Occlusive gloves and skin conditions: is there a problem? Results of a cross-sectional study in a semiconductor company.

BACKGROUND: Although there is poor scientific evidence that working with occlusive gloves is as damaging as wet work, prolonged glove occlusion is considered to be a risk factor for developing hand eczema similar to wet work. OBJECTIVES: To assess the effects of wearing occlusive gloves during the whole working day, without exposure to any additional hazardous substances, on skin condition and skin barrier function. METHODS: We investigated 323 employees of a semiconductor production company in Germany: 177 clean-room workers wearing occlusive gloves during the whole shift (exposed group) and 146 employees working in administration (control group). A standardized interview was performed, the skin condition of both hands was studied using the quantitative skin score HEROS, and transepidermal water loss (TEWL) and stratum corneum hydration were measured. RESULTS: There was no significant difference in skin condition between the two subgroups. Values for TEWL and corneometry were significantly higher in exposed participants (P < 0·05). However, the TEWL values were similar to control values if participants took off the occlusive gloves at least 30 min before the measurement. Hence, the effect of occlusion on skin barrier function seems to be transient. CONCLUSIONS: Prolonged wearing of occlusive gloves with clean hands and without exposure to additional hazardous substances does not seem to affect the skin negatively.

Intra-operative myocardial ischaemia cannot be detected by analysis of transmitral inflow patterns in patients undergoing off-pump coronary surgery.

BACKGROUND AND OBJECTIVE: Transmitral inflow patterns have been used for detection of myocardial ischaemia. However, its diagnostic value has not been tested in anaesthetized and mechanically ventilated patients undergoing coronary artery bypass graft surgery. METHODS: Transmitral inflow patterns were studied by transoesophageal Doppler echocardiography in 43 patients undergoing coronary artery bypass graft surgery without cardiopulmonary bypass after opening of the sternum (baseline) and during grafting of the left anterior descending artery. Peak early (E) and peak late (A) transmitral velocities and their ratio (E/A) were recorded. Myocardial ischaemia was defined by standard criteria using two-dimensional echocardiography and seven-lead electrocardiogram. RESULTS: Thirty-one patients (64 +/- 8 yr, 9 women) fulfilled the predefined inclusion criteria for analysis. During distal revascularization, 16 patients showed myocardial ischaemia and 15 did not. The use of vasoactive drugs, haemodynamic findings and transmitral inflow patterns were similar in both groups at baseline and during grafting. In the ischaemic group, E was 67.1 +/- 13.9 cm s-1 at baseline and 69.5 +/- 23.2 cm s-1 during grafting, and the E/A ratios were 1.3 +/- 0.3 and 1.4 +/- 0.9, respectively. In the non-ischaemic group, E was 64.0 +/- 17.1 cm s-1 at baseline and 60.9 +/- 14.8 cm s-1 during grafting, and the E/A ratios were 1.4 +/- 0.7 and 1.2 +/- 0.3, respectively. CONCLUSIONS: Analysis of Doppler findings of transmitral inflow patterns did not allow for detection of myocardial ischaemia during surgical revascularization of the myocardium.

Clinical outcome after composite grafting of calcified left anterior descending arteries.

AIM: The treatment of a severely calcified left anterior descending coronary artery (LAD) remains a challenge in cardiac surgery. The objective of this retrospective study was to assess the early clinical outcome obtained from LAD reconstruction, which was performed using a combination of both, saphenous vein and the left internal thoracic artery (LITA) as a composite graft, in order to achieve complete revascularization. METHODS: Between January 1998 and December 2003, 71 patients, 13 female and 58 male, with a mean age of 67+/-9.12 years were retrospectively analyzed. All patients suffered from a severe 3-vessel disease with a diffusely calcified LAD. The design of the reconstruction consisted in a long arteriotomy of the LAD grafted with a matched segment of the saphenous vein using the plaque exclusion technique to avoid endarterectomy. The LITA was then anastomosed to the saphenous vein in an end-to-end configuration. With this design, the saphenous vein was used first as a ''patch'' reconstruction of the LAD and second as an elongation for the LITA. The clinical outcome was assessed by mailed questionnaires or by telephone interview with the responsible cardiologist or general practitioner. RESULTS: The follow-up was 100%, comprising a mean follow-up time of 17+/-11.8 months. Overall mortality was 7% (N=5/71). Four cardiac deaths and 1 non cardiac-related death were registered. The in-hospital mortality was 2.8% (2/71); 2 cardiac-related deaths and one non cardiac-related death were observed after 30 days (4.2%). Postoperative myocardial infarction without heart failure was seen in 4 patients (5.4%). In addition, an episode of transitory cerebral ischemia was observed in 1 patient (1.4%). No further postoperative complications occurred. At the time of evaluation, 67% of the patients were in functional class CCS 0 and 33% in functional class CCS I to II. CONCLUSIONS: Composite graft reconstruction without endarterectomy is an alternative treatment option for severely calcified LADs with a good early clinical outcome.

