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Biomedical subjects

S D Slater

Publications and source records attributed to S D Slater.

At least 19 recordsLinked to original sources
PubMed2005

Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study.

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30-49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years (standardised incidence ratio (SIR)=2.14; 95% confidence interval (CI) 1.22-3.48; standardised mortality ratio (SMR)=2.90; 95% CI 1.45-5.19), with greatest risks for those with diabetes diagnosed at ages 10-19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

Adolescent↗
PubMed2005

Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95.

AIMS: To assess pregnancy outcomes, in particular birthweight, in a large population-based cohort of women in Scotland with pre-gestational insulin-treated diabetes mellitus. METHODS: Data about diabetes from the Diabetes UK cohort were linked to data on births from the Scottish Hospital In-Patient Record System. This identified 1112 eligible singleton deliveries during 1979-95 to 706 insulin-treated women. RESULTS: One thousand and eighty-four (97.5%) deliveries resulted in a live-born infant and 28 (2.5%) in a stillbirth. There were 13 (1.2%) neonatal deaths. The mean birthweight of the live-born infants was 3421 g, 1.06 standard deviations greater than that of infants in the Scottish general population after correcting for sex and gestational age. Forty-three per cent of live-born babies in the study were large (> Scottish 90th percentile) and 4% small (< 10th percentile) for their sex and gestational age. Macrosomia, defined as birthweight > or = 4000 g, occurred in 23% live-born babies and its prevalence was significantly inversely related to duration of maternal diabetes. However, the mean birthweight of infants born to mothers with diabetes for 20 or more years was still 0.90 standard deviations greater than in the general population. Prevalence of macrosomia increased with increasing number of previous pregnancies, but was not associated with maternal height or smoking habits. Stillbirth and neonatal death rates were, respectively, 4.7 (95% confidence interval = 3.3, 6.8) and 2.4 (1.4, 4.1), times higher than those in the general population. CONCLUSIONS: The frequency of adverse pregnancy outcomes in women with pre-existing insulin-treated diabetes was much higher than in the Scottish general population, and changed little during the study period. A detailed quantification of the independent effect of duration of mother's diabetes on birthweight revealed a continuous inverse correlation between these two variables.

Adult↗
PubMed2004

Mortality of South Asian patients with insulin-treated diabetes mellitus in the United Kingdom: a cohort study.

AIMS: To investigate mortality in South Asian patients with insulin-treated diabetes and compare it with mortality in non South Asian patients and in the general population. METHODS: A prospective cohort study was conducted of 828 South Asian and 27 962 non South Asian patients in the UK with insulin-treated diabetes diagnosed at ages under 50 years. The patients were followed for up to 28 years. Ethnicity was determined by analysis of names. Standardized mortality ratios (SMRs) were calculated, comparing mortality in the cohort with expectations from the mortality experience of the general population. RESULTS: SMRs were significantly raised in both groups of patients, particularly the South Asians, and especially in women and subjects with diabetes onset at a young age. The SMRs for South Asian patients diagnosed under age 30 years were 3.9 (95% CI 2.0-6.9) in men and 10.1 (5.6-16.6) in women, and in the corresponding non South Asians were 2.7 (2.6-2.9) and 4.0 (3.6-4.3), respectively. The SMR in women was highly significantly greater in South Asians than non South Asians. The mortality in the young-onset patients was due to several causes, while that in the patients diagnosed at ages 30-49 was largely due to cardiovascular disease, which accounted for 70% of deaths in South Asian males and 73% in females. CONCLUSIONS: South Asian patients with insulin-treated diabetes suffer an exceptionally high mortality. Clarification of the full reasons for this mortality are needed, as are measures to reduce levels of known cardiovascular disease risk factors in these patients.

Adult↗
PubMed2003

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes.

AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. METHODS: A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. RESULTS: There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. CONCLUSIONS/INTERPRETATION: The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.

Adolescent↗
PubMed1999

The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus.

AIMS: To assess mortality in patients with diabetes incident under the age of 30 years. METHODS: A cohort of 23 752 diabetic patients diagnosed under the age of 30 years from throughout the United Kingdom was identified during 1972-93 and followed up to February 1997. Following notification of deaths during this period, age- and sex-specific mortality rates, attributable risks and standardized mortality rates were calculated. RESULTS: The 23 752 patients contributed a total of 317 522 person-years of follow-up, an average of 13.4 years per subject. During follow-up 949 deaths occurred in patients between the ages of 1 and 84 years, 566 in males and 383 in females. All-cause mortality rates in the patients with diabetes exceeded those in the general population at all ages and within the cohort were higher for males than females at all ages except between 5 and 15 years. The relative risk of death (standardized mortality ratio, SMR), was higher for females than males at all ages, being 4.0 (95% CI 3.6-4.4) for females and 2.7 (2.5-2.9) for males overall, but reaching a peak of 5.7 (4.7-7.0) in females aged 20-29, and of 4.0 (3.1-5.0) in males aged 40-49. Attributable risks, or the excess deaths in persons with diabetes compared with the general population, increased with age in both sexes. CONCLUSIONS: This is the first study from the UK of young patients diagnosed with diabetes that is large enough to calculate detailed age-specific mortality rates. This study provides a baseline for further studies of mortality and change in mortality within the United Kingdom.

