Prognostic significance of liver metastases as first site of generalisation in patients with breast cancer--a retrospective analysis.

Of 672 patients with metastatic breast cancer, 24 evaluable patients with primary liver metastases were analysed with regard to their prognostic variables and survival. In 50% of these patients, liver metastases were found within the first 8.5 months after the diagnosis of breast cancer. The median survival of 10 months (range 0-60+ months) was extremely unfavourable. The median survival of hormone-receptor-positive patients (11 months) was significantly longer than that of patients with hormone-receptor-negative tumours (4 months) (P = 0.025). Patients with elevated lactate dehydrogenase (LDH), glutamic-oxaloacetic transaminase (GOT) (> 50 U/I), or bilirubin levels at diagnosis had a significantly shorter median survival than patients with normal laboratory parameters (P = 0.001, P = 0.047, and P = 0.056, respectively). This retrospective study confirms the short survival time for breast cancer patients with liver metastases as initial site of relapse. Hormone-receptor status and the laboratory parameters LDH, GOT, and bilirubin were identified as important prognostic factors for survival.

A double-blind randomized-phase II trial comparing immunization with antiidiotype goat antibody vaccine SCV 106 versus unspecific goat antibodies in patients with metastatic colorectal cancer.

This article reports on the first double-blind randomized clinical study with an antiidiotype antibody vaccine in patients with metastatic colorectal carcinoma. The study was performed to determine immunological parameters, efficacy, and tolerability of the vaccine. Forty-two patients with metastatic colorectal cancer were randomly assigned to multiple immunizations with goat IgG antiidiotype vaccine SCV 106 (n = 21) or unspecific goat IgG as controls (n = 21). The antiidiotype vaccine mimicked the 17-1A glycoprotein antigen associated with colorectal cancer. Of the 42 patients entered, 39 were evaluable for efficacy (SCV 106, n = 18; controls, n = 21). Twenty-nine patients raised antibodies to the vaccines (immunological responders, SCV 106, n = 12; controls, n = 17). Only in the SCV 106 group was a significant increase (p = 0.002) of titers with specificity of antitumor antibody 17-1A found. According to the International Union Against Cancer (UICC) criteria no tumor response was observed. However, in the SCV 106 group the relative increase of carcinoembryonic antigen (CEA) levels between entry and observed disease progression was lower (p = 0.03) and disease progression was determined less frequently by development of new metastases (p = 0.001). On an intention-to-treat basis, the survival time difference between the two groups was not significant. Comparison of immunological responders in both groups revealed a significant survival advantage of the SCV 106-treated patients compared with controls (mean 67 versus 39 weeks; p = 0.01). Immunizations were well tolerated. Vaccination of immunologically responding metastatic colorectal carcinoma patients with SCV 106 leads to slowed disease progression and tumor dissemination and significantly prolongs survival time.

Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection.

In collagenous colitis, the literature is conflicting concerning where in the colon the lesions are most likely to be present and most severe. Conflicting data furthermore shed doubt on the sensitivity of the histological detection of the morphological abnormalities and the threshold criteria for diagnosis. We addressed these questions in 56 patients with collagenous colitis. Two hundred ninety-one coded biopsy specimens were analyzed according to six standardized sites from cecum to rectum. Subepithelial collagen deposits were subjectively graded in hematoxylin and eosin (H&E) sections and quantitatively measured in trichrome-stained sections, respectively. Semiquantitative grading was also done for inflammatory changes of the lamina propria and abnormalities of the surface and crypt epithelium. The transverse colon yielded the largest percentage of biopsy specimens (83%) interpreted as diagnostic of collagenous colitis and also had the largest percentage of biopsy specimens with inflammatory changes (98%). Biopsy specimens from both the rectosigmoid and the right colon (ascending and cecum) were significantly less likely to be diagnostic (P<.01). Only 66% of specimens obtained from the rectosigmoid were diagnostic, and 18% of these were interpreted as normal. Subepithelial collagen deposits proved to be significantly thicker in the transverse (median, 46.8 microm; range, 12 to 212.4) and descending (median, 49.2 microm; range, 6 to 230.4) than in the rectosigmoid (median, 33.6 microm; range, 9.6 to 178.8) and right colon (median, 35.4 microm; range, 6 to 140.4), respectively (P<.01). Almost all biopsy specimens (97%) had collagen deposits thicker than 10 microm. However, the subjective interpretation "diagnostic of collagenous colitis" proved to be most consistent with a threshold of 30 microm. Our results indicate that biopsy specimens from at least as proximal as the transverse colon should be obtained to definitely rule out collagenous colitis. Furthermore, it is evident that in a given biopsy specimen, markedly abnormal subepithelial collagen deposition had to be present for an unequivocal histological diagnosis of collagenous colitis.