Impact of female gender on the early outcome in off-pump coronary artery bypass surgery.

BACKGROUND/OBJECTIVE: Female gender is an independent risk factor for adverse outcome after conventional coronary bypass surgery (CABG). The objective of this retrospective study was to evaluate the influence of the gender on the early outcome in "off pump" coronary bypass surgery without extracorporeal circulation (OPCAB). PATIENTS AND METHOD: Between January 2001 and December 2003, a total of 225 patients, 49 female and 176 male, underwent OPCAB surgery for multivessel disease at our institution. Operations were performed by the same surgeon. The relationship between OPCAB surgery and clinical outcome with major and minor adverse events was assessed with univariate analysis. RESULTS: The same operative technique was applied for both female and male patient groups. No conversion to conventional CABG with cardiopulmonary bypass was necessary. The overall in-hospital mortality was 1.3% (3 of 225 patients), all of them in the male patient group (p = 0.08). Female patients showed a lower rate of postoperative atrial fibrillation than male patients (6% vs. 15%; p = 0.08). The incidence for further postoperative complications such as rethoracotomy for bleeding, stroke, delirium, pneumonia and wound infection was identical and statistically not different in both groups. CONCLUSIONS: In OPCAB surgery, female gender plays not a predictive role for postoperative adverse events and complications influencing morbidity and mortality. In selected female patients OPCAB surgery has a beneficial effect on early clinical outcome.

Selection bias of elderly patients with chronic angina referred for catheterization.

BACKGROUND: Registry patients are generally older and more sick than patients enrolled in trials questioning the generalizability of trial results. We assessed whether such a selection bias also exists in elderly patients with chronic angina referred for catheterization. METHODS AND RESULTS: All 119 patients age>or=75 years with Trial of Invasive versus Medical Therapy in the Elderly (TIME) inclusion but no major exclusion criteria referred for catheterization during the TIME trial inclusion period in four TIME centers were registered and followed-up for one year. Registry patients differed from the 188 trial patients in the same hospitals in that they were younger, somewhat more frequently male, with less antianginal drugs and studied more often after acute chest pain at rest but with more comorbidities than study patients. Left ventricular ejection fraction and vessel disease were similar. One year mortality was 11.4% in registry and 9.6% in invasive TIME patients but differences disappeared after adjustment for baseline differences. Symptomatic status after one year was similar too. CONCLUSIONS: In elderly patients with chronic angina, a bias in the selection for invasive management exists which seems different from that reported in younger patient settings. After adjustment for these selection factors, however, one-year outcome was remarkably similar in registry and trial patients.

Protecting the endothelial integrity of internal thoracic arteries.

BACKGROUND: Previous functional studies on human internal thoracic arteries, comparing the effect of the traditional harvesting method (occlusion with a clip) with a method leaving the artery perfused, revealed considerably impaired endothelial function associated with enhanced contractility after clipping. We have now investigated whether these observations could be correlated (1) with plasma markers of endothelial dysfunction, and (2) with structural changes in the endothelial layer. METHODS: 32 patients were randomly distributed into groups of clipped and perfused arteries. Arterial blood samples were obtained from both the artery and extracorporeal circulation to determine sP-selectin, sE-selectin, sL-selectin, and thrombomodulin using enzyme-linked immunosorbent assay. Arteries from three patients were examined by scanning electron microscopy. RESULTS: Concentrations of sP-selectin and thrombomodulin were significantly higher in plasma from clipped arteries compared to perfused arteries, whereas sE-selectin and sL-selectin concentrations were similar within the groups. Scanning electron microscopy revealed significant structural changes and loss of endothelial cells in clipped arteries. CONCLUSION: Biochemical and structural results support our findings that leaving the internal thoracic artery perfused preserves endothelial function in the arterial graft.

Safety of heart-lung machines during prolonged standby.

