Incidence and management of ulcers in diabetic Charcot feet

This study followed 115 patients with diabetes--who between them had 140 feet with Charcot's arthropathy--over six to 114 months (median: 48). A total of 43 patients (37%) developed ulcers in 53 feet. Their treatment was multifactorial. An offloading regimen was adopted, with the use of crutches and therapeutic sandals with soft, individually moulded insoles, followed by adjusted or bespoke shoes. Recalcitrant ulcers were treated with surgery in 16 patients (37%). Antibiotics were needed by 21 patients (49%). The incidence of ulceration was 17% per year. The median time interval between the acute component of Charcot's arthropathy and ulcer development was 36 months (range: 0-120 months). In seven patients, the ulcer developed during the acute phase. In 12 patients the ulcers were localised to the rockerbottom deformity in the mid-foot region, but in 31 patients other regions were affected. Dynamic footprint analysis was used to help adjust the offloading shoe/insole on the rockerbottom deformity. Such ulcers took twice as long to heal as other ulcers. Surgical treatment comprised: major amputation (two patients), arthrodesis for unstable ankle (three patients), toe amputations (seven patients), resection of the rockerbottom deformity (one patient) and other revisions (three patients). One patient died with an unhealed ulcer. There is a four-fold risk of ulcers in diabetic Charcot deformity compared with the overall risk of foot ulcers in diabetic feet. Healing was achieved in 40 patients (93%). The surgical intervention rate of 37% in ulcer cases in Charcot feet was low compared with the literature.     

The action of cysteinyl-leukotrienes on intracellular calcium mobilization in human detrusor myocytes

OBJECTIVE: To investigate the presence of leukotriene D4 receptors in fura-2-loaded human detrusor smooth muscle cells (DSMCs) by examining the ability of leukotriene D4 to raise intracellular-free Ca2+ concentration ([Ca2+]i), to determine the origin of the leukotriene D4-mediated rise in [Ca2+]i and to investigate whether the specific leukotriene D4 receptor antagonist montelukast inhibits the Ca2+ response induced by leukotriene D4. MATERIALS AND METHODS: Detrusor muscle biopsies were obtained from patients with benign noninvasive bladder diseases undergoing cystoscopy. DSMCs were isolated using an explant technique and maintained in culture. Only primary cultures or cells passaged up to three times were used for experiments. DSMCs were characterized with immunohistochemical staining and their identity confirmed by transmission electron microscopy. [Ca2+]i was measured in single DSMCs using the Ca2+ probe fura-2 and fluorescence-ratio microscopy. RESULTS: Immunohistochemical staining showed that 80-99% of the cells were positive for smooth muscle alpha-actin. The ultrastructural features of the cultured cells were those of smooth muscle cells and showed no differentiation in a fibroblastic or myofibroblastic direction. Leukotriene D4 increased the level of [Ca2+]i in a dose-dependent manner. Calcium was mobilized almost exclusively from intracellular Ca2+ stores. There was a dose-dependent inhibition of the increase in [Ca2+]i by montelukast. CONCLUSION: The present study is the first to show the presence of specific leukotriene D4 receptors in human detrusor myocytes. This may have implications for a potential pathophysiological role of leukotriene D4 in patients with interstitial cystitis and other functional or inflammatory bladder disorders.     

CD8 T cell-mediated rejection of intestinal allografts is resistant to inhibition of the CD40/CD154 costimulatory pathway

BACKGROUND: Disruption of the CD40/CD154 pathway inhibits rejection in numerous models. The importance of this pathway on intestinal allograft rejection was examined in this study. METHODS: Intestinal grafts from B6C3F1 mice transplanted into C57BL/6 recipients were assessed histologically for rejection. RESULTS: The monoclonal antibody to CD154, MR1, failed to inhibit rejection in wild-type mice. Similarly, CD154-/- recipient mice rejected intestinal allografts. MR1 did inhibit early rejection in CD8-/- mice, but had no effect in CD4-/- recipients. All MR1-treated CD8-/- recipients eventually developed rejection. No benefit was observed when blockade of the CD40/CD154 pathway by MR1 was combined with blockade of the CD28/B7 pathway by mCTLA4Ig. CONCLUSIONS: These data suggest that CD4+ T cells mediating intestinal allograft rejection may be more dependent upon the CD40/CD154 pathway than CD8+ T cells. This finding highlights the importance of identifying agents that suppress CD8+ T cell-mediated rejection.     

Immunization of pigs against influenza virus infection by DNA vaccine priming followed by killed-virus vaccine boosting

In a previous study of particle-mediated DNA vaccination of pigs, it was found that administration of an influenza virus hemagglutinin (HA) gene elicited low levels of virus-specific antibody, but did not provide significant protection from challenge infection (as evidenced by virus shedding in nasal secretions). However, the vaccinated pigs developed high antibody titers after exposure to the challenge virus, suggesting strong priming of humoral immune responses by DNA vaccination. In the present study, pigs given a conventional, inactivated influenza virus vaccine 4 weeks after a priming dose of HA DNA developed higher levels of virus-specific serum antibodies and were protected from challenge virus infection to a significantly greater degree than pigs that received two doses of DNA vaccine.     

