Transplantation of the diaphragm in rats.
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Biomedical subjects
Publications and source records attributed to S Levine.
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Previous studies have shown that adrenalectomy prevents the normal acquisition of schedule-induced polydipsia (SIP), while corticosterone (CORT) administration reinstates this behavior in adrenalectomized (ADX) rats. These studies investigated which corticosteroid receptor is responsible for mediating CORT effects on SIP. In Experiment I the effects of dexamethasone (DEX) and CORT on the acquisition of SIP were studied. DEX and CORT pellets (respectively 15 mg and 200 mg) were implanted subcutaneously in ADX rats. CORT but not DEX replacement was able to reinstate SIP in ADX rats. Because DEX binds almost exclusively to glucocorticoid receptors (GRs), while CORT binds to both GRs and mineralocorticoid receptors (MRs), results from Experiment I indicated that occupancy of GRs alone is not sufficient for SIP acquisition. In Experiment II CORT pellets of different concentrations (1, 10, 50, 200 mg) were implanted in ADX rats in order to determine whether MRs alone, or a combination of GRs and MRs are required for SIP reinstatement. Results from Experiment II showed that the 1 and 10 mg CORT pellets were not able to reinstate SIP in adrenalectomized rats, while animals implanted with 50 or 200 mg pellets did exhibit the behavior. These results indicate that occupancy of both MRs and GRs is required for SIP acquisition.
Intravenous injection of antigen is the fastest and most effective way of eliciting anaphylactic shock in previously sensitized rats. When intravenous injection is difficult or undesirable, subplantar challenge is a preferable alternative to the intraperitoneal route.
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OBJECTIVE: This study was undertaken to measure the medication error rates associated with verbal orders compared with handwritten and computer-entered orders in an acute-care children's hospital. METHODS: All medication and intravenous fluid orders for a 3-month interval were entered into a computer database. For the same interval, all errors pertaining to the transmission of a medication or intravenous fluid order were also entered into the database. Errors were detected by the hospital pharmacy, which continuously reviews all inpatient medication and intravenous fluid orders for potential errors before dispensing. Errors were also detected by nurses on the floors, who submit incident reports when medication or intravenous fluid errors occur. RESULTS: Verbal orders were associated with significantly lower error rates than either handwritten orders or computer-entered orders (2.6, 8.5, and 6.3 per 1000, respectively), with transcription errors and dosage errors in particular being reduced. Total error rates did not differ between residents and attending physicians. Error rates did not differ between verbal, written, and computer orders for medications with a low frequency of verbal orders and therefore presumed greater complexity. However, the verbal order error rates seemed more sensitive to order complexity than order error rates in general. CONCLUSIONS: The hypothesis that verbal orders are more prone to transmission error than written or computer orders is not supported by the findings in this study. Identifying medications with high levels of order complexity for restriction of verbal order use seems justified. Suggested guidelines for verbal order transmission are presented.
These studies investigated behavioral and hormonal responses to stress in developing mice. Experiment 1 examined the effects of 24-hr maternal deprivation on corticosterone (CORT) secretion and ultrasonic vocalization (UVZ) rate in 4-, 8-, and 12-day-old mice. At these ages, exposure to a novel environment resulted in minimal changes in CORT secretion. Maternal deprivation increased pups' CORT secretion in an age-dependent fashion but did not affect their UVZ rate. The aim of experiment 2 was to test the effects of chlordiazepoxide (CDP), an anxiolytic compound, on CORT secretion and UVZ in both normally reared and in maternally deprived 8-day-old mice. CDP administration elevated CORT secretion in a dose-dependent fashion, producing larger CORT increases in deprived (DEP) animals. CDP affected UVZ only in nondeprived (NDEP) animals: UVZ rate was decreased by high CDP doses. Overall, these findings demonstrate that the infant mouse shows a period of stress hyporesponsiveness similar to the rat and that maternal presence contributes to inhibit adrenocortical activity. CDP administration, but not novelty exposure, increased CORT secretion in 8-day-old normally reared mice suggesting that during the stress hyporesponsive period, the HPA axis is capable of responding only to specific stimuli. Changes in HPA axis activity and UVZ rate resulting from maternal deprivation and/or CDP challenge do not seem to be directly related.
During the healing phase of a chemical peritonitis, one or several skeletal muscle fibers develop, de novo, in the peritoneum of the adult of weanling rat diaphragm. One week after the initial injury the new muscle fibers are narrow and have central nuclei and cross-striations. The fibers increase progressively in caliber and the nuclei take up a subsarcolemmal location. The newly formed muscle fibers are separated from the intrinsic diaphragmatic muscle by an elastic membrane and by a hand of hyaline connective tissue. They are separated from the peritoneal surface by a zone of granulation tissue. Most new fibers are oriented at right angles to the intrinsic diaphragmatic muscle fibers. Their location and orientation suggest an origin from mesothelium or from fibroblasts in the granulation tissue rather than from the intrinsic diaphragmatic muscle. A similar phenomenon can be induced in the pleura on the other side of the diaphragm. In contrast, damage to the diaphragmatic muscle by injection of aluminum lactate does not engender myogenesis in the location described despite active regeneration in the intrinsic muscle.
The cytokine interleukin-1 (IL-1) is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis. During postnatal development, the rat appears to be hyporesponsive to many stimuli which activate the HPA system in adulthood. Since hyporesponsiveness depends to a large extent on the stimulus, these experiments investigated the ontogeny of the HPA axis and interleukin-6 (IL-6) responses to IL-1 beta. Six-, 9-, and 18-day-old pups were injected with human recombinant IL-1 beta and plasma ACTH, corticosterone (CORT) and IL-6 levels were measured. IL-1 beta administration resulted in age-dependent endocrine and immune responses. The younger neonates secreted less ACTH and CORT and more IL-6. This was not due to a lowered capacity of the pituitary to synthesize and secrete ACTH since peptide levels following adrenalectomy did not reveal age differences. These data suggest that the diminished response to IL-1 beta is due to the immaturity of neural circuits which may be required to fully activate the HPA axis to immune signals.
Squirrel monkeys show unusually prolonged elevations in plasma cortisol when separated from like-sex social companions. To determine whether this hypersecretion of cortisol reflects a deficiency in feedback mechanisms that normally inhibit the prolonged activation of the pituitary-adrenal axis, we simultaneously measured plasma cortisol and corticotropin (ACTH) in 30 juvenile monkeys housed in established groups, individual cages, and newly formed groups. As found in recent longitudinal studies of adults, when juveniles were living without companions, mean cortisol titers were consistently higher than those observed when the same juveniles were living in like-sex social groups. When cortisol was elevated, however, ACTH titers were significantly and chronically reduced. These results suggest that elevated cortisol does inhibit ACTH synthesis or release, and that hypercortisolism in squirrel monkeys living without companions is not a consequence of chronic elevations in ACTH. Similar peculiarities in pituitary-adrenal activity are evident in a number of affective disorders in human beings.
OBJECTIVES: We sought to investigate whether reduced respiratory muscle endurance contributes to increased dyspnea and decreased exercise capacity in patients with chronic heart failure. BACKGROUND: In patients with heart failure, the sensation of dyspnea may be related to abnormalities of respiratory muscle function, such as diminished strength or endurance, or both. METHODS: Respiratory muscle endurance was assessed by measuring maximal sustainable ventilatory capacity in 15 patients with congestive heart failure and 8 normal subjects using progressive isocapnic hyperpnea. Near-infrared spectroscopy of an accessory respiratory muscle, Borg scale recordings of perceived dyspnea, time in inspiration, time per breath and minute ventilation were measured. Exercise testing with measurement of oxygen consumption was also performed. RESULTS: Maximal voluntary ventilation (normal subjects 167 +/- 40, heart failure group 89 +/- 31 liters/min) and maximal sustainable ventilatory capacity (normal subjects 90 +/- 23, heart failure group 53 +/- 22 liters/min) were significantly reduced in patients with heart failure (both p < 0.05). No significant accessory respiratory muscle deoxygenation was observed in either group. Borg scale recordings at maximal sustainable ventilatory capacity were comparable in both groups. At rest, the inspiratory duty cycle (i.e., time in inspiration divided by the time per breath) was comparable in the two groups (normal subjects 0.34 +/- 0.09, heart failure group 0.37 +/- 0.12, p = NS). However at maximal sustainable ventilatory capacity, only normal subjects had a significant increase in the inspiratory duty cycle (normal subjects 0.49 +/- 0.04, heart failure group 0.36 +/- 0.10, p < 0.05). This finding suggests obstruction to airflow in patients with congestive heart failure. Values for peak exercise minute ventilation did not differ significantly from values in maximal sustainable ventilatory capacity in either group and were significantly correlated (r = 0.84, p < 0.0001). CONCLUSION: Respiratory muscle endurance as assessed by maximal sustainable ventilatory capacity is reduced in patients with heart failure.
Rats were sensitized to chicken ovalbumin or human gamma-globulin by inoculation without adjuvants into the peritoneal cavity in the healing phase of a chemical peritonitis. This phase is associated with striking enhancement of lymphatic absorption. Small doses of antigen sensitized the rats for subsequent induction of anaphylaxis, but large doses were almost completely ineffective (inverse dose-response relation). When certain adjuvants were added to the antigen, both high and low doses of antigen were effective sensitizers for anaphylaxis. Neither high nor low doses of antigen sensitized if injected without adjuvants into the unprepared peritoneal cavity or by any other route. The effects of sensitization with low or high doses of antigen and the results of inoculation by effective and ineffective routes were interpreted in terms of the balance between absorption into the lymphatics and into the systemic blood circulation. Supplemental antigen inoculated into the systemic circulation was able to tip the balance against sensitization even when sensitization was done with potent adjuvants and by a favorable route. Splenectomy had little or no effect on suppression by supplemental antigen.