BACKGROUND: Coronary artery bypass surgery is increasingly performed without an extra-corporeal circuit. A heart-lung machine (HLM) is kept on standby for safety reasons, but rarely used. The tubes of the machines are currently discarded after every operation. Costs and waste would be avoided if HLMs could stay on standby for longer periods of time. We therefore investigated the sterility of intra-tube fluid over time. MATERIALS AND METHODS: Four machines were tested. The tube system was fixed and filled with priming solution. Samples of intra-tube fluid and fluid from the fluid bags were taken after 0, 12, 24, 36, 48 and 72 h. Microbiological cultures were performed by direct inoculation and membrane filtration and incubated up to 14 days. Endotoxin levels were also determined. RESULTS: Bacteria were grown from two samples only and were considered as contaminants. Endotoxin concentrations never exceeded acceptable levels. CONCLUSION: To keep HLMs on standby for 72 h is probably safe. The prolonged use of HLMs will contribute to cost and waste reduction in open heart surgery.

Short- and long-term outcome after lung resection for invasive pulmonary aspergillosis.

BACKGROUND: Lung resection for invasive pulmonary aspergillosis (IPA) is controversial. Neutropenia, thrombopenia and poor general condition may increase perioperative morbidity and mortality, and the redeeming benefit is questionable. Therefore we analyzed short- and long-term outcome after lung resection for IPA. METHODS: 41 patients with hematological disease underwent lung resection for suspected IPA: lobectomy (23 patients), wedge-resection (16) and enucleation (2). RESULTS: 4 (10%) patients developed major complications: pleural aspergillosis, bronchial stump insufficiency, severe bleeding, ARDS. 11 (27%) patients showed minor complications: pleural effusion (6), pneumothorax (2), seroma (2) and hematothorax (1). 30-day mortality was 10 % (4 of 41 patients): two died of bacterial septicemia, two of disseminated aspergillosis. One (2%) death was possibly surgery-related. IPA was cleared in 87% of patients, fungal relapse occurred in 4 (10%) patients. Overall survival was 65%, 58% and 40% at 6 months, 12 months and 5 years. CONCLUSION: Lung resection for IPA even in profound cytopenia is feasible with acceptable morbidity and mortality. Fungal infection can be cured in more than 80 % of patients. Long-term outcome can be achieved if the hematological disease is under control.

The value of heparin concentration monitoring in off-pump coronary bypass surgery.

BACKGROUND/OBJECTIVE: In recent years, a remarcable increase in off-pump coronary bypass surgery (OPCAB) was observed. The identical anticoagulation treatment in cardiac surgery with cardiopulmonary bypass (CPB) and OPCAB makes the hemodynamic management in OPCAB procedures essential, since a perioperative compensation of blood loss is difficult and the hemodynamic stability has to be maintained by infusions. The aim of this study was to evaluate the circulating heparin concentration measurement in OPCAB patients by using the heparin/protamine titration method with Hepcon/HMSplus (HMS). PATIENTS AND METHOD: In 8 patients (3F/5M) undergoing elective OPCAB, the calculated heparin dose was administered and heparin concentration was registered together with activated clotting time (ACT) 5 min after administration. Measurements were carried out in 45 min periods and additional heparin was administered if the measured heparin concentration was lower than the calculated. The protamin dose was also automatically calculated by HMS. RESULTS: The mean operation time was 155 +/- 36 min (80-210) with 2.3 bypass grafts per patient. There was a significant difference between the demand for heparin as determined by HMS and the conventionally calculated value (p<0.05). Similarly, the calculated and measured concentration of heparin diverged significantly from each other (p<0.05), independent of ACT. In spite of an initially higher administration of heparin as calculated by HMS, the concentration of circulating heparin was below the estimated value in 7 patients which made a further administration of heparin necessary. The 24 h postoperative blood loss was 550 +/- 176 mL (300-850). No rethoracotomy for bleeding was necessary. CONCLUSIONS: HMS could be a useful method for appropriate anticoagulative treatment in OPCAB procedures, if there is a sufficient hemodynamic management with restrictive administration of infusions guaranted during surgery.

[Ambulatory long-term management of a left ventricular assist device. Current modality in terminal heart failure]. / Ambulante Langzeitbetreuung mit einem Linksherzunterstützungssystem. Eine zeitgemässe Modalität in der Behandlung der terminalen Herzinsuffizienz.

