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Biomedical subjects

R J Spooner

Publications and source records attributed to R J Spooner.

At least 19 recordsLinked to original sources
PubMed2004

Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease.

BACKGROUND: Azathioprine is a useful agent in the management of inflammatory bowel disease. Its use is limited by its side-effect profile. Marrow toxicity occurs in approximately 3.2% of patients and is known to be associated with diminished thiopurine methyltransferase enzyme activity resulting from genetic polymorphisms. AIM: To evaluate the cost-effectiveness of screening for thiopurine methyltransferase gene polymorphisms prior to initiation of azathioprine therapy. METHODS: Analysis of the literature was undertaken to calculate the expected frequency of leucopenia and its relationship with thiopurine methyltransferase polymorphisms in a model of theoretical inflammatory bowel disease patients. Decision analysis was then applied to assess the cost of a pre-treatment genotyping strategy, taking account of direct costs and cost per life-year saved. RESULTS: In 1000 inflammatory bowel disease patients treated with azathioprine, 32 will develop myelosuppression and one will die because of this. Of those who develop myelosuppression during azathioprine therapy, 32% are attributable to lower thiopurine methyltransferase activity. Pre-treatment genotyping costs pound 347 per life-year saved for a 30 year old and pound 817 per life-year saved for a 60 year old. This compares favourably with other health care technologies. CONCLUSION: The use of pre-treatment screening for thiopurine methyltransferase polymorphisms in inflammatory bowel disease patients commencing azathioprine therapy represents good value for money.

Adult↗
PubMed2004

A tale of two sisters.

Hereditary haemochromatosis is the most common inherited disorder in white populations, whereas non-alcoholic steatohepatitis (NASH) is becoming the most common reason for referral for investigation of abnormal liver function tests (LFTs). This report describes two sisters, from similar environments, who were referred to the clinic after being found to be C282Y homozygotes and to have abnormal LFTs. One sister had developed features of haemochromatosis and the other had developed NASH. These cases illustrate the potential non-penetrance of HFE gene mutations and the need to investigate abnormal LFTs fully, even when there is a positive genetic test at the outset.

Diabetes Mellitus, Type 2↗
PubMed2000

Aetiology of seroma formation in patients undergoing surgery for breast cancer.

Surgery for primary breast cancer and regional nodes often involves the use of suction drains post-operatively. It is believed that the fluid accumulating following axillary surgery is lymph from divided lymphatics or alternatively serum, although the composition of this fluid has never been studied in detail. Drain fluid following surgery for primary breast cancer was analysed for a number of haematological and biochemical parameters. Comparison of these values with plasma concentration produced a ratio that was compared with established lymph to plasma ratios. Haematological analysis indicates minimal contamination with blood. Comparison of drain fluid to plasma ratios with known lymph to plasma values for biochemical parameters showed that this fluid is compositionally different from lymph, but is similar to inflammatory exudate. Altering surgical technique to close dead space may avert the need for wound drainage, lead to reduced hospital stay and reduce the incidence of 'seroma' formation.

Journal Article↗
PubMed2000

Determinants of raised C-reactive protein concentration in type 1 diabetes.

As a marker of systemic inflammation, raised C-reactive protein (CRP) concentrations which are still within the normal range have been associated with an increased incidence of coronary heart disease (CHD) in non-diabetic subjects. This study aimed to establish potential determinants of raised CRP concentrations in type 1 diabetic patients. We used a sensitive assay to measure 'low-level' CRP concentrations in 167 type 1 patients (93M, 74F, median age 30 years, range 13-67). Stepwise multivariate analysis was used to relate these CRP levels to known cardiovascular risk factors and demographic data. Only six patients had established CHD (median CRP 3.34 mg/l vs. 0.83 mg/l, p=0.032). In subjects without overt CHD, multivariate analysis showed increases in subject age (p=0.0025), BMI (p=0.001) and HbA(1) (p=0.012) to be associated with a higher CRP concentration, as was female sex (p=0.026) and a history of CHD in a first-degree relative (p=0.018, n=57). The duration of diabetes, current smoking status, presence of microvascular complications, lipid status and presence of hypertension were unrelated. This study suggests that some of the risk factors associated with CHD in type 1 patients are also independently predictive of high CRP concentrations. The reasons for this, and whether intervention would prove useful, require further investigation.

Adolescent↗
PubMed1997

Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. UK Haemophilia Centre Directors' Organisation.

