Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Traumatic or septic aortic regurgitation: diagnosis by oesophageal echocardiography

Severe aortic regurgitation was discovered in a young man 21 days after blunt chest trauma and after a prolonged febrile state with positive blood cultures. Using transoesophageal echocardiography (TEE), it was possible to make the differential diagnosis between traumatic rupture and endocarditis as the cause of valvular insufficiency. The use of TEE in the initial evaluation of severe thoracic trauma with an unclear clinical picture is recommended. This method is easy to use at the bedside and gives precise information on the aortic valve and the ascending aorta.     

Immunohistochemical characterization of the 'intimal proliferation' phenomenon in Sneddon's syndrome and essential thrombocythaemia

Cellular changes were immunocytochemically characterized in skin vessels of five patients with idiopathic generalized racemose livedo (Sneddon's syndrome), and one patient with localized racemose livedo associated with essential thrombocythaemia. Antibodies against α-smooth muscle-actin, tropomyosin, desmin, vimentin, factor VIII-related antigen, human endothelial cells (CD31), human macrophages (CD68), and HLA-DR positive cells (CR3/43) were used. Conventional light microscopy showed, in all cases, intimal thickening of ascending arteries and arterioles as a result of an accumulation of cells and extracellular hyalinized material. None of the specimens showed infiltration with polymorphonuclear leucocytes or macrophages. The cells in the region of the intimal hyperplasia showed intense positive immunostaining for α-smooth muscle actin and tropomyosin. Staining for the intermediate filament desmin was localized to the resident smooth muscle cells of the media, whereas staining for vimentin was found in all types of cells in both the intima and media. Positive immunostaining for factor VIII-related antigen and CD31 was strictly confined to the endothelial cells lining the narrowed lumina of the vessels. No positive staining with either antibody was observed in totally occluded vessels. Cells in the subintimal space did not show reactivity for CD68 in any of the specimens, but two cases showed solitary cells with positive staining for HLA-DR in this region. There were no differences in staining pattern between Sneddon's syndrome and essential thrombocythaemia with any of the antibodies. Our results support the assumption that the ‘intimal proliferation’ in both diseases is caused by colonization of the subendothelial space with contractile cells of possibel smooth muscle origin. The similarities in histopathology and immunocytochemistry might indicate that in both diseases platelet-derived factors play a causative role.     

Clinical and histological patterns of dermatofibromas of the nail apparatus

True fibromas develop as painless slow-growing nodular tumours. They may appear in any portion of the nail apparatus. The clinical features vary according to their anatomical site. In contrast, the histological features, consisting of a dermal hypocellular reticular nodule with ill-defined demarcation, were similar in all our patients, and factor XIIIa was negative.     

A method for sonographic counting of the lower vertebral bodies in newborns and infants.

PURPOSETo determine whether the lumbosacral junction of the vertebral column can be identified with sonography in newborns and infants and thus serve as a method for counting the lumbar and sacral vertebral bodies.METHODSIn 32 newborns and infants, the number of ossified vertebral bodies distal to the lumbosacral junction was counted with sonography and radiography.RESULTSSonographic and radiographic findings agreed in 29 of 32 examinations (91%).CONCLUSIONSThe lordotic transition at the lumbosacral junction can be identified with sonography in the majority of newborns and infants, allowing intraspinal structures to be related to a specific vertebral level.     

Differential Effect of Diarrhea on FK506 Versus Cyclosporine A Trough Levels and Resultant Prevention of Allograft Rejection in Renal Transplant Recipients

Diarrhea is the most frequently reported adverse event in patients treated with mycophenolate mofetil. Twenty-six renal transplant patients on a mycophenolate mofetil-based immunosuppressive regime with persistent afebrile diarrhea were examined. Diarrhea caused a significant rise in FK-506 trough levels despite intake of stable doses, necessitating FK-506 dose reductions of 30% to obtain pre-diarrhea trough levels. In contrast, trough levels of cyclosporine A remained stable without dose adjustments. This suggests that absorption and/or metabolism is differentially altered for FK506 compared with cyclosporine A in patients with diarrhea. In nine patients mycophenolate mofetil was reduced or stopped because of persistent diarrhea without identifiable cause. This resulted in end-stage renal disease because of chronic rejection in two patients, and in acute rejection in two patients, all taking FK506 and steroids. Therefore, dose adjustments of FK506 in patients with diarrhea must be carefully monitored, especially when doses of mycophenolate mofetil are also reduced.     

Dietary mannan-oligosaccharides and their effect on chicken caecal microflora in relation to Salmonella Enteritidis colonization

This study first investigates the effects of mash diet, or mash supplemented with either 2.5% mannose-oligosaccharide (MOS) or palm kernel meal (PKM), on the microflora of the hen caecal contents. Second, it investigates the effect of caecal contents of hens (HCC) fed mash or mash supplemented with MOS or PKM on the major microflora groups of chicks, and their inhibitory effect on Salmonella enterica serovar Enteritidis (PT4) colonization. Finally, this study investigates the effect over time of diets supplemented with MOS or PKM on S. Enteritidis colonization and the microflora of chicks. In hens, supplemented diets increased Bifidobacterium spp., while decreasing members of Enterobacteriaceae and Enterococcus spp., compared with the mash diet. Chicks dosed with the HCC showed, on average, increased numbers of anaerobes, while the numbers of aerobes decreased including coliforms and S. Enteritidis compared with controls without HCC. In chicks fed the MOS-supplemented or PKM-supplemented diets, S. Enteritidis colonization decreased over time, compared with mash alone. Four-week-old PKM birds showed an increase in Bifidobacterium spp. and Lactobacillus spp., with a decrease in S. Enteritidis compared with week 2. Generally, the HCC and diets supplemented with MOS or PKM affected the birds intestinal microflora by increasing the Bifidobacterium spp. and Lactobacillus spp., while decreasing the Enterobacteriaceae groups. They also reduced susceptibility in young chickens to colonization by S. Enteritidis.