Biomedical subjects
Publications and source records attributed to D R Baldwin.
Classical radiographic features of patients presenting with silicosis are diffuse interstitial shadowing with subsequent enlargement of hilar nodes, sometimes with "eggshell" calcification. Five case histories are described of workers who were exposed to silica and presented initially with bilateral hilar lymphadenopathy without radiographic evidence of interstitial lung disease. One case progressed to show features of silicosis.
Relating the concentrations of active antimicrobial at the potential site of infection to MIC, may give some indication of clinical efficacy. Where relatively insusceptible pathogens are involved, site concentrations are likely to be important predictors of efficacy. Unfortunately, there are sources of errors in measurement which make the values obtained imprecise. Despite this, broad trends are beginning to emerge, especially with bronchial biopsy concentrations. In bronchial biopsies, cephalosporins reach approximately 35 to 55% of simultaneous serum concentrations, in whole lung tissue 15 to 50% and in ELF 15 to 35%. The observed site to serum ratios are consistent with the permeability characteristics of cephalosporins and the barriers to movement of drugs into sites of infection. There is evidence that inflammation may alter the barriers to infection and for the cephalosporins site penetration may be higher. Further work is necessary to establish a clear relationship between site concentrations in the lung and clinical efficacy.
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The purpose of this study was to examine the effect of differential housing on humoral immunity following exposure to an acute stressor. Forty male Sprague-Dawley adult rats were randomly assigned to either a singly housed or group-housed (five rats/cage) condition. Approximately 2 weeks after the start of the study, all animals were immunized with 1 ml of a 10% suspension of sheep red blood cells (SRBC) in saline. After the injections, half of the animals from each housing condition were subjected to an acute stressor (forced swim, 60 min/day for 3-5 days). Animals exposed to the acute stressor displayed adrenal gland hypertrophy and reduced thymus and spleen weights compared to the unstressed (control) animals. Both behavioral stimuli (housing and forced swim) demonstrated no effect on antibody production to SRBC. However, singly housed animals showed an increase in lymphocyte percentage, and corticosterone and glucose levels regardless of subsequent exposure to acute stress. Within a treatment condition, there were no significant correlations between the immune and endocrine measures. It was concluded that reduced social contact (i.e., individual housing) with subsequent exposure to an acute stressor does not appear to inhibit immunological responsiveness to an antigen.
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Promotion of sputum expectoration by chest physiotherapy is an essential part of cystic fibrosis management. The role of exercise in improving sputum expectoration and lung function in these patients is more contentious. We therefore investigated the effect of adding an exercise programme to conventional chest physiotherapy in eight adult subjects (four male) with cystic fibrosis. Subjects were treated on two non-consecutive days of the second week of a course of in-patient antibiotic therapy in a cross-over fashion. On the exercise and physiotherapy day, subjects exercised 60 min before physiotherapy. On the physiotherapy alone day, subjects rested for 60 min instead of exercising. Physiotherapy was administered on both study days (postural drainage, percussion, deep breathing, vibrations, forced expiratory technique and coughing). Lung function tests were performed at baseline, after exercise or rest and again immediately and 30 min after physiotherapy. Sputum weights were measured in the 60 min of exercise or rest (period A) and for the 60 min physiotherapy period and 30 min after physiotherapy (period B). Mean total sputum expectoration (period A and B) was 14 g on physiotherapy alone and 21.5 g (4.8) on exercise and physiotherapy (mean difference 7.5 g, 95% CI 1.4-13.6 g, P = 0.02). Mean sputum weights during period A (i.e. rest vs. exercise) on physiotherapy alone and exercise and physiotherapy were 2.6 and 7 g respectively (mean difference 4.4 g, 95% CI-0.07-8.8 g, P = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: The effect of adrenergic