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Biomedical subjects

J Fleming

Publications and source records attributed to J Fleming.

At least 91 records · Page 5Linked to original sources

Serial pulmonary function tests in the diagnosis of P. carinii pneumonia.

The predictive value of serial versus isolated measurements of transfer factor for carbon monoxide (TLCO) in the diagnosis of pneumocystis carinii pneumonia (PCP) in a cohort of 474 HIV-1 seropositive patients, with all stages of HIV disease, was evaluated. Two groups of patients were studied, one group with serial lung function measurements (Group 1) and another with only a single set of measurements (Group 2). During the study period 118 patients performing serial tests developed a respiratory illness of which 58 were performing monthly and 60 three monthly measurements of lung function (Group 1). In 36 patients from Group 1, where PCP was diagnosed, monthly lung function tests showed a decrease in TLCO from 68% (+/- 3.2) (SEM), (8 weeks prior to illness), to 44% (+/- 2.5) predicted normal at presentation, whereas in 22 patients who did not have PCP, TLCO fell from 71% (+/- 4.5) to 57% (+/- 3.1). TLCO was thus reduced to lower values in these with PCP than in those without PCP (p < 0.05). A fall of TLCO of 5% from initial values when used as predictive for presence of PCP had a sensitivity of 75% and a specificty of 28% (positive predictive value 56%; negative predictive value 48%). TLCO was < 70% predicted in 72/78 patients with PCP who performed only single lung function tests (Group 2), which gave a sensitivity of 92% and a specificity of 71% as a diagnostic test for PCP when compared with the cohort as a whole. The positive predictive value was 34%, negative predictive value was 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Biodistribution of Lipiodol following hepatic arterial injection.

Thirteen patients undergoing selective coeliac angiography before insertion of an indwelling hepatic arterial cannula underwent injection of 3 ml radiolabelled Lipiodol (2 MBq 131I) into the hepatic artery at the end of the procedure. At subsequent laparotomy 1-9 days later, biopsies were taken from normal liver and metastases. The radioactivity of this material was measured to establish the tumour:liver ratios. Two patients with large metastases (> 10 cm in diameter) had low ratios. In the remainder, the median ratio at 24 h was 1.5:1 (range 1.1-2.5:1; n = 5) and 2.6:1 (range 1.5-64.0:1; n = 6) at 3-9 days. Four patients underwent single photon emission computed tomography, which confirmed selective retention of Lipiodol in small metastases, although no activity was detected in a large deposit (> 15 cm) 10 days after injection. The tumour:liver ratio in the other three patients increased from 3.0-5.6:1 on day 1 to 4.5-7.2:1 on day 6. This study suggests that Lipiodol may be a useful therapeutic delivery agent to small colorectal liver metastases.

Humans↗

Cerebrospinal fluid antibodies to coronavirus in patients with Parkinson's disease.

The etiology of Parkinson's disease remains unknown, and a search for environmental agents continues. In 1985, Fishman induced infection of the basal ganglia by a coronavirus in mice. Although coronavirus is recognized primarily as a respiratory pathogen in humans, its affinity for the basal ganglia led us to investigate its possible role in human Parkinson's disease. The cerebrospinal fluid of normal controls (CTL) (n = 18), and patients with Parkinson's disease (PD (n = 20) and other neurological disease (OND) (n = 29) was analyzed in a blinded manner by enzyme-linked immunosorbent assay [measurements in optical density (OD) units] for antibody response to four coronavirus antigens: mouse hepatitis virus JHM (J) and A59 (A), and human coronavirus 229E (E) and OC43 (O). When compared with CTL, PD patients had an elevated (p less than 0.05) mean OD response to J (0.0856 vs. 0.0207) and A (0.1722 vs. 0.0636). Response (p greater than 0.05) to O (0.0839 vs. 0.0071) was greater than that to E (0.1261 vs. 0.0743). When compared to OND, PD patients had an elevated mean OD response to J (0.0856 vs. 0.0267, p less than 0.05). Responses (p greater than 0.05) to A (0.1722 vs. 0.0929) and O (0.0839 vs. 0.0446) were greater than that to E (0.1261 vs. 0.0946). These results suggest that there may be an association between coronavirus and PD.

Antibodies, Viral↗

Sulphasalazine therapy in rheumatoid arthritis: qualitative changes in lymphocytes and correlation with clinical response.

Clinical and immunological parameters in 14 patients with rheumatoid arthritis (RA) receiving sulphasalazine (SASP) were evaluated, to determine whether their clinical response was reflected by any quantitative changes in their peripheral blood lymphocytes after 12 weeks. Whilst disease activity markers fell significantly, no such changes were noted in the percentage or absolute numbers of lymphocytes or their subsets. The lymphocytes of a further 21 patients before and after receiving SASP for 12 weeks were then studied qualitatively. The suppression mediated by in vitro SASP on ex vivo PHA stimulated lymphocytes showed a decrease at 12 weeks. This change was more marked and reached statistical significance only in those patients who showed a good clinical response. It is postulated that this may in some way be related to expression of activation markers and concomitant SASP binding.

