Tamsulosin attenuates abdominal aortic aneurysm growth.

BACKGROUND: Tamsulosin, an α1A-adrenergic receptor inhibitor, is prescribed to treat benign prostatic hyperplasia in men >60 years of age, the same demographic most susceptible to abdominal aortic aneurysm. The goal of this study was to investigate the effect of tamsulosin on abdominal aortic aneurysm pathogenesis. METHODS: Abdominal aortic aneurysms were induced in WT C57BL/6 male mice (n = 9-18/group), using an established topical elastase abdominal aortic aneurysm model. Osmotic pumps were implanted in mice 5 days before operation to create the model, administering either low dose (0.125 µg/day tamsulosin), high dose (0.250µg/day tamsulosin), or vehicle treatments with and without topical application of elastase. Blood pressures were measured preoperatively and on postoperative days 0, 3, 7, and 14. On postoperative day 14, aortic diameter was measured before harvest. Sample aortas were prepared for histology and cytokine analysis. RESULTS: Measurements of systolic blood pressure did not differ between groups. Mice treated with the low dose of tamsulosin and with the high dose of tamsulosin showed decreased aortic diameter compared with vehicle-treated control (93% ± 24 versus 94% ± 30 versus 132% ± 24, respectively; P = .0003, P = .0003). Cytokine analysis demonstrated downregulation of pro-inflammatory cytokines in both treatment groups compared with the control (P < .05). Histology exhibited preservation of elastin in both low- and high-dose tamsulosin-treated groups (P = .0041 and P = .0018, respectively). CONCLUSION: Tamsulosin attenuates abdominal aortic aneurysm formation with increased preservation of elastin and decreased production of pro-inflammatory cytokines. Further studies are necessary to elucidate the mechanism by which tamsulosin attenuates abdominal aortic aneurysm pathogenesis.

Equal treatment: no evidence of gender inequity in osteoporosis management in a coordinator-based fragility fracture screening program.

We evaluated gender imbalance in osteoporosis management in a provincial coordinator-based fracture prevention program and found no difference by gender in treatment of high-risk fragility fracture patients. This establishes that a systemic approach with interventions for all fragility fracture patients can eliminate the gender inequity that is often observed. INRODUCTION: The purpose of this study was to evaluate an Ontario-based fracture prevention program for its ability to address the well-documented gender imbalance in osteoporosis (OP) management, by incorporating its integrated fracture risk assessments within a needs-based evaluation of equity. METHODS: Fragility fracture patients (≥ 50 years) who were treatment naïve at screening and completed follow-up within 6 months of screening were studied. Patients who underwent bone mineral density (BMD) testing done in the year prior to their current fracture were excluded. All participants had BMD testing conducted through the Ontario OP Strategy Fracture Screening and Prevention program, thus providing us with fracture risk assessment data. Our primary study outcome was treatment initiation at follow-up within 6 months of screening. Gender differences were compared using Fisher's exact test, at p < 0.05. RESULTS: After adjusting for subsequent fracture risk, study participants did not show a statistically significant gender difference in pharmacotherapy initiation at follow-up (p > 0.05). 68.4% of women and 66.2% of men at high risk were treated within 6 months of screening. CONCLUSION: Needs-based analyses show no difference by gender in treatment of high-risk fragility fracture patients. An intensive coordinator-based fracture prevention model adopted in Ontario, Canada was not associated with gender inequity in OP treatment of fragility fracture patients after fracture risk adjustment.

Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis.

BACKGROUND: Iron supplementation may increase disease activity in ulcerative colitis, possibly through the production of reactive oxygen species from the Fenton reaction. AIM: To assess the effects of two doses of oral iron on intestinal inflammation and oxidative stress in experimental colitis. METHODS: Colitis was induced in rats by giving 5% dextran sulphate sodium in drinking water for 7 days. First, using a 2 x 2 factorial design, rats with or without dextran sulphate sodium received the regular diet or a diet containing iron 3%/kg diet. Second, rats with dextran sulphate sodium-induced colitis were supplemented with iron 0.3%/kg diet and compared with rats on dextran sulphate sodium and regular diet. The body weight change, histological scores, colon length, rectal bleeding, plasma and colonic lipid peroxides, colonic glutathione peroxidase and plasma vitamin E and C were measured. Faecal analysis for haem and total, free and ethylenediaminetetra-acetic acid-chelatable iron was also performed. RESULTS: Iron 3% and iron 0.3% increased the activity of dextran sulphate sodium-induced colitis, as demonstrated by higher histological scores, heavier rectal bleeding and further shortening of the colon. This was associated with increased lipid peroxidation and decreased antioxidant vitamins. Faecal iron available to the Fenton reaction was increased in a dose-dependent manner. CONCLUSIONS: Iron supplementation taken orally enhanced the activity of dextran sulphate sodium-induced colitis and is associated with an increase in oxidative stress.

