Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis

BACKGROUND: CD11a/CD18 comprise subunits of leukocyte function associated antigen (LFA-1), a T-cell surface molecule important in T-cell activation, T-cell emigration into skin, and cytotoxic T-cell function. OBJECTIVE: We explored the immunobiologic and clinical effects of treating moderate to severe psoriasis vulgaris with a single dose of humanized monoclonal antibody against CD11a (hu1124). METHODS: This was an open label study with a single dose of hu1124 at doses of 0.03 to 10 mg/kg. Clinical (Psoriasis Area and Severity Index [PASI]) and immunohistologic parameters (epidermal thickness, epidermal and dermal T-cell numbers, and keratinocyte intercellular adhesion molecule 1 [ICAM-1] expression) were followed. RESULTS: Treatment with hu1124, at doses higher than 1.0 mg/kg (group III), completely blocks CD11a staining for at least 14 days in both blood and psoriatic plaques. At 0.3 to 1.0 mg/kg, T-cell CD11a staining was completely blocked; however, blockade lasted less than 2 weeks (group II). Only partial saturation of either blood or plaque cellular CD11a was observed at doses of hu1124 between 0.01 and 0.1 mg/kg (group I). This pharmacodynamic response was accompanied by decreased numbers of epidermal and dermal CD3(+) T cells, decreased keratinocyte and blood vessel expression of ICAM-1, and epidermal thinning. Statistically significant drops in PASI compared with baseline were observed in group II patients at weeks 3 and 4 and in group III patients at weeks 2 through 10. No significant drop in PASI score was observed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and included mild chills, abdominal discomfort, headache, and fever. At a single dose of 0.6 mg/kg or higher, headache was the most common dose-limiting toxicity observed. CONCLUSION: Targeting CD11a may improve psoriasis by inhibiting T-cell activation, T-cell emigration into the skin, and cytotoxic T-cell function.     

Radial cortical and trabecular bone densities of men and women standardized with the European forearm phantom

We previously showed that it is possible to cross-calibrate peripheral bone densitometers using the European Spine Phantom (ESP). We have now performed a multinational study of cross-calibrated radius bone density based on normal subjects of both sexes in eight European centers. Six centers were equipped with machines made by Scanco or Stratec for determining distal radial trabecular bone density by quantitative computed tomography (QCT) and two were equipped with Lunar SP2 single photon absorptiometry (SPA) equipment for measuring midshaft cortical bone density. Subjects recruited ranged from 20 to over 80 years of age. Over one hundred and fifteen men were studied by QCT and a different cohort of 104 men were studied with SPA; the equivalent figures for women were 235 and 123. Reference ranges were derived for bone density against age for each of the four groups, and their applicability is discussed in relation to between-center differences in the results obtained. There were insignificant differences (P>0.05 with Bonferroni correction) between centers in the values obtained by QCT in the different populations. However, there were considerably larger and highly statistically significant differences between midshaft cortical bone density values of about 10% of overall means between subjects from eastern Finland and central Belgium (P<0.001), with higher Finnish values. Women had considerably lower radial trabecular bone density values than men at all ages, a result that differentiates the radius from the spine. This sex difference widened after menopause. These results have important implications for understanding the contribution of bone density to the differential risk of Colles' fracture in the two sexes and suggest that further work is needed to establish young normal reference ranges for radial bone density in Europe.     

Comparison between the Skin Snip Test and Simple Dot Blot Assay as Potential Rapid Assessment Tools for Onchocerciasis in the Postcontrol Era in Ghana

Successful control of onchocerciasis through mass distribution of ivermectin needs to be coupled with reliable, sensitive, specific, yet affordable diagnostic methods to monitor and ensure the efficacy of such measures. The effort put into the development of diagnostic methods for onchocerciasis that can substitute for or work in combination with the present “gold standard,” the skin snip test, has resulted in the discovery of a number of immunogenic proteins with potential use as diagnostic tools in the postcontrol era. Most of these proteins have now been produced through recombinant DNA techniques. However, when costs are not a trivial issue, none of them have yet found their way into the areas where the disease still exists. In the present study, we have evaluated the performance of a simple dot blot assay which uses a mixture of native proteins designated PakF as a serious contender in the quest for a less invasive and more sensitive method to detect Onchocerca volvulus infection in areas with diverse endemicities. Our results indicate that the assay we propose is more sensitive than the skin snip test and shows high specificity, both characteristics required for a suitable tool for the monitoring of onchocerciasis in the postcontrol era.     

