Health effects of landfill sites. Analyses require high quality data.
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Congenital Abnormalities↗
Biomedical subjects
M Morgan
Publications and source records attributed to M Morgan.
Detection of hypoxia in human squamous cell carcinoma by EF5 binding.
Localization and quantitation of 2-nitroimidazole drug binding in low pO2 tumors is a technique that can allow the assessment of hypoxia as a predictive assay. EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] is such a drug, and it has been shown to be predictive of radiation response in rodent tumors. Using fluorescence immunohistochemical techniques, we provide data on the presence, distribution, and levels of EF5 binding as a surrogate for hypoxia in human head and neck and uterine cervix squamous cell cancers (SCCs). Six patients with SCC were studied. Four patients had head and neck tumors, and two had uterine cervix cancers. The incubation of fresh tissue cubes in EF3 under hypoxic conditions ("reference binding") demonstrated that all tumors were capable of binding drug, and that this binding varied by a factor of 2.9-fold (174.5-516.1) on an absolute fluorescence scale. In the five patients treated at the lowest drug doses (9 mg/kg), in situ binding was quantitatable. For all six patients, the maximum rate of in situ binding varied by a factor of 6.7 between the lowest and highest binding tumor (24.8-160.3) on an absolute fluorescence scale. In tumors with high binding regions, intratumoral heterogeneity was large, extending from minimal fluorescence (<1%) up to 88.6% of reference binding. In tumors with minimal binding, there was little intratumoral heterogeneity. These studies demonstrate substantial heterogeneity of in situ binding between and within individual squamous cell tumors.
Adult↗
Assessment of the in vitro and in vivo genotoxicity of Thalomid (thalidomide).
Thalomid is the FDA-approved commercial formulation of thalidomide currently used in the US to treat erythema nodosum leprosum, a complication of leprosy. The genotoxicity of Thalomid thalidomide was assessed in the Ames reverse mutation, AS52/XPRT mammalian cell forward gene mutation, and mouse bone marrow micronucleus assays. The Ames and AS52 assays were performed with and without S9. In the Ames, Salmonella typhimurium strains TA1535, 1537, 98, 100, and 102 and Escherichia coli strain WP2 uvrA were used. Assays were performed by using plate incorporation and liquid pre-incubation systems at thalidomide doses of 50-10,000 microg/plate. In the AS52 assay, Chinese hamster ovary cells were plated with fortified Ham's F12 medium and incubated overnight. The medium was then incubated with 1-1000 microg/ml thalidomide. After a series of aspirations, washings, reconstitutions, and incubations, mutant AS52 cells were fixed and stained. Colonies were then counted and the relative survival frequencies compared to negative controls. In the mouse micronucleus assay, Crl:CD-1 albino mice were dosed with 500, 2,500, and 5,000 mg/kg thalidomide and sacrificed over 72 h. Femurs were flushed with fetal bovine serum and the suspensions centrifuged. The supernatant was aspirated and the cell pellet resuspended and stained. Polychromatic erythrocytes were scored for micronucleated polychromatic and normochromatic erythrocytes. Thalidomide did not increase revertant frequencies in all bacterial strains. It also did not produce any significant increase in the average mutant frequencies of AS52 cells and mouse micronucleated polychromatic erythrocytes. We conclude that Celgene's Thalomid thalidomide is non-genotoxic.
Animals↗
Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a Phase II study of the gynecologic oncology group.
PURPOSE: A multicenter Phase II trial was conducted to evaluate the activity and toxicity of gemcitabine in patients with previously treated squamous cell carcinoma of the uterine cervix. PATIENTS AND METHODS: Patients were required to have measurable disease with adequate performance status, bone marrow, hepatic, and renal function. Histologic confirmation of the primary diagnosis as squamous cell cancer of the uterine cervix was mandatory. Patients were allowed one prior chemotherapy regimen, usually cisplatin-based. The initial dose of gemcitabine was 800 mg/m(2) weekly times three with 1 week off until progressive disease or adverse effects prohibited further therapy. Doses were escalated or reduced based on previous cycle toxicity. RESULTS: Twenty-seven patients were entered into the trial. One patient never received the drug and 1 patient was inevaluable for response. A median of two cycles were administered to each patient (range: 1-7 cycles). The overall response rate (two partial responses) was 8% with 21% of patients having stable disease. The median progression-free interval was 1.9 months (range: 0.5-9.0) and overall survival was 4.9 months (range: 1.5-16.3). Two patients had grade 4 neutropenia; 1 patient had grade 4 anemia. The median WBC nadir in the 13 patients experiencing any leukopenia was 2300/microl (range: 400-3800). There was only one episode of grade 4 gastrointestinal toxicity. CONCLUSIONS: Gemcitabine as a single agent demonstrated minimal antitumor activity in previously treated patients with squamous cell cancer of the uterine cervix. Since gemcitabine in the dose and schedule employed is known to potentiate the cytotoxicity of cisplatin and radiotherapy (the current standard therapies for this disease), further development of gemcitabine would only be indicated in combination with these treatment modalities.
