Tamoxifen and risk of endometrial cancer.
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Antineoplastic Agents, Hormonal↗
Biomedical subjects
F Marsh
Publications and source records attributed to F Marsh.
Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: retrospective study of the Camelford water incident.
OBJECTIVE: To establish whether people exposed to drinking water contaminated with 20 tonnes of aluminium sulphate in the Camelford area of Cornwall in the south west of England in July 1988 had suffered organic brain damage as opposed to psychological trauma only. DESIGN: Retrospective study of affected people. PARTICIPANTS: 55 affected people and 15 siblings nearest in age to one of the group but who had not been exposed to the contaminated water were studied. MAIN OUTCOME MEASURES: Various clinical and psychological tests to determine medical condition and anxiety levels in affected people. Assessment of premorbid IQ (pFSIQ) with the national adult reading test, a computerised battery of psychomotor testing, and measurement of the difference in latencies between the flash and pattern visual evoked potentials in all participants. RESULTS: The mean (SE) pFSIQ was above average at 114.4 (1.1). The most sensitive of the psychomotor tests for organic brain disease was the symbol digit coding (SDC) test (normal score 100, abnormal <85). PARTICIPANTS performed less well on this test (54.5 (6.0)) than expected from their pFSIQ (P<0.0001) and a little less poorly on the averaged less discriminating tests within the battery (86.1 (2.5), P<0.0001). In a comparison with the 15 sibling pairs (affected people's age 41.0 (3.3) years v sibling age of 42.7 (3.1) years (P=0.36) the exposed people had similar pFSIQ (114.7 (2.1)) to their siblings (116.3 (2.1), (P=0.59) but performed badly on the symbol digit coding test (51.8 (16.6)) v (87.5 (4.9) for siblings, P=0.03). The flash-pattern differences in exposed people were greater than in 42 unrelated control subjects of similar age (27.33 (1.64) ms v 18. 57 (1.47) ms, P=0.0002). The 15 unexposed siblings had significantly better flash-pattern differences than their affected siblings (13.4 (2.4) ms v 29.6 (2.9) ms, P=0.0002). No effect of anxiety could be shown on these measurements from the analysis of the anxiety scores of exposed people. CONCLUSION: People who were exposed to the contaminated water at Camelford suffered considerable damage to cerebral function, which was not related to anxiety. Follow up studies would be required to determine the longer term prognosis for affected individuals.
Adolescent↗
Elevation of carcinoembryonic antigen and CA-125 in a patient with multivisceral tuberculosis.
A case of a middle-aged African-American woman with weight loss, ascites, a bilateral pleural effusion with no infiltrate, and a clinical diagnosis of a metastatic gynecological tumor is presented. Her carcinoembryonic antigen (CEA) and CA-125 levels were elevated (400 micrograms/L and 331 micrograms/L, respectively). She underwent an exploratory laparotomy and a dilation & curettage for biopsies and cultures. Pathological examination showed Langhans' type giant cells on peritoneal biopsy. An endometrial curette biopsy showed granulomatous endometritis and acid-fast bacilli. Cultures grew Mycobacterium tuberculosis. The patient presented with a fibroid tumor that could have contributed to her elevated CA-125 level, but after antituberculous treatment was started and tumor markers were repeated after 1 year, the CEA level decreased to 1.2 micrograms/L and CA-125 to 9 micrograms/L without surgical resection of the tumor. A review of the literature revealed only three cases in which patients had elevated CA-125 in multivisceral tuberculosis. No cases were reported in which both CEA and CA-125 levels were elevated in multivisceral tuberculosis. Possible causes of elevated CEA and CA-125 levels are discussed.
Antitubercular Agents↗
Chronic hepatitis C in patients with sickle cell disease.
OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) antibody in patients with sickle cell disease and to analyze the nature of chronic liver disease in these patients. METHODS: A total of 99 patients attending a comprehensive sickle cell and thalassemia program at the Interfaith Medical Center, Brooklyn, NY, participated in the study. Eighty-five patients had sickle cell anemia (ss), eight had sickle C disease (sc), and six had sickle B thalassemia. History of blood transfusion, i.v. drug use, homosexuality, and alcohol abuse was obtained with a questionnaire and chart review. All patients were screened for HCV antibody by a first generation enzyme-linked immunosorbent assay. All positive results were confirmed with radioimmunoblot assay II (RIBA II). Patients were also checked for the presence of hepatitis B surface antigen. ALT levels were measured, and percutaneous liver biopsies were performed in patients positive for HCV antibody and greater than 1.5 times the normal ALT levels. RESULTS: Antibody to HCV was detected in 10/99 patients (10.10%). Seven of 30 patients (23.33%) who received more than 10 U of packed red blood cells were positive for HCV antibody. Only 3/38 (7.9%) patients with less than 10 U of packed red blood cells in the past were positive for HCV antibody. None of the patients who never received blood transfusion were positive for HCV antibody (0/31 or 0%). A total of seven liver biopsies were performed in patients positive for HCV antibody. Two out of seven specimens (28.57%) showed significant liver damage. One revealed cirrhosis, and the other showed chronic active hepatitis. The remainder of liver biopsies (5/7; 71.42%) showed only mild portal inflammation. CONCLUSIONS: The prevalence of HCV antibody is directly related to the number of blood transfusions in patients with sickle cell disease. Chronic HCV infection could be a major cause of cirrhosis of the liver in these patients.
Adolescent↗
The significance and work-up of minor gastrointestinal bleeding in hospitalized nursing home patients.
Twenty-seven consecutive admissions from nursing homes who underwent a gastrointestinal (GI) consult for coffee ground vomitus or occult GI bleeding to evaluate the outcome were reviewed retrospectively to determine whether a GI work-up was or would have been useful. There were 15 deaths, all associated with severe infection or respiratory failure. Endoscopy, barium studies, and a history of nonsteroidal anti-inflammatory drug use or peptic ulcer disease did not affect the management or outcome. No patient developed major GI bleeding. When nursing home patients present with coffee ground vomitus or newly found occult blood in the stool, efforts should be made to identify and vigorously treat any acute underlying infection or respiratory failure. Endoscopy is not helpful in this clinical situation. Both the primary care physician and the GI consultant should be aware of these associations and should focus on the underlying etiology.
Aged↗
Autonomic nerve dysfunction in COPD as assessed by the acetylcholine sweat-spot test.
Patients with hypoxic chronic obstructive pulmonary disease (COPD) have evidence of a subclinical parasympathetic autonomic neuropathy, with apparent preservation of sympathetic function. However, these cardiovascular-respiratory tests might have been biased by concomitant chest disease, the acetylcholine sweat-spot test avoids this bias. This sweat-spot test assesses sympathetic nerve function, it relies upon the fact that denervated sweat glands do not produce sweat. 35 patients with hypoxaemic COPD and seven age matched normal subjects were studied. Following intradermal injection of 0.1 of 1% acetylcholine into the dorsum of the feet, the number of sweatglands able to respond in a given surface area was recorded. Cardiovascular autonomic nerve function, arterial oxygen and carbon dioxide tensions, lung function and cigarette consumption were also recorded. The acetylcholine sweat-spot test was highly repeatable in eight COPD patients, no person with normal or frankly abnormal function being wrongly assigned. The age matched control subjects had normal acetylcholine sweat-spot scores and cardiovascular autonomic tests. The acetylcholine sweat-spot test was abnormal in 24 patients, borderline in 8 and normal in 3 patients. The abnormal sweat-spot test group had significant worse FEV1, arterial blood gases and autonomic function. The acetylcholine sweat-spot score correlated with the severity of arterial hypoxaemia (r = 0.78, p < 0.001) and with the parasympathetic cardiovascular tests (r = 0.80, p < 0.001). In conclusion, patients with hypoxaemic COPD have a parasympathetic cardiovascular and a peripheral sympathetic autonomic neuropathy. The acetylcholine sweat-spot test is repeatable, easy to perform and a sensitive indicator for autonomic dysfunction in breathless individuals with COPD.
Acetylcholine↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Pregnancy and the liver.
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Cholestasis, Intrahepatic↗
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↗