Natural killer cell activity and autologous mixed lymphocyte response of splenic,mesenteric lymph node,and colonic lymphocytes during DMH-induced colon carcinogenesis in the rat

Twoin vitro models of immune surveillance were used to examine the immune status of the gut-associated lymphoid tissue, mesenteric lymph nodes, and spleen during the early stages of 1,2-dimethylhydrazine (DMN)-induced colon tumorigenesis. DMH-and vehicletreated Fischer rats were sacrificed at one of three time points; one week, two months, or five months after cessation of treatment. Colonic, lymph node, and splenic natural killer cell cytolytic activity toward YAC-1 tumor targets and T-cell response to autologous la-induced balstogenesis were measured at each time point. We found little change in natural killer cell activity or T-cell proliferation induced by autologous Ia gene products at these time periods.This investigation was supported in part by grant CA26917 from the National Cancer Institute, Department of Health and Human Services.     

Curcumin Reduces Burn Progression in Rats

Objectives Cutaneous burns are dynamic injuries with a central zone of necrosis surrounded by a zone of ischemia. Conversion of this ischemic zone to full necrosis over the days following injury is due in part to highly reactive oxygen radicals. Curcumin is a component of the Oriental spice turmeric that has been shown to have antioxidant and antiapoptotic properties. The authors hypothesized that treatment of burns with curcumin would reduce the conversion of the ischemic zone to full necrosis. Methods This was a randomized controlled experiment. Twenty Sprague‐Dawley rats were used. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 × 20–mm full‐thickness burns separated by three 5 × 20–mm unburned interspaces (zone of ischemia). Animals were randomized to curcumin or vehicle by oral gavage 30 minutes before injury and at 24, 48, and 72 hours after injury. Wounds were observed at one, two, and three days after injury for visual evidence of necrosis in the unburned interspaces. Full‐thickness biopsy specimens from the interspaces were evaluated with hematoxylin and eosin staining seven days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi‐square tests. Results Forty comb burns with 120 unburned interspaces were created, evenly distributed between curcumin and vehicle alone. The percentage of interspaces that progressed to full‐thickness necrosis at one, two, three, and seven days after injury in the curcumin and vehicle groups were 30% versus 63% (p = 0.003), 30% versus 70% (p < 0.001), 63% versus 95% (p = 0.02), and 63% versus 95% (p = 0.02), respectively. Conclusions Pretreatment of rats with oral curcumin followed by once‐daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.     

Complex urethral disruptions: In pursuit of a successful reconstruction

OBJECTIVES: We analyzed the methods and outcomes of urethroplasty in men with complex urethral disruptions. METHODS: The medical records of 40 men with complex urethral disruptions were analyzed. Surgical methods were individualized according to stricture location, severity and length of the stricture, bladder neck characteristics and presence of complicating factors. Patients were divided into four groups based on the above characteristics. RESULTS: End-to-end urethroplasty performed in six patients with short bulbar strictures (<3 cm) was successful in all. Elaborated perineal repair was performed in 10 patients with intermediate (3-6 cm) strictures with or without complicating factors. Elaborated perineal repair with urethral substitution was performed in nine patients with long segment stricture (>6 cm). Abdominal transpubic repair was successfully applied to patients with rectourethral fistula or lacerated bladder neck. Success rate of anastomotic urethroplasty was 95% while over all success rate was 85%. CONCLUSION: Guidelines for urethral reconstruction of complex urethral disruptions are predicated on stricture length, location, bladder neck characteristics and associated complicating factors. End-to-end urethroplasty with stricture excision is highly reliable for short strictures for which previous operative repair have failed. Elaborated perineal repair is extremely versatile for intermediate and longer strictures with associated complicating factors. Abdominal transpubic urethroplasty is effective for patients with rectourethral fistula or lacerated bladder neck.     

Poliomyelitis trends in Pondicherry, south India, 1989-91.

