Biomedical subjects
Publications and source records attributed to O Bonny.
We report on a case of a 31-year-old patient suffering from long-standing peripheral edema with severe hypoalbuminemia, but without proteinuria. Differential diagnosis, diagnostic work-up and the therapeutic options in this unusual case are discussed. The general practitioner must keep in mind a broad range of causes when seeing every-day-patients with peripheral edema, although the correct etiology can be found easily in most cases.
Uric acid stones occur in 10% of all kidney stones and are the second most-common cause of urinary stones after calcium oxalate and calcium phosphate calculi. The most important risk factor for uric acid crystallization and stone formation is a low urine pH (below 5.5) rather than an increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrhea or severe dehydration. Uric acid stone disease can be prevented and these are one of the few urinary tract stones that can be dissolved successfully. The treatment of uric acid stones consists not only of hydration (urine volume above 2000 ml daily), but mainly of urine alkalinization to pH values between 6.2 and 6.8. Urinary alkalization with potassium citrate or sodium bicarbonate is a highly effective treatment, resulting in dissolution of existing stones. Urinary uric acid excretion can be reduced by a low-purine diet. Potassium citrate is the treatment of choice for the prevention of recurrence of uric acid calculi. Allopurinol reduces the frequency of stone formation in hyperuricosuric patients with recurrent uric acid stones and/or gout.
The number of patients requiring chronic renal replacement therapy due to hypertension and diabetic nephropathy has increased steadily over the past decade in Switzerland. The level of blood pressure represents one of the major risk factors for the progression of renal diseases. Thus, treatment of hypertension is the cornerstone in the primary and secondary prevention of diabetic nephropathy and in particular in decreasing the rate of progression of chronic renal diseases. The WHO guidelines for the treatment of hypertension recommend a target blood pressure of < 130/80 mmHg for patients with renal failure and/or diabetes mellitus. Blood pressure should be lowered to < 125/75 mmHg in patients with proteinuria > 1 g/d and renal failure regardless of the etiology of the renal disease. Based on several intervention studies it is well established that antagonists of the renin-angiotensin system should be part of the antihypertensive regime in those patients. Besides their antihypertensive action, it has become evident that the renoprotective effect of these agents is also mediated by factors independent from changes in blood pressure. However, in most patients with chronic renal failure it is often necessary to use multiple drugs to lower blood pressure to target values. Often a combination of an ACE-inhibitor with a calcium-channel blocker is used for this purpose. The goal of the antihypertensive therapy in these patients is not only to lower blood pressure to reduce cardiovascular risk, but also to reduce proteinuria and to reduce the rate of loss in renal function or even prevent further progression.
The highly amiloride-sensitive epithelial sodium channel (ENaC) is an apical membrane constituent of cells of many salt-absorbing epithelia. In the kidney, the functional relevance of ENaC expression has been well established. ENaC mediates the aldosterone-dependent sodium reabsorption in the distal nephron and is involved in the regulation of blood pressure. Mutations in genes encoding ENaC subunits are causative for two human inherited diseases: Liddle's syndrome, a severe form of hypertension associated with ENaC hyperfunction, and pseudohypoaldosteronism (PHA-1), a salt-wasting syndrome caused by decreased ENaC function. Transgenic mouse technologies provide a useful tool to study the role of ENaC in vivo. Different mouse lines have been established in which each of the ENaC subunits was affected. The phenotypes observed in these mice demonstrated that each subunit is essential for survival and for regulation of sodium transport in kidney and colon. Moreover, the alpha subunit plays a specific role in the control of fluid absorption in the airways at birth. Such mice can now be used to study the role of ENaC in various organs and can serve as models to understand the pathophysiology of these human diseases.
The autosomal recessive form of type I pseudohypoaldosteronism (PHA-I) is an inherited salt-losing syndrome resulting from diminution-of-function mutations in the 3 subunits of the epithelial Na+ channel (ENaC). A PHA-I stop mutation (alpha(R508stop)) of the ENaC alpha subunit is predicted to lack the second transmembrane domain and the intracellular COOH-terminus, regions of the protein involved in pore function. Nonetheless, we observed a measurable Na+ current in Xenopus laevis oocytes that coexpress the beta and gamma subunits with the truncated alpha subunit. The mutant alpha was coassembled with beta and gamma subunits and was present at the cell surface at a lower density, consistent with the lower Na+ current seen in oocytes with the truncated alpha subunit. The single-channel Na+ conductance for the mutant channel was only slightly decreased, and the appearance of the macroscopic currents was delayed by 48 hours with respect to wild-type. Our data suggest novel roles for the alpha subunit in the assembly and targeting of an active channel to the cell surface, and suggest that channel pores consisting of only the beta and gamma subunits can provide significant residual activity. This activity may be sufficient to explain the absence of a severe pulmonary phenotype in patients with PHA-I.
Explore the source record for details and available documents.
The high Km glucose transporter GLUT2 is a membrane protein expressed in tissues involved in maintaining glucose homeostasis, and in cells where glucose-sensing is necessary. In many experimental models of diabetes, GLUT2 gene expression is decreased in pancreatic beta-cells, which could lead to a loss of glucose-induced insulin secretion. In order to identify factors involved in pancreatic beta-cell specific expression of GLUT2, we have recently cloned the murine GLUT2 promoter and identified cis-elements within the 338-bp of the proximal promoter capable of binding islet-specific trans-acting factors. Furthermore, in transient transfection studies, this 338-bp fragment could efficiently drive the expression of the chloramphenicol acetyl transferase (CAT) gene in cell lines derived from the endocrine pancreas, but displayed no promoter activity in non-pancreatic cells. In this report, we tested the cell-specific expression of a CAT reporter gene driven by a short (338 bp) and a larger (1311 bp) fragment of the GLUT2 promoter in transgenic mice. We generated ten transgenic lines that integrated one of the constructs. CAT mRNA expression in transgenic tissues was assessed using the RNAse protection assay and the quantitative reverse transcribed polymerase chain reaction (RT-PCR). Overall CAT mRNA expression for both constructs was low compared to endogenous GLUT2 mRNA levels but the reporter transcript could be detected in all animals in the pancreatic islets and the liver, and in a few transgenic lines in the kidney and the small intestine. The CAT protein was also present in Langerhans islets and in the liver for both constructs by immunocytochemistry. These findings suggest that the proximal 338 bp of the murine GLUT2 promoter contain cis-elements required for the islet-specific expression of GLUT2.
Hypoglycaemia can occur if the endogenous liver glucose output is lower than the glucose uptake in insulin-sensitive and insulin-insensitive tissues. The onset of hypoglycaemia induces the production of counterregulatory hormones such as glucagon, epinephrine, growth hormone and cortisol, and symptoms of neuroglycopenia. The correlation between biological hypoglycaemia and the symptoms associated with low blood sugar is particularly poor in diabetic patients and in patients with suspected postprandial hypoglycaemia. It is important to discriminate between fasting and postprandial hypoglycaemia. Idiopathic postprandial hypoglycaemia should be diagnosed clinically without further laboratory assessment, whereas the etiology of a fasting hypoglycaemia needs to be clarified further by laboratory testing, as it is potentially life-threatening.