BACKGROUND: Most people with haemophilia who were treated with blood products before the introduction of virus-inactivation procedures were infected with the hepatitis-C virus (HCV). However, there is little quantitative information about the long-term effects on mortality of such infection. METHODS: We carried out a cohort study of mortality from liver cancer and liver disease in 4865 haemophilic men and boys in the UK. They were treated between 1969 and 1985 with blood products carrying a high risk of HCV infection, and were followed up from first recorded exposure to Jan 1, 1993. FINDINGS: Based on death-certificate information, mortality was 16.7 times higher than in the general population for liver disease (95% CI 12.5-22.0; 51 deaths), and 5.6 times higher (1.8-13.0; five deaths) for liver cancer. For men and boys with severe haemophilia who were not infected with HIV-1, the cumulative risks of death from chronic or unspecified liver disease or from liver cancer in the 25 years since first recorded exposure to high HCV-risk products were 1.4% (0.7-3.0) at all ages, and 0.10% (0.01-0.7), 2.2% (0.8-6.1), and 14.3% (4.5-40.9) for those with first recorded exposure at ages under 25, 25-44, and 45 or older. For those with haemophilia and HIV-1 infection, the corresponding risks were 6.5% (4.5-9.5) at all ages, and 3.8% (2.1-6.8), 17.1% (10.0-28.5), and 18.7% (6.4-47.6) in the three age-groups. In those with severe haemophilia, age-standardised all-cause mortality was stable during 1969-84 but increased during 1985-92 in both HIV-1-infected and HIV-1-uninfected groups. Among those not infected with HIV-1, the increase in all-cause mortality resulted largely from deaths attributed to chronic or unspecified liver disease or liver cancer in men aged over 45. INTERPRETATION: There is an emerging risk of mortality from liver disease and liver cancer in the UK haemophilia population in individuals both infected and uninfected with HIV-1, which probably results from infection with hepatitis C.

Adult↗
PubMed1996

Importance of age at infection with HIV-1 for survival and development of AIDS in UK haemophilia population. UK Haemophilia Centre Directors' Organisation.

BACKGROUND: Greater age at infection with HIV-1 is known to be associated with shorter time to development of AIDS, but the size of the differences between people infected in infancy and those infected in old age has not been examined in a single large population of patients with death as an endpoint. We, therefore, investigated the role of age at seroconversion in the entire UK population of haemophiliacs. METHODS: We studied 1216 HIV-1-infected haemophilia patients in the UK who were registered with the National Haemophilia Register and were alive on Jan 1, 1985. Their estimated ages at HIV-1 seroconversion ranged from 8 months to 79 years. FINDINGS: 10 years after seroconversion 67% (95% Cl 64-69) of the population were still alive. Survival was strongly related to age at seroconversion (86% [82-90], 72% [68-76], 45% [39-51], and 12% [5-21] at 10 years among those patients who seroconverted at ages < 15, 15-34, 35-54, and > or = 55). This steep age-gradient in survival was not explained by deaths expected in the absence of HIV infection or by confounding with other factors such as haemophilia type or severity. The age-gradient was steeper for survival (ie, time from HIV-1 infection to death) than for time to diagnosis of AIDS, partly because survival after an AIDS diagnosis was poorer in older patients, and there was also a substantial increase in mortality among HIV-infected patients who did not satisfy the formal AIDS definition and this increase was greater in older patients. INTERPRETATION: Age at infection with HIV-1 is a more important determinant of survival than has previously been appreciated. Age should, therefore, be considered in future studies of disease progression, and studies that compare people infected at different ages should provide insight into the biology of the immune response to HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Ranitidine reduces phosphate binding in dialysis patients receiving calcium carbonate.

BACKGROUND: In a previous controlled study we showed that ranitidine significantly reduced the phosphate binding of aluminium hydroxide in patients with renal failure, probably increasing intragastric pH. METHODS: In this study we have investigated the effect of ranitidine on the phosphate binding of calcium carbonate in fifteen dialysis patients. Ranitidine 300 mg or a placebo tablet was taken before breakfast for two 4-week periods in a double-blind crossover trial with no washout period. The mean daily dose of calcium carbonate was 2 g and neither the dose nor the patient's diet was changed during the study period. Blood was taken at 2-weekly intervals for serum phosphate, calcium, albumin, and alkaline phosphatase measurements, and at the end of each treatment period for parathyroid hormone (PTH) level. RESULTS: Serum phosphate concentrations were significantly higher during the ranitidine than the placebo phase, 1. 78 (+/-0.43 SD) versus 1.59 (+/-0.49 SD) mmol/l (P<0.001). Serum calcium, albumin, PTH, and alkaline phosphatase concentrations did not differ between the two treatment periods. CONCLUSION: This study shows that ranitidine has a significant adverse effect on the phosphate binding of calcium carbonate in patients with renal failure.

Adult↗
PubMed1995

Mortality before and after HIV infection in the complete UK population of haemophiliacs. UK Haemophilia Centre Directors' Organisation.

