Biomedical subjects
Publications and source records attributed to C Stephens.
New results on Bacillus subtilis sporulation suggest that size differences between the post-septation compartments trigger differential gene expression, which is then coordinated by communication between the nascent mother cell and forespore compartments.
We have characterized genetic alterations at the molecular level in 49 scleroderma and 45 control families using variable number tandem repeats (VNTRs). Additionally, paired fibroblast cell lines from the 'affected' and 'unaffected' skin and peripheral blood leucocytes of 30 patients were also examined. All families in this study were typed for Class I Cw alleles and Class II-DRB, -DQA and -DQB to confirm family membership. There were significant rises in the level of VNTR mutations in scleroderma patients (36.7%, n = 18), their siblings (16.3%, n = 13) and offspring (21.7%, n = 15). The level of VNTR mutations in the control group was 0.6% (n = 5). These mutations did not correlate with the presence of autoantibodies and no patient was taking a known clastogenic drug. The most common VNTR site for mutation was pYNZ22 (17p13.4). Differences were also seen in the VNTR alleles between fibroblast and lymphocyte DNA from the same patient, as measured by size alteration of one of the alleles. We have found that VNTRs are unstable in scleroderma patients, relatives and offspring. The reason for the genomic changes remains unknown, but previous studies have implicated the presence of a clastogen.
The purpose of this study was to evaluate the feasibility of chronic oral administration of etoposide with granulocyte-macrophage colony-stimulating factor (GM-CSF) [sargramostim (Immunex)] coadministration or premedication; to estimate and compare the frequency of toxicities accompanying etoposide administration alone, etoposide/GM-CSF coadministration and etoposide with GM-CSF premedication. Thirty-nine patients with advanced treatment-refractory malignancies were enrolled to this study. Eligible patients were randomized to one of three treatment arms: daily oral etoposide alone for 21 days (arm A); daily oral etoposide for 21 days with GM-CSF, 250 micrograms/m2, s.c. twice daily for the first 10 days of etoposide administration (arm B); or daily oral etoposide for 21 days with GM-CSF twice daily for the sixth through second days preceding etoposide administration (arm C). Courses of treatment were repeated every 28 days. Etoposide dosages for each arm were 25, 50, 75 and 100 mg/m2/day. At least three patients were treated at each dosage level until dose-limiting toxicity was observed. Patients had twice weekly blood counts and weekly clinical examinations to assess toxicity. Patients with measurable or evaluable evidence of cancer were assessed for antitumor response after every other course of therapy. Nadir neutrophil counts at each dosage level were compared between treatment arms by non-parametric Wilcoxen rank sum tests. GM-CSF coadministration (arm B) or premedication (arm C) with daily chronic oral etoposide was feasible and did not lead to excessive hematological toxicity. Pairwise comparisons of neutrophil nadirs for the first course of therapy for each treatment arm did not demonstrate any significant differences and, at most, a slight trend favoring improved neutrophil nadirs was shown for arm C compared to arm A (p = 0.07). Dose intensity as measured by mean days of etoposide administered per patient for each arm suggested only slight improvement in etoposide tolerance for treatment arms B and C. The conclusion, GM-CSF can be safely administered to patients receiving chronic daily oral etoposide. It appears that GM-CSF provides no clinically useful improvement in granulocyte tolerance of therapy.
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In February 1991, the Intensive Care Unit (ICU) at Liverpool Hospital was extended and relocated to a larger area. It soon became apparent that noise levels within the newly renovated unit were particularly worrying to patients, staff and relatives. A Continuous Quality Improvement (CQI) group was formed to investigate, and develop measures to reduce these noise levels. Through the implementation of various CQI tools a study plan was developed to investigate the noise problem. The study plan included: a patient, relative and staff questionnaire; a literature search; identification of levels of noise using a sound level meter; contracting a noise consultant to visit and review the ICU environment. The results of the CQI investigations revealed that there was an inappropriately high level of noise in the ICU. Several key contributing factors were also identified. These findings provided the basis for several positive measures to be undertaken including: the installation of sound absorbing ceilings; removal of rubbish bin lids; revision of the telephone ringing system; revision of the mobile x-ray machine; prioritisation of audible machine alarms; education of staff in noise level awareness; The application of the Continuous Quality Improvement (CQI) process to the noise problem facilitated the exploration of the source of noise, the effects on staff and patients, and ways to reduce noise levels in the intensive care environment.