Arthritis, Rheumatoid↗

Bronchopulmonary Kaposi's sarcoma in patients with AIDS.

BACKGROUND: Kaposi's sarcoma is the most common secondary neoplasm to complicate HIV infection and may cause pulmonary disease. METHODS: A prospective study was carried out in 140 consecutive patients who were HIV seropositive and required bronchoscopy for new respiratory symptoms of at least two weeks' duration, with either a chest radiographic abnormality or abnormality of pulmonary function. The patients were classified into those with single local endobronchial lesions of Kaposi's sarcoma or generalised widespread lesions. Before bronchoscopy all patients had routine simple pulmonary function tests and chest radiography. RESULTS: Thirty nine (21%) patients had evidence of cutaneous Kaposi's sarcoma. Nineteen of the 39 were found to have endobronchial Kaposi's sarcoma lesions at bronchoscopy, but none of those who did not have cutaneous Kaposi's sarcoma. Respiratory symptoms of cough and breathlessness and radiographic abnormalities were attributed to Kaposi's sarcoma in this group, except in four patients who had concomitant pneumocystis pneumonia. Eight patients had local endobronchial Kaposi's sarcoma lesions and 11 had extensive lesions. Patients with extensive lesions had more widespread radiographic abnormalities; four of the patients with local endobronchial lesions had normal chest radiographs. All patients had reduced transfer factor for carbon monoxide and transfer coefficient, whereas patients with extensive endobronchial lesions also had reductions in forced expiratory volume in one second and forced vital capacity. Median survival (with palliative chemotherapy with vincristine and bleomycin) was only seven months. In three patients who needed further diagnostic bronchoscopy endobronchial lesions had regressed while they were having chemotherapy. CONCLUSIONS: This study suggests that endobronchial Kaposi's sarcoma is a relatively common finding in patients with AIDS and is particularly common in patients with cutaneous Kaposi's sarcoma who present with respiratory illness. Endobronchial Kaposi's sarcoma causes respiratory disease and abnormalities of pulmonary function. Pulmonary Kaposi's sarcoma should be considered as a possible cause for respiratory illness in any patient with cutaneous Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo.

Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into the coronary vasculature of anesthetized dogs and of isolated perfused rabbit hearts to assess the role of this channel in the maintenance of basal coronary resistance. Infusion of glibenclamide at a concentration of 55-80 microM in the dogs resulted in a twofold steady-state increase in coronary resistance with resultant tissue ischemia. Infusion of 1 microM glibenclamide in the isolated hearts resulted in a 67% increase in coronary resistance with resultant tissue ischemia. The ischemic changes were reversible upon removal of the drug. These findings indicate that the ATP-sensitive K+ channel plays a significant role in the maintenance of basal coronary resistance in vivo. Higher concentrations of glibenclamide (80-100 microM) in the in vivo dog heart consistently gave rise to an oscillating pattern of coronary flow. These oscillations were either eliminated or decreased in amplitude and frequency by the infusion of 8-phenyltheophylline, a specific competitive inhibitor of adenosine receptors. 31P-nuclear magnetic resonance spectroscopy performed at the peaks and troughs of these oscillations revealed oscillation of the phosphorylation potential at the same frequency. Thus adenosine release caused by tissue ischemia appears to play a major role in creating the oscillating pattern of coronary blood flow, that occurs during the inhibition of ATP-sensitive K+ channels by glibenclamide.

Adenosine Triphosphate↗

Pulmonary function in human immunodeficiency virus infection. A prospective 18-month study of serial lung function in 474 patients.

To investigate the development of a reduced DLCO in patients with HIV-related disease, we studied 474 HIV-seropositive patients and performed serial lung function measurements over 18 months. The mean values of DLCO at presentation were lower in patients with more advanced HIV disease compared with asymptomatic HIV-seropositive patients (DLCO 88% of predicted). When compared with the DLCO in asymptomatic HIV-seropositive patients, the DLCO had reduced values in patients with persistent generalized lymphadenopathy (PGL) (82% of predicted, p less than 0.05), acquired deficiency syndrome-related complex (ARC) (73% predicted, p less than 0.001), nonpulmonary Kaposi's sarcoma (KS) (72% of predicted, p less than 0.001), nonpulmonary complications of AIDS excluding KS (73% of predicted, p less than 0.001), pulmonary KS (63% of predicted, p less than 0.001), pulmonary mycobacterial infection (68% of predicted, p less than 0.05), pyogenic infection (70%, p less than 0.05), acute Pneumocystis carinii pneumonia (PCP; 49%, p less than 0.001), and following recovery from PCP (71%, p less than 0.001). Serial lung function measurements over 18 months revealed no change in DLCO within any patient group, and in particular there was no tendency for a gradual decline. Clinical deterioration due to the development of PCP was associated with a reduction in DLCO. Conversely, in patients recovering from PCP, there was a partial improvement in DLCO over 3 months. Zidovudine (AZT) use did not affect DLCO within any diagnostic group or the recovery in DLCO following PCP. However, cigarette smoking was associated with further reductions in DLCO in all patient groups and with an impaired recovery of DLCO following acute PCP.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

Laboratory evaluation of the Pall LG6 leukocyte depleting arterial line filter.

