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Biomedical subjects

F Marsh

Publications and source records attributed to F Marsh.

17 recordsLinked to original sources
PubMed1992

Treatment of opioid-induced constipation with oral naloxone: a pilot study.

Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone, including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions.

Adult↗
PubMed1991

The development of exo-erythrocytic schizonts of Plasmodium berghei in vitro from gamma-irradiated and non-irradiated sporozoites: a study using confocal laser scanning microscopy.

Confocal scanning laser microscopy has been used to study the distribution of antigens expressed by the liver stages of Plasmodium berghei in cultured hepatoma cells. The 3-dimensional images obtained of intact parasites clearly show complex patterns of antigen expression not apparent when using conventional IFAT or immunoelectron microscopy. A liver-stage specific antigen (Pbl 1) was shown to be confined to the parasitophorous vacuole; the vacuole has extensive diverticulae extending into the host cell. Small parasites were detected for the first time in 'mature' cultures. These did not represent a distinct population, but the 'tail' of a broad continuum of parasite sizes. Irradiated sporozoites produce a transient population of slow-growing parasites which express a very limited range of antigens de novo in the invaded hepatoma cell. A comparison of the reactivity of normal EE parasites with anti-circumsporozoite antibody and with anti-Pbl 1 suggests that the former reagent may reliably be used to identify sporozoites invading host cells, but should not be used to determine the number of parasites that successfully undergo intrahepatic development. Anti-Pbl-1 indicates on 33% of invaded sporozoites identified by anti-CSP subsequently differentiate.

Animals↗
PubMed1991

Liver function tests in nonparenteral cocaine users.

Cocaine-induced hepatotoxicity is well known in animal models, and many cases of it have been reported in human beings. We reviewed the results of liver function tests performed on admission in 71 randomly selected hospitalized nonparenteral cocaine abusers. We found 11 patients to have elevated levels of aspartate aminotransferase that were less than 28 U above the upper limit of normal. Five of them also had elevated levels of alanine aminotransferase that were less that 12 U above the upper limit of normal. Two patients had isolated elevations in alanine aminotransferase (less than 9 U above the upper limit of normal), and two patients had elevations in alkaline phosphatase (less than 50 U above the upper limit of normal). There was not correlation with regard to age, sex, duration of drug use, last dose, amount of use, or timing of blood tests. This minimal elevation of liver enzyme levels is common, but severe hepatotoxicity is uncommon.

Adult↗
PubMed1990

Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis.

The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis. Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days. Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10. By the end of the ten day study all patients had recovered clinically and had a normal dialysate. For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0). For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6). In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition.

Aztreonam↗
PubMed1990

Endoscopic leukemic polyposis.

Gastrointestinal involvement in leukemia and lymphoma is common and may present with varying clinical manifestations (1). We report a case of gastrointestinal bleeding with endoscopic findings of diffuse leukemic polyposis and the response to radiotherapy, with a brief review of the literature.

Aged↗
PubMed1989

Disturbance of cerebral function by aluminium in haemodialysis patients without overt aluminium toxicity.

The psychomotor function of 27 long-term haemodialysis patients with apparently normal cerebral function, who had only mildly raised serum aluminium (mean 59 [SEM 9] micrograms/l), was measured by means of a computerised version of the symbol digit coding test. Compared with those of control subjects matched for age and the patients' estimated premorbid IQ, the patients' response times were significantly longer (2.51 [0.10] vs 1.88 [0.05] s). Abnormalities were also detected in five other computerised tests of psychomotor function. The mean activity of erythrocyte dihydropteridine reductase (DHPR), which is inhibited by aluminium, rose during 3 months' desferrioxamine treatment in most of the 15 patients so treated. Although there was no relation between baseline psychomotor function and either indices of cumulative aluminium exposure or erythrocyte DHPR activity, changes in DHPR induced by desferrioxamine correlated with changes in psychomotor performance (r = 0.62). The flash-stimulated visual evoked potential (measured in 10 patients) was delayed (133.4 [2.4] ms), although the pattern-stimulated visual evoked potential remained normal (101.8 [3.2] ms). The difference between the visual evoked potentials stimulated by flash and pattern was significantly greater in the patients than in the controls (31.6 [4.3] vs 19.4 [2.4] ms) and was significantly related to the symbol digit coding response times and to the oral aluminium intake. The results suggest that much more rigorous exclusion of aluminium from the dialysate and diet of dialysis patients is necessary.

