Biomedical subjects

J R Clarke

Publications and source records attributed to J R Clarke.

At least 73 records · Page 4Linked to original sources

PubMed1993

Comparison of the squeeze technique and transcutaneous oxygen tension for measuring the response to bronchial challenge in normal and wheezy infants.

The aim of this study was to compare the fall in transcutaneous oxygen tension (PtcO2) as an outcome measure during bronchial provocation with histamine, with changes in airway function measured by the squeeze technique in healthy infants and those with wheezing disorders. PtcO2 was measured during histamine challenge in 20 infants, aged 6-16 months, of whom 14 had recurrent cough or wheeze (lower respiratory illness, LRI), and 6 were healthy. All were symptom free at the time of testing. The minimum value of PtcO2 after each nebulization was compared with the minimum baseline value. The response to increasing concentrations of histamine was also assessed by measuring maximal flow at functional residual capacity (VmaxFRC) by the squeeze technique. The inhaled concentration of histamine causing a 30% fall in VmaxFRC was calculated to give the provoking concentration (PC30). Baseline VmaxFRC was lower in symptomatic infants (117 mL/s) than the normal infants (322 mL/s; P < 0.005), but the PC30 was not significantly different (7.7 and 5.7 g/L, respectively). There was no difference in baseline PtcO2 between the two groups. The infants with LRI had significant reductions in PtcO2 at both the final and preceding concentrations of histamine, whereas the normal infants had a significant and smaller reduction in PtcO2 only at the provoking concentration. Reduction in PtcO2 during bronchial challenge was a less sensitive index of bronchial response in healthy infants than in infants with a history of recurrent LRI.

Asthma↗

PubMed1993

The epidemiology of HIV-1 infection of the lung in AIDS patients.

OBJECTIVE: To examine the relationship between HIV-1 infection of cells obtained by bronchoalveolar lavage (BAL) from the lung and the pathogenesis of AIDS. DESIGN: Prospective study of 121 consecutive HIV-1-seropositive patients undergoing investigation for respiratory symptoms or abnormal chest radiograph. METHODS: Polymerase chain reaction (PCR) for the detection of HIV-1-specific proviral DNA. Cocultivation of leukocytes obtained from BAL with donor cord blood leukocytes (CBL) to isolate HIV-1. RESULTS: HIV-1 was detected by PCR in the lung cells of 78 out of 121 (65%) patients. It was detected in 55% of patients who had been seropositive for less than 1 year, but in over 80% of patients who had been seropositive for more than 3 years. HIV-1 was isolated from 61 out of 106 (58%) individuals. The ability to detect or isolate HIV-1 from the lung correlated directly to CD4 cell count in peripheral blood. HIV-1 was detected significantly more frequently in the BAL cells of smokers compared with non-smokers (P = 0.01). CONCLUSIONS: HIV-1 was frequently detected and isolated from the lung of AIDS patients undergoing a respiratory episode. HIV-1 infection of the lung became more frequent with time from serodiagnosis. Patients who smoked were more likely to succumb to HIV-1 infiltration into the lung and HIV-1 infection of the lung was associated with progression to death.

Adult↗

PubMed1993

Pulmonary function hysteresis during compression to, and decompression from 31.3 ATA.

Tracheal gas density breathing heliox at 31.3 atmospheres absolute (O2 at 0.42 ATA) is 6.287 g l-1, or approximately 5.5 times greater than air at 1 ATA. This constitutes a significant respiratory load, previously shown to induce respiratory adaptation. During a saturation dive to 31.3 ATA, five divers were exposed to this load for 16 days. This project aimed at investigating possible hysteresis in pulmonary function during dive compression, adaptation and decompression phases. Pulmonary function tests were performed at the surface in air, and at four pressure stops during compression and decompression, with divers breathing the helium-oxygen gas mixture. Significant hysteresis patterns were observed for pooled maximal voluntary ventilation, forced expired volume at 1 s, peak expiratory flow, and maximum expiratory flows (P < 0.05), with post-adaptation flows consistently exceeding those observed during compression. Two mechanisms may explain these observations. Differences may be attributable to positive effort-dependence in the forced expiratory flow; or it is possible the subjects adapted to the respiratory load by modifying neural input to airway smooth muscle, thereby modifying airway resistance.