The transfer of the critically ill patient is often complex and difficult, and may contribute to increased morbidity. It is therefore valuable to have an understanding of the practical problems relating to patient transfer, and common management strategies, in order to minimise adverse outcomes. Key issues in the process of transporting the critically ill patient in metropolitan Sydney include: (i) particular problems and pitfalls during the transfer process; (ii) risk factors in transferring patients and the appropriateness of escorts and transfer procedures; (iii) procedures for arranging a patient transfer; (iv) the role of the NSW Medical Retrieval Co-ordination Centre (MRCC); (v) preparation of the patient for transfer, (vi) education of staff on the concept of safe matching of patient needs to appropriate escorts; and (vii) the need for a co-ordinated patient transfer system to Sydney metropolitan hospitals. An understanding of these issues, and an appropriate response to them from hospital staff will ensure safe and efficient transportation of critically ill patients in metropolitan Sydney.
An outbreak of ventilator-associated Pseudomonas aeruginosa respiratory infections in an intensive care unit of a teaching hospital was found to be associated with contaminated food coloring dye. Serotyping and bacteriocin typing indicated that the same strain of Pseudomonas was isolated from the food dye and from the respiratory cultures of the majority of patients. This observation lends credence to the importance of gastric colonization preceding pneumonia in ventilated patients.
The process of urbanization could be described as one of the major global environmental changes directly affecting human health today. Populations particularly affected are in developing countries where rapid urban growth has been accompanied by massive urban poverty. Urban environmental health impacts, particularly the impact on adults of an environment of poverty, are still poorly understood. Definitions of the urban environment tend to be physical, excluding the complex ramifications of a social setting of disadvantage. This paper provides a brief overview of existing knowledge on the links between environment, poverty and health in urban areas of developing countries, with an emphasis on the policy implications implied by research on health differential between groups within cities. The paper argues that urban poverty and inequalities in conditions between groups within cities present a central crisis confronting urban policy in terms of human health and quality of life. The paper suggests that definitions of the urban environment tend to consider only the physical, and not the social complexity of the urban setting. The review concludes that the scale and the complexity of the urban crisis in developing countries demands a real commitment to re-thinking the management of cities to address multiple deprivation. The paper suggests that this challenges urban professionals who continue to act with a bias towards unintegrated single sector solutions despite claims to the contrary.
A study of community awareness of mosquitos and related subjects in the residential areas of two Tanzanian cities (Dar es Salaam and Tanga) showed that residents were well aware of mosquitos. Almost all claimed to use some form of domestic mosquito control product for their personal protection, and many spend a significant portion of the household income on this. The problems of nuisance-biting and malaria transmission are usually not separated and are considered to be the result of poor environmental hygiene, for which both residents and local authorities are responsible. Although Culex mosquitos are not a primary target of the Urban Malaria Control Project (UMCP), the persistence of nuisance-biting has made residents sceptical and dissatisfied with insecticide spraying. The residents' priorities are evidently not the same as those of the health authorities, yet mutual cooperation is essential. In order to maintain community support, campaigns aimed at malaria vectors should consider the need for additional measures to control Culex mosquitos, such as those now being tried by the UMCP. Mosquito breeding sites are non-specifically associated with rubbish and standing water of all kinds, and so the actions that the community considers necessary for mosquito source reduction tend to be poorly targeted. Residents do not recognize that some sources produce malaria mosquitos while others produce nuisance mosquitos. The environmental anti-mosquito measures currently promoted by health education and other forms of propaganda are also poorly targeted. While some of them are directed at important Culex breeding sites, others are aimed at sites of little importance for mosquitos of any kind.(ABSTRACT TRUNCATED AT 250 WORDS)
This article addresses the development of data linkage methods for the analysis of urban environmental health problems and the development of appropriate policies and discusses, based on existing experience of data linkage in São Paulo (Brazil), the potential for routine environmental health monitoring and management in a major developing country industrial centre. The article looks briefly at two major environmental health problems in São Paulo: first, air pollution which has potential impacts on health of the whole population; and second, environmental differentials in conditions between groups within cities, which have substantial health effects on the economically deprived. The article argues that the health impact of environmental differentials in São Paulo is large, but unmonitored as a serious environmental health threat. In contrast, air pollution is monitored routinely, although its health effects are relatively small at present. The paper concludes with a discussion of policy implications of environmental health monitoring--which potentially require a substantial shift in attitudes of the urban wealthy.
