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Biomedical subjects

A D Paterson

Publications and source records attributed to A D Paterson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Association study between the dopamine D4 receptor gene and schizophrenia.

The dopamine D4 receptor is of major interest in schizophrenia research due to its high affinity for the atypical neuroleptic clozapine and a high degree of variability in the receptor gene (DRD4). Although several genetic linkage analyses performed on schizophrenia multiplex families from different regions of the world have either excluded or failed to prove that DRD4 is a major genetic factor for the development of schizophrenia, analyses for moderate predisposing effects are still of significant interest. We performed a study examining differences in allele frequencies of 4 different DRD4 polymorphisms in schizophrenia patients and age, sex, and ethnic origin matched controls. None of these 4 polymorphisms showed evidence for genetic association with schizophrenia, although a trend towards excess of the allele with 7 repeats in the (48)n bp exon III polymorphism was observed. Complexities in the DRD4 genetic investigation and further analytic approaches are discussed.

Female↗
PubMed1995

Long-term haloperidol elevates dopamine D4 receptors by 2-fold in rats.

Chronic treatment of rats with neuroleptics results in elevated numbers of dopamine D2-like receptors. The present study was done to determine whether neuroleptics altered the density of one type of dopamine D2-like receptors, namely the dopamine D4 receptor. We here describe the effect of a one-month treatment with haloperidol on dopamine D4 receptor mRNA and protein levels in rat striatum. Endogenous levels of dopamine D4 receptor mRNA in rat striatum are very low and, therefore, reverse transcription and subsequent amplification were used for quantification. Dopamine D4 receptor density was, because of the absence of a dopamine D4 receptor specific [3H]ligand, determined by the difference between the number of binding sites for [3H]nemonapride and [3H]raclopride. Scatchard analysis of [3H]nemonapride and [3H]raclopride binding show that treatment for one month with halperidol elevates the density of dopamine D4 receptors in rat striatum by approximately 2-fold, whereas dopamine D2 and D3 receptors together show a 19% higher receptor density. Dopamine D4 receptor mRNA was also approximately increased by 2-fold.

Animals↗
PubMed1995

Genetic anticipation in schizophrenia: pro and con.

Recently, it has been demonstrated that unstable trinucleotide repeats are the etiologic factor in myotonic dystrophy, fragile-X syndrome, Kennedy's disease, Huntington's disease, spinocerebellar ataxia type 1, and dentatorubral-pallidoluysian atrophy. All available evidence suggests that these expanded trinucleotide repeats, or unstable DNA, are the biological basis of the clinical phenomenon of genetic anticipation. Two components of anticipation, increased severity and earlier age of onset in subsequent generations, have been widely observed in schizophrenia. We review the evidence for and against genetic anticipation in schizophrenia. Although the major criticisms of the anticipation hypothesis can be questioned, so can the evidence in favor of it. We conclude that molecular genetic approaches might be the most useful means of resolving ambiguity in clinical arguments about the origin of the anticipation-like phenomenon in schizophrenia.

Age of Onset↗
PubMed1992

Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease.

OBJECTIVE: To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease. DESIGN: Three year retrospective study. SETTING: Subregional nephrology service serving a mixed urban and rural population of 800,000. SUBJECTS: 60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants). MAIN OUTCOME MEASURES: Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin. RESULTS: All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures. CONCLUSION: Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.

Adult↗
PubMed1991

The attitudes of heroin users and matched non-users to drugs and drug users.

Compared with matched controls, heroin users were more tolerant of substance use and perceived themselves as slightly more unemployed, depressed, neat and aggressive. Both groups thought crack cocaine, heroin and alcohol dangerous. Heroin users were most in favour of cannabis, followed by controls who had used cannabis, with only controls who had never used cannabis being against it. It is concluded that the stereotype of a heroin user was not strongly believed by these heroin users or their peers.

Adult↗
PubMed1987

Causes of death in diabetic patients with impaired renal function. An audit of a hospital diabetic clinic population.

Of over 2000 diabetic patients whose serum creatinine had been measured regularly, 107 died between January, 1983, and March, 1985, and 27 (median age at death 66 years) had renal impairment (serum creatinine over 130 mumol/l). Cause of death was determined from clinical and necropsy data. 11 died of cardiovascular disease and 10 of causes unrelated to cardiac or renal disease; in only 6 was renal impairment the main cause of death. All 6 had severe physical and/or social disabilities and 2 were over the age of 75. Median serum creatinine in patients who died was 269 mumol/l (range 135-1135 mumol/l) and exceeded 500 mumol/l in only 5. Of the few patients who would have received RRT under a more liberal dialysis policy, all had severe physical disabilities.

Adult↗
PubMed1986

Removal and replacement of Tenckhoff catheter at a single operation: successful treatment of resistant peritonitis in continuous ambulatory peritoneal dialysis.

8 episodes of persistent and 4 of recurrent bacterial peritonitis in 11 patients on continuous ambulatory peritoneal dialysis (CAPD) were treated successfully by the removal and immediate replacement of the Tenckhoff catheter. Intraperitoneal antibiotics, which had previously failed to produce clinical resolution of the peritonitis, were continued unchanged. Dialysate culture yielded Staphylococcus epidermidis (3 cases), Staphylococcus aureus (1 case), pseudomonas species (5 cases), acinetobacter (1 case), and no growth in 2 cases. Clinical and microbiological resolution was achieved in all 12 cases within 36 h. CAPD continued uninterrupted in 10 cases. 1 patient required temporary haemodialysis for 6 weeks because of dialysate leakage and later restarted CAPD. 1 patient chose haemodialysis as his long-term treatment when his new catheter failed mechanically on the second postoperative day. Replacement of the Tenckhoff catheter at a single operation without interrupting CAPD reduces the demand which temporary haemodialysis of these patients makes on centre dialysis facilities and may preserve the peritoneal cavity for dialysis by preventing the formation of adhesions.

