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Biomedical subjects

S M Mauer

Publications and source records attributed to S M Mauer.

At least 163 records · Page 9Linked to original sources
PubMed1982

Kidney complications.

Diabetic glomerulosclerosis in man and in all spontaneous-onset and chemically induced diabetes in experimental models is characterized by diffuse increase in mesangial matrix and glomerular basement membrane thickening. The most prominent features of the biochemical changes in the glomerular basement membrane are increase in the collagen-like components, decreased sialic acid, and increased glucosylation. However, the heterogeneity of the various glycoprotein components of the glomerular basement membrane and related components of the mesangium make comparative biochemistry difficult. Increased glomerular blood flow with no apparent alterations in the glomerular filtration coefficient in diabetes may be attributed to altered vascular control mechanisms which may include both hormonal mediation as well as changes in end-organ responsiveness. Although proteinuria is a common manifestation of diabetic involvement of the glomerulus, there is little biochemical or physiologic evidence as to the specific causes of increased glomerular filtration apparatus permeability. Further information as to the pathogenesis of diabetic vascular disease of the kidney and the ability to reverse pathologic changes by correction of the metabolic milieu will require analysis of carefully selected animal models. Particular care in experimental design must include the ability to integrate pathology, physiology, and biochemistry in each model in order to relate the information to human renal diabetic complications.

Animals↗
PubMed1982

A double balloon catheter technique for alloxan diabetogenesis in the dog.

Venous injection of alloxan monohydrate is a standard method to produce a canine model of diabetes. Others have reported mortalities greater than 45 per cent and yields of diabetic dogs of less than 36 per cent with this technique. In this study, a new method for alloxan diabetogenesis is reported upon: alloxan monohydrate is injected intravenously with protection of the renal arteries at the time of injection by a 7F, triple lumen double balloon catheter placed in the abdominal aorta. The balloons are inflated under fluoroscopic control to occlude the renal arteries at the time of injection. Forty-three age-matched beagle dogs were initially injected with 60 milligrams per kilogram of alloxan monohydrate: 26 or 61 per cent became diabetic-defined as persistently doubled fasting serum glucose and glucosuria; ten failed to become diabetic, 23 per cent, and seven died, 16 per cent. The ten initial failures were reinjected with 65 milligrams per kilogram of alloxan monohydrate: six or 60 per cent then became diabetic, three were persistent failures, 30 per cent, and one dog died, 10 per cent. Thus, the over-all yield of diabetic dogs was 74 per cent, with an 18 per cent mortality. Minimal renal damage occurred, as evidenced by creatinine clearance, blood urea nitrogen and renal biopsy studies. These results suggest a significantly improved method--a twofold improvement over standard success rates with a twofold less mortality--of producing diabetic dogs by alloxan injection.

Alloxan↗
PubMed1981

The kidney in diabetes.

The kidneys as a target organ for secondary microvascular complications of diabetes mellitus represents a health problem of enormous social cost. Recent studies in man and animals strongly support the concept that the primary responsibility for diabetic nephropathy rests with the metabolic derangements of the diabetic state. However, these metabolic derangements have complex biological effects; it is unlikely that hyperglycemia, per se, produces all of the nephropathic influences of diabetes. Alterations in microvascular hemodynamics in diabetes probably contribute to glomerular pathology. These alterations may be based upon disturbed vasoactive control mechanisms regulating angiotensin and prostaglandin secretion and metabolism. Although much remains to be learned about the pathogenesis of glomerular basement membrane and mesangial thickening in diabetes, these central structural abnormalities appear separable. Mesangial thickening is reversible by cure of the diabetic state in rats whereas glomerular basement membrane thickening is not. Treatment for the diabetic patient with end-stage renal failure has recently improved markedly. Although presently, kidney transplants from living related donors appear best, cadaver transplants and long-term hemodialysis are reasonable options.

Basement Membrane↗
PubMed1981

Varicella in children with renal transplants.

Nineteen of 160 children developed varicella between eight days and 6.4 years following renal transplantation. Eight had severe varicella characterized by prolonged fever and new vesicle formation with rash involving mucous membranes. The severe group had an increased incidence of thrombocytopenia and markedly elevated liver enzyme values. Two patients of this group had bladder paralysis and another died. In three children post-transplant varicella represented a second attack of the disease. Children maintained on azathioprine therapy for three days or more after onset tended to have severe varicella. No graft loss occurred consequent to stopping azathioprine. Children with transplants at risk should have zoster immune plasma or globulin upon exposure, and azathioprine therapy should be stopped at onset of varicella. Corticosteroid therapy should be continued in order to avoid stress-induced Addisonian crisis.

Adolescent↗
PubMed1980

Obstructive uropathy, renal failure, and sepsis in the neonate--a surgical emergency.

Two infants who had obstructive uropathy accompanied by renal failure and sepsis are reported herein. Diagnostic and therapeutic techniques used to treat this type of surgical emergency are discussed in the order they were performed, as follows: (1) resuscitation for severe fluid and electrolyte disturbances; (2) gathering of cultures and initiation of antibiotic therapy; (3) the decision of whether or not dialysis is required, as well as when and how diagnostic evaluation should proceed; (4) the decision of whether dialysis is necessary or whether correction of obstructive uropathy can begin; and (5) the choice of the best operative procedure for this individual. This article emphasizes the necessity for a multidisciplinary team approach to these patients.

