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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 343 records · Page 19Linked to original sources
PubMed1994

Identification of novel transcripts complementary to the Marek's disease virus homologue of the ICP4 gene of herpes simplex virus.

Libraries of cDNA were generated from polyadenylated RNAs derived from Marek's disease virus (MDV)-transformed cell lines by directional cloning of oligo-(dT)-primed cDNAs in lambda gt22A. Analysis of the libraries for viral sequences showed that a number of cDNA clones originated from transcripts mapping in the BamHI A region of the MDV genome. Sequencing and fine mapping of these cDNAs suggested that the RNA transcripts expressed from this region were either in the sense or antisense direction with respect to the MDV homologue of the ICP4 gene of herpes simplex virus. The longest cDNA clone from antisense transcripts was 2756 bp long and partially overlapped the 5' end of the coding region of the ICP4 gene. The cDNA clone contained at least four introns, shown by comparison of its sequence with the sequence of the ICP4 gene. The presence of introns was confirmed by PCR analysis. All the introns have the consensus splice donor and acceptor signals at their 5' and 3' ends respectively. Northern blot analysis showed that the ICP4 gene homologue of MDV was abundantly transcribed only in lytically infected fibroblasts, whereas transcripts complementary to the ICP4 gene were the major transcripts in MDV-transformed cell lines and lymphomas. The transcripts complementary to ICP4 consist of two major RNA species approximately 15 kb and 1.32 kb long. The results suggest that there might be an inverse relationship between the abundance of ICP4 transcripts and their complementary transcripts in MDV-infected and transformed cells.

Amino Acid Sequence↗
PubMed1994

Observer variability in the histopathological reporting of abnormal rectal biopsy specimens.

AIMS: To study the consistency of reporting of abnormal rectal biopsy specimens, especially in the differentiation of inflammatory bowel disease from other causes of abnormality. METHODS: Sixty rectal biopsy specimens were identified from patients presenting with bloody diarrhoea. These were then circulated to the 11 consultant pathologists in the study who filled in a proforma with a list of 12 diagnostic categories and 22 features. RESULTS: Forty one of the 60 cases were examples of inflammatory bowel disease. In 33 of these cases nine or more pathologists had made the diagnosis. Further categorisation into ulcerative colitis and Crohn's disease showed better recognition of ulcerative colitis. In the 19 cases of non-inflammatory bowel disease recognition of pseudomembranous colitis and solitary rectal ulcer syndrome was good, but the results were poorer in the case of infective colitis. CONCLUSION: The findings suggest that a group of consultant pathologists can differentiate between inflammatory bowel disease and other causes of an abnormal rectal biopsy specimen and can also recognise pseudomembranous colitis and solitary rectal ulcer syndrome satisfactorily.

Biopsy↗
PubMed1994

Observer variability in histopathological reporting of malignant bronchial biopsy specimens.

AIMS: To evaluate the ability of histopathologists to classify lung carcinomas on bronchial biopsy material using the current World Health Organisation (WHO) classification. METHODS: Eleven histopathologists each reviewed 100 randomly selected bronchial biopsy specimens which had originally been reported as showing lung carcinoma. A single haematoxylin and eosin stained section from each case was circulated and a standard proforma completed. These were analysed using kappa statistics. RESULTS: The histopathologists were excellent at distinguishing between small cell and non-small-cell carcinoma kappa = 0.86), but not so good at subclassifying the non-small cell carcinoma group kappa = 0.25). CONCLUSIONS: The clinically important distinction between small cell and non-small cell carcinoma of the lung is reliably made by competent histopathologists even on limited material.

Biopsy↗
PubMed1994

Papuloerythroderma and cutaneous T cell lymphoma.