Low-intensity laser irradiation improves skin circulation in patients with diabetic microangiopathy.

OBJECTIVE: Diabetic foot problems due to angiopathy and neuropathy account for 50% of all nontraumatic amputations and constitute a significant economic burden to society. Low-intensity laser irradiation has been shown to induce wound healing in conditions of reduced microcirculation. We investigated the influence of low-intensity laser irradiation by means of infrared thermography on skin blood circulation in diabetic patients with diabetic microangiopathy. RESEARCH DESIGN AND METHODS: Thirty consecutive patients with diabetic ulcers or gangrenes and elevated levels of glycosylated hemoglobin were randomized by blocks of two to receive either a single low-intensity laser irradiation with an energy density of 30 J/cm2 or a sham irradiation over both forefoot regions in a double-blind placebo-controlled clinical study. Skin blood circulation as indicated by temperature recordings over the forefoot region was detected by infrared thermography. RESULTS: After a single transcutaneous low-intensity laser irradiation, a statistically significant rise in skin temperature was noted (P < 0.001 by ANOVA for repeated measurements), whereas in the sham-irradiated control group, a slight but significant drop in temperature (P < 0.001) was found. Subsequently performed contrasts for comparison of measurements before and after irradiation revealed significant temperature increases at 20 min of irradiation time (P < 0.001), at the end of the irradiation (P < 0.001), and 15 min after stopping the irradiation (P < 0.001). In the sham-irradiated feet, the drop in local skin temperature was not significant at 20 min (P = 0.1), but reached significance at the end of the sham-irradiation procedure (P < 0.001) and 15 min after the end of sham irradiation (P < 0.001). CONCLUSIONS: The data from this first randomized double-blind placebo-controlled clinical trial demonstrate an increase in skin microcirculation due to athermic laser irradiation in patients with diabetic microangiopathy.

Biliary Wallstent endoprosthesis in malignant hilar obstruction: long-term results with regard to the type of obstruction.

AIM: To evaluate the clinical efficacy of percutaneously placed biliary Wallstents in the management of malignant hilar obstruction with regard to the obstruction type. PATIENTS AND METHODS: Sixty-six Wallstents were inserted in 41 patients with inoperable hilar obstruction: 13 patients had a type I obstruction according to Bismuth-classification, 18 a type II, eight a type III, and two a type IV obstruction, respectively. Clinical follow-up data were obtained from all the patients and the referring physicians. RESULTS: Stent placement was technically successfully in all patients. The procedure-related death rate was 2% (one patient), but the overall 30-day mortality rate was 39%, mostly due to advanced malignant disease, cardiac failure or pneumonia. Stent occlusion was found in 11 patients (27%) after 87 days (mean; range, 8-190 days). After stent placement, the mean stent patency was 96 days and the mean survival was 131 days with no significant difference between patients with obstruction type I, II and III. Multivariate analysis revealed that patients with obstruction due to gallbladder carcinoma had a significantly shorter survival than patients with cholangio-carcinoma or hilar obstruction due to metastases. CONCLUSION: Overall, the insertion of Wallstent endoprostheses offers moderate results for palliation of hilar biliary obstruction regardless of the type of obstruction. In patients with cholangiocarcinoma, long-term results are good even for complicated strictures (type III). In patients with hilar obstruction due to gallbladder carcinoma the outcome is generally poor, regardless of the type of obstruction.

Recombinant Bet v 1, the major birch pollen allergen, induces hypersensitivity reactions equal to those induced by natural Bet v 1 in the airways of patients allergic to tree pollen.