BACKGROUND AND PURPOSE: Despite the frequent use of clinical rating scales in multicenter therapeutic stroke trials, no generally acceptable method exists to train and certify investigators to use the instrument consistently. We desired to train investigators to use the National Institutes of Health Stroke Scale in a study of acute stroke therapy so that all examiners rated patients comparably. METHODS: We devised a two-camera videotape method that optimizes the visual presentation of examination findings. We then measured the effectiveness of the training by asking each investigator to evaluate a set of 11 patients, also on videotape. We tabulated the evaluations, devised a scoring system, and calculated measures of interobserver agreement among the participants in this study. RESULTS: We trained and certified 162 investigators. We found moderate to excellent agreement on most Stroke Scale items (unweighted kappa > 0.60). Two items, facial paresis and ataxia, exhibited poor agreement (unweighted kappa < 0.40) and should be revised in future editions of the scale. Performance improved with video training compared with previous studies. Inclusion of the motor rating of the unaffected limbs in the total score did not affect reliability. CONCLUSIONS: Video training and certification is a practical and effective method to standardize the use of examination scales. Two cameras must be used during the taping of patients to accurately present the clinical findings. This method is easily adapted to any study in which a large number of investigators will be enrolling patients at multiple clinical centers.
Tympanoplasty and tympanostomy tubes were developed at the same time and have dramatically changed the treatment of chronic middle ear disease. One hundred forty-nine children who had tubes inserted between ages 6 months and 8 years for chronic otitis media with effusion have been prospectively followed up for an average of 4 years. Fourteen percent developed tympanic membrane perforations. No preoperative factor completely predicted the development of perforation. A majority of the perforations closed spontaneously. Three ears had noncontiguous observations of perforations during follow-up. The implications of these findings are discussed with respect to tympanoplasty.
A patient with adult acid maltase deficiency (AMD) developed severe obstructive sleep apnea (OSA) and respiratory insufficiency. Weaning failure was followed by diffuse pneumonia and death. At autopsy, profound muscle replacement by fibrofatty tissue was noted in the tongue and diaphragm, while the accessory and nonrespiratory muscles were variably preserved. To our knowledge, this case represents the first detailed clinical description of OSA associated with adult AMD. In addition, we suggest that severe tongue weakness due to fatty metamorphosis, in concert with macroglossia, provides a unique pathophysiologic mechanism for OSA.
OBJECTIVES: Studies of the health effects of job strain have focused on morbidity and mortality as outcomes. This is the first study to examine the relationship of job strain to more comprehensive health status measures that encompass health-related quality of life. METHODS: In a national cross-sectional survey, 1319 working men and women, aged 18 through 64 years, completed a modified version of the Job Content Questionnaire that classified workers' jobs into four categories: high strain, passive, low strain, and active. Subjects also completed the Medical Outcomes Study Short-Form Health Survey and a health distress scale. Logistic regression analyses were employed that controlled for age, race/ethnicity, gender, and education. Both work and nonwork variables were included. RESULTS: Job strain was significantly associated with five of nine components of health-related quality of life: physical functioning, role functioning related to physical health, vitality, social functioning, and mental health. Job strain made a modest yet statistically significant contribution beyond the effects of chronic illness and psychosocial variables. CONCLUSIONS: The results provide justification for further investigating the role of job strain as an independent risk factor for health-related quality of life.
The objective of this study was to model, for patients at risk of recurrent depression, the cost-utility of maintenance therapy with sertraline compared with treatment of acute episodes with dothiepin ('episodic treatment'). Using clinical decision analysis techniques, a Markov state-transition model was constructed to estimate the lifetime costs and quality-adjusted life-years (QALYs) of the 2 therapeutic strategies. The model follows 2 cohorts of 35-year-old women at high risk for recurrent depression over their lifetimes. Model construction and relevant data (probabilities) for performing the analysis were based on existing clinical knowledge. Two physician panels were used to obtain estimates of recurrence probabilities not available in the literature, health utilities, and resource consumption. Costs were obtained from published sources. The baseline analysis showed that it costs 2172 British pounds sterling ($US3692, 1991 currency) to save an additional QALY with sertraline maintenance treatment. Sensitivity analysis showed that the incremental cost-utility ratio ranged from 557 British pounds sterling to 5260 British pounds sterling per QALY. Overall, the resulting ratios are considered to be well within the range of cost-utility ratios that support the adoption and appropriate utilisation of a technology. Based on the study assumptions, long term maintenance treatment with sertraline appears to be clinically and economically justified choice for patients at high risk of recurrent depression.
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