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Biomedical subjects

J R Curtis

Publications and source records attributed to J R Curtis.

At least 109 records · Page 6Linked to original sources
PubMed1985

Clastogenic agents in the urine of coffee drinkers and cigarette smokers.

Organic material from the urine of smokers, coffee drinkers, and controls was extracted and separated into 3 fractions of differing hydrophobicity using preparative reversed-phase high-pressure liquid chromatography. Fractions were assayed for clastogenic activity using Chinese hamster ovary cells. Smoking, coffee drinking, or both habits together resulted in a substantial increase in the genotoxicity of organic material in all 3 fractions. The clastogenicity of fractions 1 and 2 (the two most hydrophilic) was abolished by the addition of either catalase or superoxide dismutase to the Chinese hamster ovary cell system, suggesting the involvement of active oxygen species in the clastogenic response. Clastogenicity of fraction 3, however, was resistant to the action of catalase and superoxide dismutase. Fractions were tested for their ability to generate hydrogen peroxide in vitro during a 10-min incubation at elevated pH. Fractions 2 and 3, but not fraction 1 from smokers, coffee drinkers, or those with both habits generated significantly more hydrogen peroxide at high pH than did the corresponding fractions from control subjects. For fractions 2 and 3 but not 1, the ability of a sample to generate hydrogen peroxide at high pH was positively correlated with its ability to generate chromosome aberrations at neutral pH in tissue culture. The data indicate that both coffee drinking and cigarette smoking result in the appearance of clastogenic materials in urine, and suggest that such clastogenic agents may produce chromosome aberrations via the production of active oxygen species.

Animals↗
PubMed1984

The significance of fibrinogen derivatives in plasma in human renal failure.

The concentrations in plasma of fibrinogen derivatives fibrinopeptide A (FPA), beta 15-42 antigen and fragment E (FgE) antigen have been determined in patients with renal failure and compared to the concentrations of the platelet release products, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4). In 'partial renal failure' (51Cr-EDTA clearance rate 4-60 ml/min) FPA, beta 15-42 antigen, FgE antigen and beta TG levels were significantly raised above a normal laboratory control group. These levels were further raised in a group of patients whose disease required regular maintenance haemodialysis (51Cr-EDTA clearance rate less than 4 ml/min). PF4 levels were not significantly raised in either group. A statistical analysis of all patient results revealed that FPA, beta 15-42 antigen and FgE antigen levels all correlated with beta TG levels but not with PF4 levels. It is known that beta TG is catabolized by the kidney but PF4 is not and that elevated beta TG levels in renal failure are caused by impaired elimination rather than increased production. These results suggest that the plasma levels of these three fibrinogen derivatives are elevated in renal disease at least in part by decreased elimination rather than by increased thrombin and plasmin activities alone.

Adolescent↗
PubMed1984

Urinary iron loss in the nephrotic syndrome--an unusual cause of iron deficiency with a note on urinary copper losses.

Two patients with long-standing nephrotic syndrome are described in whom urinary iron losses may have contributed towards an iron deficiency state. Seven other nephrotic patients were also studied. Increased urinary iron excretion was found in six out of nine patients and increased urinary copper excretion in all eight patients in whom it was measured. Trace metal losses in the urine in nephrotics may be important clinically.

Adult↗
PubMed1984

Objective assessment of heparin requirements for hemodialysis in humans.

The abilities of four heparin regimens to inhibit activation of blood coagulation, fibrinolysis, and the platelet release reaction in humans during renal dialysis have been assessed by visible examination of the extracorporeal circulation and by use of radioimmunoassays to FPA, beta 15-42 antigen, beta gamma G, and PF4. A subcutaneous injection of 5000 IU of heparin administered 1 hour before dialysis in two patients was either unable to sustain dialysis because of excess fibrin formation or allowed elevated plasma FPA and beta gamma G concentrations during dialysis. Injection of 10,000 IU heparin s.c. in five patients could sustain dialysis in only three patients for 5 hours, and allowed progressively increasing concentrations of FPA, beta gamma G, and PF4, as well as fibrin formation, in the extracorporeal circulation. A lower dose of heparin administered intravenously (2500 IU bolus plus 1000 IU/hr) to six patients was also unable to prevent elevations in FPA and beta gamma G 4 hours and 5 hours after the initiation of dialysis. Intravenous administration of heparin at a dose of 5000 IU bolus plus 1500 IU/hr completely suppressed generation of FPA during 5-hour dialysis and was free of visible fibrin formation in the extracorporeal circulation in 13 patients. The concentration of the fibrinolytic system marker beta 15-42 antigen did not change significantly in any of the regimens, and the concentration of PF4 altered in response to infused heparin as well as to inadequate heparinization. We conclude that complete inhibition of activation of coagulation and suppression of the platelet release reaction occurs when high plasma heparin levels (greater than or equal to 0.5 IU/ml) are maintained during dialysis: lower heparin levels may be compatible with dialysis in some patients, but they allow generation of fibrin and the platelet release reaction, which pose a potential risk to the dialysis procedure and to the patient.