The Pall LG6 arterial line filter has been designed to remove free circulating leukocytes from the arterial line of the extracorporeal circuit employed in openheart surgery. The filter was evaluated and compared to a control filter (Pall Stat-Prime) in terms of its general blood handling characteristics, particularly with regard to the associated level of leukocyte removal. The gross air handling characteristics of the filters were also assessed together with pressure drop. It was found that the filters differed little in terms of all factors studied other than the level of leukocyte depletion. The LG6 filter was associated with substantial levels of leukocyte depletion, particularly the depletion of neutrophils. Over the 90 minute perfusion period the LG6 filter was found to be associated with a neutrophil depletion rate of around 70% while preferentially sparing lymphocytes. This compared to a 10-20% depletion rate in the control filter. This was achieved without apparently compromising the performance of the filter in terms of the other factors studied.

Animals↗

The effects of pulsatile flow on the leukocyte depleting qualities of the Pall LG6 leukocyte depleting arterial line filter: a laboratory investigation.

The Pall LG6 arterial line filter has, in a previous publication, demonstrated its inherent leukocyte depleting qualities. This initial study was however carried out under continuous flow conditions. The present study was designed to assess the effectiveness of the LG6 filter in performing this leukocyte removal function under the more dynamic conditions of pulsatile flow. In addition to leukocyte depletion, the general blood handling and degree of energy absorption associated with the LG6 and Stat-Prime filters was also assessed. The results demonstrated that the LG6 filter was unaffected by the flow regime employed in terms of leukocyte removal and platelet depletion. There was a higher level of measured haemolysis associated with the use of pulsatile rather than nonpulsatile flow, however, this was the case with both filter types and was not found to be the case when generated values were computed. The LG6 filter absorbed more energy than the Stat-Prime filter as reflected by energy equivalent pressure (EEP) measurement, but this difference did not reach a level which was considered to be clinically significant.

Animals↗

Attitudes of medical professionals towards patients with eating disorders.

A questionnaire examining attitudes to patients with eating disorders was completed by 352 medical and nursing staff in a general hospital. Patients with eating disorders were less liked than patients with schizophrenia and were seen as responsible for their illness almost to the same degree as recurrent overdose takers. Factor analysis showed a first factor in which patients with eating disorders were construed as vulnerable to external pressures (from others, the media) while also self-inducing their illness, and this was associated with treatment recommendations for education, urging the patient to take self-control and psychotherapy. The professions differed significantly in attitudes.

Adult↗

Biodistribution of lipiodol following hepatic arterial injection.

Lipiodol, a derivative of poppy seed oil, has been used angiographically to improve visualisation of small liver tumours. We have utilised this finding to determine whether intrahepatic arterial injection of lipiodol can be used as a vehicle to deliver selectively 131I into liver tumours. Two groups of rats were studied. Group 1 (control, no liver tumour) received 0.1 ml 131I-lipiodol (1 microCi) into the hepatic artery. Animals were killed at regular time intervals over 30 days and organs were submitted to well-counting. Over 90% of activity remained in the liver at 6 h. Eighty per cent activity was lost from the normal liver, to be excreted in the urine over 30 days. Group 2 animals received intraportal injections of 7.5 x 10(5) MC28 sarcoma cells. Multiple liver metastases were present after 14 days. Animals were similarly studied at each time interval and samples from tumour and normal liver were submitted to well-counting. Lipiodol was selectively retained within tumour and cleared from normal liver. 131I-lipiodol may prove valuable as a delivery agent for radio/chemotherapy to liver metastases.

Animals↗

Intravenous cocaine challenges during desipramine maintenance.

Intravenous challenges with placebo and cocaine doses ranging from 0.125 to 0.5 mg/kg were administered to five subjects using a within subjects design during placebo and active desipramine (DMI) maintenance at a fixed dose of 150 mg daily for at least 10 days. The "high" reported after cocaine infusion was not altered by DMI, but "desire for cocaine" after a single dose was attenuated. Together with the results of clinical trials of DMI for cocaine abuse, these laboratory results suggest that DMI may reduce cocaine craving both during and between cocaine binges. Physiologically, baseline heart rate was higher on DMI, but the incremental heart rate response to cocaine was attenuated.

