Cerebral phaeohyphomycosis caused by Ramichloridium mackenziei is universally fatal. All reported cases with long-term follow-up have indicated 100% mortality despite antifungal therapy and surgical intervention. We describe the case of a 62-year-old patient who underwent renal transplantation and had a cerebral abscess caused by R. mackenziei. The infection progressed despite surgical evacuation and therapy with liposomal amphotericin B, itraconazole, and 5-flucytosine. The patient was subsequently treated with the investigational triazole posaconazole oral suspension, 800 mg/day, in divided doses. Treatment with posaconazole resulted in progressive clinical and radiologic improvement. The patient is alive four years after diagnosis and maintained on posaconazole therapy. This case supports the potential role of this extended-spectrum azole in the treatment of this serious fungal infection of the central nervous system.
We conclude that the allocation of blood group A2 kidneys for blood group O and B recipients is a practical way to expand the donor pool for these transplant candidates. PP may be important for reducing the levels of anti-A1 and anti-A2 antibodies and for reducing the risk of hyperacute rejection. Splenectomy seems to be unnecessary.
The effect of the newly developed, nonpeptide, calpain inhibitor, PD 150606, on hypoxia and ionomycin-induced increases in calpain activity in rat proximal tubules (PT) was determined. PD150606 inhibited both hypoxia and ionomycin-induced calpain activity as determined by the fluorescent substrate N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methyl coumarin (N-succinyl-Leu-Leu-Val-Tyr-AMC). This decrease in calpain activity was accompanied by dose-dependent cytoprotection against hypoxia and ionomycin-induced cell membrane damage. PD150606 had no effect on cathepsin B and L activity in PT as measured by the fluorescent substrate, benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methyl coumarin (Z-Phe-Arg-AMC). The effects of low intracellular pH (pHi) or low free cytosolic calcium [Ca2+]i on this hypoxia-induced calpain activity were also determined. Both low pHi and low [Ca2+]i attenuated the hypoxia-induced increase in calpain activity. This attenuation of calpain activity was observed early before hypoxia-induced membrane damage and was associated with marked reduction in the typical pattern of hypoxia-induced cell membrane damage observed in this model. To identify the isoform of calpain activated in rat proximal tubules, normoxic, hypoxic and ionomycin treated tubules were fractionated by MONO-Q anion exchange chromatography and the fractions were assayed for calpain activity. A single peak of calpain activity characteristic of mu-calpain was found. The calcium dependency of the calpain activity was in the nanomolar range, further confirming that the activity was the low Ca(2+)-sensitive mu-calpain. The present study suggests that in rat proximal tubules: (1) PD 150606 is a specific inhibitor of calpain and not cathepsins B and L; (2) the cytoprotective effects of low pHi and low [Ca2+]i are mediated, at least in part, by inhibition of calpain activity; and (3) the predominant active form of calpain is the isoenzyme mu-calpain.
In the present study, we directly monitored nitric oxide (NO) with an amperometric NO-sensor in suspensions of rat proximal tubules. Hypoxia-stimulated NO generation was characterized by an initial rise and a subsequent sustained increase which preceded cell membrane damage as assessed by lactic dehydrogenase (LDH) release. In contrast, the NO concentration remained unmeasurable in normoxic controls. Nitro-L-arginine-methyl ester (L-NAME) prevented the hypoxia-induced increase in NO in a dose dependent manner in parallel with incremental cytoprotection. The hypoxia-induced elevation in NO and the associated membrane injury were both markedly prevented by extracellular acidosis (pH 6.95). In vitro proximal tubular nitric oxide synthase (NOS) activity (3H-arginine to 3H-citrulline assay) was pH dependent with optimum activity at pH 8.0 and greatly reduced activity at acidic pH even in the presence of calcium and co-factors. However, glycine, a well recognized cytoprotective agent, did not attenuate the NO concentration during hypoxia. The present study therefore provides direct evidence that NO is generated by rat proximal tubules during hypoxia and demonstrates that the protective effect of low pH against hypoxic rat tubular injury is associated with an inhibition of this NO production.
Introduction:Nephrolithiasis is a common problem worldwide especially in areas of the hot climate like Saudi Arabia. The aim of this analysis was to study the characteristics of urinary stones in Eastern Saudi Arabia and to report the following: Composition of urinary stones, age and gender distribution, seasonal variation of stone development, comorbid conditions associated with stone development and the incidence of urinary stones.Methods:All urinary stones that were submitted to the Johns Hopkins Aramco Healthcare, previously Saudi Aramco Medical Services Organization for analysis from January 2011 through January 2013 were analyzed.Results:A total of 384 urinary stones were collected and submitted for analysis from 347 patients. There was a male predominance with a male: female ratio of 3.9:1. The average age was 48.5 ± 12.8 years. Weight abnormality was predominant in both genders, and especially females. Calcium-based stones constituted the great majority (84.6%) followed by uric acid stones (12.8%). The other forms of stones were rare. More stones were recovered during the hot season, May to September. The calculated annual incidence of urolithiasis was 111/100,000 individuals.Conclusion:Calcium based stones are the most common urinary stones observed in Eastern Saudi Arabia. There is a clear association between the diagnosis of urinary stones and the hot season
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