agonists in asthma depends on their net effect on microvascular leakage, mucosal oedema, vascular clearance of spasmogens, inhibition of cholinergic neurotransmission, and airway smooth muscle contractility. It has been postulated that adrenaline, by virtue of its alpha effects on the vasculature and cholinergic neurotransmission, may have additional useful properties in asthma compared with selective beta agonists such as salbutamol. METHODS: The airway effects of adrenaline (a non-selective adrenoreceptor agonist) were compared with the selective beta 2 agonist salbutamol. Their airway smooth muscle relaxant potencies and effect on histamine contraction in human bronchi in vitro were compared with their effects on airway calibre and histamine reactivity in asthmatic subjects in vivo. For the in vitro studies changes in tension were measured in response to these agents in thoracotomy specimens of human airways. In vivo the effects of adrenaline and salbutamol on airway calibre and histamine reactivity were measured in eight subjects with mild to moderate asthma in a randomised crossover study. RESULTS: Salbutamol and adrenaline had approximately equivalent airway smooth muscle relaxant potencies in vitro and bronchodilator potency in vivo. However, their effects on histamine induced contraction in vitro were significantly different from their effects on histamine reactivity in vivo. Salbutamol was less potent in vitro producing a mean (SE) 2.4 (0.15) doubling dose increase in the histamine EC20 and adrenaline a 5.2 (0.18) doubling dose increase (mean difference between salbutamol and adrenaline 2.8 doubling doses; 95% CI 1.1 to 4.5). Salbutamol had no effect on the maximal response to histamine whereas adrenaline reduced it by 54%. In contrast, salbutamol was more potent in vivo producing a mean (SE) increase in PD20 histamine of 1.84 (0.5) doubling doses whereas adrenaline was without effect increasing PD20 by only 0.06 (0.47) doubling doses (mean difference between adrenaline and salbutamol 1.78, 95% CI 0.26 to 3.29 doubling doses). CONCLUSIONS: These findings suggest that the alpha adrenergic airway effects of non-selective adrenoreceptor agonists such as adrenaline offer no additional protection against histamine-induced broncho-constriction in vivo than beta 2 selective drugs such as salbutamol, despite adrenaline providing greater protection against histamine-induced contraction in vitro. The differences between the effects of these agents in vitro and in vivo may be related to their opposing vascular effects in vivo.
This study identified the exciting nature of work for 176 registered nurses employed in urban and rural home health agencies in the southeastern United States. The results revealed that the majority of the home healthcare nurses perceived their work as moderately to highly exciting. Nurses with higher levels of work excitement selected home care because of personal fulfillment, whereas those who were less excited chose home care for schedule flexibility. Both groups, however, cited direct patient contact as a major factor in their decision to practice in the home care setting.
We studied the role of sodium transport and calcium channels in protein kinase C mediated signal-transduction pathways in bovine airway smooth muscle. 4-beta phorbol 12,13 dibutyrate (PDB), an activator of protein kinase C, caused dose-related slowly developing contraction in bovine bronchial rings with a peak effect at 60-90 min. 4-alpha PDB, an inactive analogue, was without effect. Mean peak PDB-induced contraction (measured as a percentage of the maximum response to methacholine) was reduced from 122% to 20% when experiments were carried out in calcium-free fluids +EDTA (10(-3) M). Similar reductions were seen in the presence of nifedipine and verapamil, inhibitors of voltage-dependent calcium channels. Amiloride at high concentrations (10(-3) M) reduced the contractile response to PDB from 87% to 20%, but at a concentration which inhibits the sodium entry channel (10(-6) M), amiloride was without effect. 5-N,N-hexamethylene amiloride (10(-5) M), a specific inhibitor of Na+/H+ exchange, did not alter the contraction produced by PDB. Frusemide (10(-5) M), an inhibitor of Na(+)-K(+)-Cl- cotransport, was without effect on PDB contractions. We conclude that phorbol ester-induced contraction of bovine airway smooth muscle is dependent on calcium entry via voltage-dependent calcium channels but is independent of Na+ entry, Na+/H+ exchange or Na(+)-K(+)-Cl- cotransport.