Adult↗

Drug use patterns in Northern Territory Aboriginal communities 1986-1987.

During April to November 1986 and May to October 1987, a systematic survey of patterns of use of alcohol, kava, tobacco and analgesics by Northern Territory Aboriginal people aged 15 years and older was conducted. The objectives of the study were to ascertain the prevalence of drug use, the frequency of drug use and the quantity of drugs used. In addition, information about Aboriginal people's perceptions of the drugs, their beliefs about drug use and the value of drugs in their culture was collected. This paper describes only the quantitative aspects of drug use of this population. A stratified sampling procedure was used to sample 10 per cent of the target population. Using two survey instruments, an individual questionnaire and a group questionnaire, data were gathered from 1764 Aboriginal people living in the Northern Territory. As a whole, the Northern Territory Aboriginal people have a drug consumption pattern quite distinct from urban Australians.

Journal Article↗

Effect of HIV-1 and cytomegalovirus in bronchoalveolar lavage cells on the transfer factor for lung carbon monoxide in AIDS patients.

Abnormalities in pulmonary function tests have been observed in AIDS patients with pulmonary disease. In this study, the polymerase chain reaction (PCR) was used to determine if the reductions in transfer factor for lung carbon monoxide (TLCO) were due to the presence of HIV-1 or cytomegalovirus (CMV). HIV-1 was detected in cells from bronchoalveolar lavage (BAL) in 35 out of 60 (58%) of patients. The detection of HIV-1 had no significant effect on pulmonary function. CMV was detected in the BAL of 58% of patients in this study but CMV was the sole viral pathogen in the lung of only two out of 60 (3.3%) individuals. A significant reduction in TLCO was observed in individuals with PCP where CMV was also detected in the BAL. This study shows that reduction in TLCO in HIV-seropositive patients is not due to the presence of HIV-1 or CMV alone in BAL cells.

Acquired Immunodeficiency Syndrome↗

Diagnostic value of lung clearance of 99mTc DTPA compared with other non-invasive investigations in Pneumocystis carinii pneumonia in AIDS.

Various non-invasive investigations were carried out in patients infected with HIV who had respiratory symptoms with and without pneumocystis pneumonia (with pneumonia, n = 13 (five smokers); without pneumonia, n = 22 (13 smokers]. These included chest radiography; lung function tests (forced expiratory volume in one second, forced vital capacity; transfer factor and coefficient for carbon monoxide); arterial blood gas tensions; arterial oxygen saturation at rest and on exercise; and lung clearance of diethylenetriaminepenta-acetic acid labelled with technetium-99m (99mTc DTPA). The effect of scan time (seven v 45 minutes from peak counts) and subtraction of background counts were examined. There were no significant differences between the two groups in lung function tests or arterial blood gas tensions at rest. The median clearance half time of inhaled 99mTc DTPA for the first seven minutes from peak counts was 7.2 minutes for patients with pneumocystis pneumonia and 22 minutes for those without. The median arterial oxygen desaturation on exercise was 5% in patients with pneumocystis pneumonia and 2% in those without. 99mTc DTPA lung clearance was better than the other non-invasive tests in discriminating pneumocystis pneumonia from other pulmonary disorders in patients positive for HIV. A short scan time of seven minutes was as sensitive and specific as the longer scan time of 45 minutes, and this allows the clearance of 99mTc DTPA to become a rapid screening test.

Adult↗

Transesophageal Doppler cardiac output monitoring: performance during aortic reconstructive surgery.

Transesophageal Doppler (TED) monitoring provides continuous, noninvasive monitoring of cardiac output by measurement of aortic flow velocities. Because of the effects on aortic flow dynamics resulting from atherosclerosis, aortic cross-clamping, and wide variations in arterial blood pressure, the validity of TED monitoring during aortic surgery is unresolved. The authors prospectively evaluated a second-generation TED cardiac output monitor in 42 patients undergoing aortic reconstructive surgery. Four hundred eighty-nine simultaneous measurements of TED and thermodilution cardiac output were obtained. Transesophageal Doppler measurements were highly correlated to thermodilution measurements (R = 0.94); however, Bland-Altman analysis revealed a moderate error in the TED measurements (2 SD of the bias = 1.4 L/min). Trending analysis showed that TED monitoring accurately tracked changes in thermodilution cardiac output. Placement of an aortic cross-clamp resulted in significant reductions in the accuracy of Doppler measurements. Arterial blood pressure variations did not systematically affect the accuracy of the transesophageal technique. Limitations of TED monitoring, including a difficult calibration procedure, poor performance during aortic cross-clamping, and the need for probe repositioning, suggest further development is warranted.

Aorta, Abdominal↗