BACKGROUND: Atopic allergens produced by recombinant DNA methods are promising tools for diagnosis and therapy of Type I allergy. To evaluate the immunologic properties of these molecules, it is necessary to compare them with natural allergens in vitro and in vivo. OBJECTIVE: The study was carried out to determine whether the potency of recombinant Bet v 1 (rBet v 1) is comparable to that of natural Bet v 1 (nBet v 1) in inducing allergic reactions in the nose and bronchi. METHODS: Thirteen patients allergic to birch pollen with bronchial asthma and/or rhinitis were investigated. Skin prick tests and nasal and bronchial challenges were performed with rBet v 1 and nBet v 1. RESULTS: In patients allergic to birch pollen, both allergens induced comparable skin reactions. In subjects with rhinitis rBet v 1 was equally potent in inducing nasal reactions (mean PD(+60)NR +/- SD, 10.48 +/- 17.42 microg vs 7.98 +/- 8.9 microg, p > 0.05). In patients with asthma, rBet v 1 was equally potent in inducing bronchial reactions (PD20 FEV1, 0.81 +/- 1.74 microg vs 0.62 +/- 1.44 microg, p > 0.05) as nBet v 1. CONCLUSION: No significant differences were observed between natural and recombinant allergen. We conclude that allergens produced by recombinant techniques can induce typical allergic reactions in important target organs of Type I allergy: the nose and bronchi.

Common bile duct obstruction due to malignancy: treatment with plastic versus metal stents.

PURPOSE: To compare the clinical efficacy and treatment costs of plastic versus metal biliary stents. MATERIALS AND METHODS: In a randomized trial, 101 patients with malignant common bile duct obstruction underwent transhepatic stent implantation and were followed up until death. Patients were stratified into risk and nonrisk groups. Forty-nine patients received 12-F plastic stents, and 52 received expandable metal stents. Plastic endoprostheses were placed in a two-step procedure; metal stent, in a single procedure. Kaplan-Meier analyses were used to compare patient survival and stent patency rates. RESULTS: The 30-day mortality rate was significantly lower for metal stents (five of 52 [10%]) than plastic stents (12 of 49 [24%]; P = .05). The obstruction rate was 19% (10 of 52; median patency, 272 days) for metal stents and 27% for plastic stents (13 of 49; median patency, 96 days; P < .01). Median time until death or obstruction was longer for metal stents (122 vs 81 days; P < .01). Placement of metal stents was associated with shorter hospital stay (10 vs 21 days; P < .01) and lower cost ($7,542 vs $12,129; P < .01). CONCLUSION: Use of self-expanding metal stents appears to show substantial benefits for patients and to be cost-effective.

Alcohol-induced organic cerebral psychosyndromes: partial reversal of cognitive impairments assisted by dihydroergocristine.

Chronic alcohol abusers show a specific pattern of cerebral damage associated with cognitive and behavioral defects known as the organic cerebral psychosyndrome, which is partially reversible upon discontinuation of ethanol consumption. To assess the potential of nootropic drug therapy in alcohol rehabilitation in a double-blind study design, 56 consecutive patients who participated in routine rehabilitation therapy received 2 x 3 mg/day dihydroergocristine or placebo in tablet form over 6-13 weeks. Forty-nine patients completed the protocol. Although significant improvement was seen in both groups, we could document a specific cognitive restitution effect attributable to dihydroergocristine. Significant differences in favor of the active drug group were demonstrated by Mini-Mental State Examination, Syndrome Brief Test, Paired Words Test, in the neuropsychiatric Brief Cognitive Rating Scale assessments, and in the Clinical Global Impression of Change rating. No significant between-group differences were found in the Digit Symbol Test and the Block Design Test as well as in the Brief Psychiatric Rating Scale (BPRS). Dihydroergocristine was equivalent to placebo in terms of subjective drug tolerance, lack of side effects, and laboratory parameters. Based on this profile of efficacy and safety, we recommend dihydroergocristine as an adjuvant drug in alcohol rehabilitation.

Prediction of survival after out-of-hospital cardiac arrest: results of a community-based study in Vienna.

