Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries.

BACKGROUND: The number of activated mast cells is increased in the adventitia of coronary segments with plaque rupture and in spastic atherosclerotic coronary segments. Neurogenic activation of mast cells has been demonstrated previously in other tissues. Here we identified and quantified contacts between mast cells and nerves in the adventitia of normal and atherosclerotic coronary segments. METHODS AND RESULTS: Normal (types 0 or I) and atherosclerotic (lesion types II, III, and IV) coronary segments from 22 unselected autopsy cases were stained for mast cells and sensory nerves by a histochemical double-labeling method. Contacts between mast cells and sensory nerves were quantified morphometrically and also identified by confocal microscopy. Coronary arteries obtained during heart transplantation were stained for the neuropeptides capable of stimulating mast cells, ie, substance P and calcitonin gene-related peptide. In the adventitia of atherosclerotic coronary segments with type IV lesions, the numbers of mast cells and mast cell-nerve contacts (104+/-15 mast cells/mm(2) and 30+/-5 nerve contacts/mm(2); mean+/-SEM) were significantly greater than in segments with type III lesions (79+/-12 [P<0.001] and 24+/-6 [P<0.001]), those with type II lesions (54+/-4 [P<0.001] and 12+/-2 [P<0.001]), or those with normal intima (31+/-3 [P<0.001] and 4+/-1 [P<0.001]). The nerve fibers connected with mast cells contained both substance P and calcitonin gene-related peptide, which identified them as sensory nerves. CONCLUSIONS: Neurogenic stimulation of mast cells in the adventitia of coronary arteries may release vasoactive compounds, such as histamine and leukotrienes, which can contribute to the complex neurohormonal response that leads to abnormal coronary vasoconstriction.

Elevation of substance P-like peptides in the CSF of psychiatric patients.

Using a radioimmunoassay procedure substance P-like activity was measured in samples of human CSF obtained from 12 patients with major depressive disorder, 12 with schizophrenia, and 15 control cases diagnosed as psychiatrically normal. Levels were significantly higher in CSF of patients with depressive disorder as compared with schizophrenic patients or controls. Chemical characterization revealed that the measured activity was less basic than substance P itself and might be due to C-terminal fragments. A component reacting with an antiserum highly specific for the substance P[1-7]fragment was found in CSF of patients with depressive disorder. The results indicate that substance P-related peptides may be biological markers in psychoses, particularly in major depressive disorder.

Abnormal in vivo response to sodium nitroprusside after porcine single lung transplantation.

The chronic increase of pulmonary vascular resistance after lung transplantation is only partly due to an active increase in baseline vasomotor tone, but the nature of the acute pulmonary hypertension after ischemia and reperfusion is not known. We studied the effects of sodium nitroprusside on pulmonary hemodynamics during reperfusion in porcine left lung allotransplants. In twelve pigs (weight: 18 to 24 kg) pulmonary arteries of the native and the transplanted lung were cannulated for right-heart bypass. The total blood flow was 2 L/min. Flow distribution between the lungs was measured at equal mean pulmonary artery pressure, and pulmonary vascular resistance at equal and constant flow-i.e., 1 L/min to each lung. After baseline measurements sodium nitroprusside (1, 3, and 9 microg/kg/min) was administered to six animals (SNP group). The control group (n=6) received an equal amount of the vehicle. After 30 min of discontinuation of the drug infusion, the schedule was repeated. In the transplanted lung, pulmonary vascular resistance decreased in all animals during the first hour of reperfusion. During the second drug infusion pulmonary vascular resistance was significantly lower in the SNP group compared with the control group only at the highest infusion rate of the drug (9 microg/kg/min), which also induced a 44% decrease in systemic vascular resistance. Arterial oxygen tension remained comparable in the two groups throughout the study. Our data suggest that other factors besides active vasoconstriction may contribute to the acute increase of pulmonary vascular resistance after lung transplantation.

Single lung allotransplantation in pigs. A morphologic study of tissue preservation with modified Euro-Collins and fluorocarbon solutions.

