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Biomedical subjects

M A Lewis

Publications and source records attributed to M A Lewis.

At least 109 records · Page 6Linked to original sources

The increased risk of venous thromboembolism and the use of third generation progestagens: role of bias in observational research. The Transnational Research Group on Oral Contraceptives and the Health of Young Women.

A matched case-control study was undertaken in 10 centers in Germany and the United Kingdom to explore the association of current use of major combination oral contraceptives with the occurrence of venous thromboembolism. The cases recruited were 505 women aged 16-44 years with venous thromboembolism, controls were 1877 women (at least 3 controls per case) matched for 5-year age group and region without VTE. The main outcome measures were odds ratios derived by comparing current use of a specific oral contraceptive or group of OC against current use of other groups or against no current use of OC. The odds ratios (95% confidence intervals) for venous thromboembolism were: for third generation products (low dose ethinyloestradiol, gestodene and desogestrel) versus second generation products (low dose ethinyloestradiol, no gestodene and desogestrel, 1.5 (1.1 to 2.0), for third versus second generation products with norgestimate included in third generation, 1.6 (1.2 to 2.2). The odds ratios for current use for women aged 16-44 of specific progestagens versus levonorgestrel-containing compounds were 1.7 (1.1 to 2.6) for gestodene, 1.8 (1.2 to 2.6) for desogestrel, 1.9 (1.0 to 3.6) for norgestimate and 1.3 (0.7 to 2.5) for progestagen-only pills. For women aged 25 to 44 likely to be exposed to any of these progestagens, odds ratios for the comparison of progestagens versus levonorgestrel showed a successive increase by market introduction ranging from 1.5 (0.9 to 2.5) for desogestrel with 30 micrograms oestrogen content (introduced 1981) to 2.8 (1.3 to 6.5) for desogestrel with 20 micrograms oestrogen content (introduced 1992) significant in linear trend analysis (p = 0.00012). The influence of norgestimate classification as third or second generation product does not significantly alter the results regarding the association of third generation products and venous thromboembolism. A direct comparison of current use of norgestimate (which is primarily metabolized to levonorgestrel) versus levonorgestrel shows an increased odds ratio. The trend of increasing risk of progestagens by recency of market introduction when compared with levonorgestrel is strongly indicative of the existence of external bias due to attrition of susceptibles.

Adolescent↗

Measuring public hospital costs: empirical evidence from the Dominican Republic.

Effective analysis of hospital performance requires the existence of accurate cost and output data. However, these are missing ingredients in most developing countries due to lack of information systems or other sources of data. Typically, expenditures are substituted for actual costs in analyzing hospital finance. This paper presents a methodology and analysis of the actual costs of inpatient, emergency, and outpatient services in a Dominican hospital. Through applying a set of survey instruments to a large sample of patients, the study measures and costs all hospital staff time, in-kind goods (drugs, medical supplies, reagents, etc.), overhead, and the depreciated value of plant and equipment related to the treatment of each patient. The results are striking. The budget is over 50% higher than the actual costs of services, reflecting the high cost of waste, down time, and low productivity. For example, high fixed costs translate into immunizations that on the average cost over 20% more than outpatient surgical interventions. The most disturbing finding is that although physicians represent the bulk of personnel spending, the surveys could account for only 12% of the contracted time of staff physicians, including time dedicated to treatment, supervision, administration, and teaching. As a proportion of the hospital total budget, personnel spending represents a high 84%. Yet staff costs for patient treatment never exceed 12%. These results suggest gross inefficiency, chaotic medical care organization, and poor hospital management.

Ambulatory Care↗

Childhood steroid-sensitive nephrotic syndrome: does the histology matter?

Renal biopsy specimens from 51 children with steroid-sensitive nephrotic syndrome who were following a frequently relapsing or steroid-dependent course were reviewed by two histopathologists. In all cases the biopsy was performed prior to the commencement of an 8-week course of cyclophosphamide. The clinical courses of these patients both prebiopsy and for a minimum of 2 years after completion of cyclophosphamide therapy were analyzed using retrospective case note analyses. The distribution of histologic diagnoses differed significantly from that reported by the International Study of Kidney Disease in Children in their study of children who underwent biopsy at the time of presentation, there being an excess of focal segmental glomerulosclerosis and mild mesangial hypercellularity in this series. The prebiopsy clinical course did not predict for histologic diagnosis, and there was no correlation between prebiopsy course or histology and postcyclophosphamide course. The findings of this study support the clinical impression that steroid sensitivity rather than histology is the major determinant of prognosis in childhood nephrotic syndrome and that frequency of relapse alone is not an indication for biopsy.