Antiviral efficacy and pharmacokinetics of oral adefovir dipivoxil in chronically woodchuck hepatitis virus-infected woodchucks.

The antiviral efficacy of orally administered adefovir dipivoxil was evaluated in an 18-week study (12 weeks of treatment and 6 weeks of recovery) conducted with woodchucks chronically infected with woodchuck hepatitis virus (WHV). Adefovir dipivoxil is a prodrug of adefovir designed to enhance its oral bioavailability. Following administration of 15 mg of adefovir dipivoxil per kg of body weight in four WHV-infected animals, the mean maximum concentration of adefovir in serum was 0.462 microg/ml, with an elimination half-life of 10.2 h, and the oral bioavailability of adefovir was estimated to be 22.9% (+/-11.2%). To study antiviral efficacy, the animals were divided into three groups. There were six animals each in a high-dose group (15 mg/kg/day) and a low-dose group (5 mg/kg/day). A vehicle control group consisted of five animals because WHV DNA was detectable only by PCR at the time of the study in one of the original six animals. Efficacy was evaluated by determining the levels of WHV DNA in serum. The geometric mean WHV DNA level for the high-dose group diminished by >40-fold (>1.6 log(10)) after 2 weeks of treatment and >300-fold (>2.5 log(10)) at 12 weeks. There was a >10-fold reduction in five of six low-dose animals by 2 weeks, but levels were unchanged in one animal. By 12 weeks of treatment there was a >45-fold (>1.6 log(10)) reduction of WHV DNA levels, and serum WHV DNA levels were below the limit of quantification in three of six animals. Viral DNA levels returned to pretreatment levels during the 6-week recovery period. There were no clinically significant changes in body weight, hematology, or serum chemistry values, including bicarbonate or lactate, in any of the treated animals. No histologic evidence of liver injury was apparent in the biopsies. Under the conditions of this study, adefovir dipivoxil was an effective antihepadnaviral agent.

Effect of iron supplementation on oxidative stress and intestinal inflammation in rats with acute colitis.

In this study, we investigated the effect of intraperitoneal iron dextran (100 mg/100 g body weight) on oxidative stress and intestinal inflammation in rats with acute colitis induced by 5% dextran sulfate sodium. In both colitis and healthy animals, disease activity index, crypt and inflammatory scores, colon length, plasma and colonic lipid peroxides, and plasma vitamins E, C, and retinol were assessed. The results showed that iron-supplemented groups had moderate iron deposition in the colonic submucosa and lamina propria. In the colitis group supplemented with iron, colon length was significantly shorter; disease activity index, crypt, and inflammatory scores and colonic lipid peroxides were significantly higher; and plasma alpha-tocopherol was significantly lower compared to the colitis group without iron supplementation. There was no intestinal inflammation and no significant increase in colonic lipid peroxides in healthy rats supplemented with iron. In conclusion, iron injection resulted in an increased oxidative stress and intestinal inflammation in rats with colitis but not in healthy rats.

The future of intestinal pacing.

Pacing the human heart, first done in 1952, is commonly used today. Pacing the canine stomach and small intestine has also been accomplished and has been used to treat a variety of disease models, including dumping, the short bowel syndrome, gastroparesis, the Roux stasis syndrome, and tachygastria. In contrast, pacing the human stomach and small intestine has not progressed as far. Pacing of these organs in man has only been done for short intervals. Moreover, no clear-cut therapeutic applications have as yet emerged. Nonetheless, pacing holds promise as a future therapeutic modality for a variety of disorders of the human stomach and small bowel.

Morphologic characterization of castor oil-induced colitis in ponies.