In the present study the functional and morphologic effects of two pulmoplegic solutions are evaluated. Single left-lung allotransplantation with ligation of the right pulmonary artery was performed in 15 piglets (13-20 kg). The lungs were preserved after donor prostaglandin E-1 treatment with single pulmonary artery flush with either modified Euro-Collins solution (mECS) (9 pigs) or oxygenated fluorocarbon emulsion (FC-43) (6 pigs) and transplanted after 6-hr storage in cold Physiosol solution. Tidal volumes of 15 ml/kg x fr (18) with 40% inspired oxygen were used for ventilation during reperfusion. Function of the transplanted lung was monitored for 4 hr postoperatively by determining pa CO2 and pa O2 levels from arterial samples and by noninvasive monitoring of end-tidal CO2 values and arterial oxygen saturations. Sequential morphologic changes in pulmonary artery flow surface and lung tissue were studied after 6-hr storage and 4-hr reperfusion, using light, scanning, and transmission electron microscopy (LM, SEM, TEM). There was no mortality. After transplantation the mECS group experienced significant hypoxia and hypercarbia and had low end-tidal CO2 values as signs of defective oxygenation and gas exchange, whereas the FC-43 group was normoxic and normoventilated without disturbed elimination of carbon dioxide. After storage and reperfusion, LM showed signs of increased vascular permeability and reperfusion damage--more evident in the mECS group compared with the FC-43 group--while the lymphoid cell population was more intensely activated in the latter group. Electron microscopy after storage showed good overall preservation of structures in both groups. After reperfusion preservation of pulmonary artery flow surface and lung tissue was estimated to be moderate in the mECS group, whereas it was good-to-moderate in the FC-43 group by SEM (NS). TEM of lung tissue, however, showed significantly better-preserved alveolar epithelial lining in the FC-43 group compared with the mECS group. In conclusion, oxygenated fluorocarbon (FC-43) pulmoplegia gave better functional and morphologic preservation of lung grafts compared with modified Euro-Collins solution.

Immunohistochemical detection of pulmonary cytochrome P450IA and metabolic activities associated with P450IA1 and P450IA2 isozymes in lung cancer patients.

The main polycyclic aromatic hydrocarbon-inducible cytochrome P450 was studied in lung tissue from 57 lung cancer patients by immunohistochemistry, using a monoclonal antibody (1-7-1) that recognizes P450IA1 and P450IA2 isozymes. The intensity of immunostaining was compared with the pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), and with P450IA2-related metabolic activity estimated from the ratio of caffeine metabolites in urine. Immunostaining was not observed in peripheral lung tissue of nonsmokers or ex-smokers but was seen in the bronchiolar and alveolar epithelium of all patients who were smokers and had a peripheral carcinoma (16/16) and of 60% (10/17) of those who had a bronchial carcinoma. AHH activity was positively related to the intensity of immunostaining, and an almost 2-fold increase due to smoking was detected in the ratios of caffeine metabolites. These results demonstrate that tobacco smoke induces P450IA1 in the lung and probably P450IA2 in the liver, and suggest a role for certain metabolic phenotypes of P450IA1 in peripheral pulmonary carcinoma.

Management of delayed esophageal perforation with mediastinal sepsis. Esophagectomy or primary repair?

Ninety patients with esophageal perforations were operated on at our institutions between 1970 and 1992. Thirty-four of them were seen after delayed diagnosis (> 24 hours) with mediastinal sepsis caused by perforation of the thoracic esophagus. There were 18 patients with spontaneous ruptures, 11 with instrumental perforations (including one caused during laparotomy), and 3 perforations caused by foreign bodies. One patient had perforation of an esophageal ulcer into the pericardium and another had perforation of an esophageal diverticulum into the mediastinum. Nineteen patients underwent primary repair of the perforation with cleansing and drainage of the mediastinum and the pleural cavity. The remaining 15 had primary extirpation of the thoracic esophagus, irrigation of the mediastinum with antibiotics, cervical esophagostomy, gastrostomy, and drainage of the mediastinum and pleural cavity. Nineteen of the 34 patients survived (hospital mortality 44%). Of patients with primary repair, only six survived (in-hospital mortality 68%), whereas only two patients treated with esophagectomy died (in-hospital mortality 13%). The difference was highly significant (p = 0.001). The most common cause of death was multiorgan failure resulting from sepsis. Postoperative complications developed in four patients treated with primary repair (two sepsis, one empyema, and one anuria) and in seven patients treated with esophagectomy (two empyema, two sepsis, one pneumonia, one mediastinal abscess, and one brain abscess). After healing of the mediastinitis, the esophagogastric continuity was reconstructed with colon in 11 patients and stomach in two patients. In the management of delayed esophageal perforation with mediastinal sepsis, esophagectomy is superior to primary repair alone, which often leads to mediastinal leakage, continued sepsis, and death.

Experimental piglet lung transplantation: histological bioptic changes and autopsy findings.