Adrenal Cortex Hormones↗

Alkylation of 2'-deoxynucleosides and DNA by quinone methides derived from 2,6-di-tert-butyl-4-methylphenol.

4-Alkylphenols, such as the antioxidant 2, 6-di-tert-butyl-4-methylphenol (BHT), exhibit toxicities that appear to be mediated by their oxidative metabolism to electrophilic quinone methides. Reactions of these Michael acceptors with simple nucleophiles and proteins have been reported, but little information is available on quinone methide binding to the competing nucleophilic sites in DNA. In the present investigation, 2'-deoxynucleoside adducts generated in vitro with two BHT-derived quinone methides, 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone and 6-tert-butyl-2- (2'-hydroxy-1',1'-dimethylethyl)-4-methylenecyclohexa-2,5-dieno ne (BHTOH-QM) were isolated and identified. Both quinone methides produced adducts at the 1- and N2-positions of deoxyguanosine (dG) and the N6-position of deoxyadenosine (dA). In addition, a labile adduct formed at the 7-position of dG, which degraded to the corresponding 7-alkylguanine derivative. Additional work was conducted with BHTOH-QM, the more reactive of the two quinone methides. This species also formed stable adducts at the N4-position of deoxycytosine (dC) and the 3-position of thymidine and formed a labile adduct at the 3-position of dC that underwent hydrolytic cleavage to regenerate dC. In mixtures of deoxynucleosides treated with [14C]BHTOH-QM, alkylation occurred primarily at the N2- and 7-positions of dG and the N6-position of dA and occurred secondarily at the 1-position of dG. Treatment of calf thymus DNA with this quinone methide yielded N6-dA and N2-dG adducts with the former predominating. The unstable 7-dG adduct was detected by analysis of the 7-alkylguanine product from depurination. These results demonstrate that quinone methides are most likely to damage DNA through alkylation of the exocyclic amino groups of purine residues and possibly also by attack at the 7-position of dG followed by depurination.

Alkylation↗

Peritonitis, functional catheter loss and the sitting of the Dacron cuff in chronic peritoneal dialysis catheters in children.

Functional peritoneal dialysis catheter loss due to persistent or recurrent peritonitis is a common clinical problem in paediatric patients. To examine the effect of positioning of the cuff on infection and loss rate we compared catheters where the cuff was buried in the rectus sheath (deep cuffs) with those where the cuff was sutured to the external oblique muscle, just below the subcutaneous fascia (superficial cuffs). Of 62 catheters inserted into 35 patients (median age 7.76 yrs, range 0-17 yrs) 28 were lost through peritonitis of which 19 (68%) were due to Staph. aureus infection, usually associated with exit site colonisation or infection. 12 out of 20 catheters with superficial cuffs were lost through infection compared with 16 out of 42 with deep cuffs (relative risk reduction 37%, p = ns). Controlling for patient age and infecting organism made no difference to this statistic. 15 out of 21 catheters inserted into patients < 2yrs of age were lost through peritonitis compared to 13 out of 41 catheters inserted into patients over 2 yrs of age (p = 0.037). We conclude that although siting of the Dacron cuff in the rectus sheath is somewhat protective against penetrating infection this is still a major problem in the infant and young child where alternative strategies for the prevention of Staph. aureus infection need to be sought.

Adolescent↗

Hydrolytic and depolymerising enzyme activity of Prevotella intermedia and Prevotella nigrescens.

OBJECTIVE: Prevotella intermedia has been reported to be associated with periodontal disease whilst P. nigrescens has predominantly been isolated from more specific conditions and healthy sites. The aim of the present study was to compare the enzyme activity of these species. MATERIALS AND METHODS: Nine strains of P. intermedia and 12 strains of P. nigrescens were studied. Lipolytic, saccharolytic, nucleolytic and proteolytic activity was determined by traditional microbiological and chromogenic substrate methods. RESULTS: All strains hydrolysed gelatine, casein, DNA and RNA. Lipase activity was produced by all strains except P. nigrescens ATCC 33563T. Lipolytic activity of P. nigrescens strains decreased as the environmental glucose concentration was increased. Only two strains, both P. intermedia, hydrolysed benzyl-arg-rho-nitroanilide. All strains hydrolysed alkaline rho-nitrophenolphosphate (except P. intermedia DAL100), produced glycylprolyl dipeptidase activity and demonstrated elastase-like activity. All but three strains (2 P. intermedia and I P. nigrescens) hydrolysed suc-ala-ala-pro-phe-rho-nitroanilide. Overall, no qualitatively analysed enzyme activity was exclusive to all strains of either species. Quantitatively analysed activity exhibited a high degree of variability both within and between species. CONCLUSIONS: P. intermedia and P. nigrescens degrade natural and synthetic substrates, but intra- and interspecies activity is variable.

