Biomedical subjects
Publications and source records attributed to P Lewis.
In the wake of the Child B rationing controversy, the Anti-Rationing Group challenged purchasers to allow them to scrutinise their practice. Eight health authorities accepted and, say Colin Roberts and colleagues, the results show public money being needlessly wasted on a staggering scale.
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The aim of this study was to assess the adequacy of existing services across a whole health district for those aged 75 years, in an attempt to detect shortfalls and biases in the provision of services. This study was carried out as a cross-sectional survey using community based nurses in the county of South Glamorgan. 1376 people in their 75th year who were registered with a general practitioner were visited, and their problems assessed by community based nurses. There was a marked difference in the results of the assessment for different services. It was estimated that 76% of the 75-year olds would benefit from additional health services, and 37% from social services. There was a striking difference between the services in the proportion of people whose problems were satisfactorily solved, according to the criteria used by the community nurses. The proportion of problems that were solved varied according to the degree of dependency of the individuals, and the service involved. Some services showed a clear trend to care more for dependent people; services with a relatively undeveloped home delivery system seemed likely to discriminate against people who were dependent.
We studied 23 DMD and eight BMD patients using cardiac echo, 24 h ECG and positron emission tomography (PET) with the radiotracers N-13 ammonia and F-18 fluorine deoxyglucose. The ECG was abnormal in 23 cases with alterations in the PR and/or QT intervals, abnormal Q waves in the lateral leads and ST segment depression. Twenty-four hour ECG showed that patients were more likely to produce premature ventricular ectopic beats with advancing age and 17 patients had paroxysmal ST segment depression. LV function was normal or mildly reduced in 24 cardiac echoes. PET studies were visibly abnormal in 15 patients. Regional perfusion defects involving the apex, lateral or anterior left ventricular walls were present, nine cases demonstrated a corresponding increase in glucose metabolism. Three out of 15 demonstrated matched perfusion/metabolism defects. One BMD had severe LV dilation with globally poor perfusion and metabolism. The abnormalities seen with PET were confirmed with both quantitative and semi-quantitative analysis of radioactive counts. Similar results were obtained for both DMD and BMD, where both groups demonstrated significant regional perfusion/metabolism mismatches. We have shown a reduced uptake of N-13 ammonia which is indicative of a reduction in myocardial perfusion. The use of N-13 ammonia to measure perfusion has been validated in animal studies. PET with either N-13 ammonia- or oxygen labelled water can be used to measure myocardial perfusion. We chose N-13 ammonia as this was most readily available to us.
Temozolomide, a new oral cytotoxic agent, was given to 75 patients with malignant gliomas. The schedule used was for the first course 150 mg/m2 per day for 5 days (i.e. total dose 750 mg/m2), escalating, if no significant myelosuppression was noted on day 22, to 200 mg/m2 per day for 5 days (i.e. total dose 1000 mg/m2) for subsequent courses at 4-week intervals. There were 27 patients with primary disease treated with two courses of temozolomide prior to their radiotherapy and 8 (30%) fulfilled the criteria for an objective response. There were 48 patients whose disease recurred after their initial surgery and radiotherapy and 12 (25%) fulfilled the criteria for an objective response. This gave an overall objective response rate of 20 (27%) out of 75 patients. Temozolomide was generally well tolerated, with little subjective toxicity and predictable myelosuppression. However, the responses induced with this schedule were of short duration and had relatively little impact on overall survival. In conclusion, temozolomide given in this schedule has activity against high grade glioma. However, studies evaluating chemotherapy in primary brain tumours should include a quality-of-life/performance status evaluation in addition to CT or MRI scanning assessment.
1. Clinical pharmacology is a key activity in drug discovery and drug development with much to contribute to drug innovation. 2. However, very few clinical pharmacologists choose the pharmaceutical industry as their ultimate career. 3. Medical alumni of the RPMS clinical pharmacology department illustrate this; only four industrial careers vs thirty professors of clinical pharmacology or medicine.
