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Biomedical subjects

S J Semple

Publications and source records attributed to S J Semple.

At least 55 records · Page 3Linked to original sources

Arterial desaturation in HIV positive patients undergoing sputum induction.

Arterial oxygen saturation (SaO2) was monitored continuously during and immediately after sputum induction in 41 HIV positive patients with respiratory symptoms and in 20 symptomless medical and nursing staff, who acted as control subjects. Arterial oxygen desaturation (defined as SaO2 less than or equal to 92%) occurred during sputum induction and persisted for up to 20 minutes after the end of the procedure in 11 of the 20 patients with Pneumocystis carinii pneumonia and in nine of the 21 patients with other respiratory diagnoses. None of the control subjects showed oxygen desaturation. Neither the severity of chest radiographic abnormalities, the alveolar-arterial oxygen gradient (both measured before sputum induction), nor baseline SaO2 prospectively identified the patients who developed oxygen desaturation. Two patients, one with pneumocystis pneumonia, developed dyspnoea and had a fall in arterial oxygen saturation to 84% within 10 minutes of starting sputum induction. The procedure was abandoned in both patients and in two further patients, who developed severe nausea and reaching but no oxygen desaturation. Sputum induction in HIV positive patients with respiratory symptoms may induce a fall in SaO2 that persists after this procedure. This may be important if other procedures are performed soon after sputum induction.

Adult↗

Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease.

Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗

Carotid chemoreceptor response to increases in CO2 output.

The effect on carotid chemoreceptor activity of alterations in PaCO2 oscillations produced by venous CO2 loading via the small intestines was studied in anaesthetised cats, which were paralysed and ventilated at constant frequency. Changes in PaCO2 oscillations were assessed from continuously recorded oscillations of arterial pH. Chemoreceptor activity was averaged over 20-50 pH cycles to determine the amplitude (csnd ampl) and mean level (csnd mean) of the respiratory fluctuation in discharge frequency during control and CO2 loaded periods. Two groups of 5 cats were studied. In both groups, the amplitude of the PaCO2 oscillations increased by an overall average of 74.5% (standard error, SE = 9.2) with minimal change in mean PaCO2 (average increase 0.7 mm Hg), in response to an increase in VCO2 of 77.5% (SE = 7.4). When isoxia was maintained (Group 1) csnd ampl increased by 51.3% (SE = 11.1) and csnd mean by 17.3% (SE = 7.8). In Group 2, PaO2 rose by 16.7 mm Hg (SE = 1.5) during CO2 loading and both csnd ampl and csnd mean decreased by 7.4% (SE = 9.3) and 2.3% (SE = 13.3) respectively. The results demonstrate a sensitivity of chemoreceptors to changes in VCO2 which is influenced by small changes in PaO2.

Animals↗

Glucocorticoid therapy for severe Pneumocystis carinii pneumonia.

The majority of patients with AIDS and Pneumocystis carinii pneumonia respond to treatment with either high-dose cotrimoxazole or IV pentamidine. Glucocorticoids have been given as 'adjuvant' therapy in those patients who fail to respond to cotrimoxazole or pentamidine. This article discusses the role of glucocorticoids therapy in the treatment of severe Pneumocystis carinii pneumonia and reviews the evidence for their efficacy.

Glucocorticoids↗

Caregiving and the stress process: an overview of concepts and their measures.

This paper views caregiver stress as a consequence of a process comprising a number of interrelated conditions, including the socioeconomic characteristics and resources of caregivers and the primary and secondary stressors to which they are exposed. Primary stressors are hardships and problems anchored directly in caregiving. Secondary stressors fall into two categories: the strains experienced in roles and activities outside of caregiving, and intrapsychic strains, involving the diminishment of self-concepts. Coping and social support can potentially intervene at multiple points along the stress process.

Adult↗

Treatment of cytomegalovirus retinitis with zidovudine and ganciclovir in patients with AIDS: outcome and toxicity.

Sixteen patients with the Acquired Immunodeficiency Syndrome (AIDS) and cytomegalovirus retinitis were treated with ganciclovir alone (9 patients) or ganciclovir and zidovudine (6 patients). The duration of effective treatment, that is the number of weeks during which there was no deterioration in visual symptoms or retinal appearance, was comparable in both groups. However, six of the seven patients receiving concurrent therapy had to cease treatment temporarily because of bone marrow toxicity compared with one of the nine patients treated with ganciclovir alone. It is concluded that continuous concurrent therapy with oral zidovudine and intravenous ganciclovir is not possible unless unlimited supportive therapy including blood transfusion, is available.