Adolescent↗
PubMed1999

The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus.

AIMS: To measure cause-specific mortality, by age, in patients with insulin-treated diabetes incident at a young age. METHODS: A cohort of 23 752 patients with insulin-treated diabetes diagnosed under the age of 30 years, from throughout the United Kingdom, was identified during 1972-93 and followed to February 1997. Death certificates have been obtained for deaths during the follow-up period and cause-specific mortality rates and standardized mortality ratios by age and sex are reported. RESULTS: During the follow-up period 949 deaths occurred and at all ages mortality rates were considerably higher than in the general population. Acute metabolic complications of diabetes were the greatest single cause of excess death under the age of 30 years. Cardiovascular disease was responsible for the greatest proportion of the deaths from the age of 30 years onwards. CONCLUSIONS: Deaths in patients with diabetes diagnosed under the age of 30 have been reported and comparisons drawn with mortality in the general population. To reduce these deaths attention must be paid both to the prevention of acute metabolic deaths and the early detection and treatment of cardiovascular disease and associated risk factors.

Adolescent↗
PubMed1998

Proliferation of parenchymal epithelial cells enhanced in chronic pancreatitis.

This study was performed to determine whether pancreatic parenchymal epithelial cells in human chronic pancreatitis tissues retain a biologically significant capability to proliferate and, if so, within which epithelial compartment proliferation occurs. The techniques of immediate per-operative in vitro labelling with bromodeoxyuridine (BrdU) and conventional immunohistochemistry for Ki-67 antigen expression were used to identify proliferating cells. Concordance between the two techniques was confirmed in all tissues examined. In normal pancreas, proliferation was restricted to acinar epithelial cells, with no activity in the ductules. In chronic pancreatitis of both chronic obstructive and chronic calcifying types, the number of proliferating cells in the acini was significantly increased. A small population of proliferating cells was also apparent within ductules in chronic calcifying pancreatitis, but not in chronic obstructive pancreatitis. This investigation has shown that loss of parenchymal epithelium occurring in chronic pancreatitis is not caused by a primary failure of pancreatic 'stem-cell' proliferation, but is due to disproportionate attrition of differentiated parenchymal epithelial cells by a mechanism, possibly stromal in origin, which remains hitherto unidentified. The presence of proliferating ductular cells in chronic calcifying pancreatitis, but not chronic obstructive pancreatitis, suggests that distinct pathogenic processes may be operating in the former condition, which is classically regarded as secondary to ductal obstruction by stones, and in this single respect might be considered to be identical to chronic obstructive pancreatitis. Preservation of 'stem-cell' function supports the belief that regeneration of pancreatic parenchymal tissue could be a feasible proposition if biologically appropriate management strategies were developed to treat chronic calcifying pancreatitis.

Adult↗
PubMed1995

Expression of transforming growth factor-beta 1 in chronic pancreatitis.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine which modifies tissue stromal matrix synthesis, cell proliferation and immune function. In the present study, we have used a mouse monoclonal antibody to the latent (intracytoplasmic) form of TGF-beta 1 to compare its expression in 144 cases of human chronic pancreatitis (both obstructive and chronic calcifying) with that of 10 control pancreatic specimens. In all the control specimens, and most of those with chronic pancreatitis, cytoplasmic immunoreactivity was identified in pancreatic duct and ductular epithelium, in islet cells and in vascular smooth muscle and endothelium. Two distinct patterns of ductular epithelial staining emerged: in morphologically normal tissues, only individual distal ductular/centroacinar cells stained but in chronic pancreatitis (whether chronic calcifying or chronic obstructive) the staining was panductular. Positive cytoplasmic immunostaining of acinar epithelial cells was found in 3% of pancreatitis specimens but in none of the normal controls. There was no staining of fibroblasts. Synthesis of TGF-beta 1 appears to be normally restricted to a population of epithelial cells located in terminal/centroacinar regions of the ductules (together with occasional ductal cells) whereas in chronic pancreatitis, TGF-beta 1 is expressed in most ductular and ductal epithelial cells.

Case-Control Studies↗
PubMed1994

Alfred Ernest Maylard, 1855-1947: Glasgow surgeon extraordinaire.

