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1.  Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1. 
Infection and Immunity  1996;64(7):2716-2723.
We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen.
PMCID: PMC174131  PMID: 8698500
2.  Setting standards of prescribing performance in primary care: use of a consensus group of general practitioners and application of standards to practices in the north of England. 
BACKGROUND: There is considerable variation in prescribing, and existing standards against which primary care prescribing is routinely judged consist largely of local or national averages. There is thus a need for more sophisticated standards, which must be widely applicable and have credibility among the general practice profession. AIM: A study aimed to develop a range of criteria of prescribing quality, to set standards of performance for these criteria, and apply these standards to practices. METHOD: A consensus group consisting of eight general practitioners and a resource team was convened to develop and define criteria and set standards of prescribing performance using prescribing analyses and cost (PACT) data. The standards were applied to 1992-93 prescribing data from all 518 practices in the former Northern Regional Health Authority. RESULTS: The group developed criteria and set numeric standards for 13 aspects of prescribing performance in four areas: generic prescribing, prescribing within specific therapeutic groups, drugs of limited clinical value and standards based on prescribing volume. Except for generic prescribing, standards for individual criteria were achieved by between 9% and 34% of practices. For each criterion, a score was allocated based on whether the standard was achieved or not. Total scores showed considerable variation between practices. The distribution of scores was similar between fundholding and non-fundholding practices, and also between dispensing and non-dispensing practices. CONCLUSION: Using a consensus group of general practitioners it is possible to agree criteria and standards of prescribing performance. This novel approach offers a professionally driven method for assessing the quality of prescribing in primary care.
PMCID: PMC1239506  PMID: 8745847
5.  Survival of patients with advanced urothelial cancer treated with cisplatin-based chemotherapy. 
British Journal of Cancer  1996;74(10):1655-1659.
The aim of the present retrospective study was to assess long-term survival after cisplatin-based chemotherapy in 398 patients with advanced urothelial transitional cell carcinoma (TCC) treated at seven international oncological units. Various combinations of cisplatin, methotrexate, vinblastine (or vincristine) and doxorubicin were used. The complete response rate according to the WHO criteria was 17%. Partial responses were obtained in 42% of the patients. The overall cancer-related 2 year and 5 year survival rates were 21% and 11% respectively. Based on multivariate analyses, a good prognosis group could be identified comprising patients with a good performance status with disease confined to lymph nodes (14%) or patients with T4b disease only. These patients had a 28% 5 year survival rate, which, in part, has to be related to post-chemotherapy consolidation treatment in patients with pelvis-confined disease (radiotherapy, 26%; total cystectomy, 11%). Fifteen patients died of chemotherapy-related complications and in 16% of the patients toxicity led to discontinuation of treatment. Modern cisplatin-based chemotherapy leads to long-term survival and cure of selected patients with advanced urothelial transitional cancer. In routine clinical practice, chemotherapy should be offered to good prognosis patients; those presenting with a good performance status and a non-metastasising T4b tumour or with metastases confined to lymph nodes. Post-chemotherapy consolidation treatment by surgery or radiotherapy should always be considered. Such chemotherapy requires oncological expertise in order to avoid unnecessary toxicity.
PMCID: PMC2074866  PMID: 8932351
6.  Primary care in the United States. 
BMJ : British Medical Journal  1996;313(7063):955-956.
PMCID: PMC2352338  PMID: 8892403
7.  Mutations in the homologous ZDS1 and ZDS2 genes affect cell cycle progression. 
Molecular and Cellular Biology  1996;16(10):5254-5263.
The Saccharomyces cerevisiae ZDS1 and ZDS2 genes were identified as multicopy suppressors in distinct genetic screens but were found to encode highly similar proteins. We show that at semipermissive temperatures, a yeast strain with a cdc28-1N allele was uniquely deficient in plasmid maintenance in comparison with strains harboring other cdc28 thermolabile alleles. Quantitative analysis of plasmid loss rates in cdc28-1N strains carrying plasmids with multiple replication origins suggests that a defect in initiating DNA replication probably causes this plasmid loss phenotype. The ZDS1 gene was isolated as a multicopy suppressor of the cdc28-1N plasmid loss defect. A zds1 deletion exhibits genetic interactions with cdc28-1N but not with other cdc28 alleles. SIN4 encodes a protein which is part of the RNA polymerase II holoenzyme-mediator complex, and a sin4 null mutation has pleiotropic effects suggesting roles in transcriptional regulation and chromatin structure. The ZDS2 gene was isolated as a multicopy suppressor of the temperature-sensitive growth defect caused by the sin4 null mutation. Disruption of either ZDS1 or ZDS2 causes only modest phenotypes. However, a strain with both ZDS1 and ZDS2 disrupted is extremely slowly growing, has marked defects in bud morphology, and shows defects in completing S phase or entering mitosis.