Adult↗
PubMed1989

High-dose calcium carbonate with stepwise reduction in dialysate calcium concentration: effective phosphate control and aluminium avoidance in haemodialysis patients.

To reduce potentially toxic aluminium exposure, the phosphate binding agent aluminium hydroxide was replaced by high-dose oral calcium carbonate in 15 haemodialysis patients. Stepwise reduction in dialysate calcium concentration (from 1.75 to 1.35 mmol/l and then to 1.05 mmol/l) was made when necessitated by hypercalcaemia. After 6 months, the mean daily dose of calcium carbonate was 62 mmol (range 25-150 mmol). This dose maintained good control of plasma phosphate (baseline, 1.34 +/- 0.32 mmol/l (mean +/- SD); 12 weeks, 1.30 +/- 0.22 mmol/l; 24 weeks, 1.51 +/- 0.31 mmol/l). Calcium x phosphate product did not rise significantly (baseline, 3.41; 12 weeks, 3.44; 24 weeks, 4.02). Apart from a transient early increase, ionised calcium did not change significantly (baseline, 1.23 +/- 0.10 mmol/l; 12 weeks, 1.24 +/- 0.10 mmol/l). Intact (1-84) parathyroid hormone concentration decreased from 241 pg/ml to 116 pg/ml (median values, P less than 0.05) after 12 weeks. This simple and well-tolerated regimen almost completely eliminated oral aluminium exposure, effectively controlled plasma phosphate and calcium concentrations, and reduced hyperparathyroidism.

Administration, Oral↗
PubMed1989

Acute pancreatitis in sickle cell crisis.

A case of acute pancreatitis, complicated by pseudocyst formation, is described in a patient with sickle cell crisis. The differential diagnosis is discussed and the literature reviewed.

Acute Disease↗
PubMed1988

Aluminium chelation therapy in dialysis patients: evidence for inhibition of haemoglobin synthesis by low levels of aluminium.

To investigate the possibility that aluminium may exacerbate anaemia in dialysis patients with only modest aluminium accumulation, 15 patients whose exposure to aluminium had been low were treated for three months with the aluminium chelating agent desferrioxamine, 30 mg/kg intravenously at the end of each dialysis session. Serum aluminium concentrations before treatment were 5-125 micrograms/ml. After one month of desferrioxamine, serum aluminium (including the chelate) had risen from 54.6 (SEM 11.2) to 167.0 (27.5) micrograms/l; and after three months haemoglobin had risen from 8.46 (0.70) to 10.43 (0.80) g/l. Mean cell volume and mean cell haemoglobin concentration also increased significantly. The maximum rise in haemoglobin correlated with the patients' aluminium burden as estimated by the mean serum aluminium concentration after one month of desferrioxamine therapy (r = 0.85). The greatest response to desferrioxamine occurred in patients with a baseline serum aluminium of 15-75 micrograms/l (mean increase in haemoglobin 38%). The results indicate that even the modest aluminium accumulation found in most dialysis patients has a pronounced inhibitory effect on haemoglobin synthesis. The possible toxic effect of aluminium should be considered in all anaemic dialysis patients.

Adult↗
PubMed1987

Outcome in patients on continuous ambulatory peritoneal dialysis and haemodialysis: 4-year analysis of a prospective multicentre study.