Regulatory factors that initiate forespore-specific transcription during Bacillus subtilis sporulation respond to adenosine nucleotide ratios.
A project concerned with the study of intra-urban health differentials in S. Paulo city, Brazil, is described. A brief outline of urban problems in the city is presented, followed by a review of the locally published literature on the subject of geographical differentials (stratification by socioeconomic status and environment). Two topics are introduced: geographical subdivision of the area studied and the methods used to choose the socio-environmental indicators for the construction of a deprivation index with to stratify the city. Suggestions are made as to possible applications of results achieved by the project.
A posterior crossbite may pose long-term risk through causing associated displacement in the mandibular path of closure. In this paper the authors review the current opinions on treatment of such a problem.
Computer-based teaching has been used in the Department of Child Dental Health of the University of Bristol Dental School for almost 10 years to provide students with additional practice in the assessment of malocclusion and the planning of orthodontic treatment. In this article, the authors describe a study of the usefulness of computer-based learning packages for general practitioners and offer guidelines for others wishing to set up such a scheme.
OBJECTIVE: To investigate the contributions of the major histocompatibility complex (MHC) and C4 alleles to systemic sclerosis (SSc), and to pulmonary fibrosis and autoantibody expression in SSc, by analysis at the DNA level. METHODS: One hundred fifteen patients with SSc were tested serologically for alleles of the class I MHC loci, and were tested for class II alleles (DRB, DQA, and DPB) by a combination of restriction fragment length polymorphism (RFLP) analysis and oligonucleotide probes with polymerase chain reaction amplification. C4 was studied by protein phenotyping and RFLP analysis in 80 patients. Correlations were made between disease status, pulmonary fibrosis, and expression of anticentromere antibodies (ACA) and anti-Scl-70. RESULTS: The C4A-null phenotype was found to provide the strongest disease association factor of the MHC region (P = 0.000064, relative risk [RR] = 2.8, etiologic fraction [EF] = 32.1). The primary MHC susceptibility allele was found to be DQA2 (Pcorr = 0.0009, RR = 2.5, EF = 35.6), which is in linkage disequilibrium with both DR3 and DR11. DR2 was protective, but only for female patients (P = 0.0021, RR = 0.42, protective fraction = 19.4). DR52a was the primary MHC allele associated with pulmonary fibrosis in SSc patients. Expression of ACA was associated with the presence of either DR1 or DR4 (P = 0.0015, RR = 6.7, EF = 78.0). Anti-Scl-70 expression correlated with an acidic residue of DP beta (DPB1:69:E) (P = 0.0063, RR = 4.6, EF = 53.1). CONCLUSION: Of all the potential markers of disease susceptibility analyzed, the C4A locus was the strongest. C4AQ0 and DQA2 are independent susceptibility factors for SSc. The development of pulmonary fibrosis in SSc patients can be predicted using combined MHC and autoantibody analysis. The MHC alleles associated with the expression of disease-specific autoantibodies are not markers for disease susceptibility.
Extracorporeal membrane oxygenation (ECMO) is a commonly used technique in the management of newborn respiratory failure. However, few studies have addressed the optimal nutritional support of these critically ill neonates. Eleven newborns undergoing ECMO for respiratory failure were studied at various levels of intravenous caloric and nitrogen intake, using nitrogen balance techniques, to assess optimal nutritional support necessary to achieve positive nitrogen balance. Nonprotein nitrogen calories > 60 kcal/kg/d, and nitrogen > 240 mg/kg/d were necessary to achieve positive nitrogen balance, while maximum positive balance was seen with nitrogen intake > 400 mg/kg/d. These data suggest that newborns treated with ECMO can achieve positive nitrogen balance with modest amounts of caloric and nitrogen intake.