Adult↗

PubMed1993

Delivery of salbutamol by metered dose inhaler and valved spacer to wheezy infants: effect on bronchial responsiveness.

The efficacy of a new valved spacer device, the Babyhaler inhaler (Glaxo) for administering metered dose inhaler treatment via a facemask to infants was assessed. In a double blind, single dose study, salbutamol (800 micrograms) or placebo were given on separate days to 12 sedated, sleeping, wheezy infants during a symptom free interval. Lung function was measured before and after administration and the bronchial response to aerosol challenge with methacholine was then assessed using the squeeze technique. A small increase in heart rate and a drop in arterial oxygen tension followed salbutamol administration. No other change in lung volume or air flow obstruction was detected. Bronchial responsiveness decreased significantly after the administration of salbutamol by Babyhaler, the PC30 (provoking concentration of methacholine causing a 30% fall in maximal flow at functional residual capacity by the squeeze technique) increasing from a median of 3.8 g/l after placebo to 12.5 g/l after salbutamol. The Babyhaler is an effective device for administering bronchodilator to wheezy infants. The small scale of the response may be attributable to the uncertain effect of beta agonists in this population. Furthermore, pulmonary deposition of inhaled aerosols may be reduced in nose breathing, sleeping infants.

Albuterol↗

PubMed1993

Relation of HIV-I in bronchoalveolar lavage cells to abnormalities of lung function and to the presence of Pneumocystis pneumonia in HIV-I seropositive patients.

BACKGROUND: HIV is present in bronchoalveolar lavage cells of some but not all HIV seropositive patients. Abnormalities of lung function have been described in such patients in the absence of clinically overt pneumonia or other respiratory infections. It is possible that the presence of HIV in alveolar macrophages could account for these abnormalities. It is also possible that the presence of HIV in alveolar macrophages contributes to immunosuppression and an increased incidence of opportunistic infections. METHODS: This was a prospective study of 157 HIV seropositive patients requiring diagnostic bronchoscopy for investigation of new respiratory symptoms, chest radiograph abnormality, or pneumonic illness. Presence of HIV in bronchoalveolar lavage cells obtained at diagnostic bronchoscopy was determined by polymerase chain reaction to detect proviral DNA and in vitro cocultivation to detect productive virus infection. With these two techniques the presence or absence of HIV in bronchoalveolar lavage was compared with the presence of abnormalities of lung function or presence of Pneumocystis pneumonia. RESULTS: HIV was detected in bronchoalveolar lavage cells in 65% of patients by means of the polymerase chain reaction and 59% with cocultivation. With both methods of detection there was no association between the presence or absence of HIV and the presence of Pneumocystis pneumonia; nor was there a relation between the presence of HIV and abnormalities of lung function. CONCLUSION: The presence of HIV in bronchoalveolar lavage cells does not predispose to an increased incidence of Pneumocystis pneumonia; nor does it contribute to abnormalities of lung function.

Bronchoalveolar Lavage Fluid↗

PubMed1993

Evidence for human immunodeficiency virus infection of the lung.

Pulmonary disease is a frequent manifestation in the terminal stages of acquired immune deficiency syndrome (AIDS), and is caused mainly by a number of opportunistic microorganisms, most commonly Pneumocystis carinii. Despite the extensive involvement of the lung in the pathogenesis of AIDS, until recently little was known about the role of human immunodeficiency (HIV). In this review we will discuss the cellular tropism and phenotypic characterisation of HIV strains isolated from the lung. The available literature on HIV infection of the lung is reviewed, and the mechanisms of HIV-induced pathogenesis in the lung is discussed.

AIDS-Related Opportunistic Infections↗

PubMed1993

Uterine morphology and the distribution of granulated metrial gland cells in the virgin and pregnant short-tailed field vole, Microtus agrestis.

The morphology of the uterine wall in the virgin pregnant and postpartum short-tailed field vole (Microtus agrestis) was studied with particular reference to the distribution of granulated metrial gland (GMG) cells. In comparison with the mouse, the changes which occur in the uterine wall during pregnancy and into the postpartum period are broadly similar. However, unlike in the mouse, GMG cells were a feature of the uterine wall in virgin mice and of the antimesometrial decidua in pregnancy. In pregnancy, GMG cells were not found in the lumina of blood vessels in the uterine wall or in the maternal blood spaces of the fetal placenta. During early pregnancy, giant interstitial trophoblast cells invade the decidualising endometrium. No association was found between uterine leucocytes, including GMG cells, and interstitial trophoblast cells, indicating that the trophoblast invasion is not influenced by leucocytes.