In a study in seven large renal units in England, the morbidity and mortality of all patients starting continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis during 1983-85 were monitored prospectively over a 4-year period and related to reasons for choice of therapy and potential risk factors. 610 new patients (median age 52 years, range 3-80 years) started CAPD; 16% had diabetes mellitus and 21% cerebrovascular or cardiovascular disease. 329 patients (median age 48 years, range 5-77 years) started haemodialysis; 7% had diabetes mellitus and 17% cerebrovascular or cardiovascular disease. The Kaplan-Meier patient survival estimates at 4 years were 74% for haemodialysis and 62% for CAPD; technique survival figures for the same period were 91% for haemodialysis and 61% for CAPD. Cox's proportional hazards regression analysis showed that cerebrovascular/cardiovascular disease, age over 60 years, and diabetes mellitus were important predictors for survival in CAPD patients; there were no risk factors associated with permanent change to haemodialysis. In the haemodialysis group early change to CAPD was associated with presence of cerebrovascular or cardiovascular disease. The major cause of drop-out in both groups was transplantation. The mean length of hospital admission was 14.8 days per patient-year for CAPD and 12.4 days per patient-year for haemodialysis.

Adolescent↗
PubMed1987

Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis.

Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.

Adult↗
PubMed1987

Silicone-induced hypercalcaemia in haemodialysis patients.

Silicone spallation from the roller-pump insert in dialysis blood lines leads to the accumulation of silicone in haemodialysis patients, which in turn leads to a foreign-body reaction with granuloma formation. We have studied two patients in whom documented silicone accumulation has been associated with both granuloma formation and significant, persistent hypercalcaemia. In both patients plasma levels of immunoreactive parathyroid hormone and 1,25-dihydroxyvitamin D were low or undetectable. In one patient, hypercalcaemia responded only partially to corticosteroids, but completely to naproxen. Both patients were changed to silicone-free blood lines and their hypercalcaemia subsequently resolved. The results indicate that in some haemodialysis patients, silicone accumulation and granuloma formation may lead to hypercalcaemia that is independent of 1,25-dihydroxyvitamin D, and that may instead reflect altered prostaglandin metabolism.

Adult↗
PubMed1987

Multi-centre study on outcome of treatment in patients on continuous ambulatory peritoneal dialysis and haemodialysis.

In a multi-centre study by seven large renal units in the United Kingdom, the morbidity and mortality of all patients starting CAPD and haemodialysis during a 2-year period (1983-1984) has been monitored prospectively and related to reasons for choice of therapy and potential risk factors. Over this period 338 new patients (mean age 48; range 3-77 years) started CAPD; 17% had diabetes mellitus and 25% had cerebro/cardiovascular disease. One hundred and seventy-five patients (mean age 45; range 5-73 years) started haemodialysis; 6% had diabetes mellitus and 14% had cerebro/cardiovascular disease. The Kaplan-Meier actuarial patient survival estimates at 2 years were haemodialysis 84% and CAPD 83%, whilst technique survival figures for the same period were haemodialysis 92% and CAPD 80%. Cox's regression analysis showed that cerebro/cardiovascular disease and age greater than 60 years were most important predictors for survival in CAPD patients, in whom smoking appeared to be a significant risk factor, for permanent change of therapy to haemodialysis. The major cause of 'drop out' in both groups was transplantation, whilst hospitalisation was 14.9 days per patient year for CAPD and 12.8 for haemodialysis patients. Within the CAPD group a temporary change to haemodialysis (less than 2 months) occurred on 106 occasions (each of mean of 19 days duration), amounting to 10 days per patient year of therapy. CAPD was used twice as often as haemodialysis for managing new patients. After 2 years hospitalisation technique and patient survival were comparable in the two groups, with cerebro/cardiovascular disease, age, and smoking being significant predictors of outcome.

Adolescent↗
PubMedDate not supplied

Neurofibrillary neuronal degeneration in dialysis dementia: a feature of aluminum toxicity.

Neurofibrillary material was found in cortical neurons in two patients who died with dialysis encephalopathy. The cytoplasm of these neurons contained large amounts of aluminum and whole-brain and blood aluminum levels were high. These findings suggest that in dialysis encephalopathy aluminum has a specific effect on neuronal protein synthesis, resulting in the accumulation of neurofilaments in cortical neurons. This neurofibrillary neuronal degeneration resembles that found in experimental aluminum toxicity, but differs in several respects from the neurofibrillary tangles characteristic of Alzheimer's disease.

Adult↗