An 83-year-old man had the typical cutaneous features of papuloerythroderma of Ofuji. There were reduced numbers of lymphocytes and platelets in his peripheral blood but the eosinophil count was normal. Skin biopsy showed a nondiagnostic infiltrate of T lymphocytes in the dermis. Treatment with topical steroids and UVB phototherapy was ineffective. Twelve months after presentation, a further skin biopsy revealed atypical lymphoid cells invading the epidermis and the skin adnexae. A diagnosis of malignant lymphoma was made; no evidence of extracutaneous spread was found. Photochemotherapy produced rapid resolution of the skin eruption and clearance of the cutaneous infiltrate. Papuloerythroderma may be a manifestation of a cutaneous lymphoma.

Aged↗
PubMed1994

What determines mortality risk in male former cigarette smokers?

OBJECTIVES: The purpose of this study was to examine what factors determine the mortality experience of male ex-cigarette smokers, those who no longer smoke at all and those who changed to pipe or cigar smoking. METHODS: A cohort study was undertaken with 18-year mortality data on 19,018 men. RESULTS: Ex-cigarette smokers had an intermediate mortality risk compared with never and current smokers. Ex-cigarette smokers who switched to pipe smoking had higher mortality than those who no longer smoked at all. The mortality rates for pipe and cigar smokers who were former cigarette smokers were higher than those for pipe or cigar smokers who had never smoked cigarettes. Ex-cigarette smokers who consumed more than 20 cigarettes per day for more than 20 years experienced increased mortality for both coronary heart disease and neoplasms, even after 30 years of cessation. CONCLUSIONS: These results support the notion that an elevated mortality risk may be seen for ex-cigarette smokers, even after they have given up smoking for many years. Ex-cigarette smokers who change to a pipe have a greater mortality risk than those who no longer smoke at all.

Adult↗
PubMed1994

Use of vancomycin hydrochloride for treatment of Clostridium difficile enteritis in Syrian hamsters.

As part of an 18-month carcinogenicity study, 680 Syrian hamsters (Mesocricetus auratus) received daily gavage doses of fenazaquin, an experimental miticide. Mortality associated with severe enteritis was noticed beginning when the hamsters were 4 months old and ranged from one to five deaths per month until the hamsters were about 10 months old, when 41 deaths occurred in a 1-month period. Ante- and postmortem findings were consistent with those reported for antibiotic-induced enteritis in hamsters. Clostridium difficile was isolated from 12 of the 13 samples of cecal contents analyzed. Toxin assays of C. difficile isolates collected from 11 affected animals were positive for both cyto- and enterotoxins. Daily oral administration of vancomycin hydrochloride at a dose of 20 mg/kg was initiated when the hamsters were about 10 months old. Deaths due to C. difficile enteritis were significantly decreased within 2 weeks, and treatment was continued for 3 months. A trial withdrawal period for a subset of 64 hamsters (approximately 16% of the total population) was initiated to evaluate survival after discontinuation of the antibiotic treatment. Clostridium difficile enteritis recurred within 2 weeks and caused 19 deaths during the next month; therefore, these hamsters were returned to daily vancomycin treatment for the remainder of the study. With the exception of severe gaseous distention of the ceca, which caused death in 17 (< 4% of the total population) of the affected hamsters, vancomycin treatment did not cause any major adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pre-emptive administration of clonidine prevents development of hyperalgesia to mechanical stimuli in a model of mononeuropathy in the rat.

Traumatic nerve injury in man can often result in the development of neuropathy. An animal model of neuropathic hyperalgesia is produced by loose ligation of the sciatic nerve in the rat. We have examined the effect of pre-emptive treatment with a number of drugs on the development of hyperalgesia in this model. Animals received clonidine (1 mg.kg-1, s.c.), morphine (5 mg.kg-1, s.c.), (+/-)-baclofen (40 mg.kg-1, s.c.), carbamazepine (50 mg.kg-1, s.c.) or vehicle (4 ml.kg-1, s.c.) 30 min prior to loose ligation or sham-operation. Morphine- and clonidine-treated animals were administered a second dose of drug 6h following surgery. Twenty-six or twenty-nine days following surgery, the ipsilateral (ipsi.) and contralateral (contra.) paw withdrawal thresholds were determined using an Algesymeter. In vehicle-treated animals the ipsilateral paw withdrawal threshold (118 +/- 7 g) was significantly lower (P < 0.0001, paired t-test) than the contralateral (195 +/- 7 g). In contrast, in animals pre-treated with clonidine no significant difference between ipsilateral (200 +/- 9 g) and contralateral (191 +/- 7 g) paw withdrawal thresholds was detected. Morphine pre-treatment was less effective in preventing development of hyperalgesia; however, whilst the ipsilateral (146 +/- 18 g) paw withdrawal threshold tended to be lower than the contralateral (183 +/- 8 g), this was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Cholesterol lowering and mortality: the importance of considering initial level of risk.

