Biomedical subjects
Publications and source records attributed to S Wilson.
We describe the case of a 57-year-old woman who presented with colocolic intussusception due to a lipoma. The lesion was removed by laparoscopic right hemicolectomy. Benign colorectal pathology, such as colonic lipoma, is ideally suited for laparoscopic treatment.
The cloned human beta-3 adrenoceptor was expressed in Chinese hamster ovary cells at three different levels (130, 400 and 3000 fmol/mg). The potency and intrinsic activity of a range of agonists in functional assays with these cell lines rose as a function of increasing receptor density. Operational analysis of concentration-response data allowed calculation of functional affinity and efficacy of agonists at the human beta-3 adrenoceptor. The data highlighted the low efficacy of BRL 37344 ¿(RR,SS)-(+/-)-4-[(2-(2-(3-chlorophenyl)-2-hydroxyethyl)amino)-propyl] phenoxyacetate¿ for the human beta-3 adrenoceptor, which may explain its lower potency at the human receptor despite its higher affinity relative to isoprenaline. The potency of catecholamines at the human beta-3 adrenoceptor was found to be 1 to 2 orders of magnitude higher when determined in an intact cell cAMP accumulation assay compared with a membrane-based adenylyl cyclase activation assay. The reason for this enhanced sensitivity is not clear, but the result is that the potency of the natural agonist noradrenaline in the intact cell is considerably higher than predicted either from its ligand binding affinity, or from its potency in membrane-based assays. Much smaller enhancements in sensitivity were observed for compounds of the aryloxypropanolamine class such as CGP 12177 [(+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one], with the result that the rank order of potency of such agonists at the beta-3 adrenoceptor was altered. In particular, CGP 12177 exhibited high relative potency in the cyclase assay, but low relative potency in intact cell assays. These findings highlight the importance of selecting appropriate expression levels and appropriate assay methodology when cloned receptors are used to characterize agonists.
Research evidence on asepsis is patchy, ambivalent and cannot always be generalised. There is no substitute for assessment of the individual circumstances before each procedure. Handwashing is vital, well researched and uncontroversial.
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Four studies were conducted in the Fischer 344 rat to determine the disposition of orally gavaged olestra. Twenty-four rats were used for each study. Three olestra samples, differing in the degree of saturation of the fatty acid chains, were tested; one sample was heated to simulate olestra's intended use in preparing fried foods. In addition, a sucrose polyester (SPE) sample containing 28% short-chain penta- and lower polyesters was tested. All test samples were uniformly labeled with 14C in the sucrose moiety. Urine, feces, and CO2 were continuously collected and counted. Urine also was analyzed for [14C]sucrose by HPLC. If olestra were absorbed and systemically metabolized, [14C]sucrose would be excreted in the urine. Rats were killed 1, 3, 7, and 21 days after dosing, and tissues were collected and counted. Tissue lipids were extracted and analyzed for intact olestra or SPE by HPLC. Less than 0.15% of the dose of 14C was absorbed from the olestra samples, and about 1.3% from the SPE sample. The disposition of the absorbed radiolabel suggested that its source was glucose and fructose resulting from the intestinal hydrolysis of short-chain penta- and lower sucrose polyesters. For rats dosed with olestra, < 8 x 10(-4)% of the dose of radiolabel was recovered in the olestra-containing fraction of lipids extracted from liver, the target organ for absorbed olestra, and no [14C]sucrose was found in urine, indications that olestra essentially was not absorbed. Heating olestra did not change this result.(ABSTRACT TRUNCATED AT 250 WORDS)