Ten ponies (160-250 kg, ages 17 months to 20 years) developed severe diarrhea within 24 hours of castor oil administration (2.5 ml/kg orally). The diarrhea was most severe between 24 and 48 hours post-dosing and subsided by 72 hours. Ponies were euthanatized at 24, 48, and 72 hours post-dosing and intestine was evaluated histologically and ultrastructurally. Twenty-four hours after dosing, the mucosa of the cecum and ventral colon had extensive superficial epithelial erosion and neutrophil infiltration. In the ileum, the epithelium of villous tips was separated from the lamina propria. Scanning electron microscopic examination of the cecal mucosa revealed that basement membranes were exposed in most areas except within necks of crypts. Ultrastructurally, changes in superficial enterocytes of the cecum and ventral colon were characterized by loss of microvilli, distortion of the cytoplasmic terminal web, expansion of the cytoplasmic matrix with formation of precipitates, and widening of intercellular spaces between junctional complexes. Enterocytes located within necks of crypts were flattened along the basement membrane and extended to margins of erosions. Venules within the superficial lamina propria were occluded by fibrin thrombi. Erosions in the cecum and ventral colon of ponies examined 48 hours after treatment were less extensive than those of ponies examined at 24 hours. At 48 hours post-dosing, basement membranes adjacent to crypts were covered by cuboidal enterocytes characterized ultrastructurally by sparse, irregularly shaped microvilli located on broad cytoplasmic protrusions and by numerous free ribosomes. These features indicated that immature enterocytes had migrated from crypts to resurface the eroded mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in coagulation factors in patients with burns during acute blood loss.

A prospective study was undertaken to determine the change in coagulation factors in patients undergoing tangential excisions of burn wounds when red blood cells preserved with ADSOL (adenine, dextrose, saline, and mannitol) and crystalloid solution were used for volume replacement. Nine patients with burns were studied, three on two separate occasions. No patient had a history of a bleeding disorder or had taken aspirin within 10 days of surgery. Results of preoperative coagulation studies were all within normal limits. The initial levels of coagulation factor and rates of removal were compared with those of 12 patients without burns who were undergoing elective surgery and who also had massive intraoperative blood loss. Coagulation factor levels measured included the platelet count, fibrinogen, factors V, VIII, and IX. These were determined before blood loss and each time loss and replacement of one third of a patient's calculated blood volume occurred during a tangential excision of a burn wound. The data showed that patients with burns have significantly higher baseline levels of platelets, fibrinogen, and factor VIII than patients without burns do. The removal rates of platelet and factor IX are significantly lower among patients with burns than among patients without burns. No patient in the study group developed a coagulopathy or received fresh frozen plasma or platelet supplementation. These findings suggest that the intraoperative blood losses that occurred during tangential excisions of burn wounds were made safe by the higher than normal preoperative levels of platelets, fibrinogen, and factor VIII and by the slow wash-out curve for platelets and factor IX. Prophylactic use of either fresh frozen plasma or platelet concentrates is not indicated unless a specific deficit or coagulopathy has been identified.

Influence of dietary protein, fat or amino acids on the response of weanling swine to aflatoxin B1.

Two experiments were conducted using corn from clean or aflatoxin B1 (AFB1)-contaminated (182 ppb) sources. Weanling pigs (28 d) were fed one of eight dietary treatments arranged in a 2 x 2 x 2 factorial design. In Exp. 1 (192 pigs), treatments varied in corn source (clean or AFB1-contaminated), CP level (18 or 20%) and added fat (0 or 5%). At the end of the 28-d growth trials, plasma samples were obtained. An AFB1 x CP level interaction was detected (P less than .05) for growth rate (ADG), feed intake (FI) and feed/gain ratio (F/G). Feeding AFB1 reduced (P less than .05) ADG (.30 vs .37 kg/d) and FI (.57 vs .66 kg/d) and increased F/G (1.88 vs 1.78) of pigs fed 18% CP diets. Performance of pigs fed 20% CP diets was not altered by AFB1. Adding 5% fat to diets improved (P less than .05) F/G but did not improve ADG of pigs fed AFB1. There was an AFB1 x CP x fat interaction (P less than .05) for plasma cholesterol. Adding fat or increasing the CP level prevented the depression of plasma cholesterol in pigs fed AFB1. In Exp. 2 (96 pigs), all diets contained 18% CP and the treatments varied in corn source (clean or AFB1-contaminated), added L-lysine HCl (0 or .25%) and added DL-methionine (0 or .15%). Feeding AFB1 reduced (P less than .05) ADG of pigs fed the 18% CP diet (.44 vs .50 kg/d) but not of pigs fed diets supplemented with .25% lysine.(ABSTRACT TRUNCATED AT 250 WORDS)

Quasi-experimental evaluation of the Los Angeles Know Your Body program: knowledge, beliefs, and self-reported behaviors.

In 1981-1982 the Division of Cancer Control (Jonsson Comprehensive Cancer Center, University of California, Los Angeles) implemented a Know Your Body program in the Los Angeles and Santa Monica Unified School Districts. The results from this evaluation are based on analyses of over 1,400 elementary school children (ages 9-11 years) from 18 schools who were assigned to one of four comparison groups: (a) Know Your Body curriculum and health screening (N = 688 students/seven schools), (b) Know Your Body health screening only (N = 333 students/three schools), (c) Know Your Body curriculum only (N = 253 students/five schools), and (d) the control group (N = 234 students/three schools). Standardized questionnaires concerning health knowledge, beliefs, and (self-reported) behaviors were group-administered by teachers in January 1981 (pretest) and then again in March 1982 (post-test). The group receiving both the Know Your Body curriculum and the clinical screening scored higher than the control group on four out of six post-test knowledge measures, one out of three belief scales, and one out of four behavioral measures. The curriculum-only group scored higher than the control group on five out of six post-test knowledge measures and on two of three belief scales. The screening-only group did not score significantly higher than the control group on any of the outcome measures. Among children identified during the clinical screening (at pretest) as being at higher risk of developing chronic disease (N = 543), students receiving both the screening and the curriculum (N = 401) scored higher on four out of six knowledge measures and reported significantly lower consumption of both dairy products and high-cholesterol foods than "high-risk" students receiving only the clinical screening (N = 142).

A haemorrhagic syndrome in recently weaned pigs ascribed to hypovitaminosis K.

An outbreak of a haemorrhagic syndrome involved recently weaned, mixed-breed pigs in a large piggery. The pigs were fed a pelleted complete ration containing antibacterial drugs. Affected pigs failed to grow, became pale and developed large, subcutaneous haematomas. Some pigs became lame and one had epistaxis. The monthly mortality rate in the weaner house, which was previously less than 2%, exceeded 6% during the outbreak. Coagulation time, activated partial thromboplastin time and prothrombin time were prolonged in blood from some of the pigs. The outbreak resolved promptly after supplementation of the diet with vitamin K3.

Effects of background noise level on detection of tone glides.

Detection thresholds were obtained for short duration rising tone glides and falling tone glides for normal hearing listeners in quiet and with varied levels of background, broadband noise. For signal durations 50 ms, or greater, pure tones were detectable at lower levels than were rising and falling tone glides; no level effects were observed. For signal durations less than 50 ms an interaction between background noise level, signal duration, and signal class was observed. The previously reported tendency for short duration rising glides to be detected at lower sound pressures than pure tones or falling tone glides appears to be unique to a limited range of noise levels (40-75 dB).

Biofeedback as an adjunct to psychotherapy in the treatment of vaginismus.

This exploratory study examines the use of biofeedback as an adjunct to psychotherapy in the treatment of vaginismus. A set of six Sims-type graded EMG probes was constructed to provide biofeedback from the vaginal sphincter and was tested on a pilot sample of nulliparous women prior to this study. Five sequential cases of vaginismus from a clinic waiting list participated in the program. All five couples completed the program and all reported successful intercourse at its conclusion. The number of sessions devoted to biofeedback probe insertion was almost halved in comparison to previous experience with Sims dilators. Overall treatment duration was not shortened. At follow-up 6 months later, two couples reported pregnancy, one couple was having regular intercourse, and two couples had ceased intercourse. The authors conclude that biofeedback is an effective aid to learning muscle control, is acceptable to patients, and may increase the success rate by minimizing dropouts. The importance of follow-up is stressed.

Management of patients with polyps containing malignancy removed by colonoscopic polypectomy.