Aged↗
PubMed1984

Rhabdomyolysis and acute renal failure in chronic alcoholics with myopathy, unrelated to acute alcohol ingestion.

Rhabdomyolysis leading to acute renal failure necessitating hemodialysis is described in three chronic alcoholics. In each case an acute medical or surgical event, but not alcoholic intoxication, was implicated. Renal biopsies demonstrated acute tubular necrosis with intraluminal deposits consisting of Tamm-Horsfall protein and myoglobin. After recovery all three patients were demonstrated to have proximal muscle weakness with similar electromyographic abnormalities but nerve-conduction was impaired in only two. Muscle biopsies showed mixed, but predominantly type II fiber atrophy and reduced muscle phosphorylase levels. In the one patient tested the lactate response to forearm muscle ischemia was abnormal. It is postulated that chronic alcoholics may be predisposed to rhabdomyolysis and acute renal failure following acute medical and surgical stress as well as acute alcohol abuse. The muscle damage in these patients may be due to impaired intra cellular glycogen metabolism.

Acute Kidney Injury↗
PubMed1983

Plasma ranitidine concentrations after intravenous administration in normal volunteers and haemodialysis patients.

A comparison was made of the plasma concentrations of ranitidine base in 12 normal volunteers after the administration of 100 mg intravenously and in 6 patients with terminal renal failure after 40 mg intravenously off and then during haemodialysis. The plasma ranitidine concentrations were determined by radioimmunoassay. The results suggest that reduced elimination of the drug occurs in patients with severe renal failure and that there is significant removal of the drug during haemodialysis. It is suggested that dosage reduction is advisable in patients with severe renal failure and a suitable schedule for such patients is described.

Furans↗
PubMed1983

Heparin inactivation, acidosis and copper poisoning due to presumed acid contamination of water in a hemodialysis unit.

An accident in a hemodialysis unit involving 13 patients is reported. Circumstantial evidence suggests that acid contamination of the water supply to the unit resulted in inactivation of heparin with widespread extracorporeal clotting and secondary copper intoxication which proved fatal in one patient. Serum copper concentrations were raised in 6 of the 11 patients and whole blood copper concentrations were raised in 4 patients. Results of serum ceruloplasmin, whole blood lead and zinc analyses are reported together with tissue analyses for copper in the fatal case. The majority of the patients showed evidence of a metabolic acidosis.

Acidosis↗
PubMed1983

Chronic liver disease in haemodialysis patients.

Elevated serum alanine aminotransferase (ALT) for more than one year was found in 36 (28.8%) of 125 patients on maintenance haemodialysis. In 10 the ALT returned to normal spontaneously but in 26 it remained high. Liver tissue from 21 patients with high ALT and seven with normal ALT was examined. Statistically significant correlations were found between the mean ALT during the year prior to the biopsy and assessments of the lymphocytic infiltration (p less than 0.001), fibrosis (p less than 0.001) and amount of silicone particles in the liver (p less than 0.001). Epithelioid cell granulomata, lobular and portal macrophages and perivenular fibrosis were related to silicone particles. Lymphocytes were not spacially related to the particles; nevertheless, there was a significant correlation between amounts of silicone and lymphocytic infiltration (p less than 0.01). No associations were found between high ALT, hepatitis B serology, serum ferritin, parenchymal siderosis, propensity to fluid overload, alcohol abuse and HLA-B8.

Adult↗
PubMed1982

Application of the micronucleus test to exfoliated cells of high cancer risk groups: tobacco chewers.

Powdered tobacco (Khaini tobacco) with the addition of lime is commonly used by the residents of Bihar, India. The tobacco/lime mixture is usually placed on the inner side of the lower lip within the gingivolabial groove. About 42% of the users keep it at the front, the rest move the tobacco towards the left or right side within the oral cavity. Carcinomas (so-called "Khaini cancers") develop mainly at the site where the tobacco is in close contact with the mucosa. Scrapings of the mucosa were taken at sites where the tobacco is kept, then smears were prepared, stained with the Feulgen reaction and fast green, and screened for micronuclei which indicate the occurrence of chromosome aberrations in the dividing cell population of the basal layer. An elevated frequency of cells with micronuclei was found in the oral mucosa of all 27 examined Khaini tobacco users (Munda and Santal tribes) compared to that of non-chewers of similar ethnic background and dietary habits. The induction of micronucleated mucosa cells seems to be due to genotoxic agents released from the tobacco/lime mixture. In vitro, an aqueous extract of the Khaini tobacco elicits chromosome aberrations and micronuclei in cultured human fibroblasts and Chinese hamster ovary (CHO) cells. No chromosome-damaging effect was observed following the application of lime or calcium hydroxide (Ca(OH)2). The micronucleus test on exfoliated cells can provide evidence of carcinogen exposure in the tissue from which cancers will develop. This approach combines all the advantages of in vitro short-term tests for genotoxic and carcinogenic agents with those of using an intact organism with all its defence mechanisms.

