Performance of normal-weight and underweight men with marginal changes in energy intake.

This study compares the continuous response of six underweight (UW) (body mass index [BMI] < 18 kg/m2) and six normal-weight (NW) (20 < BMI < 25) men of similar age to a modest but sustained level of underfeeding and overfeeding. Habitual energy intake over 4 wk, body composition, and basal metabolic rate (BMR) were measured under metabolic-ward conditions. NW subjects were heavier by 9 kg and had 5% more body fat than UW subjects. The average BMR of UW subjects was 7.5% lower than NW subjects in absolute terms and also per kilogram fat-free mass per day but was higher by 8% when expressed per kilogram body weight per day. Three NW and three UW subjects were given a diet with 10% less energy than their habitual intake for 4 wk. They were brought back to the normal level of feeding for another 4 wk. Finally, they were overfed by 10% for 4 wk. This sequence was reversed in the remaining six subjects. Changes in body weight, BMR, and energy balance were assessed. UW subjects showed a quick and vigorous reduction in BMR (13.4%) during the 1st wk of underfeeding compared with NW subjects (8.1%). In the later weeks, the reduction was 8% in UW and 7% in NW subjects. Furthermore, UW subjects showed a tendency to resist a decrease in body weight (mean loss 180 g), unlike NW subjects (mean loss 730 g). With overfeeding, the mean increase in BMR for UW was higher (7.4%) than for NW (5.3%) subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antiangiogenic property of human thrombin

Using protein chromatography, we purified and identified human prothrombin from human plasma as antiangiogenic. Prothrombin significantly inhibited endothelial cell tube formation in vitro at 10 microg/ml. Importantly, it also inhibited bFGF-induced angiogenesis in Matrigel-plug assays performed in mice. The proteolytic activity of thrombin appeared to be critical for the antiangiogenic activity of prothrombin. For example, thrombin exhibited inhibitory effects on endothelial cell tube formation in vitro at 10 U/ml. Addition of lepirudin, a specific inhibitor of thrombin, completely blocked prothrombin's and thrombin's antiangiogenic effects in vitro. We also assessed the importance of thrombin receptors in angiogenesis. Using small peptides that activate different protease-activated receptors (PARs), we showed that activation of PAR-1 led to inhibition of endothelial cell tube formation in vitro and bFGF-induced angiogenesis in vivo. Collectively, our data suggest that thrombin's proteolytic activity can be antiangiogenic.     

In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.     

Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product.

Wilms tumor is a pediatric neoplasm that arises from the metanephric blastema. The expression of the gene encoding insulin-like growth factor II (IGF-II) is often elevated in these tumors. Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor (IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. IGF-IR mRNA levels in the tumors were 5.8-fold higher than in adjacent normal kidney tissue. Among the tumors themselves, the levels of IGF-IR mRNA in those containing heterologous stromal elements were 2-fold higher (P < 0.01) than in tumors without these elements. IGF-IR gene (designated IGF1R) expression in the tumors was inversely correlated with the expression of the Wilms tumor suppressor gene WT1, whose inactivation appears to be a key step in the etiology of Wilms tumor. Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor.     

Correction of Lower Limb Deformities Using Ilizarov's Technique

Background

India accounts for approximately 10 million orthopaedically handicapped children and adults with limb deformity. Ilizarov ring fixator could treat most of these deformities.

Methods

Twenty cases of deformities of lower limb managed with Ilizarov technique during period between March 2001 and February 2003 were studied.

Results

55% were in the age group of 11-30 years. Out of the 20 cases studied, 6 were congenital talipes equino varus, 8 were fixed flexion deformity of knee, 4 were equines deformity of the ankle and 2 were malunited fracture shaft of tibia.4 patients who had recurrence were operated for fixed flexion deformity of the knee. The main complication encountered was pin tract infection, which was seen in 15(75%) cases. In 16(80%) cases, the results were excellent with no recurrence of deformity and patients were able to walk independently. In 4 (20%) cases, recurrence was mild to moderate (10 to 20) but all of them were able to ambulate idependently and carry out their routine activities.

Conclusion

Ilizarov ring fixator is a superior compared to conventional methods for correction of deformities of lower limb.Key Words: Ilizarov method, Ligamentotaxis, Distraction     

Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity