PubMed Health⌕ Search

Biomedical subjects

M F Quinlan

Publications and source records attributed to M F Quinlan.

At least 19 recordsLinked to original sources

Diclofenac hepatitis.

We report five cases of biopsy-proven hepatitis developing between six and 20 weeks after administration of diclofenac. In one patient jaundice had previously developed following use of ibuprofen. In another the clinical, biochemical and histopathological features were those of chronic active hepatitis and treatment with corticosteroids was required. All patients recovered from their liver injury without sequelae. Resolution of symptoms occurred between three and 12 weeks following cessation of the drug, while liver function tests returned to normal between seven and 16 weeks after drug withdrawal, except in the patient with chronic active hepatitis who remained biochemically abnormal for eight months. Three of the five patients developed transient circulating autoantibodies, suggesting immune mechanisms may be important in the pathogenesis of this injury. The incidence of severe hepatic dysfunction related to the use of diclofenac appears low and is probably in the order of one case per 50-100,000 prescriptions.

Aged↗

Therapeutic intervention in a rat model of adult respiratory distress syndrome: II. Lipoxygenase pathway inhibition.

The present study was designed to investigate the role of 5-lipoxygenase (5LO) metabolites in an endotoxin (LPS)-induced model of the adult respiratory distress syndrome (ARDS) in the rat. The therapeutic value of two 5LO inhibitors and a specific LTB4 and a LTD4 receptor antagonist were examined. Rats were treated 1 hr prior to administration of aerosolized LPS. Rats were either unexposed (n = 11), or pretreated with vehicle sham (n = 63), 50 mg/kg phenidone t.i.d. (n = 7, n = 10 for assessment of mortality), 30 mg/kg SK&F 103842 b.i.d. (n = 6), 50 mg/kg SK&F 106203 t.i.d. (n = 11), or 5 mg/kg SK&F 107324 b.i.d. (n = 6) 1 hr prior to the administration of aerosolized endotoxin (LPS, 7 mg/kg) or phosphate-buffered saline (PBS, n = 22). Twenty-four hours later, blood samples were collected for hematologic evaluation and after wet lung weight was determined, broncho-alveolar lavage (BAL) was performed to measure cells counts and total protein (TP). 5LO inhibition and LTD4 receptor antagonism reduced LPS-induced mortality to zero compared to 35% in rats pretreated with vehicle sham. Pretreatment with the LTD4 receptor antagonist attenuated the LPS-induced increased in wet/dry lung weight (W/D) whereas 5LO inhibition reduced TP increases. Both 5LO inhibition and LTD4 receptor antagonism attenuated the LPS-induced BAL erythrocyte increase. The LPS-induced thrombocytopenia was attenuated by phenidone, the 5LO receptor antagonist. We conclude that the increased microvascular permeability was associated with the formation of 5LO products since 5LO inhibition lessened the severity of the LPS-induced increase in W/D and TP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Therapeutic intervention in a rat model of adult respiratory distress syndrome: III. Cyclooxygenase pathway inhibition.

Current strategies for the treatment of ARDS have been unsuccessful in reducing mortality. In the present study, we have evaluated the role of cyclooxygenase (CO) products in a rat model of ARDS by testing naproxen, indomethacin, ibuprofen, and a thromboxane A2 (TXA2) receptor antagonist (SK&F 96148). Rats were treated 1 hr prior to endotoxin (LPS) exposure and 24 hr later, survival, body weight changes, wet/dry lung weight (W/D), total protein content (TP) of the bronchoalveolar lavage (BAL) fluid, and total erythrocyte and differential leukocyte counts of the BAL fluid were measured. In addition, the following hematologic measurements were taken: hemoglobin (Hb), hematocrit (Hct), circulating erythrocyte, differential leukocyte, and platelet counts. Treatment with the TXA2 receptor antagonist reduced mortality to zero after 24 hr after LPS administration. Other compounds had no significant effect on LPS-induced mortality. Pretreatment with CO inhibitors or the TXA2 receptor antagonist attenuated the LPS-induced increase in TP and W/D. Although all compounds tended to reduce the LPS-induced increase in BAL erythrocytes, only the TXA2 receptor antagonist did so significantly. The LPS-induced increase in BAL neutrophil counts was significantly reduced by 30 mg/kg ibuprofen, but not by the other compounds. In fact, the TXA2 receptor antagonist actually exacerbated BAL neutrophil counts, but diminished the peripheral neutrophilia and lymphopenia induced by LPS. None of the CO inhibitors tested significantly affected LPS-induced hematologic responses. We conclude that by virtue of its protection against LPS-induced mortality, the TXA2 receptor antagonist was the most effective compound in this model. However, it did cause certain negative side effects such as increased pulmonary inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Therapeutic intervention in a rat model of ARDS: I. Dual inhibition of arachidonic acid metabolism.

The protective effects of altered arachidonic acid metabolism, using either methylprednisolone or a dual cyclooxygenase and 5-lipoxygenase inhibitor (SK&F 86002), were compared in a rat model of adult respiratory distress syndrome (ARDS). Rats were either unexposed (n = 9) or pretreated with vehicle (n = 25), 100 mg/kg SK&F 86002 (n = 8) or 30 mg/kg methylprednisolone (MP, n = 7) 1 h prior to the intratracheal administration of 7 mg/kg aerosolized endotoxin (LPS) or phosphate buffered saline (PBS). Twenty-four hours later, blood samples were collected and the rats were anesthetized and exsanguinated. The lungs were surgically removed, weighed and bronchoalveolar lavage (BAL) was performed. LPS caused 30-35% mortality and induced significant differences in body weight, BAL erythrocyte and neutrophil counts, lung wet/dry weight ratio (W/D), total BAL protein (TP), hemoglobin (Hb), hematocrit (HCT), and circulating leukocyte and platelet counts as compared with controls. Pretreatment with MP reduced mortality to zero and also attenuated the LPS-induced alterations in body weight, W/D, TP, BAL erythrocyte count, and circulating platelet count. However, MP exacerbated LPS-induced increases in Hb, HCT and circulating neutrophil counts while enhancing lymphopenia. Pretreatment with SK&F 86002 also reduced mortality to zero and attenuated LPS-induced alterations in W/D, TP, HCT and circulating platelet count. Like MP, SK&F 86002 exacerbated the LPS-induced lymphopenia, and increased circulating neutrophils above baseline values. We conclude that both MP and SK&F 86002 provided protection against LPS-induced responses in this model of ARDS. Mechanistically, this indicates the critical role of eicosanoid mediators in this model. Therapeutically, SK&F 86002, or a similar compound, may be beneficial in preventing the acute phase responses so harmful to ARDS patients.

Animals↗

Protein-losing enteropathy in systemic lupus erythematosus.

Two patients with systemic lupus erythematosus (SLE) presented with anasarca, pleural effusions and severe hypoalbuminema. Both were demonstrated to have protein-losing enteropathy, a rare complication of SLE. Other causes of gastrointestinal protein loss were excluded. There were marked similarities in both cases including circulating ANF with speckled staining, anti-(U1)RNP antibodies and low serum complement levels. Complete remission was achieved in both with prednisolone. Anti-(U1)RNP may be a marker for a subset of SLE in which protein-losing enteropathy is a major manifestation.

Adult↗

Liver abscess in Western Australia (1974-1983).

Over the 10 year period 1974-1983, 91 cases of liver abscess presented to the major teaching hospitals in Perth, Western Australia. Amoebic liver abscess (ALA) accounted for 37 (or 41%) of these cases, an incidence inflated by Perth's proximity to south-east Asia where amoebiasis is endemic. This frequent recent history of contact, the availability of sensitive and specific diagnostic serology and a clinical presentation usually suggesting pathology in the right upper quadrant, accounted for the consistently short delay in diagnosis of ALA. There were no deaths from ALA and a low incidence of complications such as secondary infection or rupture into the thorax. On the other hand, pyogenic liver abscess (PLA) commonly presented in a more non-specific manner and in an older age group, contributing to a long delay in diagnosis. Despite improvements in liver imaging techniques and advances in antibiotic and general supportive therapy, mortality for PLA remains high, 20% in this series. Fatal PLA was associated with multiple abscesses not amenable to drainage, increasing age, delay in diagnosis and the presence of septicaemia.

Adolescent↗

Prognostic significance of left ventricular ejection fraction after acute myocardial infarction. A bedside radionuclide study.

The prognostic significance of left ventricular ejection fraction measurements obtained at the bedside was assessed in 171 patients as soon as possible after acute myocardial infarction. Ejection fraction was measured with a radionuclide first pass portable probe method within a mean of 24 hours of the onset of major symptoms. The results were related prospectively to the subsequent incidence of ventricular fibrillation in hospital, and to hospital and postdischarge deaths in a mean follow up period of 15 (range 9-21) months. All eight episodes of primary ventricular fibrillation, all 12 deaths due to pump failure in hospital, and also 12 out of 13 postdischarge deaths occurred in that minority of 81 patients whose initial postinfarction left ventricular ejection fraction was less than 0.35. Multivariate correlation with clinical, enzymatic, and electrocardiographic indicators of myocardial infarction showed that the prognostic significance of these indicators could largely be explained by their association with low left ventricular ejection fractions. Left ventricular ejection fraction measured within the initial 24 hours after acute myocardial infarction predicts prognosis throughout the subsequent year.