Adolescent↗
PubMed1982

Acute haemolysis due to concentrated dialysis fluid.

Fatal acute haemolysis occurred in a 65-year-old man undergoing regular home haemodialysis for terminal renal failure. Circumstantial evidence indicating that the haemolysis resulted from exposure to concentrated dialysis solution was supported by in-vitro studies. Frank haemolysis in blood samples occurred at a dilution of greater than or equal to 1/2 of dialysis fluid. Osmotic fragility tests of surviving red blood cells showed 47% haemolysis at a dilution of 1/2 and greater than 90% haemolysis at a dilution of 1/1. Urgent design modifications to the proportionating machine are being undertaken to prevent such an accident recurring.

Aged↗
PubMed1982

The role of 7, 12 DMBA and three hormones in 7, 12 DMBA-induced rat mammary cancer: three hypotheses.

The investigation of the role of hormones in the development of hormone-dependent cancers is an interesting and important area of cancer research. A popular mode of examining this area is through experiments with rat or mouse mammary cancer induced by the potent carcinogen, 7, 12 dimethyl (alpha) benzanthracene (7, 12 DMBA). This paper looks at the action of three specific hormones--estrogen, progesterone and prolactin--in the 7, 12 DMBA-induced mammary cancers. Three hypothesis for their action are examined: 1) the hormone as a carcinogen, 2) the hormone as a regulator or neoplasia, and 3) the hormone as both an initiator and a regulator of neoplasia. Although the third hypothesis is probably the least popular among researchers, it will be suggested that it is the most comprehensive and the most complete in that it accounts for evidence giving rise to the first two hypotheses by incorporating both of them. The base of this third hypothesis as presented here is the structural homologies between steric hormones and 7, 12 DMBA. It is suggested that these homologies allow 7, 12 DMBA to interfere with normal hormonal action, and that this interference results in the development of these rat mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

The role of parathyroidectomy in the management of hyperparathyroidism in patients on maintenance haemodialysis and after renal transplantation.

Between March 1964 and March 1980, 36 (34 dialysis, 2 transplant) of 327 patients accepted for the maintenance dialysis/transplantation programme at Charing Cross Hospital were submitted to parathyroidectomy. There were four main indications: persistent hypercalcaemia, progressive phalangeal erosions, aseptic necrosis of the femoral head and height loss with abnormal bone biopsy despite normal hand radiographs. At parathyroidectomy, 4 glands were removed in 1 patient, 3 1/2 glands in 24, 3 glands in 7, 2 glands in 3 and a single large gland in 1 patient. The operation was followed by improvement in 28 patients, no change in 5, and progression of hyperparathyroidism in 3.2 of the 28 patients who improved later relapsed and were treated with 1,25-(OH)2 vitamin D3. 4 patients were submitted to a further parathyroidectomy and improved considerably. We would conclude that, although parathyroidectomy is an effective and safe procedure, it is to be hoped that careful monitoring of bone state and early administration of 1,25-(OH)2 vitamin D3 may reduce the need for parathyroidectomy.

Adult↗
PubMed1981

Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis.

Fifty-seven patients who had been receiving maintenance haemodialysis for a mean of 4.6 years were given 0.25-0.5 microgram oral 1,25-dihydroxy (1,25-(OH)2) vitamin D3 or a placebo in a double-blind manner for one to two years. In patients with normal radiographs (mean plasma parathyroid hormone concentration 205 microliterEq/ml) 1,25-(OH)2 vitamin D3 prevented the development of the radiological appearances of hyperparathyroidism. In patients with abnormal radiographs (mean plasma parathyroid concentration 709 microliterEq/ml) 1,25-(OH)2 vitamin D3 arrested or reversed the radiological changes of hyperparathyroidism. Nevertheless, the response was slow and the concentration of the hormone remained considerably raised (mean 445 microliterEq/ml). It is concluded from these results that giving 1,25-(OH)2 vitamin D3 to patients receiving maintenance haemodialysis who have normal hand radiographs or minimal erosions is beneficial. In patients with more advanced hyperparathyroidism parathyroidectomy should be considered unless there is a rapid response.

Adult↗
PubMed1981

Disseminated infection with mycobacterium chelonei in a haemodialysis patient.

M. chelonei ssp. chelonei was isolated over a period of 5 months from abscesses on various sites of hands and feet of a patient on maintenance dialysis. The organism was resistant in vitro to a greater number of antimicrobials and treatment in turn with gentamicin, vancomycin, erythromycin, doxycycline and co-trimoxazole had to be supplemented by surgical drainage of abscesses. Examination of the dialysis circuit revealed repeatedly the presence of M. chelonei and M. fortuitum in the water softener resin and other sites. The significance of this finding is discussed.

Abscess↗