Adult↗
Phase II trial of CI-958 in recurrent platinum-refractory ovarian carcinoma. A Gynecologic Oncology Group Study.
OBJECTIVES: The objectives of this study were twofold: (1) to estimate the anti-tumor efficacy of CI-958 in patients with measurable platinum-resistant ovarian cancer; (2) to determine the nature and degree of toxicity of CI-958 in these patients. METHODS: Patients received CI-958 560 mg/m(2) intravenously every 3 weeks and tumor measurements were performed every one to two cycles. RESULTS: In 25 cases with recurrent platinum-resistant disease, there was one partial response (PR) and six patients had stable disease (SD). CONCLUSIONS: CI-958 has minimal activity in platinum-resistant ovarian cancer at the dose and schedule tested.
Adult↗
Peritoneal fluid interleukin-6 in women with chronic pelvic pain.
OBJECTIVE: To determine the relationship between peritoneal fluid concentrations of interleukin-6 (IL-6) and chronic pelvic pain symptomatology in women with adhesions, endometriosis, or no obvious intraperitoneal pathology. DESIGN: Clinical research study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Reproductive-aged women undergoing laparoscopy for the diagnosis of pelvic pain, infertility, or sterilization were selected. INTERVENTION(S): Peritoneal fluid was collected at the time of the laparoscopy and later assayed for IL-6. Subjects completed a pelvic pain questionnaire, and operative reports were used to obtain the underlying diagnosis. MAIN OUTCOME MEASURE(S): Interleukin-6 concentrations. RESULT(S): No correlation between the presence or absence of pelvic pain, findings of adhesions or endometriosis, and the concentration of peritoneal fluid IL-6 was observed. CONCLUSION(S): The cytokine IL-6 does not seem to play a role in the genesis of chronic pelvic pain in women with adhesions or endometriosis.
Ascitic Fluid↗
'Would they be proud of us?'.
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Anesthesiology↗
Substance misuse amongst anaesthetists.
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Anesthesia Department, Hospital↗
Morphological and molecular evidence for hybridization and introgression in a willow (Salix) hybrid zone.
Hybrid zones provide biologists with the opportunity to examine genetic and ecological interactions between differentiated populations. Accurate identification of hybrid genealogies is considered a necessary prerequisite to understanding observed patterns of hybridization-related phenomena. We analysed molecular and morphological data from individuals in a hybrid zone between two species of willows (Salix sericea Marshall and S. eriocephala Michaux) and report the use of randomly amplified polymorphic DNA (RAPD), chloroplast DNA (cpDNA), and ribosomal DNA (rDNA) markers, as well as vegetative morphology and foliar chemistry data to identify individuals in terms of hybrid genealogy and to infer the direction and extent of backcrossing and introgression within the hybrid zone. A novel version of a maximum likelihood estimate approach (developed for this study) was used to calculate hybrid index scores from RAPD marker data; this method produced results similar to those obtained using traditional arithmetic methods. Distribution of rDNA, cpDNA, and chemistry data were examined within the graphical context of RAPD-based hybrid index score histograms and principal component analyses (PCA) on RAPD and morphology data. Seven of the 21 plants classified as S. eriocephala in the field were possible introgressants. Another plant presented an unequivocal example of backcrossed S. sericea chemistry and RAPD markers. Inter- and intraspecific chloroplast diversity found within the hybrid zone suggests both historic introgression (perhaps in a glacial refugium), and contemporary hybridization. Patterns of inheritance and expression within the hybrid zone suggest that morphological characters are often not expressed in a simple additive fashion, and problems associated with both morphological and molecular data are considered.
Crosses, Genetic↗
The population impact of MRSA in a country: the national survey of MRSA in Wales, 1997.