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It has remained unclear whether epidural opioid analgesia permits better recovery of postthoracotomy pulmonary function than an optimal method of systemic opioid administration. Lumbar epidural meperidine infusions were compared with intravenous patient-controlled analgesic (PCA) meperidine infusions in a prospective randomized unblinded study for 72 hours postthoracotomy. Before induction of general anesthesia, patients received a bolus of meperidine, 1 mg/kg, and an infusion of meperidine, 0.33 mg/kg/hr, was started via either a lumbar epidural or intravenous catheter. Postoperatively, the meperidine infusion rates were titrated as needed for analgesia. In addition, the intravenous group received meperidine, 10 mg per dose, as required, from a patient-controlled analgesia pump. No other opioid was administered during the study period. Patients were studied for recovery of spirometric tests of pulmonary function, visual analog pain scores, sedation, arterial blood gases, meperidine dose requirements, radiographic pulmonary complications, and neurologic signs and symptoms. A subgroup of 10 patients (5 from each group) had venous blood samples drawn every 24 hours for 96 hours and assayed for serum meperidine and normeperidine concentrations. Epidural meperidine analgesia was associated with improved postthoracotomy pulmonary function, better analgesia scores, and lower meperidine dose requirements than intravenous PCA meperidine. There were no differences between the epidural versus intravenous PCA subgroups with respect to serum meperidine or normeperidine levels. Normeperidine levels greater than 300 ng/mL were associated with an increased incidence of shakiness and/or tremors. Meperidine provides satisfactory postthoracotomy analgesia via a lumbar epidural infusion. This analgesia is associated with improved recovery of postoperative pulmonary function when compared with an intravenous PCA meperidine infusion.
To determine whether there is a difference in middle cerebral blood flow velocity in eclampsia compared to a match control of severe preeclamptic patients in the peripartum phase. Three eclamptic and six preeclamptic women had maternal middle cerebral blood flow velocity assessed antepartum and at 24 and 48 hours postpartum. We compared the effect of an eclamptic convulsion on cerebral blood flow velocity changes using analysis of variance. Cerebral blood flow velocity was significantly higher in eclamptic than in preeclamptic women (p < 0.01) and rose significantly in the post-convulsive phase. Cerebral blood flow velocity was significantly elevated in eclamptic women compared with preeclamptic women in a setting of minimal change in mean arterial pressure.
Meropenem, a new carbapenem with improved stability in the presence of human dehydropeptidase-I[1], was evaluated in three prospective, multicenter, randomized, controlled clinical trials in North America. We compared the in vitro activity of meropenem and conventional antimicrobial agents for the treatment of intraabdominal, obstetric/gynecologic, and skin or soft tissue infections as well as the responses of pathogens to all of these agents. The trials of the drug for intraabdominal infection were double blind, and those for the obstetric/gynecologic and soft tissue infections were open labeled. Overall, MICs of meropenem for pathogens were lower, and the pathogen response rates were at least comparable to those for the following comparative agents: clindamycin plus tobramycin (for intraabdominal infections); clindamycin plus gentamicin (for obstetric/gynecologic infections); and imipenem and cilastatin (for skin or soft tissue infections). Meropenem has high in vitro potency and covers a broad spectrum of anaerobic and aerobic pathogens.
Seroprevalence of human T lymphotropic virus (HTLV) and human immunodeficiency virus type 1 (HIV-1) was determined among 7841 intravenous drug users (IVDUs) from drug treatment centers in Baltimore, Chicago, Los Angeles, New Jersey (Asbury Park and Trenton), New York City (Brooklyn and Harlem), Philadelphia, and San Antonio, Texas; 20.9% had evidence of HTLV infection, as determined using a p21e EIA for screening and p21e blot for confirmation. With a type-specific EIA and blot used in combination, HTLV-II was identified in 97.6% of HTLV-positive IVDUs whose sera could be subtyped. HIV-1 seroprevalence was 13.2%. HTLV-II without HIV-1 was most common in Los Angeles and San Antonio. HIV-1 without HTLV-II was most common in New York, New Jersey, and Baltimore. Dual infection was most common in New York and New Jersey. Logistic regression analysis revealed that seroprevalence of HTLV-II was significantly greater with HIV-1 infection and increasing age and among women, blacks, and Mexican-Americans. In conclusion, it appears that among US IVDUs, nearly all HTLV infection is attributable to HTLV-II, and HTLV-II infection is associated with HIV-1 and sociodemographic background.
