Neuromuscular disease, respiratory failure and cor pulmonale.

Respiratory muscle weakness is an uncommon cause of chronic respiratory failure and a rare cause of cor pulmonale. The problem may not be apparent unless specific physical signs are sought or appropriate investigations performed. We present three patients who presented diagnostic difficulty for prolonged periods until the presence of respiratory muscle weakness was considered. Once the diagnosis was established treatment with nocturnal nasal intermittent positive pressure ventilation produced a dramatic improvement in symptoms and allowed a return to a near normal lifestyle.     

Long-term effects on pulmonary function of mantle radiotherapy in patients with Hodgkin's disease.

Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent chest radiography and pulmonary testing with spirometry, pulmonary mechanics and exercise test combined with arterial blood gas analysis, lung scintigraphy, assessment of pulmonary artery pressure with Doppler cardiography and vector ECG 10-20 years after treatment. The doses to mediastinum ranged from 35-43 (mean 40) Gy given in 26 fractions with the split-course technique. Radiographic signs of slight to moderate pulmonary fibrosis were seen in 18 patients. Minor restrictive ventilatory defects were found with decreased VC, TLC and lung compliance and increased maximal elastic recoil. Little evidence of airflow obstruction was found. Exercise capacity was decreased in three individuals but the mean value for the study group as a whole was normal. Arterial PO2 at maximum exercise was reduced but no patient had diminished hemoglobin saturation. Lung scintigraphy showed defects in 21 patients, mostly consisting of slight abnormalities at the lung periphery and apices. The perfusion seemed to be more affected than the ventilation, suggesting primary vascular lesions. Twelve patients showed signs of right ventricular hypertrophy in vector ECG and four of these had systolic pulmonary artery pressure greater than or equal to 30 mm Hg. The observed abnormalities were mostly of a minor degree and few clinically significant long-term effects of mantle radiotherapy on pulmonary function were observed.     

Group treatment assignment for outpatients with schizophrenia: Integrating recent clinical and research findings

Many mental health clinics rely heavily on group treatment in the outpatient care of individuals with schizophrenia. Groups are used because they economize clinician time and provide social interaction for isolated patients. Empirical evidence suggests that groups, combined with medication, are at least as effective as other common treatments. Many group formats and techniques have been used. Choices are often based on pragmatism or inclination, rather than theory or experiment. The authors review recent findings from research on the neurobiology of schizophrenia, its natural history, and the impact of psychosocial factors in its course and treatment. From these findings, they elaborate research based principles for outpatient group therapy in schizophrenia. They describe three distinct formats for group treatment, and delineate the scope of use for each. Finally, they propose guidelines for assignment of patients to appropriate group treatments.Portions of this material were presented at the 1988 Hospital Community Psychiatry Institute, and at the 1989 meeting of the American Psychiatric Association.     

Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia.