Alkaline Phosphatase↗

Identification of Candida species in formalin fixed, paraffin wax embedded oral mucosa by sequencing of ribosomal DNA.

Aim-To identify Candida species in formalin fixed, paraffin wax embedded tissue by sequencing candidal rDNA.Methods-Target rDNA sequences were amplified by polymerase chain reaction (PCR) from fresh isolates of Candida and from 18 preserved oral mucosal tissue samples (16 cases of chronic hyperplastic candidiasis and two fibroepithelial polyps), shown histologically to contain Candida. Identification of Candida species within tissue was based on a comparison of the rDNA sequences obtained with those from the fresh isolates of Candida and those present in the GenBank database.Results-The PCR products obtained from 12 of the 18 tissue specimens studied were characteristic of Candida albicans. In two of these cases a second, larger PCR product was obtained and these sequences were characteristic of Candida glabrata.Conclusions-Candidal DNA was amplified successfully from formalin fixed, paraffin wax embedded tissue. Sequencing of the PCR product enabled identification of the Candida species present.

Journal Article↗

Organizing the community to target poor Latino children with asthma.

A community-university partnership to improve outcomes of care for poor Latino children (aged 6-14 years) with asthma in East Los Angeles was based on development of a community infrastructure. A family-centered educational program involved over 500 families. The Association of Latinos with Asthma and Allergy Symptoms (ALAAS) was formed. Parents report reductions in hospitalizations, emergency room, and acute care visits. Survival of the infrastructure following the end of grant funds is unlikely unless other resources offset the costs of volunteerism among poor families. Block grants to community agencies from established fund-raising groups might reduce dependency-producing practices currently employed to "help" the poor.

Adolescent↗

Outcome of pediatric cadaveric renal transplantation: a 10 year study.

This report deals with 120 cadaveric renal transplants performed in 101 pediatric recipients in this Centre in two five-year periods, 1984 to 1988 (N = 65) and 1989 to 1993 (N = 55). In the first group transplants were allocated on the basis of best size (small donors for small recipients); in the second group priority was given to beneficial HLA matching. Initial immunosuppression was either cyclosporine (CsA) monotherapy (15 mg/kg/day), or triple therapy (CsA 5 mg/kg/day, prednisolone 1 mg/kg/day and azathioprine 1 mg/kg/day) if there was delayed graft function. Patient survival at one year and five years (97.5% and 92.3%, respectively) did not differ between the two groups, although there was an improvement in graft survival at one and five years in the second period relative to the first: 69.2% and 53.8% versus 78.6% and 65.6%. This did not achieve statistical significance. One year graft survival in recipients under five years did not differ significantly from older children (72%). There was a trend to improvement in one year graft survival in the < five years of age pediatric patients in Group 2, with beneficially matched kidneys and improved immunosuppressive management. Graft losses due to acute rejection were similar in both groups. Donor age < 4 years significantly reduced one year graft survival (63% vs. 85%, P = 0.01), while recipient age had no effect. Small donor kidneys were associated with a higher incidence of graft thrombosis. Transplantation resulted in the normalization or acceleration of growth velocity in (84%) of the pre-pubertal children who completed follow up. In conclusion, we have shown that excellent patient and graft survival can be achieved in children transplanted under the age of five years. Kidneys from donors under the age of four years are associated with an unacceptable rate of graft loss. Small children do not readily accept cyclosporine monotherapy. Successful early renal transplantation offers the best chance of normal growth and development.

Adolescent↗

Ecological chaos in the wake of invasion.

Irregularities in observed population densities have traditionally been attributed to discretization of the underlying dynamics. We propose an alternative explanation by demonstrating the evolution of spatiotemporal chaos in reaction-diffusion models for predator-prey interactions. The chaos is generated naturally in the wake of invasive waves of predators. We discuss in detail the mechanism by which the chaos is generated. By considering a mathematical caricature of the predator-prey models, we go on to explain the dynamical origin of the irregular behavior and to justify our assertion that the behavior we present is a genuine example of spatiotemporal chaos.

Animals↗

Use of freshwater plants for phytotoxicity testing: a review.