To investigate difficulties in diagnosing pulmonary rejection and to create a new model to observe long-term histological consequences, 21 piglets were subjected to left single lung transplantation. Five of these transplants served as targets for unmodified rejection in piglets without immunosuppression (Group I), 13 recipients were treated with cyclosporin A, azathioprine and methylprednisolone (Group II), and in 3 cases reimplantation of an autograft was performed (Group III). In the course of postoperative graft monitoring, transthoracic/bronchial biopsies were obtained on days 3, 5, 7, 10, 14, and 20, and thereafter less frequently up to 134 days. In the unmodified rejection group, grafts consolidated in one week and histologically presented perivascular mononuclear cell infiltrates, except for one case which showed vasculitis. Lymphocytic bronchiolitis and or peribronchiolar infiltrate was present in three of the four autopsied grafts. In Group II acute rejection was detected six times in three piglets, and all except one of these specimens had a peribronchiolar component. Although no incontestable bronchiolitis obliterans developed, mild to moderate chronic obliterative vascular lesions were detected in all immunosuppressed piglets (n = 3) surviving more than 80 days. Contralateral lungs and Group III autografts showed mild changes related to the operation itself and interstitial swine endemic pneumonia (SEP). Chronic changes related to rejection were limited to the vascular wall. The mainly inflammatory bronchiolar changes are thought to present an incipient phase leading to obliterative lesions.

Pulmonary vasodilatory properties of prostaglandin E1 are blunted after experimental single lung transplantation.

BACKGROUND: Pulmonary dysfunction and right heart failure are still a common clinical problem after single lung transplantation. METHODS: In this study we investigated the pulmonary vasodilatory properties of prostaglandin E1 in pigs during the first 4 hours after left lung allotransplantation. With the use of extracorporeal circulation and total right heart bypass, the right and left pulmonary arteries could be individually perfused and the drug effect in each lung separately analyzed either at equal blood pressures or at equal blood flows in the pulmonary arteries. Twelve animals received in a randomized double-blind fashion either saline solution or an increasing prostaglandin E1 infusion (10, 25, 50, and 100 ng/kg/min; 15 minutes each). After a drug-free period of 75 minutes, the infusion schedule with 25, 50, and 100 ng/kg/min was repeated. RESULTS: During the first part of the study the highest dose of prostaglandin E1 decreased the mean systemic arterial pressure by 25%, but an almost similar decrease occurred in the control animals. During the second infusion period a 28% decrease was observed only in the animals treated with prostaglandin E1. None of the infusions was able to decrease pulmonary vascular resistance. Instead prostaglandin E1 diverted two thirds of the pulmonary blood flow toward the native lung, and this diversion manifested itself as an earlier improvement of the arterial oxygen tension in the drug-treated animals. The end-tidal carbon dioxide values measured from each lung corresponded to those from the common expiratory limb of the system, but there was a distinct gradient in the range of 14 to 20 mm Hg between the arterial and end-tidal carbon dioxide values. CONCLUSIONS: We conclude that prostaglandin E1, in doses tolerated by the systemic circulation, is ineffective in the treatment of the increased pulmonary vascular resistance after single lung transplantation.

Thromboxane receptor blockade does not attenuate pulmonary pressor response in porcine single lung transplantation.

BACKGROUND: The ischemia-reperfusion lung injury is characterized by increased pulmonary vascular resistance, edema, and subsequent deterioration of oxygenation. Other models of acute lung injury suggest that thromboxane A2 may contribute to the pulmonary hypertension after transplantation. METHODS: We studied the effects of the selective thromboxane A2 receptor antagonist SQ 30741 on pulmonary hemodynamics and gas exchange in porcine single lung transplantation using extracorporeal circulation (right heart bypass) with separate cannulations of the right and left pulmonary arteries. Pulmonary vascular resistance was measured at equal and constant flow to each lung. Flow distribution between the lungs was registered at equal pulmonary artery pressures. Twelve pigs (weight 17 to 23 kg) were studied. At the onset of reperfusion a bolus dose of the drug (5 mg/kg) was injected into both pulmonary arteries followed by an infusion (5 mg/kg/hr) for 1 hour (SQ group, n = 6). The control group (n = 6) received an equal amount of vehicle. The systemic and pulmonary hemodynamics and blood gas values were registered during 2 hours of reperfusion. RESULTS: The pulmonary vascular resistance of the transplanted lung was significantly higher compared with the native lung (p < 0.001). Administration of SQ 30741 failed to ameliorate the pulmonary pressor response of the graft in comparison with the control group. No difference was found in the systemic arterial oxygen tension between the two groups. CONCLUSIONS: Thromboxane does not seem to be among the principal mediators in the pulmonary hypertension after transplantation.