Animals↗

PubMed1992

Bronchial responsiveness and lung function in infants with lower respiratory tract illness over the first six months of life.

The aim of this study was to determine whether increased bronchial responsiveness to histamine is associated with lower respiratory tract illness (one or more episodes of wheeze or cough, or both) in infancy. Fifty four normal newborn infants who had at least one atopic parent were recruited. At a median age of 6.5 months, 45 infants, 23 with a history of lower respiratory tract illness, and 22 without, underwent pulmonary function testing during a symptom free period. The maximum flow at functional residual capacity (VmaxFRC) was calculated from partial forced expiratory flow volume curves using the squeeze technique. Bronchial responsiveness to increasing doses of histamine was assessed by determining the provoking concentration which caused a 30% decrease in VmaxFRC (PC30). The length adjusted VmaxFRC was lower for symptomatic infants before the challenge (median 125 ml/s; 95% confidence intervals (CI) 85 to 164 ml/s) compared with control infants (median 215 ml/s; 95% CI 159 to 298 ml/s). There was no significant difference in PC30 between symptomatic infants (median 10.3 g/l; 95% CI 2.8 to 23.8 g/l) and control infants (median 16.5 g/l; 95% CI 2.4 to 27.9 g/l). Bronchial responsiveness to histamine can be shown in most infants early in life and is independent of lower respiratory tract symptoms including wheezing.

Bronchi↗

PubMed1992

A study of neuropathy in HIV infection.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

AIDS-Related Opportunistic Infections↗

PubMed1992

Postgraduate prosthetic training within the community dental service.

There is a need for clinical prosthetics training for community dentists. This was apparent when a postgraduate course, which dealt with prosthetic care of elderly people, was organised for dentists working in the community dental service. Over 100 community dentists applied for 40 places. At the outset they were asked to complete a questionnaire which addressed their professional career together with their current prosthetic experience. The majority of participants were employed at dental officer level; 18 per cent were at senior dental officer level. Many of the dentists worked in districts where one or more community dentists provided all the prosthetic treatment within the community dental service. The majority of districts receive their prosthetic patients as a result of referrals from a variety of sources. Only eight dentists saw the majority of their patients at domiciliary visits; many did not see any patients in this manner. The course participants considered that their greatest clinical weakness in prosthetic skills was in the production of copy dentures and in denture design. Many of the dentists who attended the course did not provide a prosthetic service but most of them said that they anticipated that the necessity for this would increase in the future.

Adult↗

PubMed1992

The uptake and completion of dental treatment using a mobile clinic in central Birmingham, UK.

The provision of a mobile dental service at a primary school in a socially deprived, multi-ethnic area markedly increased the uptake and completion of treatment after a school dental inspection. Eighty one per cent of children who were offered treatment in the mobile clinic accepted it and 91 per cent of these completed it. In the previous year, when care was offered at a health centre within half a mile of the school, the corresponding figure was 43 and 4 per cent. Over half the children seen in the mobile clinic had not previously visited a dentist.

Appointments and Schedules↗

PubMed1991

Polyamine biosynthesis in cells infected with different clinical isolates of human cytomegalovirus.

Previous work in this laboratory showed that polyamine biosynthesis was stimulated in fibroblasts following infection with the AD169 strain of human cytomegalovirus (HCMV) or with murine cytomegalovirus (MCMV) (Tyms et al: Biophysics Research Communications 86:312-318, 1979; Advances in Polyamine Research 4:507-517, 1983). Here we compare the affect of AD169 on polyamine production in infected fibroblasts with that of the unusual Colburn strain of HCMV. The Colburn virus is unusual in that it was isolated from a 7 year old boy with encephalitis and molecular studies indicated the virus was simian like (Huang et al: Journal of Virology 26:718-723, 1978). As a consequence of CMV infection a two to ten fold increase in the spermine content of fibroblast cells is observed. Radiolabel transfer experiments show that spermine is synthesized throughout virus infection. Indeed, spermidine and spermine are specifically incorporated into the purified virions of the AD169 and Colburn strains of HCMV. Furthermore, polyamine biosynthesis is stimulated in fibroblast cells infected with a number of low passage clinical isolates of HCMV. Inhibition of polyamine biosynthesis in HCMV infection may provide a specific and novel target for antiviral chemotherapy.