Continuous data collection on all new isolates of MRSA via CoSurv has taken place in Wales since January 1996. In order to audit this data collection, and to address some of the issues that it does not include, a survey of MRSA was carried out. Questionnaires were completed by infection control teams. Rates were calculated using hospital throughput denominators. Results from the one-day prevalence survey, the two-week incidence survey, and the follow-up survey carried out on new MRSA patients identified in the incidence survey, are presented. Results were found to be broadly similar to those collected via routine surveillance. MRSA was found frequently and disproportionately in the elderly, with higher rates in male than female patients. The highest incidence of total and invasive MRSA was in males aged 75 and over (total: 12.5/1000 finished consultant episodes; invasive: 2.8/1000). Although there was a large community reservoir of MRSA, most appeared to have been acquired in hospital, since most patients had a history of hospitalization, often with multiple hospital admissions. Community-based isolates from cases with no hospital history tended to have been from ulcers. Prevalence and incidence of MRSA was relatively low compared with hospital throughput (mean prevalence: 2.4/100 occupied beds; mean incidence: 3.6/1000 finished consultant episodes), there was also quite large variation between sites, even when screening samples were removed. Patients with MRSA had strikingly long stays before isolation of the organism (prevalence survey: 39 days; incidence survey: 31 days) and highest incidence occurred in elderly care wards. The outcome survey showed that approximately half of the patients were treated with some type of antimicrobial therapy for MRSA. Decontamination therapy was associated with clearance of MRSA only when controlling for sex of the patient. The majority of patients were discharged still with MRSA, mostly to their own homes. The survey emphasizes the need to continue surveillance to detect any changes, to allow guidelines based on evidence to be developed and to monitor the effectiveness of such guidelines.
Adolescent↗
Effect of HIV-1 infection on tuberculosis and fertility in a large workforce in Kinshasa, Democratic Republic of the Congo.
To determine the effect of an HIV counseling service on the incidence of HIV and tuberculosis infection and on the fertility rate in a large workforce cohort of adult men and women from Kinshasa, Democratic Republic of Congo (formerly Zaire), we conducted a 2-year prospective longitudinal cohort study, two large Kinshasa businesses (a commercial bank and a textile factory). We determined baseline HIV-1 seroprevalence, HIV-1 and tuberculosis mortality/morbidity, and fertility rates during 24 months of follow-up on 8866 employees and 6411 wives of male employees. The baseline HIV-1 seroprevalence was 2.8% in male employees (n = 6657), 8.4% in female employees (n = 417), and 2.4% in the wives of male employees (n = 4692). The HIV-1 seroincidence per 100 person-years of follow-up in these three groups was 0.9, 0.5 and 0.8, respectively. The incidence of tuberculosis was 2.4/100 person years in persistently seropositive individuals compared with a 0.38 rate in persistently seronegative individuals (p < 0.01). The annual fertility rate in persistently seronegative women was 250.0/1000 women compared with a rate of 140/1000 in persistently seropositive women (p < 0.001). Forty-eight (44%) of 105 male employees and 17 (26%) of 60 wives of male workers who died during follow-up were HIV-1 seropositive. HIV infection was responsible for nearly one half of all deaths in this large workforce. Tuberculosis incidence was six times higher in HIV-1-infected compared with uninfected individuals. Counseling of HIV-infected women and their husbands appeared to be effective as their cumulative fertility rate was 44% lower than the rate in similarly aged uninfected women.
AIDS-Related Opportunistic Infections↗
GPs' employment of locum doctors and satisfaction with their service.
BACKGROUND: Locum doctors provide cover during normal working hours for GPs absent due to holidays, sickness, maternity leave or for educational purposes. However, there is little information on the extent of the use of locums or of GPs' perception of their services. OBJECTIVES: To examine the level of use of locum doctors by GPs, the ease of recruitment and satisfaction with their services. METHODS: A postal survey of all general practices in one of the six health regions in England was carried out. Logistic regression analysis was used to examine the independent effects on locum use of practice size and type of area, source of recruitment and GPs' satisfaction with their services. RESULTS: A total of 935 (80.6%) general practices responded. Locum GPs were employed by 81.7% of practices in the previous 12 months. Two-thirds of practices reported problems obtaining locum cover, especially at short notice and for holiday periods. One-fifth of practices employing a locum in the previous 12 months were dissatisfied with the locum. CONCLUSIONS: There are high demands for, but a considerable shortage of, locum doctors in general practice. Educational and other initiatives for GPs may contribute to increased demands for locum cover. Difficulties in recruitment may be reduced by measures to improve the conditions of employment for doctors working as locums on a longer term basis. New codes of practice for employing locums may increase satisfaction with locum services.
