Dysregulation of kidney nitric oxide synthase (NOS) I may alter renal hemodynamics in diabetes. Four types of studies were performed in anesthetized 1- to 2-wk-streptozotocin diabetic rats. 1) Glomerular filtration rate (GFR) was measured before and during NOS I blockade. Subsequent addition of nonspecific NOS blocker tested for residual NO from other isoforms. Acute systemic NOS I blockade reduced GFR only in diabetics. Nonspecific NOS blockade had no additional effect on NOS I-blocked diabetics. 2) Renal blood flow (RBF) was monitored for evidence that tubuloglomerular feedback (TGF) resets during 1 h of continuous activation with benzolamide. NOS I blockade was added to test for the role of NOS I in TGF resetting. During 1 h of TGF activation in controls, RBF initially declined and then returned to baseline. In diabetic and NOS I-blocked rats, RBF declined and remained low. 3) The ability of NOS I blockade to increase the homeostatic efficiency of TGF in diabetes was tested by micropuncture in free-flowing nephrons. The addition of NOS I blocker to the tubular fluid increased TGF efficiency in control and diabetic rats. 4) The influence of distal salt delivery on local NOS I activity was tested by micropuncture. Henle's loop was perfused at varying rates with NOS I blocker while single-nephron GFR (SNGFR) from the late proximal tubule was measured. In controls, NOS I blockade mainly reduced SNGFR when flow through Henle's loop was high. In diabetics, NOS I blockade reduced SNGFR independently of flow through Henle's loop. In conclusion, normally, salt delivered to the macula densa (MD) exerts immediate control over MD NOS I activity. In diabetes, there is ongoing overactivity of NOS I that is not regulated by MD salt.
During one hour of persistent TGF stimulation, RBF increases toward normal, but GFR does not. This requires an overall decrease in renal vascular resistance and a decrease in the ratio of efferent/afferent arteriolar resistance (RE/RA), implying a major decrease in RE. NOS I, but not angiotensin-converting enzyme (ACE), is required for RBF to increase during TGF resetting. Although the hemodynamic changes during TGF resetting resemble the response to blocking the renin-angiotensin system, these data fail to show that the increase in RBF during early TGF resetting is mediated by renin suppression.
Meningitis is a common admission diagnosis. No case series or descriptive studies on meningitis have recently been published. Additionally, no recent data exist on meningitis in the U.S. Military Health System. We reviewed charts of adult patients admitted to Naval Medical Center San Diego between January 2004 and December 2008 with an admission diagnosis of meningitis. Charts were excluded if they did not meet our case definition of meningitis, if missing data, or if meningitis was nosocomial or iatrogenic. We reviewed results of cerebrospinal fluid cultures during this period. We compared rates and characteristics, and outcomes of bacterial and aseptic meningitis. Two hundred twenty-one cases met our criteria. Of these, 208 were aseptic. Cerebrospinal fluid polymerase chain reaction testing was positive for enteroviruses and herpes simplex viruses in 42 (20.2%) and 17 (8.2%) cases, respectively. Of culture/polymerase chain reaction/serologically positive cases, the pathogens were Neisseria meningitidis (3), Streptococcus pneumoniae (3), viridans streptococci (2), Cryptococcus neoformans (2), Coccidioides immitis (2), and Mycobacterium tuberculosis (1). Three patients had poor outcomes: one died from S. pneumoniae and two had long-term neurologic deficits. Meningitis is a common admission diagnosis, but serious virulent pathogens are uncommon and adverse outcomes are rare.
Squamous cell carcinoma (SCC) is a well-known complication of immunosuppression associated with organ transplantation. It may arise de novo or from previously existing in situ lesions (Bowen's disease). Concurrent human papilloma virus infection often has an etiologic role, and SCC may follow an aggressive course in immunosuppressed patients. The authors describe a liver transplant patient in whom end-stage renal disease developed. She underwent tunneled catheter placement followed by arteriovenous graft placement. Subsequently, a large SCC in situ at the exit site of her prior tunneled hemodialysis catheter occurred. The growth was removed surgically without complication. SCC has not been reported previously to arise from a catheter exit site. This entity is common in renal and other transplant populations and may follow an aggressive course. It should be sought out by careful skin evaluation to include areas not routinely exposed to the sun.
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