We report about the first use and successful outpatient therapy with an implantable pulsatile left ventricular assist device (LVAD, Novacor) in a patient with a combined dilative and ischemic cardiomyopathy in Switzerland. The patient, a 51 year old man (112 kg, 191 cm, blood type A) developed end-stage heart failure (New York Heart Association class (NYHA) IV) while he was awaiting orthotopic heart transplantation. Due to his profession as an independent graphic-designer the patient was afraid of a long-term temporary disablement with consecutive bankruptcy. Therefore we decided and performed the implantation of a Novacor-LVAD as a bridge to transplantation with the possibility to outpatient therapy in a favourable course. The patient was supported by the device for more than five months. His cardiac functional status returned to NYHA class I, and the patient was discharged 5 weeks after implantation. He returned into his normal life and started working at 100% again. Furthermore the LVAD enabled the patient to participate in almost all activities. Five months (151 days) after implantation a donor organ became available and the patient underwent orthotopic heart transplantation. The use and successful outpatient therapy with an implantable pulsatile left ventricular assist device in our patient has proved to be save, reliable, life-saving, quality of life improving and could be an important alternative for the economic burden in heart failure therapy.

Metyrapone-induced glucocorticoid depletion modulates tyrosine hydroxylase and phenylethanolamine N-methyltransferase gene expression in the rat adrenal gland by a noncholinergic transsynaptic activation.

The hypothalamic corticotropin-releasing hormone system and the sympathetic nervous system are anatomically and functionally interconnected and hormones of the hypothalamic-pituitary-adrenocortical axis contribute to the regulation of catecholaminergic systems. To investigate the role of glucocorticoids on activity of the adrenal gland, we analysed plasma and adrenal catecholamines, tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression in rats injected with metyrapone or dexamethasone. Metyrapone-treated rats had significantly lower epinephrine and higher norepinephrine production than control rats. Metyrapone increased TH protein synthesis and TH mRNA expression whereas its administration did not affect PNMT mRNA expression. Dexamethasone restored plasma and adrenal epinephrine concentrations and increased PNMT mRNA levels, which is consistent with an absolute requirement of glucocorticoids for PNMT expression. Adrenal denervation completely abolished the metyrapone-induced TH mRNA expression. Blockage of cholinergic neurotransmission by nicotinic or muscarinic receptor antagonists did not prevent the metyrapone-induced rise in TH mRNA. Finally, pituitary adenylate cyclase activating polypeptide (PACAP) adrenal content was not affected by metyrapone. These results provide evidence that metyrapone-induced corticosterone depletion elicits transsynaptic TH activation, implying noncholinergic neurotransmission. This may involve neuropeptides other than PACAP.

Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary-adrenal axis responsiveness to restraint stress in adult male rats.

In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long-lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4-month-old male rats malnourished during their perinatal life and on age-matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid-binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma-free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative-feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.

New surface biopolymers for oxygenators: an in vitro hemocompatibility test of poly(2-methoxyethylacrylate).

BACKGROUND/OBJECTIVE: The continuous interaction of blood with artificial contact surfaces under cardiopulmonary bypass can lead to a substantial damage of blood cells and plasma factors. Surface biopolymers in oxygenation systems can help increasing the hemocompatibility, often combined with anticoagulative agents such as heparin. The poly(2-methoxyethylacrylate) [PMEA] is a new heparin-free polymer. The objective of this experimental study was to evaluate the hemocompatibility of a PMEA-coated oxygenator (Terumo Capiox RX-25) (PTX) under standardized in vitro conditions compared to two ionic-bound and one covalent-bound heparin-coated models. METHOD: Each oxygenator was mounted in a separate standardized closed circulation system. Heparinized (5 IE/mL) fresh human blood from the same donor (hemodilution: Ringer's solution) was used. Circulation time: 120 - 180 min with a flow rate of 4.0 L/min. Blood samplings: at the beginning, 5. min and every 30 min of the circulation. PARAMETERS: platelets, granulocytes, plasma factors (p-selectin, alpha-granulomeres expression, and TAT(III)-complex). After the experiment, oxygenators were dismantled and examined by scanning electron microscopy. RESULTS: All of the oxygenators led to an initial reduction of platelets and granulocytes. PTX had the lowest platelet and granulocyte reduction rates. With a lower p-selectin release compared to covalent-bound heparin-coated oxygenator and higher expression of alpha-granulomeres compared to ionic-bound heparin-coated oxygenators, the results of PTX indicated that a high number of circulating platelets were intact on the PMEA surface. TAT(III)-complex showed a steady increase in all of the oxygenators during the tests, more remarkably in PTX. In contrast to ionic-bound heparin-coated oxygenators, the electron microscopy displayed virtually no cellular accumulation on hollow fiber and housing surfaces of PTX and covalent-bound heparin-coated oxygenator. CONCLUSIONS: 1. The hemocompatibility characteristics of PTX were remarkably better than ionic-bound heparin-coated oxygenators and slightly better than the covalent-bound heparin-coated model under in vitro conditions. 2. The PMEA coating can be a useful alternative for patients with heparin-associated disorders. 3. The clinical feasibility of PTX should be evaluated under in vivo conditions.