The objective of this study was the assessment of out-of-hospital cardiac arrest and the definition of possible predictive factors for final hospital discharge. Out of a database of 89,557 consecutive missions of the Vienna emergency medical system (EMS) during 1990, there were 623 missions due to a collapse of non-traumatic origin: in 374 cases (60.0%) the patients were declared dead without further attempts at resuscitation. The remaining 249 patients were analysed for predictive factors at site. Survival to hospital admission: 109 patients survived to hospital admission (43.7%); bystander support had a small impact (P < 0.05) on survival to hospital arrival whereas age and gender had no predictive power. Most patients with ventricular tachycardia/fibrillation (VT/VF) survived primarily (69 of 117, i.e. 59.0%). Survival to hospital discharge: 27 patients were discharged from hospital care (10.8%). ECG findings on arrival of the EMS physician at the site proved to be the only powerful predictor for survival: 24 of 117 patients with VT/VF survived compared with only one of 81 with primary asystole, two of 39 with severe bradycardia, and no patient with electromechanical dissociation.

Neoadjuvant chemotherapy (MVAC) in locally invasive bladder cancer.

In order to evaluate the efficacy of neoadjuvant chemotherapy in invasive urothelial carcinoma of the bladder a retrospective analysis was performed. 54 patients without distant metastases (T2-T3b, N0-X, M0) received 3 cycles of neoadjuvant chemotherapy according to the MVAC protocol (methotrexate, vinblastine, doxorubicin and cisplatin) after transurethral resection (TUR) followed by cystectomy. 52 patients had previously undergone cystectomy immediately after TUR. Complete histopathological remission was observed in 9 patients (17.3%) after TUR and in 17 patients (31.5%) after TUR+MVAC. Neoadjuvant MVAC resulted, therefore, in a 14% higher rate of complete remissions. The overall response to TUR was significantly improved by MVAC therapy. Downstaging by neoadjuvant chemotherapy was more readily achieved in initially low-stage tumours (T2: 44.4% and 30.8%, T3a: 47.1% and 19%, T3b: 5.3% and 5.5% in patients receiving TUR+MVAC and TUR alone, respectively). Overall survival did not differ significantly between both groups. Patients who were successfully downstaged to pT0 had a significantly better prognosis, and patients resistant to chemotherapy had the poorest prognosis, showing the shortest survival. In conclusion, histopathological response at cystectomy was improved by neoadjuvant MVAC chemotherapy after TUR and can be expected to be prognostically relevant in those patients who can be downstaged to T0, although overall survival failed to be significantly increased in this relatively small patient sample.

Bronchial wall thickness: appropriate window settings for thin-section CT and radiologic-anatomic correlation.

PURPOSE: To analyze the influence of computed tomographic (CT) window settings on bronchial wall thickness and to define appropriate window settings for its evaluation. MATERIALS AND METHODS: Three inflation-fixed lungs were scanned with a section thickness of 1.5 mm by using a high-spatial-frequency algorithm. Wall thickness in 10 bronchial specimens was measured with planimetry. Window centers were altered in a range of -200 to -900 HU and window widths in a range of 400-1,500 HU. Relative and absolute differences between CT and planimetric values were calculated. CT and planimetric measures were correlated. Inter- and intraobserver variabilities were determined. RESULTS: Window widths less than 1,000 HU resulted in a substantial overestimation of bronchial wall thickness, whereas widths greater than 1,400 HU resulted in an underestimation of bronchial wall thickness. There was no interaction between "width" and "center" regarding their influence on bronchial walls (F = 0.23; P = .99). Correlation between CT and planimetry was statistically significant (r = .85; P = .0001). Differences between the two observers were not statistically significant; results of the measurements of the two observers correlated well (r = .97; P = .001). CONCLUSION: Bronchial wall thickness on thin-section CT scans should be evaluated with window centers between -250 and -700 HU and with window widths greater than 1,000 HU. Other than window settings, notably window widths less than 1,000 HU, can lead to substantial artificial thickening of bronchial walls.

Amantadine versus biperiden: a double-blind study of treatment efficacy in neuroleptic extrapyramidal movement disorders.