PMCID: PMC231525  PMID: 8816438
9.  A prescribing incentive scheme for non-fundholding general practices: an observational study. 
BMJ : British Medical Journal  1996;313(7056):535-538.
OBJECTIVE: To examine the effects of a financial incentive scheme on prescribing in non-fundholding general practices. DESIGN: Observational study. SETTING: Non-fundholding general practices in former Northern region in 1993-4. INTERVENTION: Target savings were set for each group of practices; those that achieved them were paid a portion of the savings. MAIN OUTCOME MEASURES: Financial performance; prescribing patterns in major therapeutic groups and some specific therapeutic areas; rates of generic prescribing; and performance against a measure of prescribing quality. SUBJECTS: 459 non-fundholding general practices, grouped into three bands according to the ratio of their indicative prescribing amount to the local average (band A > or = 10% above average, B between average and 10% above, C below average). RESULTS: 102 (23%) of 442 practices achieved their target savings (18%, 19%, and 27% of bands A, B, and C respectively). Band C practices that achieved their target had a lower per capita prescribing frequency for gastrointestinal drugs, inhaled steroids, antidepressants, and hormone replacement therapy. There were no other significant differences in prescribing frequency, and no reduction in the quality of prescribing in achieving practices. Total savings of pounds 1.54 m on indicative prescribing amounts were achieved. Payments from the incentive scheme and discretionary quality awards resulted in pounds 463,000 being returned to practices for investment in primary care. CONCLUSIONS: The prescribing behaviour of non-fundholding general practitioners responded to financial incentives in a similar way to that of fundholding practitioners. The incentive scheme did not seem to reduce the quality of prescribing.
PMCID: PMC2351914  PMID: 8789984
11.  Jack Kevorkian: a medical hero. 
BMJ : British Medical Journal  1996;312(7044):1434.
PMCID: PMC2351178  PMID: 8664610
12.  Cost effectiveness of treating primary care patients in accident and emergency: a comparison between general practitioners, senior house officers, and registrars. 
BMJ : British Medical Journal  1996;312(7042):1340-1344.
OBJECTIVES--To compare outcome and costs of general practitioners, senior house officers, and registrars treating patients who attended accident and emergency department with problems assessed at triage as being of primary care type. DESIGN--Prospective intervention study which was later costed. SETTING--Inner city accident and emergency department in south east London. SUBJECTS--4641 patients presenting with primary care problems: 1702 were seen by general practitioners, 2382 by senior house officers, and 557 by registrars. MAIN OUTCOME MEASURES--Satisfaction and outcome assessed in subsample of 565 patients 7-10 days after hospital attendance and aggregate costs of hospital care provided. RESULTS--Most patients expressed high levels of satisfaction with clinical assessment (430/562 (77%)), treatment (418/557 (75%)), and consulting doctor's manner (434/492 (88%)). Patients' reported outcome and use of general practice in 7-10 days after attendance were similar: 206/241 (85%), 224/263 (85%), and 52/59 (88%) of those seen by general practitioners, senior house officers, and registrars respectively were fully recovered or improving (chi2 = 0.35, P = 0.840), while 48/240 (20%), 48/268 (18%), and 12/57 (21%) respectively consulted a general practitioner or practice nurse (chi2 = 0.51, P = 0.774). Excluding costs of admissions, the average costs per case were 19.30 pounds, 17.97 pounds, and 11.70 pounds for senior house officers, registrars, and general practitioners respectively. With cost of admissions included, these costs were 58.25 pounds, 44.68 pounds, and 32.30 pounds respectively. CONCLUSION--Management of patients with primary care needs in accident and emergency department by general practitioners reduced costs with no apparent detrimental effect on outcome. These results support new role for general practitioners.
PMCID: PMC2351016  PMID: 8646050

Results 1-15 (15)