BACKGROUND AND PURPOSE: Neutrophils are critically involved with ischemia and reperfusion injury in many tissues but have not been studied under conditions of reperfusion after focal cerebral ischemia. The present studies were conducted to confirm our previous observations quantifying neutrophils in rat permanent focal stroke using a myeloperoxidase activity assay and to extend them to transient ischemia with reperfusion. In addition, leukotriene B4 receptor binding in ischemic tissue was evaluated as a potential marker for inflammatory cell infiltration. METHODS: Histological, enzymatic, and receptor binding techniques were used to evaluate neutrophil infiltration and receptor binding in infarcted cortical tissue 24 hours after permanent middle cerebral artery occlusion (n = 25) or temporary occlusion for 80 (n = 12) or 160 (n = 22) minutes followed by reperfusion for 24 hours in spontaneously hypertensive rats. RESULTS: Sham surgery (n = 26) produced no changes in any parameter measured. After permanent middle cerebral artery occlusion, neutrophil accumulation was observed histologically, but the infiltration was moderate and typically within and adjacent to blood vessels bordering the infarcted cortex. After temporary middle cerebral artery occlusion with reperfusion, marked neutrophil infiltration was observed throughout the infarcted cortex. Myeloperoxidase activity was increased (p less than 0.05) after permanent occlusion and to a greater extent after temporary occlusion with reperfusion. Myeloperoxidase activity (units per gram wet weight) in ischemic cortex was increased over that in nonischemic (control) cortex 32.2-fold, 54.6-fold, and 92.1-fold for permanent occlusion and 80 and 160 minutes of temporary occlusion with reperfusion, respectively (p less than 0.05). Sham surgery produced no changes in myeloperoxidase activity. Leukotriene B4 receptor binding also was increased (p less than 0.05) after focal ischemia and paralleled the increases in myeloperoxidase activity. Ischemic cortex-specific receptor binding (femtomoles per milligram protein) was 3.87 +/- 0.63 in sham-operated rats and 4.57 +/- 0.98, 8.98 +/- 1.11, and 11.12 +/- 1.63 for rats subjected to permanent occlusion and 80 and 160 minutes of temporary occlusion with reperfusion, respectively (all p less than 0.05 different from sham-operated). Cortical myeloperoxidase activity was significantly correlated with the degree of cortical leukotriene B4 receptor binding (r = 0.66 and r = 0.79 in two different studies, p less than 0.01). CONCLUSION: These data indicate that neutrophils are involved in focal ischemia and that there is a dramatic accumulation of neutrophils in infarcted tissue during reperfusion that can be quantified using the myeloperoxidase activity assay. Leukotriene B4 receptor binding increases in infarcted tissue in a parallel manner, which suggests that the increased leukotriene B4 binding is to receptors located on the accumulating neutrophils.     

Oxygen free radicals and pelvic adhesion formation: I. Blocking oxygen free radical toxicity to prevent adhesion formation in an endometriosis model.

Intraperitoneal superoxide dismutase (SOD) and catalase were used to block the toxic effects of superoxide anion (O2) and hydrogen peroxide (H2O2), associated with the production of endometriosis and inflammation in a rabbit model. In a two-part animal study, the combined instillation of SOD and catalase significantly reduced the formation of intraperitoneal adhesions at endometriosis sites.     

A neuromuscular monitoring system based on a personal computer

We have developed a computerized neuromuscular monitoring system (NMMS) using commercially available subsystems, i.e., computer equipment, clinical nerve stimulator, force transducer, and strip-chart recorder. This NMMS was developed for acquisition and analysis of data for research and teaching purposes. Computer analysis of the muscle response to stimulation allows graphic and numeric presentation of the twitch response and calculated ratios. Since the system can store and recall data, research data can be accessed for analysis and graphic presentation. An IBM PC/AT computer is used as the central controller and data processor. The computer controls timing of the nerve stimulator output, initiates data acquisition, and adjusts the paper speed of the strip chart recorder. The data processing functions include establishing control response values (when no neuromuscular blockade is present), displaying force versus time and calculated data graphically and numerically, and storing these data for further analysis. The general purpose nature of the computer and strip chart recording equipment allow modification of the system primarily by changes in software. For example, new patterns of nerve stimulation, such as the posttetanic count, can be programmed into the computer system along with appropriate data display and analysis routines. The NMMS has functioned well in the operating room environment. We have had no episodes of electrocautery interference with the computer functions. The automated features have enhanced the utility of the NMMS. The prime advantages of this system are (1) the ability to customize its features by altering its controlling programs, (2) the ready availability of the hardware and software, (3) the general purpose nature of the system, so that it is not limited to this one application, and (4) the adaptable nature of the system.     

Novel antagonists of the 5-HT3 receptor. Synthesis and structure-activity relationships of (2-alkoxybenzoyl)ureas.

A series of benzoylureas derived from bicycle amines were prepared and evaluated for 5-HT3 antagonist activity on the rat isolated vagus nerve. From among these compounds, those analogues which were ortho substituted by an alkoxy group on the benzoyl function were shown to be potent 5-HT3 antagonists with similar or greater potency than the standard agent ondansetron. NMR and X-ray crystallography studies showed these o-alkoxy compounds to exist as a planar, hydrogen-bonded, tricyclic ring system. In molecular modeling studies on endo-N-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl-amino] carbonyl]-2-(cyclopropylmethoxy)benzamide (30) the central hydrogen-bonded ring was able to mimic an aromatic ring present in previously reported 5-HT3 antagonists.