Anticholinergic treatment of neuroleptic extrapyramidal movement disorders (EPS) has been associated with induction of tardive dyskinesia. Also an increasing abuse of anticholinergics by schizophrenic patients is noted. Since as early as 1976, positive effects of amantadine (AMA) on neuroleptic EPS have been described, therefore a controlled study of these reports seemed worthwhile. Forty-two schizophrenic patients (of which 7 were dropouts) of three centers entered the study and were treated for EPS in a double-blind design: 18 (11 m, 7 f) with AMA and 17 (8 m, 9 f) with biperiden (BIP). Identical preparations of AMA 100 mg, tid) and BIP (2 mg, tid) were used in treatment of haloperidol-induced EPS (AMA, mean 22.4 mg haloperidol; BIP, mean 19.6 mg haloperidol). Effects of treatment and possible side effects were rated: EPS for the intensity of EPS, BPRS for quantification of psychotic symptoms, FSUCL for rating the side effects and KUSTA to document patients' mood. Ratings were recorded on days 0, 3, 7, 14, 28 and at discontinuation, respectively. All patients were treated with haloperidol and levomepromazine (for tranquilization/sleep induction) and the respective antiparkinsonian agent for 14 days. Patient characteristics did not differ significantly in either groups. In the AMA treatment group, 2 patients dropped out for noncompliance, in the BIP group, 5 (3 no effect, 1 noncompliance, 1 agitation). All results as recorded with the different rating instruments showed a significant (p < 0.01) overall improvement, whereas no significant differences between treatment groups could be determined, notably the treatment effect of both drugs on EPS was similar. Thus, the application of AMA in cases of neuroleptic EPS seems justified and is a useful alternative of anticholinergic drugs. Certain advantageous aspects of AMA treatment of EPS with regard to the glutamate hypothesis of schizophrenia and tardive dyskinesia are discussed.

[Hemodynamics and ergometric performance modified by low dosage oral contraceptives]. / Hämodynamik und ergometrische Leistung unter Einfluss eines niedrigdosierten oralen Kontrazeptivums.

In this pilot study hemodynamic parameters under base-line and performance conditions during a cycle without (N) and with low-dosed oral contraceptives (OC) were of interest. A group of 6 women (age 23.2 +/- 2.1 years) underwent 8 bicycle ergometry sessions each in both a normal cycle and in a cycle on OC. Testing was done in 3 phases of each cycle. Data were obtained on the maximum watt performance, the pulse work capacity at a heart rate of 170 beats per minute (PWC170), as well as on blood pressure and heart rate at rest and at various levels of exercise. No significant differences were found between the N and OC cycles during the follicular phase or in mid-cycle. During the luteal phase, however, faster heart rates and higher blood pressure levels were found for N cycles than in the corresponding phase under OC (p < 0.05).

Comparison of the single breath with the intrabreath method for the measurement of the carbon monoxide transfer factor in subjects with and without airways obstruction.

BACKGROUND: Measurement of the carbon monoxide transfer factor (TLCO) has traditionally been performed using the single breath method but recently the intrabreath method has been developed. The aim of this study was to compare the two methods in the clinical evaluation of patients with obstructive and non-obstructive pulmonary disorders. METHODS: Measurements of TLCO with the intrabreath method were carried out on a study sample composed of 50 patients with non-obstructive disorders and 50 with airways obstruction (FEV1/FVC < 70%) either before or after a single breath measurement of the TLCO had been performed. The method involves the continuous analysis of a single slow expirate using a computerised rapid multigas infrared analyser. TLCO, alveolar volume (VA), TLCO/VA, and inspired vital capacity (IVC) values were obtained for both groups by both methods. RESULTS: When measured with the intrabreath method the group with airways obstruction showed lower TLCO and TLCO/VA values than the non-obstructive group. VA was higher in both patient groups when measured with the intrabreath technique. The same test also showed higher TLCO values with the intrabreath method in the group with non-obstructive disorders and lower TLCO/VA values with the intrabreath method in those with airways obstruction. The corresponding parameters obtained by the two methods correlated closely, with no correlation between the magnitude of the differences with the magnitude of the readings. An index of gas mixing indicated a better distribution of the inspired air for the intrabreath method than for the single breath method. The VA values obtained with the intrabreath method showed a closer agreement to the actual total lung capacities measured by body plethysmography. CONCLUSION: The intrabreath method of determining TLCO is comparable to the traditional single breath method. Measurement of alveolar volume by the intrabreath method approximates more closely to total lung capacity, even in subjects with airways obstruction.