The management of malignant colonic polyps removed colonoscopically has been a controversial subject. A continuing series is reported of 36 patients with 37 malignant polyps removed by colonoscopic polypectomy (CP) between 1976 and 1982. Fourteen polyps contained carcinoma in situ (CIS); 13 were treated by CP alone; one was treated by CP and colectomy. Nineteen polyps contained invasive carcinoma; 13 were treated by CP alone; six were treated by CP and colectomy. Four patients had sessile polyps resected piecemeal, in which accurate staging was impossible. Two were treated with CP alone, and two had CP plus colectomy. All patients were followed with yearly colonoscopy and/or barium enema. Follow-up has been six to 84 months (mean 36 months). Twenty-seven patients whose polyps were treated by CP alone have had no evidence of recurrent tumor at the polypectomy site. Of the nine patients undergoing colectomy, six had residual tumor at the polypectomy resection site. No patients had involved lymph nodes. Our current approach to this problem is based on the degree of invasion and the status of the resection margins. Polyps containing CIS can safely be treated with CP alone. Polyps with invasive carcinoma and clear resection margins should be treated with CP and either colectomy or frequent repeat colonoscopy. This decision is a clinical one and must involve input from both the clinician and the pathologist. Those polyps whose resection margins are involved or where piecemeal excision precludes accurate pathologic assessment should undergo colectomy.

The organization of community disease prevention services: approaches to preventing lung cancer in the Los Angeles Basin.

The UCLA Jonsson Comprehensive Cancer Center initiated a broadly based community program with the goal to reduce lung cancer incidence and mortality in the Los Angeles Basin (LAB). Representatives from the medical and science communities participated with representatives from the business, legal, and legislative sectors of LAB in a number of workshops over an 18-month period. The objectives of the workshops were to involve as many community interests as feasible to identify the issues related to the lung cancer problem and to mount a strategic and broadly based plan to achieve the stated goal. More than 70 individuals participated in this effort. The principal topics identified and developed related to "Smoking and Youth," "Smoking in High Risk Adults," "Smoking in the Workplace," and "Occupational Exposures." The results of this protracted interaction and planning effort are now in evidence in a variety of action programs and intervention research across this large geographic region.

Baseline chronic disease risk factors in a racially heterogeneous elementary school population: The "Know Your Body" program, Los Angeles.

The Los Angeles "Know Your Body" (KYB) program is an organized health education activity for children designed to encourage positive health behavior and discourage or interrupt behavioral patterns that are linked to illness, injury, disability, or death. Components of KYB include a 20-week curriculum; a survey of health knowledge, attitudes, and behaviors; in-service training for elementary school teachers; and a clinical screening that provides feedback to students on selected indices. As part of a KYB field demonstration in Los Angeles conducted by the UCLA Division of Cancer Control, Jonsson Comprehensive Cancer Center, 1,503 Los Angeles and Santa Monica-Malibu children ages 9-11 in grades 4 and 5 underwent baseline health screening evaluations in March 1981, measuring height, weight, triceps skinfold thickness, serum cholesterol, pulse rate recovery following exercise, and blood pressure. The population mean for serum cholesterol was 182.6 mg/dl, with no significant racial/ethnic, sex, or age differences. Significant racial/ethnic differences were found in obesity, with Hispanics having the highest prevalence, Asians the lowest. Black students scored significantly higher in pulse rate recovery following exercise, suggesting better relative cardiovascular fitness, and Asians scored lowest. Blacks were more likely to exceed the 95th percentile in diastolic and systolic blood pressure. Overall, 48% of the children had one or more chronic disease risk factors.

Fracutre healing in rats exposed to extremely low-frequency electric fields.

Fibular osteotomies in rats were exposed to an extremely low frequency field for 14 days. By histologic evaluation it was found that the healing rate was retarded by the field. The effect (which was replicated) occurred at much lower power levels than are presently employed in electircal osteogenesis.

Temporal integration of two-component tone glides.

Temporal integration of complex signals composed of two linearly combined tone glides was studied in a 60-dB SPL noise background. When both glide tones increased or decreased in frequency, integration functions differed for durations shorter than 50 ms in a manner similar to results obtained for single-component tone glides. That is, rising two-component glides were detected at lower thresholds than were falling two-component glides. However, when one component increased in frequency and the other decreased, thresholds were the same, regardless of which component increased and which decreased.