This account concerns Alfred Ernest Maylard, 1855-1947, a surgeon of exceptional ability and a man with extraordinary energy and drive. He was appointed to the Victoria Infirmary, Glasgow, when it opened in 1890 and made an outstanding clinical and academic contribution, particularly in abdominal surgery. His organisational talents were remarkable and manifest in his influence not just upon the hospital's developments but also upon Glasgow's medical life in general. In his spare time he was a keen mountaineer and was the driving force behind the formation of the Scottish Mountaineering Club in 1889 and its first secretary and later president. He was a prolific writer in all these fields, his eminence as scientific surgeon being recognised by election to the Fellowship of the Royal Society of Edinburgh and his contribution to mountaineering by the vice-presidency of the Royal Scottish Geographical Society.

General Surgery↗
PubMed1993

Expression of major histocompatibility antigens in human chronic pancreatitis.

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p < 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.

Adult↗
PubMed1993

Paracetamol cardiotoxicity.

A 29 year old man with a significant paracetamol overdose was found to have an abnormal electrocardiograph which, in the absence of hepatic encephalopathy, was considered due to a direct cardiotoxic effect of the drug. A functional coronary insufficiency resulting from inhibition of endothelium-derived relaxing factor secondary to depletion of sulphydryl groups is postulated, and it is suggested that in paracetamol poisoning evidence of cardiotoxicity alone may be sufficient justification for treatment with acetylcysteine.

Acetaminophen↗
PubMed1992

Mutant p53 protein is expressed in Bowen's disease.

A total of 26 specimens of histologically determined, cutaneous Bowen's disease from 23 patients were investigated for the incidence of mutant p53 protein expression by an indirect immunoperoxidase technique using the monoclonal antiserum CM1 on paraffin-embedded formalin-fixed tissue sections. Its potential role as a label of cutaneous malignancy was also evaluated: 15 specimens (57.7%) showed nuclear positivity of dysplastic keratinocytes, whereas 11 specimens (42.3%) were immunonegative. Cytoplasmic labeling was never a feature. In general, labeling was predominantly diffuse in distribution although in a significant proportion it was focal. One of two concurrent basal cell carcinomas arising adjacent to plaques of Bowen's disease was immunopositive. Focal immunopositivity of "cytologically normal" adjacent epithelium was seen in six specimens (23%). The study confirms the presence of mutant p53 protein in the majority of nongenital Bowen's disease. Its identification within nuclei of the adjacent "normal" epidermis may represent a potential marker of early (visible) neoplastic transformation.

Aged↗
PubMed1992

Expression of mutant p53 gene in squamous carcinoma arising in patients with recessive dystrophic epidermolysis bullosa.

Epidermolysis bullosa, a rare genodermatosis, is characterized by increased skin fragility manifest as blistering and sometimes accompanied by scarring. The latter is particularly severe in the recessive dystrophic variant and may be complicated by the development of squamous carcinoma in up to 30% of patients. We have studied 23 such tumours in six patients with this variant, with an anti-serum to p53 protein. Twenty-six per cent of the squamous carcinomas labelled positively for mutant-type p53 protein. This low figure, however, reflects the large number of well-differentiated tumours in this series, where 14 out of 15 were negative. In the moderate to poorly differentiated examples the positivity rate was 63%. Of the three patients in the latter category, one has died from disseminated tumour and another has widespread metastases. The findings support the hypothesis that mutant p53 protein expression correlates with poorer tumour differentiation. They also suggest a possible correlation between p53 protein expression and tumour behaviour.

Carcinoma, Squamous Cell↗
PubMed1991

A comparative study of proliferation indices and ploidy in dysplastic naevi and malignant melanomas using flow cytometry.

Cell proliferation indices and DNA content have been determined in 18 intradermal naevi, 40 dysplastic naevi and 16 superficial malignant melanomas (less than 0.76 mm depth of invasion) using flow cytometry. In this study, proliferation indices of intradermal naevi and dysplastic naevi were not significantly different from each other. Abnormalities of DNA ploidy were not identified in the intradermal naevi or dysplastic naevi; whereas three of the malignant melanomas were aneuploid. In addition, cellular proliferation was increased within the group of malignant melanomas, in comparison with the naevi. This study has found no evidence to indicate that sporadic dysplastic naevi were more likely than intradermal naevi to transform to malignant melanoma, when objective criteria were employed. However, dysplastic naevi could be distinguished from some early malignant melanomas by absence of aneuploidy and by low cell proliferation indices.

Adolescent↗
PubMed1988

The misuse of intravenous cannulae.

The use of indwelling venous cannulae is commonplace and of undoubted value. However, they are associated with complications, notably thrombophlebitis and infection. This study seeks to show that they may now have become overused and abused, especially in general wards. It is recommended that the indications for them be more critically examined, that they must be routinely heparinised and regularly inspected, and be removed without unnecessary delay.

Catheters, Indwelling↗