Morphine-induced stimulation of pituitary-adrenocortical activity is mediated by activation of nitric oxide in the early stages of postnatal life in the rat.

OBJECTIVE: The first aim of the present study was to determine if morphine, a prototypic mu-opioid agonist drug, affects pituitary-adrenocortical activity in developing rat pups (first and second weeks of postnatal life). The second aim of this study was to explore, in vivo, if nitric oxide (NO) could be involved in the neurohormonal response to morphine in the early stages of postnatal life. METHODS: Plasma ACTH and corticosterone concentrations were determined by RIA in rat pups (n=5-14 rats/experimental group) after they had been killed by decapitation. In a first experiment, 1-day and 1- and 2-week-old rats were treated s.c. with morphine (20 mg/kg) or with vehicle (0.9% NaCl) and killed 5-90 min later. In a second experiment, 2-week-old pups were pretreated s.c. with naltrexone (NAL; 0.4 mg/kg or 10 mg/kg), and injected 1 h later with either morphine (20 mg/kg) or vehicle, and killed 30 min later. Some pups injected with only NAL were killed 60 or 90 min later. On the other hand, pups injected with NAL (10 mg/kg) or NAL and morphine were killed 30 min later. In a third experiment, 2-week-old pups were pretreated s.c. with N-omega-nitro l arginine methyl-ester (L-NAME; 30 mg/kg or 100 mg/kg), and injected 1 h later with either morphine (20 mg/kg) or vehicle, and killed 30 min later. Moreover, some pups injected with L-NAME (100 mg/kg) or L-NAME with morphine were killed 30 min later. In a final experiment, pups were injected s.c. with either S-nitroso-N-acetylpenicillamine (SNAP; 5 mg/kg) or vehicle, and killed 60 or 90 min later. RESULTS: Morphine administered to rat pups elicited marked rises in both ACTH and corticosterone secretion. Moreover, these responses increased with advancing postnatal age. In 2-week-old rat pups, NAL, a competitive antagonist at mu-opioid receptors, administered alone increased both plasma ACTH and corticosterone concentrations 30 min later. L-NAME, a specific NO synthase inhibitor, did not affect plasma ACTH and corticosterone concentrations 30 min later when administered alone. NAL, when concomitantly administered with morphine, was unable to block morphine responses. In contrast, morphine responses were blocked by pretreatment (60 min before) with NAL or with L-NAME. Acute injection of SNAP increased both ACTH and corticosterone release. CONCLUSION: Our results suggest that opioids have controversial effects on pituitary-adrenocortical activity in the early postnatal period in the rat, and that endogenous NO is one of the major factors in the response of the pituitary-adrenocortical axis to morphine.

Prospective evaluation of 3 risk stratification scores in cardiac surgery.

BACKGROUND: The aim of the study was to evaluate 3 different risk stratification scores in cardiac surgery, based on the hospital results of 1,299 patients. METHODS: From June 1995 to December 1997, all patients (n = 1,299) undergoing coronary artery bypass grafting (CABG) and/or heart valve surgery were prospectively enrolled. The postoperative in-hospital outcome (mortality, morbidity and length of hospital stay) was analysed in relation to three different risk stratification scores (Parsonnet, Higgins and French score). RESULTS: The results of 1,299 patients (mean age 62.8 +/- 10.2 years) were analysed. 10 patients died, accounting for a total mortality of 0.8%. 13 patients (1%) underwent cardiopulmonary resuscitation. In 25 patients (1.9%), perioperative myocardial infarction occurred. Performance of the 3 systems was assessed by evaluating discrimination with receiver operating characteristic (ROC) curves. The area under the ROC curve was 0.761 for Parsonnet, 0.786 for Higgins and 0.798 for French score. The French and the Higgins score showed an increase of in-hospital mortality, morbidity and length of stay in relation to increasing risk classes. CONCLUSION: For objective evaluation of the outcome in cardiac surgery, case-mix severity needs to be considered, which is reflected by preoperative risk stratification scores. In our study, all the 3 scores showed a high discrimination and are appropriate tools to assess mortality in cardiac surgery. Especially the French and the Higgins score (restricted to 5 groups), due to their simplicity, were useful to predict postoperative outcome in clinical routine.