Perceived barriers and biases in the medical education experience by gender and race.

This study examined barriers and biases in the medical education experience by surveying fourth-year medical students. There were 270 female and 288 male respondents; their racial background was: 21% Asian, 13% underrepresented minorities, and 66% white. Women reported that the careers they were encouraged to pursue were affected by their gender (44% versus 15%) and they were often mistaken for a nonphysician (92% versus 3%). More importantly, women reported that the lack of a mentor of either gender as a large barrier (27% versus 19%). Underrepresented minorities reported that their race caused them to feel that they had to be twice as good to be treated as an equal to other students (52% versus 6%). Underrepresented minorities identified the lack of a same-race mentor (23% versus 4%) and role model (40% versus 1%) as a large barrier. Underrepresented minorities also noted an overall lack of mentors as a large barrier (25% versus 19%). Women and underrepresented minorities from the class of 1996 reported having a medical school experience characterized by similar barriers to their professional development.     

Oesophageal propulsive force and its relation to manometric pressure.

A fixed volume capsule incorporating a force transducer and a side hole for manometric measurements was constructed and calibrated. Simultaneous measurements of the propulsive (aboral) force and the manometric pressure (intraluminal pressure) were made at 5, 10, and 15 cm above the lower oesophageal sphincter and in response to dry and wet (5, 10, and 15 ml) swallows. The propulsive force and manometric pressure waves had a simultaneous onset and were of similar duration. Peak values of propulsive force for wet swallows increased significantly as measurements were made progressively more distally within the oesophagus and were greatest in the distal oesophagus. The association between manometric pressure and propulsive force is not strong (r = 0.61) suggesting that intraluminal pressure is a poor predictor of propulsive force and hence an unreliable measure of oesophageal 'function'.     

Renal tumors in young adults.

Primary renal malignancies are relatively rare in young adults. Eighteen patients between the ages of twenty and forty years underwent nephrectomy for renal tumors at our institution between 1947 and 1989. Data were reviewed in this group regarding method of presentation, duration of symptoms, tumor histology, pathologic stage, and survival. Tumor histology parallels that of older patients, the majority being adenocarcinoma (78%). The duration of symptoms prior to seeking medical attention was long, averaging eighty-four weeks. The overall survival rate, excluding nontumor deaths, was 50 percent. No patient with nodal or distant metastases survived, regardless of histology.     

Prophylactic Antibiotic during Caesarean Sections at Komfo Anokye Teaching Hospital, Kumasi

Summary OBJECTIVES: To compare the efficacy of co-amoxiclav (amoxicillin + clavulanic acid) and the triple therapy of ampicillin + gentamycin + metronidazole as prophylactic antibiotic during Caesarean sections. DESIGN: A randomized controlled trial. SETTING: The study was conducted between March and December 2002 at Komfo Anokye Teaching Hospital, Kumasi. PARTICIPANTS: Patients undergoing caesarean section were recruited into the study and given either drug as prophylaxis. Excluded were patients who had established infections prior to the operation, had had any antibiotic in the preceding 24 hours and those allergic to any of the trial drugs. INTERVENTIONS: A total of 320 patients were recruited and randomized on a one-to-one basis into two groups, 160 receiving co-amoxiclav whilst the other 160 received the triple therapy. In either case the drug was given as a single intravenous dose after cord clamping and repeated 12 hours later. No other antibiotic was given except in cases where frank infection was apparent post-operatively. OUTCOME MEASURES: Included abdominal wound infection, cough, dysuria, fever, uterine tenderness and offensive lochia after surgery. RESULTS: Abdominal wound infection was found in rates lower than in a previous study: 3.7% in the co-amoxiclav group and 13.1% in the triple therapy group as against 15.1% in the previous study. Co-amoxiclav was statistically found superior to the Triple Therapy in preventing abdominal wound infection and uterine tenderness. There was however, no statistical difference between the two groups as far as the prevention of cough, dysuria and fever were concerned. CONCLUSION: Co-amoxiclav was found to be a better prophylactic antibiotic.