Acquired Immunodeficiency Syndrome↗

Cytomegalovirus in the lungs of patients with AIDS. Respiratory pathogen or passenger?

A total of 166 consecutive clinical episodes of pneumonitis in patients with acquired immune deficiency syndrome (AIDS) or antibody positive for human immune deficiency virus (HIV) were investigated for evidence of cytomegalovirus (CMV) infection in their lungs and at peripheral sites to determine the pathogenicity of this virus in the lung and its relationship to peripheral CMV shedding. Evidence of CMV infection was sought in bronchoalveolar lavage (BAL) fluid, blood, saliva, and urine using a specific monoclonal antibody to antigens produced by CMV-infected cells within 24 h. Although CMV was detected in 31 (19%) of BAL fluid specimens, in only six episodes was this the sole pathologic finding. In the remaining episodes either another infectious agent, Kaposi's sarcoma, or lymphoid interstitial pneumonitis was found or no pathogen was detected. None of the patients were given specific anti-CMV treatment, and all but two recovered, including those patients in whom CMV was the sole finding at BAL. The presence of peripheral shedding of CMV did not have any significance in mortality or morbidity. Our findings are in direct contrast to those in recipients of allogeneic bone marrow transplants, in whom CMV pneumonitis is associated with a high mortality. We postulate that this difference is because AIDS patients cannot mount the destructive immune response to CMV in the lung, which we believe to be the basis of the pathology seen in the former group. We conclude that CMV is not a pathogen in the lungs of patients with HIV infection, and we suggest that its presence at this site does not warrant specific therapy in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Empirical treatment without bronchoscopy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

An empirical approach to treating Pneumocystis carinii pneumonia was adopted in a prospective study of 73 men with antibodies to human immunodeficiency virus 1 (HIV-1) presenting with respiratory problems. At presentation 49 patients (group 1) were thought to have a history, findings at clinical examination, chest radiograph, and arterial blood gas tensions typical of pneumocystis pneumonia, and empirical treatment was begun immediately. Twenty four patients (group 2) were thought to have features not typical of pneumocystis pneumonia. All patients were subsequently referred for bronchoscopy to determine the diagnosis. In group 1 four patients were excluded from the analysis because bronchoscopy was not possible. Of the remaining 45, 42 had pneumocystis pneumonia, which was diagnosed at bronchoscopy in 40, and on the basis of the clinical response to co-trimoxazole in two who had negative results from investigations. Of the three patients without pneumocystis pneumonia, one patient with lymphoid interstitial pneumonitis and Branhamella catarrhalis infection would have failed to respond to empirical treatment. The other two had multiple bacterial pathogens at bronchoscopy; one already had Kaposi's sarcoma and the other would have been misdiagnosed as having AIDS. In group 2 a specific diagnosis was made at bronchoscopy in 21 cases, including pneumocystis pneumonia in seven (all had atypical chest radiographs). In three cases no diagnosis was made and spontaneous recovery occurred. Adopting an empirical approach to treatment for typical pneumocystis pneumonia (group 1) led to the correct treatment in 43 of 45 cases (95%) and would have saved 44 of the 45 of bronchoscopies in this group. Adopting an empirical approach would have caused one patient to be misdiagnosed as having AIDS. Overall, 44 out of 69 bronchoscopies (64%) would have been saved; the specificity for the diagnosis of pneumocystis pneumonia was 85% and the sensitivity was 85%. Adopting an "empirical" treatment policy for typical pneumocystis pneumonia will cause a large reduction in the number of "high risk" bronchoscopies performed.

Acquired Immunodeficiency Syndrome↗

Nebulised pentamidine as treatment for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

Nebulised pentamidine was used to treat 30 patients with Pneumocystis carinii pneumonia. Fourteen patients (group 1) received pentamidine isethionate 4 mg/kg (six patients) or 8 mg/kg (eight patients) via a standard jet nebuliser (Acorn, system 22) with a flow rate of 8 l/min. The aerosol droplets had a mass median aerodynamic diameter of 2.6 microns (geometric standard deviation (GSD) 2.9) and 46% of droplets were less than 3.9 microns. A further 16 patients (group 2) received 8 mg/kg pentamidine via a jet nebuliser with baffles to limit droplet size to below 4 microns (Respirgard II). This generated aerosol droplets with a mass median aerodynamic diameter of 0.8 micron (GSD 1.5) and 98% were less than 3.9 microns. Only three of the 14 patients in group 1 responded clinically to treatment, one after the lower dose of pentamidine. Treatment was discontinued in 10 patients and one patient died at bronchoscopy from haemorrhage. Thirteen of the 16 patients in group 2 responded. Side effects occurred infrequently; two patients from group 1 had a cough, six patients (four from group 2) had contact bleeding at bronchoscopy, and two further patients had haemoptysis. The differing response rate may be due to differences in the mean droplet size of the aerosols produced by the nebulisers. Nebulised pentamidine (8 mg/kg) when delivered by Respirgard II nebuliser appears to be as effective as conventional treatment for Pneumocystis carinii pneumonia of mild to moderate severity.