The mathematic models used to assess the benefits and cost-effectiveness of cervical screening reveal little consistency in the definition of disease status, the basic assumptions made, or the data used in the model. Conclusions derived from the models often are model and data dependent. Several authors have used simplified models and unrealistic assumptions, such as the failure to differentiate between different grades of dysplasia, or 100% sensitivity for the screening test. The Markov process assumes that the rate of transfer between states is independent of the duration of time spent in one state, and this assumption may be unsound. The difficulty with all models is in interpreting the appropriateness of the parameter values. Some are well documented, for example, stage-specific survival rates for treated patients or attendance for screening. Many, however, cannot be given a fixed value. The large number of factors that appear implicated in the incidence of and mortality from cervical cancer can lead to many feasible sets of parameter values that generate output that approaches the observed data.
OBJECTIVE: To investigate asymptomatic carriage of Haemophilus ducreyi by using polymerase chain reaction (PCR) on samples from women at high risk of infection. SUBJECTS: 213 commercial sex workers (CSWs) recruited in The Gambia, West Africa. METHODS: Genital samples (cervical, vaginal and ulcer) were tested for the presence of H ducreyi by PCR with the technique of "one tube nested primer". RESULTS: 12 CSWs were PCR positive for H ducreyi; 8 of these women had genital ulcers on examination. CONCLUSION: Using a simplified PCR technique for detecting H ducreyi we have shown that 2% of CSWs were carrying the organism without clinical symptoms or signs. This has important implications for sexually transmitted disease control programmes in areas with a high prevalence of chancroid.
Seasonal allergic rhinitis is characterized by the development of nasal mucosal inflammation in response to natural allergen exposure, and is prevented by the administration of topical corticosteroids. Interleukin-4 (IL-4), IL-5, and IL-6 may have important roles in this process, and in vitro the gene transcription for each of these cytokines is inhibited by corticosteroids. In this study we have therefore investigated the effect of seasonal allergen exposure on the expression of immunoreactivity for IL-4, IL-5, and IL-6 in nasal mucosal biopsies, and the effect of regular prophylactic treatment with the topical corticosteroid, fluticasone propionate. Following a nasal mucosal biopsy out of season, patients were randomized double-blind to receive 6 wk of treatment during the pollen season with either topical fluticasone nasal spray (200 micrograms daily) or matching placebo. Each subject underwent a repeat nasal biopsy at the end of the 6-wk treatment period. Seasonal increases in epithelial eosinophils (p = 0.046), submucosal eosinophils (p = 0.001), and epithelial mast cells (p = 0.055) occurred in the placebo--but not the fluticasone-treated patients. Submucosal mast cell numbers did not change in either group. Immunoreactivity for IL-4 and IL-6 was localized predominantly to mast cells while IL-5 was found in both mast cells and eosinophils. Numbers of IL-4+ cells in the nasal submucosa were significantly suppressed by treatment with fluticasone (p = 0.0003 for monoclonal antibody [mAb] 3H4, p = 0.041 for mAb 4D9). In contrast, fluticasone treatment failed to influence the number of IL-5 and IL-6 immunoreactive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: The purpose of this study was to examine the relationships among cumulative lifetime trauma, recent stressful events, and presence and severity of current posttraumatic stress disorder (PTSD) symptoms in Holocaust survivors and nonexposed comparison subjects. METHOD: Lifetime trauma, recent stressful events, and presence and severity of PTSD were assessed in Holocaust survivors (N=72) and comparison subjects ( N=19). RESULTS: Survivors with PTSD (N =40) reported significantly greater cumulative trauma and recent stress than survivors without PTSD (N=32) and comparison subjects. Severity of PTSD symptoms, cumulative trauma, and recent stress were significantly associated. CONCLUSIONS: The presence and severity of current PTSD were related to having experienced stressful events in addition to the Holocaust.
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