Cell Line↗

PubMed1991

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↗

PubMed1991

Recovery of the human immunodeficiency virus from fibreoptic bronchoscopes.

Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes' disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml.

Bronchoscopes↗

PubMed1991

Acute pain over the appendix. A model of the surgical decision.

The decision to do an appendectomy for a patient with right lower abdominal pain has been analysed. We have described a simple decision tree model of the tradeoffs. The three critical variables can be measured quantitatively. The probability of appendicitis has been predicted. The probability that an inflamed appendix will perforate during observation can be estimated. It can be projected that the rate of perforation is increased in the very young and old. Therefore, the minimal threshold probability of appendicitis justifying an appendectomy is lower at the extremes of age. The decision must consider not only the probabilities of outcomes, but their utilities as well. The utility of appendectomy is discussed. Experience measuring the personal utilities of appendectomy in a group of surgeons using a standard gamble technique is presented. The variation in utilities was greater than expected. The perceived ratio of the magnitude of the increased risk of an avoidable perforation compared to that of an unnecessary operation ranged from over 30:1 to less than 1:3, with a median of about 3.5:1. The ratio predicted from mortality and morbidity rates had a median range from 20:1 to 2:1. Other factors may be influencing the utility assessments. The individual's utility for appendectomy could be shown to have a large influence on the decision to operate or observe.

Abdomen, Acute↗

PubMed1990

Use of the polymerase chain reaction to detect DNA sequences specific to pathogenic treponemes in cerebrospinal fluid.

The polymerase chain reaction was used to detect Treponema pallidum in specimens of cerebrospinal fluid (CSF), as a means of diagnosing syphilis. Segments of the TmpA and 4D genes were amplified to provide an estimated threshold sensitivity of approximately 65 organisms in 0.5 ml. A spectrum of pathogens known to cause meningitis, and several non-pathogenic treponemes were unreactive. Treponema pertenue, and only one of 30 control specimens of CSF were positive. In contrast, 10 of 19 CSFs from patients being evaluated for latent or tertiary syphilis were positive, as were 7 of 28 specimens from HIV-positive patients.

Animals↗

PubMed1990

Identification of human appendicitis by in vitro nuclear magnetic resonance.

The spin-lattice relaxation time, T1 as determined by nuclear magnetic resonance techniques, correlates positively with tissue water content. The latter relationship has been observed in rabbits with experimentally induced appendicitis whose inflamed appendiceal tissues had significantly higher T1's and water contents than tissue from normal controls. The present experiment studied these relationships in humans. Tissue water content and T1 were measured on appendiceal tissue from 10 patients with documented appendicitis and from 6 controls without the disease. All T1's were determined within 30-60 min of removal of the appendix at operation. The mean in vitro T1 of appendiceal tissue from patients with appendicitis was significantly higher than that of controls (527 +/- 15 msec versus 430 +/- 17 msec, mean +/- SEM, P less than 0.002). In addition, a strong positive correlation was noted between T1 and tissue water content (r = 0.70, P less than 0.01). Based on these findings, the use of in vivo magnetic resonance imaging techniques to detect human appendicitis noninvasively warrants investigation.

Adolescent↗

PubMed1990

Detection of HIV-1 in human lung macrophages using the polymerase chain reaction.

We have used the polymerase chain reaction to investigate HIV-1 infection of lung macrophages from 44 AIDS patients with pneumonia. Proviral HIV-1 DNA was detected in the lung macrophages of 47% (21 of 44) of patients tested; 32% (seven of 21) of the patients had Pneumocystis carinii pneumonia (PCP), and 56% (11 of 21) had pneumonia caused by other aetiological agents. Matched peripheral blood specimens were obtained from 22 patients in this study, and HIV-1-specific DNA was detected in 100% (22 out of 22) of non-adherent white cell preparations tested. HIV was detected in blood monocytes of 11 out of 22 patients (50%), and a virus signal was also found in the lung macrophages of eight of these patients. Our results indicate that PCP does not predispose lung macrophages to HIV-1, nor does HIV-1 infection of lung macrophages increase the probability of contracting PCP.

Acquired Immunodeficiency Syndrome↗