STUDY OBJECTIVES: To assess the poliomyelitis trend, including study of the epidemiological features, and to correlate this with the immunisation coverage of infants. DESIGN: Three annual lameness surveys in children aged 0-60 months employing cluster sampling methods and a series of five cross sectional surveys of immunisation coverage in children aged 12-23 months of age were undertaken. SETTING: Pondicherry, India, 1988-92. SUBJECTS: More than 10,000 children in the age group of 0-60 months took part in the three annual lameness surveys and samples of 210 children aged 12-23 months were covered each year in immunisation coverage surveys. MEASUREMENTS AND MAIN RESULTS: Altogether 50 of 11,461, 24 of 10,093, and 17 of 11,218 children surveyed during 1989, 1990, and 1991 respectively had become lame as a result of poliomyelitis, giving prevalences of 4.4, 2.4, and 1.5 per 1000 children for the three surveys. The corrected prevalences of poliomyelitis were 5.9, 3.2, and 2.0 per 1000 children during 1989, 1990, and 1991 respectively. The proportion of cases aged up to 36 months fell from 48% in 1989 to 12.5% in 1990 and 6% in 1991. The age at onset was less than 1 year in most. The median age at onset was 10.7 months. About 54% of the affected children had received three doses of oral poliomyelitis vaccine (OPV) before the onset of paralysis. In 1988 immunisation coverage for the third dose of OPV was 91% and in 1992 it was 97.6%. The drop out rate for the first versus the third dose of OPV fell from 6.3 in 1988 to 1.9% in 1992. CONCLUSION: Three successive annual lameness surveys showed that poliomyelitis was declining between 1989 and 1991. Five immunisation coverage surveys conducted from 1988 to 1992 showed high initial coverage followed by an improvement in the form of almost universal coverage for OPV.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Does multi-vessel off-pump coronary artery bypass grafting reduce post operative morbidity compared to on-pump CABG?

Background Cardiopulmonary bypass (CPB) may contribute to the complications and it is assumed that eliminating cardiopulmonary bypass has the potential of reducing post operative morbidity after coronary artery bypass grafting (CABG). The study was carried out to compare mortality and morbidity in the off-pump and on-pump CABG groups. Methods We prospectively analysed 200 patients undergoing CABG. Group A consists of 100 patients underwent multi-vessel off-pump CABG and group B consists of 100 patients underwent CABG with CPB. The incidence of complications (mortality, re-exploration for bleeding, myocardial infarction, atrial fibrillation, neurological events, new onset renal failure (s. creatinine>1.6 mg/dL) pulmonary complications, length of ICU stay and hospital stay were recorded, analysed and compared. Results OPCAB patients received 2.73±0.61 grafts/patient and on-pump CABG patients received 3.39±0.75 grafts/patient (p value<0.00001). There was no significant statistical difference in mortality, incidence of stroke between OPCAB and CABG with CPB patients. Length of ICU stay was 32.84±4.22 vs 44.85±7.18 hrs (p value<0.00001) and hospital stay was 6.52±0.69 vs 7.94±0.92 days (p value<0.00001) between group A and group B respectively. Incidence of atrial fibrillation was less in OPCAB group 7% vs 12% although it was statistically not significant (p value 0.33). It was observed in our study that there was no significant deference in worsening of existing renal failure between on-pump CABG and OPCAB 6% vs 2% (P value 0.28). Blood utilization was significantly less in OPCAB group (p value<0.001). Conclusion There was no statistically significant difference in terms of mortality, incidence of stroke and new onset renal failure in both groups. But there was lesser incidence of post operative atrial fibrillation, worsening of existing renal failure in off-pump group though statistically not significant. There was significant reduction in blood utilization, length of ICU and hospital stay in OPCAB group.     

Modeling mechanisms of skull base injury for drivers in motor vehicle collisions.

OBJECTIVE: To develop biomechanical variable models for driver skull base injury mechanisms in motor vehicle collisions. STUDY DESIGN: Retrospective database review. METHODS: Biomechanical collision variables and safety restraint data were analyzed for Crash Injury Research and Engineering Network skull base trauma subjects enrolled during the recruitment period between 1996 and 2005. RESULTS: For drivers satisfying inclusion criteria (n = 26), injury resulted from contact with rigid vehicle structural elements in 82%, and occurred in 50% despite both seatbelt and air bags. Eight percent used neither seatbelts nor air bags. Seventy-two percent involved vector velocity changes greater than 30 mph. The relative morbidity of skull base injuries was also detailed. CONCLUSION: The majority of driver skull base injuries resulted from contact with rigid vehicle structural elements in high velocity crashes. Seatbelt and air bag use could not be definitively correlated with skull base injury. CLINICAL SIGNIFICANCE: Injury mechanism models can be developed that facilitate further investigations to determine impact and scope on a national scale.