Adult↗

Toxic shock syndrome -- some new features.

A thirty-year-old female presented with a high fever, conjunctivitis, confusion, vomiting, watery diarrhoea, diffuse erythroderma, shock and oliguric renal failure. Staphylococcus aureus phage 29/52 (Group 1) was isolated from a high vaginal swab. In addition to all the previously reported features which defined toxic shock syndrome, there were pustular skin vesicles, altered red cell morphology, and severe myocardial involvement. Treatment with fluid replacement, cloxacillin, haemodialysis, positive inotropic agents, and supportive measures resulted in a full recovery.

Adult↗

Gastric motility and emptying in normal and post-vagotomy subjects.

The effects of proximal gastric vagotomy (PGV) and vagotomy with pyloroplasty (V and P) on gastric motility were studied using a solid meal labelled with a radiopharmaceutical agent. In having on-line computer facilities it was possible not only to record the rate of emptying but also to analyse the relative roles of the fundus and the antrum within the overall framework of gastric emptying. In normal subjects the fundus filled and then emptied in an almost linear pattern. The antrum, however, did not completely fill until well after the meal was eaten and thereafter appeared to maintain a constant volume during the study. The redistribution of contents between fundus and antrum was reflected in the total stomach emptying curve as a delay, or lag phase before gastric emptying commenced. After both types of vagotomy fundic filling was delayed, representing a slower eating time, which was presumably due to early satiety. Antral filling and volume was disturbed only after V and P, which was also reflected by a loss of the lag phase seen on the total stomach curve. PGV retained antral function but there was significant delay in the redistribution of contents between fundus and antrum, though this did not have clinical significance. The rate of emptying was unaffected by either operation. It was concluded PGV did maintain antral function and a more normal pattern of emptying compared with V and P. After V and P the changes in antral function were considerable and these changes are probably associated with some of the complications resulting from this operation.

Adult↗

The role of bone scanning in the assessment of prostatic carcinoma.

Fifty new cases of carcinoma of the prostate were assessed prior to treatment to determine the incidence of bony metastases. The radioisotope bone scan was the most sensitive method of detecting metastases and of localising them. It was twice as accurate as the serum acid phosphatase estimation. Skeletal X-rays were the least accurate method. Forty-six per cent of patients had abnormal bone scans at presentation. The histological grade of the tumour correlated well with the bone scan. The higher the grade, the more likely was the bone scan to be abnormal. There is need for greater accuracy in detecting metastases, and the bone marrow acid phosphatase estimation, either alone or in conjunction with the bone scan, may provide this accuracy.

Acid Phosphatase↗

The initial phase of gastric emptying before and after vagotomy and pyloroplasty.

The initial phase of gastric emptying of solid food was monitored with the use of a gamma camera and on-line computer facilities. In normal subjects a consistent pattern was seen comprising an early delay in the onset of emptying ("plateau"), followed by an exponential decay curve. After vagotomy the plateau was lost, and the exponential pattern of emptying commenced once the stomach was full. There was no evidence of sudden "dumping" of contents from the stomach. The overall rates of emptying as measured by the half emptying time (T 1/2) were the same in normal and postvagotomy subjects.

Duodenal Ulcer↗

Thorotrast-induced haemangioendothelial sarcoma--a lesson from the past.

Complications following a carotid arteriogram done in 1947 with Thorotrast are described in a 47-year-old man who subsequently died from them in 1970. They included a local cervical granuloma with associated haemangioendothelial sarcoma, chromosome changes characteristic of radiation damage and widespread haemangioendothelial sarcomatous deposits in brain, lung, liver, probably arising from multicentric primary sites in the bone marrow. A survey of the use of Thorotrast as a contrast medium in Australia and New Zealand showed that its use was extremely limited. The prinicpal complications seen have been two cervical granulomas and one hepatoma.

Bone Marrow Diseases↗

Continuous monitoring of the effect of pentagastrin on gastric emptying of solid food in man.

By continuous monitoring of a solid meal labelled with a radiopharmaceutical it has been possible to determine the effects of drugs on gastric emptying and motility during a single study. Predictably hyoscine delayed, and bethanechol increased, the rate of gastric emptying. Pentagastrin initially produced marked antral activity resulting in a physiological stricture and subsequent delay in the overall rate of gastric emptying. Fundal motility was unaffected though reflux from the antrum occurred.

Gastrointestinal Motility↗