During 1977-91, 6,278 males diagnosed with haemophilia were living in the UK. During 1979-86, 1,227 were infected with the human immunodeficiency virus (HIV-1) as a result of transfusion therapy (median estimated seroconversion date, October 1982). Among 2,448 with severe haemophilia, the annual death rate was stable at 8 per 1,000 during 1977-84; during 1985-92 death rates remained at 8 per 1,000 among HIV-seronegative patients but rose steeply in seropositive patients, reaching 81 per 1,000 in 1991-92. Among 3,830 with mild or moderate haemophilia, the pattern was similar, with an initial death rate of 4 per 1,000 in 1977-84, rising to 85 per 1,000 in 1991-92 in seropositive patients. During 1985-92, there were 403 deaths in HIV seropositive patients, whereas 60 would have been predicted from rates in seronegatives, suggesting that 85% of the deaths in seropositive patients were due to HIV infection. Most of the excess deaths were certified as due to AIDS or to conditions recognized as being associated with AIDS.

Adolescent↗
PubMed1991

Salivary secretion of albumin in type 1 (insulin-dependent) diabetes.

The concentration of albumin in saliva is low in healthy humans. To determine whether alterations in capillary permeability in diabetes affects the salivary glands, the concentration of albumin in parotid saliva was measured in 26 Type 1 (insulin-dependent) diabetic patients, and compared to 32 non-diabetic control subjects. The diabetic patients were subdivided into 3 groups on the basis of the urinary excretion of albumin in timed overnight collections of urine: (1) normal albumin excretion (less than 30 micrograms/min) n = 13; (2) microalbuminuria (30-300 micrograms/min) n = 7, and (3) macroalbuminuria (greater than 300 micrograms/min) n = 6. Saliva was collected for one minute following stimulation with 1 ml 10% citric acid, and the concentration of albumin was measured by a sensitive ELISA method. No significant difference in salivary albumin concentration was found between the control group and any of the diabetic groups. Thus, although urinary albumin excretion was increased, suggesting altered capillary permeability, simultaneous leakage of albumin into saliva was not observed. Measurement of salivary albumin concentration does not, therefore, provide a marker of occult microvascular disease in diabetes.

Adult↗
PubMed1991

Apolipoprotein E phenotyping: a word of caution.

Using two different techniques, phenotyping and genotyping, we have studied allelic variation at amino acids 112 and 158 of the apolipoprotein E gene locus in 52 patients with insulin-dependent diabetes and in 58 non-diabetic controls. Phenotypes were determined by isoelectric focusing and immunoblotting of delipidated, neuraminidase-treated plasma. Genotypes were determined by using the polymerase chain reaction to amplify a 227 base pair fragment of the apolipoprotein E gene spanning both allelic sites. This was then digested with the restriction endonuclease CfoI and the alleles identified by polyacrylamide gel electrophoresis. Discrepancies between phenotype and genotype were observed in 16 (15%) of the individuals studied, 7 (13%) in the diabetics and 9 (17%) in the controls. From these results it is concluded that isoelectric focusing can lead to the erroneous assignment of apolipoprotein E phenotype even after pretreatment with neuraminidase. It is suggested that genotyping by DNA analysis is the method of choice in determining apolipoprotein E status.

Alleles↗
PubMed1990

Persistent nephrogenic diabetes insipidus, tubular proteinuria, aminoaciduria, and parathyroid hormone resistance following longterm lithium administration.

We report a patient who developed persistent nephrogenic diabetes insipidus associated with renal tubular acidosis, renal resistance to parathyroid hormone, aminoaciduria and proximal tubule pattern proteinuria in the presence of a reduced glomerular filtration rate (19-24 ml/min). A review of the previous reports of persistent nephrogenic diabetes insipidus revealed that in all patients the glomerular filtration rate had been less than 60 ml/min at presentation. Chronic renal failure may therefore predispose to the development of persistent nephrogenic diabetes insipidus in patients receiving lithium.

Acidosis, Renal Tubular↗
PubMed1990

Delayed diagnosis of Addison's disease.

Addison's disease may be difficult to diagnose because of the non-specificity of the most frequently occurring symptoms. Hyponatraemia, hyperkalaemia, and uraemia are commonly detected in sera from patients with Addison's disease. We report two patients in whom the diagnosis was delayed, despite typical biochemical abnormalities in their sera during initial presentation. A computer search of 4 weeks of biochemical data (9862 requests for electrolytes) indicated that these typical biochemical abnormalities occurred commonly in other patients, increasing the difficulty of the clinical biochemist in detecting Addison's disease. Awareness of this problem, in combination with adequate clinical information, should enable the clinical biochemist to assist in the earlier diagnosis of Addison's disease.

Addison Disease↗