Acquired Immunodeficiency Syndrome↗

Is hypercapnia necessary for the ventilatory response to exercise in man?

1. Continuous recordings of arterial pH, ventilation, airway CO2 and heart rate were made during rest and during 3-4 min periods of rhythmic leg exercise in four renal patients with arteriovenous shunts. 2. The patients were anaemic (haemoglobin 6.5-9.0 g/dl) but had a normal ventilatory response to exercise as judged by the ratio of the change in ventilation to the change in CO2 production. 3. Breath-by-breath oscillations in arterial pH disappeared for the majority of the exercise period in each patient. 4. Changes in mean arterial pH and end-tidal CO2 tension with exercise were inconsistent between subjects but consistent within a given subject. On average, mean arterial pH rose by 0.011 pH unit. Changes in end-tidal CO2 tension reflected changes in mean pHa by falling on average by 1 mmHg (0.13 kPa). 5. Hypercapnia and acidaemia were not found to be necessary for the ventilatory response to moderate exercise.

Adult↗

Derivation of CO2 output from oscillations in arterial pH.

Theory predicts that the rate of rise of the oscillation in arterial CO2 partial pressure (PaCO2) is linearly dependent on CO2 flux from venous blood to alveolar gas. We have measured, in the anesthetized cat, CO2 output (VCO2) and oscillations in arterial pH. The pH signal was differentiated to give the maximum rate of fall of pH on the downstroke of the oscillation (dpH/dt decreases max). Since oscillations in pH are due to oscillations in arterial PCO2, dpH/dt decreases max was considered to be equivalent to the maximum rate of rise of the PCO2 oscillation. VCO2 was increased by ventilating the intestines with CO2 and by the intra-arterial infusion of 2,4-dinitrophenol. VCO2 was decreased by filling the intestines with isotonic tris(hydroxymethyl)methylamine buffer. The maximum range of VCO2 covered was 7.8-51 ml/min, and the mean range was from 13.6 +/- 1.3 to 29.7 +/- 1.6 (SE) ml/min. Although CO2 loading produced a small rise and CO2 unloading a small fall in mean PaCO2, the changes were not statistically significant, so that overall the response was close to isocapnia. Over the limited range of VCO2 studied there was a highly significant linear association between dpH/dt decreases max and VCO2 which supports the contention that the slope of the upstroke of the PaCO2 oscillation is determined by the CO2 flux from mixed venous blood to alveolar gas. As such this slope is a potential chemical signal linking ventilation to CO2 production.

Animals↗

Clinical and bronchoscopic diagnosis of suspected pneumonia related to AIDS.

In a series of 25 patients with suspected pneumonia related to the acquired immune deficiency syndrome (AIDS) the first 12 underwent routine fibreoptic bronchoscopy and bronchoalveolar lavage with or without transbronchial biopsy before treatment. Eight were found to have Pneumocystis carinii pneumonia and had typical clinical presentations with a prolonged history of symptoms, including a dry cough, and bilateral diffuse alveolar or interstitial shadowing in chest radiographs. Among the subsequent 13 cases, 11 had similar clinical presentations and were treated with high doses of intravenous co-trimoxazole without bronchoscopy first. Bronchoscopy was performed in those who deteriorated at any stage or failed to improve by the fifth day of treatment. Nine patients recovered and were discharged. In two patients who died P carinii pneumonia was confirmed in one but no diagnosis was made in the other. The early and late survival in both groups of patients was similar. In patients at high risk for AIDS who have clinical features suggestive of P carinii pneumonia starting treatment with intravenous co-trimoxazole is justified. The few patients who deteriorate or fail to respond should undergo bronchoscopy with bronchoalveolar lavage and transbronchial biopsy.

Acquired Immunodeficiency Syndrome↗