L-Arginine in lung graft preservation and reperfusion.

BACKGROUND: Inhaled nitric oxide has been shown to ameliorate early lung graft dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well-ventilated lung areas, and it also modulates leukocyte-endothelium interactions. We used a porcine, single lung transplantation model to evaluate whether the benefits of exogenously administered gas could be achieved easier by adding L-arginine, the substrate of endogenous nitric oxide synthesis, as an additive to the flush solution and intravenously during reperfusion. METHODS: Six pig lungs were flushed with modified Euro-Collins solutions containing L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients received intravenous boluses of L-arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30 minutes of reperfusion. Six control animals received saline as placebo. We measured the blood flow and pulmonary vascular resistance (PVR) in the transplanted and in the native lung using a right heart bypass model. We measured blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene conjugates in pulmonary venous blood and myeloperoxidase activity of the lung tissue. RESULTS: Pulmonary vascular resistance was 4 to 5-fold higher in the transplanted lung than in the native lung, which received 80% of the total blood flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide exchange of the transplanted lung. Nor did L-arginine treatment have any effect on leukocyte sequestration or myeloperoxidase activity in the transplanted lung. The plasma antioxidant capacity in venous blood of the transplanted lung almost doubled shortly during early reperfusion without influence of L-arginine. CONCLUSIONS: L-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.

Value of high-resolution computed tomography in routine evaluation of lung transplantation recipients during development of bronchiolitis obliterans syndrome.

BACKGROUND: Chronic rejection is a major long-term complication after lung transplantation. The purpose of our study was to evaluate the role of repeated high-resolution computed tomographic examinations in monitoring the development of bronchiolitis obliterans syndrome after lung transplantation. METHODS: A total of 126 high-resolution computed tomographic examination in 13 lung transplant recipients was analyzed. During a mean follow-up period of 23 months, bronchiolitis obliterans syndrome developed in eight of the patients. A scoring system from 0 to 10 based on the number of chronic changes on high-resolution computed tomography was developed, and the score of each patient was compared with decline in the forced expiratory volume in 1 second and maximal forced expiratory flow rate of 50% of the forced vital capacity. RESULTS: The score of chronic changes, measured at 1 year after transplantation, correlated inversely with the values of forced expiratory volume in 1 second and maximal forced expiratory flow rate at 50% of the forced vital capacity (p < 0.05). Stage I bronchiolitis obliterans syndrome was associated with scores of 4 to 6 (mean 5.0), stage 2 with scores of 6 to 9 (mean 7.0), and stage 3 with scores of 6 to 9 (mean 7.7). The sensitivity of high-resolution computed tomography was 93% and its specificity was 92% when five chronic changes were used as a cutoff level. CONCLUSIONS: The progress of chronic changes on high-resolution computed tomography occurs concurrently with the development of bronchiolitis obliterans syndrome. High-resolution computed tomography may provide additional morphologic information for noninvasive evaluation of chronic lung rejection.

Somatostatin in the cerebrospinal fluid of schizophrenic patients before and after neuroleptic drug treatment.

A radioimmunoassay procedure was used to determine levels of somatostatin-like immunoreactivity in cerebrospinal fluid obtained from 9 schizophrenic patients, 7 patients with other psychiatric disorders, and 10 nonpsychiatric surgical controls. There were no significant differences in mean somatostatin baseline levels between the schizophrenic, nonschizophrenic, and surgical patients. The concentration remained almost unaltered after 4 weeks of zuclopenthixol treatment in the schizophrenia group and following various neuroleptic, antidepressant, and anxiolytic medications in the nonschizophrenic patients despite a significant decrease of overt psychopathology assessed by the Brief Psychiatric Rating Scale.

Cardiopulmonary bypass with heparin-coated circuits and reduced systemic anticoagulation.