Autonomic dysreflexia increases plasma adrenaline level in the chronic spinal cord-injured rat.

Autonomic dysreflexia (AD) occurs in up to 80% of quadriplegics and high paraplegics and is characterized by exaggerated sympathetic reflexes which induced paroxysmal hypertension. The aim of this study was to determine if plasma catecholamine levels increased during autonomic dysreflexia in the chronic spinal cord-injured (SCI) rats with special care to adrenaline. Catecholamine samples were collected before, during and 1 h after AD induced hypertension with colorectal distension. Results showed that plasma noradrenaline and adrenaline levels increased respectively 1.5-fold and 5-fold during AD in the chronic SCI rats. This suggests substantial roles for these two hormones in mediating the cardiovascular changes during AD. Knowledge of catecholamine levels during AD may thus aid in determining pathophysiology and potential pharmacologic treatments of this autonomic dysfunction.

Diazepam-like effects of a fish protein hydrolysate (Gabolysat PC60) on stress responsiveness of the rat pituitary-adrenal system and sympathoadrenal activity.

RATIONALE: Gabolysat PC60 is a fish protein hydrolysate with anxiolytic properties commonly used as a nutritional supplement. OBJECTIVE: The diazepam-like effects of PC60 on stress responsiveness of the rat pituitary-adrenal system and on sympathoadrenal activity were studied. METHODS: The activity of the pituitary-adrenal axis, measured by plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (B) of the sympathoadrenal complex, measured by circulating levels of noradrenaline (NA) and adrenaline (A), and the gamma aminobutyric acid (GABA) content in the hippocampus and the hypothalamus were investigated in male rats which received daily, by an intragastric feeding tube, for 5 days running either diazepam (1 mg/kg) or PC60 (300 or 1,200 mg/kg). Controls received only solvent (carboxymethylcellulose 1%). Six hours after the last force-feeding, the rats were subjected to 3 min ether inhalation or 30 min restraint and killed by decapitation 30 min after ether stress or at the end of restraint. RESULTS: Baseline plasma levels of ACTH, B, NA and A were not affected by either diazepam or PC60. Both ether- and restraint-induced release of ACTH, but not B, were similarly and drastically reduced by diazepam and PC60 (1,200 mg/kg). Both diazepam and PC60 (1,200 mg/kg) deleted restraint-induced NA and A increases. Both treatments also reduced the ether-induced rise of A. Basal levels of GABA were significantly increased in both the hippocampus and the hypothalamus in PC60-treated rats and only in the hippocampus in diazepam-treated ones. In controls, ether inhalation as well as restraint increased GABA content of these two brain structures. In contrast, such stress procedures performed in PC60-treated rats reduced GABA content slightly in the hippocampus but significantly in the hypothalamus. In diazepam-treated rats, GABA content of the hypothalamus was unaffected by stresses but that of the hippocampus was slightly decreased. CONCLUSIONS: Present data suggest diazepam-like effects of PC60 on stress responsiveness of the rat pituitary adrenal axis and the sympathoadrenal activity as well as GABA content of the hippocampus and the hypothalamus under resting and stress conditions. These effects of PC60 agree with anxiolytic properties of this nutritional supplement, previously reported in both rats and humans.

Morphine-like substance in leech ganglia. Evidence and immune modulation.