Both the human and animal literatures suggest that reactivity to stress is enhanced in the presence of a positive family history of hypertension. There is also some suggestive evidence, though not as strong, that a high-salt diet will enhance reactivity to stress, at least in a subpopulation of individuals. In the present study, rats with zero (Wistar-Kyoto, or WKY), one (borderline hypertensive, or BHR), or two (spontaneously hypertensive, or SHR) hypertensive parents were placed on a normal or high (8% in chow)-salt diet for 8 weeks starting at 8 weeks of age. After 6 weeks on the appropriate diet, rats were stressed daily for 5 days. Each session consisted of 28 foot shock trials preceded by a tone. On the following week, animals were instrumented with femoral artery catheters. After a 2-day recovery period, they were again subjected to the experimental paradigm, during which blood pressure was continuously monitored. Differences were found with respect to blood pressure reactivity and family history: SHR were the most reactive to the tone associated with foot shock. However, no effects of salt on reactivity were observed, despite an effect of this manipulation on basal blood pressure. The effect of foot shock itself was also studied, and revealed that BHR showed a blood pressure reactivity response intermediate between SHR and WKY. Once again, no effects of the salt manipulation were seen. In conclusion, while the data support a relationship between family history of hypertension and reactivity to stress, they do not support a relationship between salt intake and reactivity to stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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In a comparative study, the concentrations of two fluoroquinolone antimicrobials, ciprofloxacin and lomefloxacin, were measured in serum, bronchial mucosal biopsies, epithelial lining fluid (ELF) and alveolar macrophages (AM). Thirty-four subjects received either ciprofloxacin 250 mg b.d. (17 subjects) or lomefloxacin 400 mg o.d. for 4 days prior to sampling by bronchoscopic bronchial biopsy and bronchoalveolar lavage. Both ciprofloxacin and lomefloxacin showed favourable accumulation in the sites of infection with bronchial biopsy concentrations of 1.6 and 1.7 times those of serum respectively; ELF concentrations of 2.1 and 1.9 times serum; and AM concentrations of 11.8 and 20.1 times serum respectively. The MIC90 for most of the common chest pathogens was reliably exceeded by both agents except for that of Streptococcus pneumoniae.
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Cefpodoxime proxetil is a new orally administered cephalosporin which has a favorable spectrum of activity against respiratory pathogens. Concentrations of cefpodoxime in serum and bronchial mucosal biopsy were measured in 13 patients without active respiratory tract infection undergoing fibreoptic bronchoscopy. Samples were taken between 1 and 6 h after a single oral dose of cefpodoxime proxetil equivalent to 200 mg of cefpodoxime base. In twelve patients who completed the study, mean serum concentrations were 1.7 mg/L (S.E.M. 0.4) and in ten patients mean bronchial biopsy concentrations were 0.9 mg/L (S.E.M. 0.2). The mean penetration was 54% (S.E.M. 6.1). Cefpodoxime was undetectable in biopsies from two patients. The majority of serum and biopsy concentrations were in excess of the MIC90S for Haemophilus influenzae and Streptococcus pneumoniae. Cefpodoxime proxetil may be worthy of further study in clinical trials in patients with respiratory infections.
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The concentrations of cefuroxime in human alveolar macrophages (AM), epithelial lining fluid (ELF), bronchial mucosal biopsies and serum were measured after a single dose, equivalent to 500 mg of cefuroxime base, given in the form of the orally-administered pro-drug, cefuroxime axetil. Fourteen patients undergoing fibreoptic bronchoscopy with bronchoalveolar lavage were studied. The mean ELF concentration was 0.7 mg/L, that of bronchial biopsies was 1.8 mg/kg and that of serum 3.5 mg/L. AM-associated cefuroxime was detected in nine patients. To assess the in-vitro activity of the concentrations achieved at the potential sites of infection, clinical isolates of common respiratory pathogens were exposed to two concentrations of cefuroxime, based on the observed concentrations in ELF and bronchial mucosa. ELF and mucosal site concentrations were effective against Streptococcus pneumoniae (except one strain with reduced susceptibility to benzyl penicillin) and Haemophilus influenzae. The ELF concentration was less effective against Moraxella catarrhalis.
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