BACKGROUND: The improved biocompatibility of the cardiopulmonary bypass circuits made possible by the use of surface-immobilized heparin may allow for a reduction in the amount of heparin administered systemically. This study was performed to elucidate the effects of cardiopulmonary bypass using heparin-coated circuits and reduced heparinization on hemostatic variables and clinical outcome. METHODS: Thirty patients scheduled to undergo myocardial revascularization were randomized to have either a heparin-coated or an uncoated cardiopulmonary bypass circuit. Anticoagulation was induced with heparin (100 IU/kg in the coated group and 300 IU/kg in the uncoated group) and the activated clotting time was kept over 200 and 480 seconds in the coated and uncoated groups, respectively. RESULTS: The postoperative overnight loss of hemoglobin through the drains was lower in the heparin-coated group (43.6 g; range, 18.5-69.0 g) than in the uncoated group (73.0 g; range, 32.2-137.7 g) (p = 0.0015). Plasma concentrations of prothrombin fragment 1 + 2 and D-dimer were significantly more elevated after cardiopulmonary bypass in the coated group than they were in the uncoated group. Two patients in the coated group had a stroke postoperatively. CONCLUSIONS: The reduction in systemic heparinization was associated with thrombin formation, which may predispose to intravascular and cardiopulmonary bypass circuit clotting. Therefore, generous systemic heparinization may still be prudent despite the improved biocompatibility offered by heparin-coated surface.

Inhaled NO and prostacyclin during porcine single lung transplantation.

BACKGROUND: Increased pulmonary vascular resistance (PVR) and decreased arterial oxygenation frequently complicate lung transplantation. Inhaled nitric oxide (NO) and aerosolized prostacyclin (PGI2) both dilate the pulmonary vasculature and improve oxygenation in adult respiratory distress syndrome. We investigated whether similar effects would occur during early reperfusion of a lung graft. METHODS: Eighteen pigs underwent left lung transplantation. We measured blood flow distribution, mean pulmonary artery pressure, PVR, and gas exchange in each lung separately. Animals were randomized into three groups to receive NO (10 ppm/30 minutes, 40 ppm/30 minutes), nebulized PGI2 (25 microg/mL/30 minutes, 50 microg/mL/30 minutes), or no drugs (control). RESULTS: In the transplanted lung, PVR was significantly higher than in the native lung. Pulmonary vascular resistance of the transplanted lung was lower in the NO and PGI2 groups in comparison with the control group. During the first hour of inhalation, NO decreased PVR more than PGI2. Neither drug improved oxygenation in the graft. CONCLUSIONS: Nitric oxide and PGI2 decreased PVR of the transplanted lung slightly, but the effect did not produce a normal pressure in pulmonary vasculature.

Heart transplantation in repaired transposition of the great arteries.

Cardiac transplantation was carried out in a 40-year-old man with the diagnosis of repaired transposition of the great arteries and right-sided aortic arch who had end-stage cardiac failure due to myopathy of the ventricles. Because of several previous surgical repairs and the orientation of the great vessels, the operation presented some technical problems. Therefore, modifications of operative procedures were used, including recipient hypothermia, circulatory arrest, and changes in the donor heart implantation. The removal of the donor heart was modified in such a way that the graft included the aortic arch and both pulmonary arteries. With the extra length of ascending aorta and transverse arch, the innominate, left carotid, and left subclavian vessels were excised as a button, thereby leaving the distal orifice of the aorta in the superior portion of the transverse arch. For the recipient, the operation was performed using hypothermic total circulatory arrest to dissect free the huge pulmonary artery and the short right-sided aortic arch to place the clamp. Implantation of the donor heart was modified accordingly. The technical results were confirmed one and a half months later on a control digital angiogram. Thirty-five days postoperatively the patient was discharged. Six months after operation, the patient is doing better than ever before in his life. Our findings suggest that a complicated conotruncal development does not preclude cardiac transplantation.

Prostaglandin E1 or prostacyclin in Euro-Collins solution fails to improve lung preservation.

BACKGROUND: In search of the ideal composition of the flush solution for pulmonary preservation, we studied the effects of prostaglandin E1 (PGE1) and prostacyclin as an additive to Euro-Collins solution (ECS) on pulmonary hemodynamics and gas exchange in a porcine single lung transplantation model using extracorporeal circulation and right heart bypass. METHODS: Twenty-two pigs served as donors. The animals were randomized to receive either modified ECS alone (control group, n = 8), ECS with 100 micrograms/L of PGE1 (PGE1 group, n = 6), or ECS with 200 micrograms/L of prostacyclin (prostacyclin group, n = 8). Left lung transplantation was performed in 22 recipients after approximately 4 hours of cold ischemia. RESULTS: Carbon dioxide elimination was significantly depressed in the two prostaglandin groups, and the use of PGE1 was associated with a significant decrease in arterial oxygen tension compared with the control group. Both drugs were inefficient in alleviating the increase in pulmonary vascular resistance after transplantation. CONCLUSION: The use of prostaglandins as constituents of the flush solution was not followed by any improvement of early graft function after cold ischemia.