Acute Kidney Injury↗
PubMed1980

Treatment of an infant with severe chloramphenicol intoxication using charcoal-column hemoperfusion.

A 3,200 gm 12-day-old male infant with complex urologic problems underwent charcoal hemoperfusion for severe accidental chloramphenicol intoxication. Immediately prior to CH, with a serum chloramphenicol level of 98 micrograms/ml, the child was in profound shock, ashen-gray, hypothermic, and acidotic. Chloramphenicol levels indicated virtually complete removal of this drug by the CH column. Three hours of CH treatment resulted in a reduction of the chloramphenicol level to 13.5 micrograms/ml and complete reversal of the described clinical syndrome. No serious complications of CH were encountered. We conclude that chloramphenicol poisoning is treatable by CH and that this therapeutic modality may be safely carried out in infants and small children.

Anti-Bacterial Agents↗
PubMed1980

Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats.

An evaluation of platelet and vascular (aortic) arachidonic acid metabolism was performed in Lewis male rats rendered diabetic by injection of streptozotocin, and the results were compared to those in matched controls. Parameters evaluated included the release of this fatty acid from prelabeled platelets and aortas and conversion of labeled fatty acid to thromboxane B2 and 6-keto-PGF1 alpha in platelets and aortas, respectively. Diabetic rat platelets showed markedly increased release of arachidonic acid with thrombin used as the aggregating stimulus. Conversion of arachidonic acid to thromboxane B2 was slightly, but not significantly, higher in the diabetic rats. In the vessel, thrombin-stimulated release of arachidonic acid was slightly, but not significantly, increased in the diabetic animals when compared to controls. This finding was associated with a decrease in vascular production of 6-keto-PGF1 alpha both in vascular tissues incubated with arachidonic acid alone and in vascular tissues incubated with thrombin. The changes observed both in platelet and vascular metabolism of arachidonic acid were corrected by islet issue transplantation, suggesting a disease-specific effect. The changes observed in arachidonic acid metabolism suggest a significant imbalance in thromboxane A2 and PGI2 production in diabetic rats. Such changes might promote the development of the microvascular changes seen in diabetes mellitus.

Animals↗
PubMed1980

Uptake of aggregated immunoglobulin by the mouse kidney. I. Effect of endotoxin.

Endotoxin (ET) pretreatment of mice resulted in increased liver and spleen uptake and decreased circulating levels of aggregated IgC (AggIgG) compared to control animals. ET had no effect upon the uptake of AggIgG by lung or whole kidney cortex. However, immunofluorescent microscopy revealed increased localization of AggIgG in the mesangium of ET mice at 1 but not at 2 or 16 h after administration of AggIgG. These studies show that mesangial macromolecular uptake is not solely dependent upon blood levels, but appears to be influenced by unknown and probably complex variables.

Animals↗
PubMed1980

Uptake of aggregated immunoglobulin by the mouse kidney. II. Effect of hydrocortisone.

The uptake of radiolabelled (125I) aggregated human IgG (AggIgG) by the renal cortex, liver, spleen and lung was evaluated quantitatively in mice treated with hydrocortisone (HC) (25 mg) 72 h previously. AggIgG was administered in a dose of 1.5 or 3.5 mg/g body wt i.v.; tissue and blood were obtained at 1, 4 and 24 h. Renal cortical and mesangial uptake of AggIgG was significantly increased in HC animals. A rise in blood level was also observed in association with decreased splenic uptake, normal or slightly increased hepatic uptake and unchanged lung uptake. A significant increase in the kidney:lung and kidney:spleen ratios of AggIgG was induced by hydrocortisone, suggesting a relatively greater rate of loss from the spleen and liver than the renal cortex. The increased mesangial uptake may be a consequence of higher blood levels of AggIgG, as well as a direct effect of HC on the mesangium.

Animals↗
PubMed1980

Studies of the glomerular mesangium and the juxtaglomerular apparatus in the genetically diabetic mouse.

Intact and uninephrectomized genetically diabetic (db/db) mice (C57BL/KsJ) and their nondiabetic littermates (dm/m) had renal biopsies performed at 6 months of age. Renal tissues were studied by regular light microscopy and by a variety of immunohistochemical techniques. Intact db/db mice had peripheral mesangial thickening as compared to db/m mice. This thickening, predominantly due to increased mesangial matrix material, extended to the glomerular hilum and the extraglomerular mesangium of the juxtaglomerular apparatus. This abnormality was markedly increased an uninephrectomized db/db mice (db/db-UN) compared to intact db/db mice. Db/m-UN animals had slightly greater mesangial thickness than intact db/mice but less than that of db/db mice. Intact db/db mice had increased mesangial IgM staining compared to db/m mice and these differences were magnified by uninephrectomy. The IgM staining, especially in the diabetic mice, involved the peripheral mesangium and the glomerular hilum extending into extraglomerular mesangium and the distal tubule at the level of the macula densa. The tubular staining in the region of the juxtaglomerular apparatus was between the tubular basement membrane and the epithelial cells and between epithelial cells. The distal tubular epithelial cell cytoplasm also showed increased staining for IgM as the tubule coursed away from the glomerulus. These studies amplify the argument that alterations in glomerular hemodynamics influence the rate of development of diabetic glomerular lesions. Further, these diabetic mice appear to represent an important model for the study of mesangial macromolecular processing mechanisms.

Animals↗