Phytotoxicity data for aquatic plants have served a relatively minor role in regulatory decisions concerning the environmental hazard of most potential contaminants. A variety of phytotoxicity tests have been conducted with freshwater green algae, duckweed, blue-green algae, diatoms and rooted macrophytes (whole plants and seeds). Several test methods have been standardized for microalgae which are used primarily with chemicals, effluents, contaminated sediment elutriates and hazardous waste leachates. Current scientific understanding concerning the phytotoxic effects of these contaminants is based mostly on results for a few green algae. The greatest limitation of these results is their uncertain environmental relevance due to the large interspecific variation in response of standard algal test species and the unrealistic experimental test conditions. Results of the few field validation toxicity tests conducted to resolve this uncertainty have been chemical-specific and unpredictable. Aquatic vascular plants have been used less frequently than algae as test species. Duckweeds have been used more often than rooted submersed species but the uncertain nature of their sensitivities relative to animal and other plant species has limited their use. Regulatory interest in wetland protection, contaminated sediment evaluations and sediment quality criteria development will result in increased use of whole rooted plants and their seeds as test species. Overall, regardless of the test species, if phytotoxicity data are to be more available and effective in the hazard assessment process, additional information concerning species sensitivity, and environmental relevance of the results will be needed.

Journal Article↗

Lhermitte-Duclos disease associated with Cowden's disease.

The twelfth patient in the known literature with Lhermitte-Duclos disease (dysplastic gangliocytoma) occurring in association with Cowden's disease is described. The investigation, aetiology, and management of the case are discussed.

Adult↗

Private payers of health care in Brazil: characteristics, costs and coverage.

The private sector is the predominant provider of health care in Brazil, particularly for inpatient services, and financing is a mix of public (through a prospective reimbursement system) and private. Roughly a quarter of the population has private insurance coverage, reflecting rapid growth in the past decade fuelled by the crisis in the public reimbursement system and the perceived deterioration of publicly provided care. Four major forms of insurance exist: (1) prepaid group practice; (2) medical cooperatives, physician owned and operated preferred provider organizations; (3) company health plans where employers ensure employee access to services under various types of arrangements from direct provision to purchasing of private services; and (4) health indemnity insurance. Each type of plan includes a wide variety of subplans from basic individual/family coverage to comprehensive executive coverage. The paper discusses the characteristics, costs and utilization patterns of all types of privately financed care, as well as the major problems associated with private financing: the limited package of benefits and low payout ceilings, inadequate consumer information and virtually no regulation.

Brazil↗

Prevalence of penicillin resistant bacteria in acute suppurative oral infection.

Pus aspirated from acute suppurative oral infections in 78 patients (age range 13-76 years) yielded a total of 331 bacterial strains consisting of 143 facultative anaerobes (predominantly Streptococcus spp.) and 188 strict anaerobes (predominantly Prevotella spp.). Seventy-five isolates (23%) were resistant to penicillin (MIC > 1 mg/L), 37 (11%) were resistant to ampicillin (MIC > 2 mg/L) and 16 (5%) isolates were resistant to amoxycillin/clavulanic acid (MIC > 2 mg/L). Samples from 43 (55%) of the patients yielded at least one penicillin resistant isolate and within this group 30 samples (73%) contained at least one strain which produced beta-lactamase. A history of antibiotic therapy during the 6 months before enrollment in the study did not influence the isolation of penicillin resistant bacteria. It is concluded that penicillin resistant bacteria are often present in the microflora of acute dental infection.

Acute Disease↗

Multicystic renal dysplasia diagnosed in the antenatal period: a note of caution.

OBJECTIVE: To document the urological problems associated with multicystic renal dysplasia (MCRD), to assess the efficacy of radiological methods for following the natural history of MCRD and to review current experience in the light of historical data regarding this condition. PATIENTS AND METHODS: From January 1982 to December 1992 data were obtained prospectively on 62 patients (41 boys and 21 girls, age range 1-11 years) who had a diagnosis of MCRD suspected on antenatal ultrasonography. All patients had the diagnosis confirmed with radioisotope scans and micturating cystograms. Serum creatinine was measured in each patient and repeated clinically as indicated. Follow-up was from 1 to 11 years, with a clinical review and an annual ultrasonogram. The natural history of these patients was compared with those in other published studies. RESULTS: Of the 62 patients, 12 had associated vesicoureteric reflux. Four patients developed impaired renal function during the course of observation and 10 patients required urological surgery for other pathologies. In the patients managed conservatively, 38% underwent no resolution on sequential ultrasonograms during the 2-year follow-up, and in four children, where complete resolution of the MCRD had occurred on ultrasonography, significant cellular renal masses were excised at subsequent surgery. CONCLUSION: Patients with MCRD have significant associated urological malformations and the natural history in such patients is unpredictable. We do not regard MCRD as an entirely benign condition and feel that all patients require appropriate investigation of their urinary tract and long-term follow-up where conservative treatment is instituted. From the natural history of these patients, reviewed in conjunction with the literature, we recommend that decisions for management can only be taken with the full informed consent of the parents and that surgical excision is offered as part of that process.

Child↗