Prevention of perinatal group B streptococcal infection: current controversies

Group B streptococcus (GBS) is the most frequent cause of neonatal sepsis in the United States. The Centers for Disease Control and Prevention (CDC) issued guidelines for its prevention in 1996. This article details areas of controversy with those guidelines and offers recommendations for resolution. We recommend that a prevention policy be adopted by all hospitals. If a screening-based policy is chosen, compliance is essential. Penicillin is the antibiotic of choice for GBS prevention. Increasing resistance to clindamycin and erythromycin might eliminate them as alternative choices in patients allergic to penicillin. Group B streptococcal prophylaxis might not be necessary in women who have repeat elective cesarean delivery. In asymptomatic women, a positive urine culture for GBS should be considered clinically equivalent to a positive vaginal or rectal sample for screening. Neonatal sepsis caused by organisms other than GBS must be monitored carefully by all hospitals providing obstetrics services.     

Sentinel node staging of early breast cancer using lymphoscintigraphy and the intraoperative gamma detecting probe

Lymphoscintigraphy combined with intraoperative gamma-probe detection of sentinel lymph nodes in patients with inoperable early primary breast cancers is effective for staging the disease. The clinical alternative is axillary lymph node dissection, which is a far more invasive procedure and is accompanied by significant morbidity. Accuracy of staging is enhanced by immunohistochemical staining of micrometastases, which pathologists can easily perform for one to three sentinel lymph nodes, but not for 20 to 30 nodes, using axillary dissection procedure. Optimum methodology is presented for performing sentinel lymph node imaging and is important for accurate identification of sentinel node(s).     

Suppression of maternal virus load with zidovudine, didanosine, and indinavir combination therapy prevents mother-to-fetus HIV transmission in macaques

Recently, we developed a maternal-fetal macaque model using a highly pathogenic HIV-2 strain, HIV-2287, to study the time course of HIV transmission in utero. Most pregnant macaques (Macaca nemestrina) infected with HIV-2287 (10-103 infective doses) transmitted HIV to their fetuses, as verified by positive identification of virus-infected mononuclear cells and free viral RNA in fetal blood. To determine whether an antiretroviral drug combination therapy composed of two dideoxynucleosides, azidothymidine (15 mg/kg) and dideoxyinosine (15 mg/kg), and a protease inhibitor, indinavir (25 mg/kg), could completely inhibit mother-to-fetus HIV transmission, we administered these drugs orally through gastric catheters to five pregnant macaques infected with 10 infective doses of HIV-2287. Beginning 30 minutes after HIV inoculation, the dams were given the combination antiviral therapy three times daily until delivery by cesarean section. Drug treatment reduced the maternal virus load to a minimally detectable level but did not prevent primary HIV-2287 infection. All fetal and infant blood samples were virus negative by internally controlled RNA polymerase chain reaction (QC-RNA-PCR) and virus coculture assays. Fetal and infant CD4+ T-cell levels remained normal throughout the experiment. These findings strongly suggest that combination chemotherapy with azidothymidine, dideoxyinosine, and indinavir can suppress maternal viral load enough to prevent mother-to-fetus transmission of HIV.     

A laboratory study evaluating the release of hydroxyl ions from various calcium hydroxide products in narrow root canal-like tubes

AIM: The aim of the present study was to describe pH changes in a variety of buffering solutions within a narrow test tube containing either a gutta-percha point with incorporate calcium hydroxide, a commercial calcium hydroxide paste (Calcicur) or a freshly mixed paste of calcium hydroxide in distilled water. METHODOLOGY: The test material was placed centrally in a test tube of 2 mm inner diameter. Saline (1%) was placed at one end, whilst the buffering solutions were introduced at the other. The pH of the buffering solutions was monitored using electrodes placed at each end of the test tube. RESULTS: It was found that the pH 4.01 buffer strongly resisted pH changes at levels below 6.0, whilst saliva and bovine serum was buffered less and more evenly in the whole range up to pH 11.5. The calcium hydroxide containing gutta-percha points caused the pH to increase quickly in the sodium chloride solution to levels above 11.5. However, in bovine serum, in saliva and in the pH 4.01 buffer the pH remained below 8.5, 8.0 and 6.0, respectively, 1 mm from the point. In contrast, the release of hydroxyl ions from the two calcium hydroxide pastes brought pH above pH 11.5 irrespective of the buffering of the solutions 5 mm from the paste. CONCLUSION: It is concluded that Calcicur and the calcium hydroxide-water mixture contained substantially more available calcium hydroxide than did the calcium hydroxide containing gutta-percha points, with the result that the release of hydroxyl ions from the points was limited in comparison to that from the pastes.