OBJECTIVE: To investigate the level of risk of death from coronary heart disease above which cholesterol lowering treatment produces net benefits. DESIGN: Meta-analysis of results of randomised controlled trials of cholesterol lowering treatments. METHODS: Published and unpublished data from all identified randomised controlled trials of cholesterol lowering treatments with six months or more follow up and with at least one death were included in the meta-analysis. The analyses were stratified by the rate of death from coronary heart disease in the control arms of the trials. MAIN OUTCOME MEASURES: Death from all causes, from coronary heart disease, and from causes other than coronary heart disease. RESULTS: In the pooled analysis, net benefit in terms of total mortality from cholesterol lowering was seen only for trials including patients at very high initial risk of coronary heart disease (odds ratio 0.74; 95% confidence interval 0.60 to 0.92). In a medium risk group no net effect was seen, and in the low risk group there were adverse treatment effects (1.22; 1.06 to 1.42). In a weighted regression analysis a significant (p < 0.001) trend of increasing benefit with increasing initial risk of coronary heart disease was shown. Raised mortality from causes other than coronary heart disease was seen in trials of drug treatment (1.21; 1.05 to 1.39) but not in the trials of non-drug treatments (1.02; 0.88 to 1.19). Cumulative meta-analysis showed that these results seem to have been stable as new trials appeared. CONCLUSION: Currently evaluated cholesterol lowering drugs seem to produce mortality benefits in only a small proportion of patients at very high risk of death from coronary heart disease. Population cholesterol screening could waste resources and even result in net harm in substantial groups of patients. Overall risk of coronary heart disease should be the main focus of clinical guidelines, and a cautious approach to the use of cholesterol lowering drugs should be advocated. Future trials should aim to clarify the level of risk above which treatment is of net benefit.

Cholesterol↗
PubMed1993

Distribution of neuropeptides in dorsal root ganglia of the rat; substance P, somatostatin and calcitonin gene-related peptide.

We have used sensitive and specific radioimmunoassays to examine the differential distributions of three neuropeptides, substance P (SP), calcitonin gene-related peptide (CGRP) and somatostatin (SST), in dorsal root ganglia (DRG) from levels C1 to L6 of the spinal column. SP and CGRP content both varied in proportion to ganglion wet weight, with greatest levels in cervical and lumbar DRG. By contrast, SST content showed a distinct distribution, with maximum levels in rostral, cervical DRG. We speculate that the distribution of these neuropeptides may be due to the influence of target-derived neurotrophic factors, and may underlie the particular sensitivity of the hind limbs to adjuvant arthritis in the rat.

Animals↗
PubMed1993

Weighting in the dark: resource allocation in the new NHS.

National allocation of resources to regional health authorities and by them to districts is now determined by a weighted capitation formula. The national formula was derived from regression analysis, with hospital utilisation as an index of need for health care--a method which has fundamental limitations. This paper argues that the search for an empirically based resource allocation formula of high precision in the name of promotion of equity is largely fruitless given the impossibility of measuring the true need for, and costs of, providing health care, especially with the limited data available. The inclusion of measures of social deprivation is also poorly thought out. The availability of data from the 1991 census, which included a question regarding long-standing illness, together with the intention of the Department of Health to review the weighted capitation formula using this information may stimulate much work but little light. It is essential that the impact of resource allocation formulas is justifiable on grounds other than the composition of any particular formula.

Delivery of Health Care↗