Nitecapone as an additive to crystalloid cardioplegia in patients who had coronary artery bypass grafting.

BACKGROUND: Nitecapone has been shown to have a protective effect against ischemia-reperfusion injury in experimental heart transplantation and in Langendorff preparations. This prospective, randomized study assessed the effects of nitecapone in patients who had coronary artery bypass grafting. METHODS: Thirty patients with normal myocardial function were randomly divided into control patients (n = 15), who received crystalloid (Plegisol) cardioplegia, and nitecapone patients, who received nitecapone in a 50 microM solution (n = 15) in Plegisol. Cardioplegia was administered as an initial dose of 15 mL/kg of body mass after cross-clamping and 2 mL/kg every 15 minutes. Simultaneous coronary sinus and aortic blood samples, and myocardial biopsies were taken at 1, 5, and 10 minutes after unclamping. Hemodynamics were measured invasively for 24 hours and with transesophageal echocardiography for 3 hours after cardiopulmonary bypass. RESULTS: There were no adverse effects. The incidence of ventricular arrhythmias was significantly lower in the treatment group during the recovery period (p = 0.02). Cardiac output and stroke volume did not differ significantly between the groups. The conjugated dienes gradient between the aorta and the coronary sinus increased significantly during the first minute of reperfusion in the control group (p = 0.02) compared with the nitecapone group. Myeloperoxidase activity in myocardial biopsies was higher in the control group (2.3 times higher at 5 minutes and 3.2 times higher at 10 minutes) than in the nitecapone group (p = 0.13). CONCLUSIONS: Nitecapone did not exert any significant hemodynamic effects in patients with normal ejection fraction.

Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.

A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.

Dynorphin A and substance P in the cerebrospinal fluid of schizophrenic patients.

Radioimmunoassay procedures were used to assay levels of dynorphin A (DYN A) and substance P-like activity (SP) in cerebrospinal fluid (CSF) obtained from 10 schizophrenic patients before and after neuroleptic treatment, from 10 matched patients with other psychiatric disorders before and after treatment, and from 10 nonpsychiatric surgical controls. The highest mean concentration of CSF DYN A was found in the schizophrenic group on admission (significant vs. nonpsychiatric controls). The concentration remained almost unaltered after 4 weeks of zuclopenthixol treatment despite a highly significant decrease of overt psychopathology assessed by the Brief Psychiatric Rating Scale (BPRS). There was no significant difference between the mean CSF DYN A levels of the nonschizophrenic psychiatric patients and the surgical controls. When all psychiatric patients were pooled together, there was a significant correlation between the level of CSF DYN A and the BPRS total score. With regard to CSF SP levels, no statistically significant differences were observed within or between the groups studied. Neither was there a significant correlation between the concentration of CSF SP and overt psychopathology. Nevertheless, the mean CSF SP concentration of three patients with major depression was clearly higher than the corresponding mean concentration of the other patients in the nonschizophrenic group.

Altered regulation of breathing after bilateral lung transplantation.

In our previous animal studies on dogs, regulation of breathing was found to be altered after en bloc transplantation of the heart and both lungs. During carbon dioxide (CO2) inhalation the minute volume was increased due to an increase of tidal volume after transplantation whereas before transplantation both respiratory frequency and tidal volume increased. The success of the heart-lung transplantation was based on experiments on baboons as no long-term survivors were obtained in dogs. It was thought that the regulation of breathing is different in dogs and primates. We therefore decided to study the regulation of breathing in humans after bilateral lung transplantation during CO2 stimulation. The regulation of breathing was tested 2 to 4 months after bilateral lung transplantation in six patients. Six healthy subjects with intact lungs were tested as controls. The test persons were allowed to breathe first room air, then 5% CO2 in air for 4 min and then room air again. The frequency of respiration, tidal volume and minute ventilation were recorded using a phneumotachograph. Simultaneously samples of arterial blood were drawn from a cannulated brachial artery for analysis of pressure of arterial oxygen (PaO2), pressure of arterial carbon dioxide (PaCO2), base excess (BE) and pH. During inhalation of CO2 for 4 min the minute volume doubled in both transplant patients and in controls. The tidal volume of the transplant patients increased significantly more than that of the controls (P < 0.005) whereas respiratory frequency increased significantly only in the controls with intact lungs (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)