Binding experiments followed by measurement of nitric oxide release revealed an opiate alkaloid high affinity receptor with no affinity to opioids, representing a new mu-subtype receptor in the brain of the leech Theromyzon tessulatum. In addition, evidence of morphine-like substances was found in immunocytochemical studies and HPLC coupled to electrochemical detection (500 mV and 0.02 Hz). Based on previous evidence of the involvement of morphine as an immune response inhibitor, we demonstrate that in leech ganglia injection of lipopolysaccharide (LPS; a potent immunostimulatory agent derived from bacteria) provoked an increase in the level of ganglionic morphine-like substances after a prolonged latency period of 24 h (from 2.4 +/- 1.1 pmol per ganglion to 78 +/- 12.3 pmol per ganglion; P < 0.005; LPS injected 1 microg x mL-1); this effect is both concentration- and time-dependent. Finally, we have demonstrated that morphine, after binding to its own receptor, inhibits leech immunocyte activation through adenylate cyclase inhibition and nitric oxide release. This report confirms that morphine is an evolutionarily stable potent immunomodulator.

Age does not influence early and late tumor-related outcome for bronchogenic carcinoma.

BACKGROUND: The influence of age on early and late outcome after surgical resection of bronchogenic carcinoma is unknown. In an attempt to clarify this issue, we reviewed the outcome of 212 consecutive patients with primary lung cancer who had surgical treatment for bronchogenic carcinoma. METHODS: Ninety-two patients were younger than 50 years (group 1), and 120 patients were older than 70 years of age (group 2). Squamous cell carcinoma and adenocarcinoma were the most common histologic types in both groups. According to the new international staging classification, a similar proportion of stage I, II, and III were observed in both groups. RESULTS: Only the rate of pneumonectomy was significantly higher in younger patients (41% versus 22%, p = 0.002). The overall operative mortality rate in group 1 was 2.2% and 2.6% after pneumonectomy. In group 2 the overall mortality rate was 2.5% and 3.8% after pneumonectomy. Advanced age did not affect operative mortality. The adjusted (tumor-related) survival rate at 5 years was 56% in group 1 and 53% in group 2 (p = 0.93). The adjusted survival rate for patients with stage I was 61% in group 1 and 65% in group 2 (p = 0.21), and for stage IIIa 39% in group 1 and 48% in group 2 (p = 0.43). The adjusted 5-year survival rate was 56% in group 1 and 59% in group 2 for squamous cell carcinoma (p = 0.53) and 49% in group 1 and 42% in group 2 for adenocarcinoma (p = 0.76). CONCLUSIONS: Perioperative risk and midterm survival were similar in younger and older patients after surgical resection of bronchogenic carcinoma. We believe that this result is because surgical candidates constitute already a highly selected group of patients. From these data it is not possible to conclude that biologic behavior of lung cancer is more aggressive in younger patients.

Influence of morphine treatment in pregnant rats on the mineralocorticoid activity of the adrenals in their neonates.

Exposure of pregnant rats to morphine, from day 11 to day 18 of gestation, was previously reported to induce both an adrenal atrophy and hypoactivity of the glucocorticoid function in newborns at term, but did not affect, in vitro, the responsiveness of those glands to adrenocorticotrophin hormone (ACTH) concerning corticosterone release. Moreover, these effects were mediated by maternal hormones from the adrenal glands. In the present work, we investigated the effects of a prenatal morphine exposure on the mineralocorticoid activity of the adrenals in neonates. The first aim of the present study was to determine in these newborns 1) the adrenal and plasma aldosterone concentrations at birth time and during the early postnatal period 2) the plasma levels of Na+ and K+ at birth time, 3) the in vitro responsiveness of the newborn adrenals to angiotensin II (A(II)) and ACTH. The second aim of our study was to investigate the mineralocorticoid activity of the adrenals in newborns from adrenalectomized mothers treated with morphine during gestation. According to present data morphine given to intact mothers induced in newborns a severe adrenal atrophy but increased adrenal aldosterone content and plasma aldosterone level. However, prenatal morphine was unable to affect significantly Na+/K+ ratio in both mothers and newborns. In vitro, the adrenals of neonates from morphine-treated mothers were unresponsive to An and ACTH for promoting aldosterone release; in contrast, aldosterone secretion was significantly stimulated by high potassium levels (55 mEq). Maternal adrenalectomy performed one day before the beginning of morphine treatment prevented morphine-induced adrenal atrophy but was unable to affect significantly the adrenal mineralocorticoid function of the offspring. Such data suggest that a prenatal morphine exposure stimulated both aldosterone synthesis and release in neonates. However, this basal hyperfunction did not appear to be coupled with an enhanced adrenal responsivity to AII or ACTH. Prenatal morphine-induced hyperactivity of the mineralocorticoid function of the newborn adrenals, which drastically contrast with hypoactivity of the glucocorticoid one, was independent of adrenal factors from maternal origin.