Biomedical subjects
Publications and source records attributed to E Tabachnik.
The diagnosis of typhoid fever (TF) is usually established by culturing S. typhi from the blood or by serology. In this report we describe three patients in whom the diagnosis of TF was made by the isolation of S. typhi from gastric contents, despite negative blood urine and stool cultures. Culture of gastric contents has not previously been recognized as a diagnostic tool in this disease.
The relationship between release of leukotriene C4 (LTC4) from nasal mucosa in vivo and from peripheral blood leukocytes (PBLs) in vitro was examined in 18 patients with untreated rhinitis allergic to the house dust mite, Dermatophagoides pteronyssinus, and in 20 nonallergic control subjects following challenge with the specific allergen. Allergic patients were subjected to intranasal and PBL challenge with D pteronyssinus and a nonrelevant allergen, Artemisia vulgaris. In all allergic patients, intranasal challenge by D pteronyssinus, but not by A vulgaris, resulted in a release of substances from the nasal mucosa that reacted in a radioimmunoassay with antiserum to LTC4. Dermatophagoides pteronyssinus challenge in vitro of PBLs from the same patients, but not A vulgaris challenge, induced release of the same immunoreactive material into the supernatant. By comparison, the nonallergic subjects challenged with D pteronyssinus showed significantly lower LTC4 levels in their nasal secretions and PBL supernatants. The results show that, following specific allergen challenge, the release of LTC4 by the allergic nasal mucosa is similar in extent and nature to that of PBLs, indicating that these procedures can be used as tools to measure the efficacy of topically and systemically administered antiallergic drugs.
Cough capacity was evaluated in 22 patients with muscular dystrophy (MD) using subjective cough assessment, cough flow-volume curves, maximum expiratory pressures (MEP), forced vital capacity (FVC), and peak expiratory flow rates (PEFR). In ten of the 22 patients transients of peak flow were generated during cough flow-volume maneuvers, indicating dynamic compression of the airways, which is considered important in the physiology of an efficient cough. Patients who could not generate peak flow transients had significantly reduced PEFR, FVC, and MEP values. Measurement of MEP was the most sensitive predictor of flow transient production during coughing; all of the patients who exhibited transients had MEP values of above 60 cmH2O, whereas the highest value of MEP recorded in patients without transients was 45 cmH2O. Three of the 12 patients who were unable to generate flow transients were considered to have an adequate cough by subjective assessment. We concluded that the measurement of MEP is extremely useful for assessment of cough strength in patients with MD.
This study was undertaken to investigate the effect of ketotifen on the immune system of asthmatic children receiving prophylactic treatment with ketotifen. E. rosettes, mitogenic response to phytohemagglutinin (PHA) and concanavalin A (Con A) as well as Con A induced suppression were measured in 15 asthmatic patients before and 1-3 months after treatment with ketotifen (1 mg x 2/day), and in 20 normal healthy controls. No significant difference in immunological parameters studied were found between the pre and post treatment periods in the asthmatic patients, neither was any difference demonstrated between the asthmatic and control group studied.
Measurements of cellular immunity including the percentage of T-cell mitogenic response of lymphocytes to phytohemagglutinin (PHA) and concanavalin A (Con A), as well as Con A-induced suppressor function, were determined in 20 asthmatic children (mean age 12.4 +/- 0.6 years) before and after 6 months of theophylline therapy. Only 9 of the 20 children patients that commenced the study completed the entire 6 months of therapy. A group of 37 healthy children (mean age 12.6 +/- 0.3 years) served as control. During the 6-month period of therapy, theophylline levels were maintained between 10 and 20 micrograms%. No significant difference in any of the parameters examined were found between the initial 20 asthmatic patients and the control group. Furthermore, in the 9 patients that were evaluated before and after 6 months of theophylline therapy no significant change in lymphocyte function including suppressor function was detected. We conclude that the beneficial effect of long-term theophylline therapy in asthmatic children is probably not related to an immuno-modulatory effect.
Erythrocyte glutathione peroxidase (GPX) levels were determined in 56 asthmatic children. Lowest levels were found during acute asthmatic attack (13.53 +/- 2.94 IU) which were significantly less than controls (20.4 +/- 5.44 IU) (P less than .001). Post-attack levels 1 week later rose significantly (16.77 +/- 2.63 IU), but were still less than normal values (P = .001). GPX levels (16.96 +/- 3.28 IU) were less than controls (P less than .03) even in patients with mild symptomatology. Asymptomatic patients receiving theophylline had normal levels. Low GPX activity in asthmatic patients may play a role in the pathogenesis of the disease.
It has been suggested that cysteinyl-containing leukotrienes (LT) are important mediators in bronchial asthma. Since leukotrienes have been shown to mediate the leukocyte adherence inhibition (LAI) phenomenon observed in cancer-bearing host we have devised a modified LAI assay which determines the acquisition of non-adherence properties of leukocytes following a challenge with pure synthetic LT. Our results demonstrate that peripheral blood leukocytes of asthmatic individuals acquire non-adherence properties when challenged with pure synthetic leukotriene C4 and D4, a property not shared by peripheral blood leukocytes of control healthy individuals. Furthermore, we demonstrate that LT activity as manifested by the LAI assay is dependent on cyclooxygenase products, since 2 X 10(-6) M Indomethacin abrogated the LT-induced LAI and is restored by the addition of 2 X 10(-6) M prostaglandin E2 which is also synergistic to LT activity. Our results further suggest the possibility that leukotriene activity is dependent on calcium ions since it was negated by known calcium antagonists. It is thus suggested that the LT-induced LAI may serve as a tool for the study of the interrelationship between the metabolic pathways of arachidonic acid and calcium ion homeostasis.
