt has been made to focus on populations of similar genetic make-up. The incidence of type 1 diabetes is a little higher in Norway than in the United States, whereas the prevalence of type 2 diabetes may be twice as high in the United States as in Norway; marked differences in the prevalence of obesity is probably a significant causative factor. There seems to be no striking difference in the prevalence of microalbuminuria in people with diabetes in the two populations, whereas there are insufficient data to compare the prevalence of overt proteinuria. The incidence of patients with a diagnosis of diabetic nephropathy as the cause of ESRF entering RRT in the two study populations showed marked differences; the incidence for 1997 was 8.9/million population in Norway and 113/million population in the United States. The proportion of type 2 diabetes was 46% in Norway and 64% in the US (1997). It is unlikely that the marked difference in incidence of RRT can be explained by differences in type 2 diabetes prevalence alone. The populations may not be directly comparable, and differences in the size of study populations and in the choice of renal diagnosis in patients with diabetes as a comorbid factor at the beginning of RRT may introduce uncertainties. Further, data on other factors--such as incidence of death before RRT is indicated, quality of care, and health care delivery, expressed as degree of blood pressure and metabolic control--were not available. Differences in acceptance of diabetes patients into RRT programs are not believed to contribute significantly. Norway is seeing a development toward increasing body weight and a change toward a more sedentary lifestyle, together with an increasing prevalence of type 2 diabetes earlier in life than has previously been the case. An increase in diabetic nephropathy and need for RRT because of type 2 diabetes must therefore be expected in Norway. To understand differences and to best design preventive programs, further comparative studies of the two populations seem warranted.
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PMID:Diabetic nephropathy and end-stage renal failure: the Norwegian story. 1117 23


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