Antimicrobial management of septic arthritis of the hand and wrist.

PURPOSE: The optimal antimicrobial treatment for patients with hand or wrist septic arthritis is unknown. We report the treatment outcomes in patients with these infections. METHODS: The medical records of 40 consecutive adult patients with hand or wrist septic arthritis treated at our institution from 2000 to 2008 were retrospectively reviewed. The primary outcome measure was treatment failure (histopathologic or microbiologic evidence of relapsed infection from the same joint or a contiguous anatomic area). RESULTS: Involved joints were the wrist (n = 10, 25 %), metacarpal-phalangeal (n = 11, 27.5 %), proximal interphalangeal (n = 8, 20 %), distal interphalangeal (n = 10, 25 %), and thumb interphalangeal (n = 1, 2.5 %). Methicillin-sensitive (n = 15, 45 %) and -resistant (n = 7, 17.5 %) Staphylococcus aureus were the most common pathogens. Surgical therapies included open arthrotomy with debridement (n = 33, 82.5 %), arthroscopic debridement (n = 2, 5 %), and aspiration alone (n = 5, 12.5 %). Most patients (23/40, 58 %) received less than 1 week of parenteral antimicrobial therapy. Only two patients developed definite antimicrobial treatment failure, one of whom had an atypical mycobacterium infection. Patients with subacute to chronic infections were at high risk for finger amputation. CONCLUSIONS: When combined with surgical debridement, relatively short courses of parenteral antimicrobial treatment (<1 week) supplemented with oral therapy for an additional 2-3 weeks is usually sufficient antimicrobial therapy for hand or wrist septic arthritis.

Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene.

Mice homozygous for the Leprdb3J (db3J) mutation are null for all known isoforms of the leptin receptor (LEPR). These animals are obese, hyperphagic, cold intolerant, insulin resistant, and infertile. Mice homozygous for the Leprdb (db) mutation (lacking the B isoform only) have the same phenotype as db3J animals. To better understand the function(s) of the LEPR isoforms in vivo, we generated db3J/db3J and db/db mice bearing a transgene (neuron-specific enolase [NSE]-Rb) expressing the B isoform of LEPR, the isoform capable of activating the signal transducer and activator of transcription (STAT) pathway, under the control of the neuron-specific enolase enhancer/promoter. The NSE-Rb transgene was expressed in the brain, with low levels of expression in adrenals, testis, and white adipose tissue. LEPR-B transgene expression in NSE-Rb db3J/db3J mice partially corrected the increased fat mass, hyperphagia, and glucose intolerance while restoring fertility in males and rescuing the cold intolerance in both sexes. The body weights of NSE-Rb transgenic mice that possessed the full complement of short LEPR isoforms (NSE-Rb db/db mice) were similar to those of NSE-Rb db3J/db3J mice, suggesting that the short LEPR isoforms play little role in body weight regulation. Based on quantitative analysis of hypothalamic neuropeptide gene expression in the transgenic animals, we infer full restoration of leptin sensitivity to proopiomelanocortin (POMC) neurons, partial correction of leptin sensitivity in agouti gene-related protein (AGRP)/neuropeptide Y (NPY) neurons, and a lack of effect on leptin sensitivity of melanin concentrating hormone neurons. Thus, hypothalamic POMC and AGRP/NPY neurons are primary candidates as the mediators of the effects of the NSE-Rb transgene on energy homeostasis, ingestive behavior, the neuroendocrine system, and glucose metabolism.

Ontogeny of hyperphagia in the Zucker (fa/fa) rat.

The ontogeny of hyperphagic behavior in the Zucker fatty (fa/fa) rat was examined. Wild-type, +/fa, and fa/fa pups aged postnatal day 5 (P5), P9, P12, P15, and P18 were evaluated using a test that measured ingestive behavior independent of the dam. The independent ingestive test consisted of giving pups access to a test solution [half-and-half (cream and milk)] on a tissue on the floor of a test chamber for 20 min. The latency to ingest and the intake (weight gain and percent weight gain) were measured and normalized to +/fa littermates. Pups were tested once to eliminate any effects of test experience. fa/fa Pups ingested significantly more than lean pups (+/+ and +/fa) on P12, P15, and P18, but not on P5 or P9. The latencies of fa/fa pups did not differ significantly from the latencies of +/+ pups except on P18, when the latencies of fa/fa pups were significantly shorter. The latencies of +/fa pups were significantly longer than the latencies of fa/fa or +/+ pups on P5 and P12. These results demonstrate that hyperphagia in fa/fa rats emerges between P9 and P12 under the test conditions used.