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The disposition of intravenously and orally administered theophylline was compared in 10 patients with cystic fibrosis (CF) and 10 healthy volunteers. The mean total body clearance of the patients with CF was twice that of the control subjects (p less than 0.001). The volume of distribution of theophylline was also greater in the patients with CF (p less than 0.05). These observations indicate that if theophylline is used in patients with CF, doses larger than those commonly given to asthmatics may be required to maintain therapeutic serum concentrations.
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There is no evidence that any type of therapy, including hyposensitization therapy, will directly influence prognosis. The long-term prognosis of childhood asthma is less optimistic than previously believed. Approximately 30% of the patients who become symptom-free in adolescence relapse and become symptomatic in early adulthood. Blair's recent 20-yr follow-up report on 267 childhood asthmatics revealed that only 50% had become almost or completely symptom-free. Moreover, there is evidence that 60% of those who become symptom-free still demonstrate bronchial hyperreactivity and are liable to wheeze again if challenged with an appropriate stimuli. Therefore, the dictum that most children "outgrow" their asthma is incorrect and a more likely explanation is that most childhood asthmatics "outgrow" their pediatricians.
A new technique to measure ventilation, based on the separate contributions of rib cage and abdomen to tidal volume, the respiratory inductive plethysmograph was evaluated in 20 healthy children. The accuracy of the method was determined by simultaneously measuring tidal volume with a pneumotachograph in the standing, sitting, supine, left lateral decubitus, and prone postures. Comparison of these two techniques showed mean correlation coefficients greater than 0.96, mean slopes between 0.98 and 1.11, and mean SEE of less than 8% in all postures studied. Breathing through a mouthpiece connected to a pneumotachograph resulted in a substantial change in the pattern of breathing and a mean increase in tidal volume of 32% (P less than 0.05). In the standing and sitting postures, rib cage contribution to tidal volume was predominant (greater than 65%) whereas in the recumbent postures abdominal contribution was predominant (greater than 61%). We conclude that the RIP is an accurate means of measuring ventilation in children and that it avoids the artifacts caused by using a conventional respiratory measuring apparatus.
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The effect of sleep state on ventilation and the mechanics of breathing was studied in nine normal adolescents by use of a respiratory inductive plethysmograph and surface electromyogram electrodes. Minute ventilation was state dependent (P less than 0.01), decreasing by a mean of 8% from wakefulness to nonrapid-eye-movement (NREM) sleep and increasing 4% from NREM to rapid-eye-movement (REM) sleep. These changes were caused by changes in respiratory rate. Tidal volume (VT) was not affected by sleep state (P greater than 0.10). The pattern of breathing during wakefulness was similar to that of REM sleep. During NREM sleep intercostal and diaphragmatic muscle activity increased by a mean of 34% and 11%, respectively, as compared with wakefulness, indicating an increase in the respiratory work load. This was accompanied by a substantial increase in rib cage contribution to VT. REM sleep was associated with a marked decrease in intercostal muscle activity (P less than 0.05) and a diminished rib cage contribution; VT was maintained due to a mean increase of 34% in diaphragmatic muscle activity (P less than 0.05).
The effect of sleep state on the ventilatory pattern and chest wall mechanics was studied in 8 asthmatic adolescents (mean age +/- SD, 13.6 +/- 1.3 yr) using a respiratory inductive plethysmograph and surface electromyogram (EMG) electrodes. During rapid eye movement (REM) sleep we observed a mean decrease of 43% in intercostal EMG activity. This was associated with paradoxical inward motion of the rib cage to the extent that the rib cage compartment contributed negatively to tidal volume. Accompanying the abnormal chest wall mechanics there was a mean increase of 45 +/- 38% in diaphragmatic EMG activity, as well as a substantial increase in abdominal contribution to tidal volume. However, despite the increased diaphragmatic activity, tidal volume decreased during REM sleep. The abnormal chest wall mechanics during REM sleep were also associated decreased mean inspiratory flow rates and prolongation of the duty cycle (TI/Ttot). The mean maximal decrease in hemoglobin oxygen saturation during sleep compared with that during wakefulness was 3.9%.
Nine children with bronchopulmonary dysplasia were studied at a mean age of 8.4 years. Persistent respiratory symptoms were common. Pulmonary function tests demonstrated airway obstruction and abnormal blood gas levels in most. In six of eight children results of methacholine challenge tests were positive, indicating bronchial hyperreactivity. Abnormal chest radiographs persisted in eight children. The bronchial hyperreactivity is a likely consequence of airway damage in infancy and is the probable reason for episodic wheezing in the early years of life. Improvement in expiratory flow rates following bronchodilator inhalation suggests that such therapy may improve function in these children.
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