Attitude of Health Personnel↗
Measuring process and outcomes: professional compliance, professional opinions and patients' well-being.
This paper examines how professional and patient behavioural variables are conceptualized, their application in relation to guideline implementation and the different methods that may be employed in their assessment. The type of guideline and the process of development of guidelines are shown to influence the choice of indicators, with important issues for the assessment of professional compliance being raised by the development of patient-centred guidelines which require that clinical management takes account of patients' beliefs and preferences. Methodological problems relating to the use of routine data as indicators of professional compliance are discussed. The differing roles and contributions of quantitative and qualitative research in the assessment of professional and patient opinions are also examined. The paper advocates the development of guides to good practice in the assessment of these behavioural variables rather than specifying a uniform approach, and identifies questions requiring further research, especially in relation to patients' evaluations and satisfaction.
Family Practice↗
Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer.
Previous epidemiologic observations consistently suggest that suppression of ovulation, tubal ligation, and hysterectomy reduce the risk of ovarian cancer and that perineal talc use increases the risk. We examined these and other risk factors in the context of a new hypothesis: that inflammation may play a role in ovarian cancer risk. Ovulation entails ovarian epithelial inflammation; talc, endometriosis, cysts, and hyperthyroidism may be associated with inflammatory responses of the ovarian epithelium; gynecologic surgery may preclude irritants from reaching the ovaries via ascension from the lower genital tract. We evaluated these risk factors in a population-based case-control study. Cases 20-69 years of age with a recent diagnosis of epithelial ovarian cancer (767) were compared with community controls (1,367). We found that a number of reproductive and contraceptive factors that suppress ovulation, including gravidity, breast feeding, and oral contraception, reduced the risk of ovarian cancer. Environmental factors and medical conditions that increased risk included talc use, endometriosis, ovarian cysts, and hyperthyroidism. Gynecologic surgery including hysterectomy and tubal ligation were protective. Tubal ligation afforded a risk reduction even 20 or more years after the surgery. The spectrum of associations provides support for the hypothesis that inflammation may mediate ovarian cancer risk.
Adult↗
Comparison of vaginal misoprostol and gemeprost as pre-treatment in first trimester pregnancy interruption.
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Abortifacient Agents, Nonsteroidal↗
Lack of peripheral neuropathy in Beagle dogs after 53 weeks oral administration of thalidomide capsules.
Thalidomide (Thalomid) is approved for use in the US to treat complications from leprosy. Peripheral neuropathy is a dose-limiting adverse event in humans. As part of a nonrodent regulatory toxicology study, Beagle dogs were fed orally via encapsulation for 53 weeks. A component of this study was to determine if the dogs developed peripheral neuropathy. Twenty-eight male and 28 female Beagle dogs approximately 8-10 months of age were used. They were dosed at 43, 200 or 1000 mg/kg for 53 weeks followed by a 4-week treatment-free recovery period. Nerve function was assessed by electrophysiological measurements of the tibial nerve prior to dosing and at weeks 13, 27, 38 and 51. Representative dogs from each group were sacrificed at 26, 53 and 58 weeks and histologic and ultrastructural evaluations were performed on the sural nerve. Thalidomide had no effect on sensory nerve conduction velocity, duration or amplitude of the action potential. At 27 weeks, mean sensory nerve action potential amplitude for females at 43 mg/kg was significantly greater than control but was not evident at 39 weeks. Mean duration of sensory nerve action potential seemed to increase with similar magnitude over time in all dose groups including controls. Histological and ultrastructural evaluation of sections of sural nerve did not identify treatment-induced differences between control and thalidomide-dosed animals after 26 and 53 weeks of treatment. Additionally, no differences were observed following a 5-week treatment-free period at week 58. In contrast to humans, Beagle dogs did not develop thalidomide-induced peripheral neuropathy under conditions of the study.
Action Potentials↗
The new posterior resins and a simplified placement technique.
BACKGROUND: New heavy-body (packable) composites have been developed for use in posterior direct resin restorations. These materials are promoted as having better handling characteristics and higher physical properties than previous microhybrid composites. METHODS: The authors describe an incremental layering technique that takes advantage of the improved handling characteristics and proposed reduced shrinkage and greater depth of cure. CLINICAL IMPLICATIONS: When this new technique is used with one-bottle adhesives and improved instrumentation, posterior heavy-body composites can be placed faster, easier and possibly more predictably than when medium-body resins and previous techniques are used.
Composite Resins↗