Adult↗
PubMed1986

A comparison of fine needle aspiration cytology and tru-cut tissue biopsy in the diagnosis of acute renal allograft rejection.

Simultaneous Tru-cut biopsies and fine needle aspirations (FNAs) performed over a 2-year period on patients following renal transplantation were assessed by independent pathologists. When there was histological evidence of rejection, FNAs also demonstrated cellular features of rejection in 83% of cases, and this increased to 92% with repeated sampling. The presence of monocytes and histiocytes in FNAs correlated with vascular features of rejection on biopsy and failure to reverse the rejection process with steroids.

Biopsy↗
PubMed1985

Treatment of malignant hypercalcaemia with clodronate.

We have assessed the effects of clodronate (dichloromethylene diphosphonate; Cl2MDP 0.8-3.2g daily by mouth for up to 3 months) in 17 episodes of hypercalcaemia and osteolysis due to carcinoma. Clodronate reduced serum calcium in 14 episodes and bone resorption in all patients. These remained suppressed for the duration of treatment, but recurred promptly when treatment was stopped. Clodronate may be a useful measure for controlling hypercalcaemia and osteolysis in patients with carcinoma.

Adult↗
PubMed1983

Drug treatment of primary hyperparathyroidism: use of clodronate disodium.

Clodronate disodium (dichloromethylene diphosphonate), a specific inhibitor of bone resorption, was given by mouth (1.0-3.2 g daily) to nine patients with primary hyperparathyroidism for two to 32 weeks so that its clinical and metabolic effects could be evaluated. Bone resorption decreased in all patients as judged by a fall in the fasting urinary calcium to creatinine and hydroxyproline to creatinine ratios. Serum calcium concentration was increased in all patients before treatment and fell in response to treatment to values near the upper end of the normal range. Hypercalcaemia and hypercalciuria recurred when treatment was stopped. In three patients treated for longer than 19 weeks clodronate failed to sustain the reduction in serum calcium concentration but the concentration remained below pretreatment values. These results suggest that clodronate may be of use in the medical management of primary hyperparathyroidism, particularly in patients in whom suppression of bone disease is desirable before surgery or in whom surgery is contraindicated.

Aged↗
PubMed1983

The use of dichloromethylene diphosphonate for the management of hypercalcaemia in multiple myeloma.

We have assessed the effects of the diphosphonate, dichloromethylene diphosphonate (Cl2MDP), in 19 patients with hypercalcaemia and increased bone resorption due to myeloma. Cl2MDP (800-3200 mg daily by mouth or 300 mg daily by intravenous infusion) decreased plasma calcium and biochemical indices of increased bone resorption in 16 of 19 patients. This effect persisted for the duration of treatment (up to 14 weeks). Prolonged treatment was associated with a progressive rise in serum alkaline phosphatase and only a transient fall in hydroxyproline suggesting the stimulation of bone repair. Since myeloma is associated with significant morbidity and mortality due to progressive bone loss, these results suggest that long-term treatment of myeloma with Cl2MDP is worthy of further study.

Aged↗
PubMed1982

Platelet sialic acid in malignant disease.

n-Acetylneuraminic acid (NANA) was measured in the platelets and serum of normal subjects, patients with malignant disease, and patients with acute myocardial infarction. The malignant disease group had a mean platelet NANA 24% below normal and a serum NANA 68% above normal. Both results were highly significant. Samples from patients with acute myocardial infarction showed slightly reduced platelet NANA and slightly raised serum NANA, neither change being significant. There was no correlation between platelet and serum NANA in the neoplastic group.

Blood Platelets↗
PubMed1981

Biochemical markers of bone turnover in Paget's disease.

The two most commonly used biochemical markers of bone turnover are the serum alkaline phosphatase and the urinary excretion of peptide-bound hydroxyproline, both of which are increased in Paget's disease. Serum alkaline phosphatase is assumed to be derived from osteoblasts during the process of bone formation, whereas small peptides containing hydroxyproline are excreted in the urine following the degradation of bone collagen. The alkaline phosphatase is probably the more useful measurement for diagnosis and for following response to treatment, whereas hydroxyproline, although very sensitive, presents technical difficulties in collection and measurement. Several other biochemical changes in Paget's disease indicate abnormal bone metabolism. These include increased urinary excretion of hydroxylysine and its glycosides derived from collagen, as well as the release into the circulation and subsequent urinary excretion of fragments of pro-collagen indicative of increased collagen formation. Proteins specific to bone, such as osteocalcin, are increased in serum, bone, such as osteocalcin, are increased in serum, as are various enzymes possibly derived from bone cells, including acid phosphatase and proline imino-peptidase. Treatment of Paget's disease results in a fall in urinary hydroxyproline before alkaline phosphatase. This indicates that drug treatment, whether with diphosphonates, calcitonin or mithramycin, has a primary action to inhibit bone resorption, with a subsequent adaptive reduction in bone formation rate.

Alkaline Phosphatase↗