MAb NS 88 directed against breast cancer cells, which is internalized and translocated to the cell nucleus, was conjugated with histone and labeled with 125I. 125I-MAb-histone complexes (M(r) 250,000) were internalized by breast and cervical cancer cells and localized in the cytoplasm and chromatin. Electrophoretic analysis of the cells extracted from the conjugates revealed the same molecular weights of the cytoplasmic and chromatin complexes as those of the native conjugate. Nicotine (0.1%), which suppresses lysosomal degradation, stabilized the conjugates within the cell and prolonged the presence of nondegraded complexes inside the cytoplasm and chromatin from 1 day to at least 3 days. MAb-histone complexes, but not MAb alone, inhibited RNA synthesis and proliferation of cervical and breast cancer cells. A new application of internalized MAbs as the vehicles for protein inhibitors of transcription or replication is discussed.
The effectiveness of low-dose intravenous insulin boluses to improve study quality in F-18 FDG myocardial scans is investigated. Seventeen patients were imaged using a protocol in which only diabetic patients with fasting blood glucose levels > 8 mmol/l were given insulin. Fifty-three patients were imaged using a protocol in which all patients were given 1-3 IU intravenously of insulin immediately before F-18 FDG injection, based on fasting blood glucose levels. Scan quality was rated as poor, good, or excellent. Using the conventional protocol, 29% of the scans were poor quality (uniterpretable), 47% were good, and 23% were excellent. Using the low-dose intravenous insulin boluses protocol; 2% were poor, 53% were good, and 45% were excellent (P = 0.01). There were no significant differences in the proportion of diabetic patients, age, or fasting blood glucose levels. Low-dose intravenous insulin bolus is an easy and safe method of improving myocardial F-18 FDG scan quality in nondiabetic and diabetic patients.
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The chance of a baby born to an HIV-positive mother being HIV positive itself is 1 in 6. HIV infection cannot be diagnosed in utero. A diagnosis of HIV infection may not be excluded until the baby is 15 months old. There is no sound evidence that pregnancy worsens maternal HIV disease. The options of caesarean section and vaginal delivery are discussed but the decision does not need to be made until after 36 weeks. The risk of transmitting the virus in breastmilk should always be discussed and the mother advised to bottle feed. The prescribing of zidovudine needs full and informed explanation.
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Fibrosing colonopathy was first described in cystic fibrosis (CF) children in 1994. We have done a nested case-control study to identify possible associations with this condition. A case ascertainment within the UK CF population to identify any cases that occurred between January, 1984, and April, 1994, found 14 cases, all under 14 years and confirmed by independent histopathological review. All had presented since April, 1993; 12 were boys and six had received some or all of their care in Liverpool. Each case was matched, by date of birth, with four controls from the UK CF Registry. Information was obtained about cases and controls from their case records and by a structured interview with the families. In the 12 months before surgery, there was an association between the occurrence of fibrosing colonopathy and use of high-strength pancreatic enzyme preparations. This association was dose related. Odds ratio per extra 1000 high-strength capsules was 1.45 (95% CI 1.14-1.84). For use of protease, the odds ratio per million extra units per kg was 1.55 (1.19-2.03). For usage of individual high-strength products at any time during the 12 months before surgery some differences were observed; for Creon 25000 the odds ratio was 0.38 (0.10-1.42), for Nutrizym 22 43.4 (2.51-751), and for Pancrease HL 8.4 (1.95-36.1). These last two confidence intervals are extremely wide and compatible with these two products having the same odds ratios. Laxative use was independently predictive (odds ratio 2.42 [1.20-4.94]). We conclude that there is a dose-related association between high-strength pancreatic enzyme preparations and fibrosing colonopathy.
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A midwifery group practice approach has been developed for the care of high-risk mothers at the Chelsea & Westminster Hospital. The team of six midwives working with the professor of obstetrics, the consultant obstetrician and a physician cares for a caseload of 200 high-risk women a year. Midwives are able to acquire and maintain the skills necessary to care for high-risk mothers. Audit of the scheme is essential and will be complemented by a satisfaction survey completed by clients, midwives and doctors.
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We report a 72-year-old patient with thoracic myelopathy due to isolated ossification of the ligamentum flavum at T9-T10. Severe paraparesis had developed before the lesion was identified when thinning of a segment of the lower thoracic spinal cord was suspected on a second MRI examination. The diagnosis was then established by CT.