Interaction of bromocriptine and cyclosporine in insulin dependent diabetes mellitus: Results from the Canadian open study

Although cyclosporine A (Cy-A) is effective in modifying the initial course of newly diagnosed insulin dependent diabetes mellitus (IDDM) it has a number of side effects, particularly renal, which limit its use. In this study we investigated the potential synergistic effects of bromocriptine (BCR) therapy in treating patients with newly diagnosed IDDM. Three groups of patients were treated: (1) fourteen patients on Cy-A who required a decrease in their dose due to elevated creatinine; (2) four newly diagnosed patients whose initial therapy consisted of low dose (5 mg/kg/day) Cy-A and 10 mg/day of BCR; (3) eight patients whose glucagon-stimulated connecting-peptide (C-peptide) levels were greater than 0.3 nmol/l but whose insulin requirements were over 0.3 U/kg/day and whose Cy-A was to be discontinued. The results suggest that there was no statistically significant difference in stimulated C-peptide, glycosylated haemoglobin, daily insulin dose or serum creatinine. However, the trend suggested that BCR may have some protective effect on preserving endogenous insulin secretory capacity, although glycosylated haemoglobin and daily insulin dose increased. The results do not suggest that patients with newly diagnosed IDDM significantly benefit from concurrent BCR and Cy-A therapy.     

Interleukin-12 is produced by macrophages in response to live or killed Bordetella pertussis and enhances the efficacy of an acellular pertussis vaccine by promoting induction of Th1 cells.

Using a murine respiratory infection model, we have demonstrated previously that infection with Bordetella pertussis or immunization with a whole-cell pertussis vaccine induced antigen-specific Th1 cells, which conferred a high level of protection against aerosol challenge. In contrast, immunization with an acellular vaccine, consisting of the B. pertussis components detoxified pertussis toxin, filamentous hemagglutinin, and pertactin adsorbed to alum, generated Th2 cells and was associated with delayed bacterial clearance following challenge. In this study, we demonstrated that addition of interleukin-12 (IL-12) either in vitro or in vivo enhanced type 1 T-cell cytokine responses induced with an acellular vaccine. Furthermore, the rate of bacterial clearance in mice coinjected with IL-12 and the acellular vaccine was similar to that observed following immunization with a potent whole-cell vaccine. Analysis of IL-12 secretion by murine macrophages suggested that this cytokine is produced in vivo following B. pertussis infection or immunization with the whole-cell vaccine. IL-12 was detected in the supernatants of lung, splenic, and peritoneal macrophages infected with live B. pertussis or stimulated with heat-killed whole B. pertussis or B. pertussis lipopolysaccharide. In contrast, IL-12 could not be detected following stimulation of macrophages with the bacterial antigens filamentous hemagglutinin, detoxified pertussis toxin, and pertactin, the components of acellular vaccines. Our findings suggest that induction of endogenous IL-12 may contribute to the high efficacy of pertussis whole-cell vaccines and also demonstrate that it is possible to attain these high levels of protection with a less reactogenic acellular vaccine incorporating IL-12 as an adjuvant.     

Another Look at the Relationship of Electrodermal Activity to Electrode Contact Area

The present study was undertaken lo reexamine the hypothesis that the relationship between skin conductance and electrode size is monotonic and linear. Skin conductance activity was recorded from 48 right-handed male subjects using 6 different sixes of electrode collars ranging in exposed surface area from .131 cm² to .786 cm². The dependent measures were skin conductance level (SCL); skin conductance response (SCR) amplitude to a series of 8 loud tones; latency, rise time, and recovery half-time of the first tone elicited response; (he largest self-generated SCR; and the number of nonspecific responses. The results indicated a significant linear relationship between contact area and SCL, stimulus and self-generated SCR amplitude, and the number of nonspecific responses. Latency was not affected by electrode size although the other time-based measures were. Differences in skin conductance activity were found among different palmar recording sites. The observed linear relationship between electrode size and electrodermal measures has implications for current models of electrodermal activity and for the comparison of results across studies in which different electrode contact areas are used.     

Later-life planning for older adults with mental retardation: a field experiment

A quasi-experimental design was used to assess the efficacy of a leisure education-based later-life planning model for 10 older adults with mental retardation. Prior to the initiation of the planning process, they were interviewed and completed three standardized scales designed to assess life and leisure satisfaction and leisure constraints. A comparison group completed these scales but did not participate in the planning process. At the completion of the study, both groups completed the same scales. Results demonstrated that the planning-process group had significantly higher life and leisure satisfaction at the end of the study. Many participants also made changes to their lifestyles consistent with plans made during the study. Results suggest that a later-life planning process may contribute to the quality of life of older adults with mental retardation.     

Management and relationships in total purchasing pilots. Relevance for primary care groups

Primary Care Groups (PCGs) represent a natural evolution of the various models--total purchasing, multifunds and locality commissioning--embraced by the term "primary care commissioning". They will involve large numbers of different professionals working together to commission improved health care for their populations. The total purchasing pilots (TPPs) were the subjects of an extensive evaluation which has highlighted the significance of developing and improving relationships between the key players as a prerequisite for the successful implementation of their strategy. Management arrangements were central to this success. Similar considerations will be of crucial importance for the PCGs which are considerably larger and more complex organisations than the TPPs.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Comprehensive mutational scanning of the p53 coding region by two- dimensional gene scanning

A comprehensive mutational scanning test for the p53 coding region based on multiplex PCR and two-dimensional DNA electrophoresis was designed and evaluated. In a 2-step multiplex PCR, the p53 coding region (exons 2-11) was amplified as a single 8646-bp fragment by long- distance PCR in step one. This fragment served as a template for the subsequent co-amplification of the individual exons in two multiplex groups in step two. The multiplex products were then separated, first on the basis of size in non-denaturant polyacrylamide gels and then on the basis of sequence by denaturing gradient gel electrophoresis (DGGE). Primers for optimal PCR, melting behavior and 2-D gel distribution were designed using a recently developed computer program. The resulting two-dimensional gene scanning (TDGS) test was evaluated by screening, in a blinded fashion, 29 coded DNA samples from Li- Fraumeni syndrome patients with previously identified germline mutations. All mutations were correctly detected. This assay provides an accurate, cost-effective and non-radioactive method for simultaneous mutational scanning of all p53 coding exons.      

Patterns of admissions for children with special needs to the paediatric assessment unit.

BACKGROUND: Children with special needs present a challenge to those involved in their care. AIMS: To determine the role of the acute assessment unit for these children. METHODS: Case notes and other records were reviewed for information on referrals, admissions, readmission within 7 and 28 days, length of stay, and management of 86 children registered for special needs. The study covered five years between January 1997 and December 2001. RESULTS: Of the 86 children, 48 (58%) were boys; 62 children had cerebral palsy and 52 learning disability. There were 914 episodes, with 44% of these being self referrals and 35% from general practitioners; 35.5% of the episodes were managed in the assessment unit. The average length of stay in hospital was 5 days, ranging from <24 hours to 63 days; 37.5% of those admitted to the ward stayed for less than 24 hours. Respiratory tract infections and seizures were the main reasons for referral and admission. CONCLUSION: Children with special needs tend to have a predictable pattern of conditions requiring inpatient care. One third of the inpatients episodes did not need a prolonged stay in hospital. This latter group of children could be managed at home with support of community nurses. Integrated care pathways need to be developed to minimise disruption to their lives. Appropriate resources should be made available to achieve these goals.