[Sensitization to inhaled allergens in the Vienna population]. / Sensibilisierung gegen Inhalationsallergene in der Wiener Bevölkerung.

The present study investigated the sensitization to inhalatory allergens in a randomized cross-section of the population of Vienna (altogether 3000 men and women). A representative sample of 600 persons was invited to an examination consisting of a skin prick test and determination of serum total IgE and allergen-specific IgE. In addition, the same tests were performed in persons with asthma or allergic rhinitis on the basis of a history of these conditions in the replies to a screening questionnaire. Our results showed comparatively high sensitization rates to grass pollen (28%), house dust mite (25%) and cat dander (20%) in the randomized group A. In the symptom-free "healthy" subgroup of the randomized population sample (Group B) there were remarkably high sensitization rates to house dust mite (21%), grass pollen (17%) and cat dander (12%). For the group with allergic rhinitis (Group D) sensitization to grass pollen exceeded 60%, followed by cat dander (44%), birch pollen (36%) and house dust mite (35%). In the asthmatic persons (Group C) the leading allergens were cat dander (40%) and the house dust mite (37%), followed by grass pollen (33%) and birch pollen (20%). Regarding the overall sensitization to inhalatory allergens 61% of the asthmatic group showed a positive prick test. Increased serum levels of total IgE or specific IgE were found in 76% of cases, which underlines the allergic origin of this disease. In the randomized group 51% were sensitized to inhalatory allergens, whilst 39% were subclinically sensitized without ever having had any allergic complaints.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvant intravesical mitoxantrone after transurethral resection of primary superficial transitional cell carcinoma of the bladder. A prospective randomised study.

A prospective randomised controlled clinical trial began in 1989 on 126 patients with superficial transitional cell carcinoma of the bladder (pTa-pT1, grades 1-3) to compare the efficacy of adjuvant topical mitoxantrone after transurethral resection versus no further treatment. 62 patients received no further treatment, 64 patients received weekly 20 mg mitoxantrone intravesically for 6 weeks after differentiated TUR of all visible tumours. The endpoint of the study was any progression of stage or grade or further recurrences. The median follow up was 29 months--the minimum follow up was 24 months. The percentage of recurrences (25.8 versus 23.4), the recurrence rate (1.2 versus 0.9), the overall disease free interval and the tumour progression rate showed no statistically significant differences (P > 0.05 Mantel-Cox test). Only the comparison of time to recurrence in tumours with recurrences showed a statistically significant difference, with a longer disease free interval for the TUR plus mitoxantrone group (P = 0.016 Mantel-Cox test).

[Topical immunotherapy (KLH) vs. chemotherapy (Ethoglucid) in prevention of recurrence of superficial bladder cancer. A prospective randomized study]. / Topische Immuntherapie (KLH) vs. Chemotherapie (Ethoglucid) in der Rezidivprophylaxe oberflächlicher Harnblasenkarzinome. Eine prospektiv randomisierte Studie.

A prospective randomized controlled study on the effect of KLH (keyhole limpet hemocyanin) versus etoglucid in the prevention of recurrences in primary and recurrent superficial transitional cell carcinoma of the bladder (stage pTa-pT1, grades 1-3 according to the recommendations of UICC and WHO) after complete transurethral resection of the tumor started in 198. Patients in group 1 (n = 76) were immunized with 1 mg KLH intracutaneously, after which they received bladder instillations of 30 mg (30 ml) KLH weekly for 6 weeks and then monthly for 1 year. Patients in group 2 (n = 85) received weekly bladder instillations of 0.565 g etoglucid (50 ml 1% solution) for 6 weeks and then monthly for 1 year. The percentage of recurrences, recurrence rate, disease-free interval and tumor progression rate were evaluated for both treatment groups. The end-point of the study was progression in stage or grade or more than two recurrences during the observation period. The shortest follow-up was 12 months, the mean follow-up, 27.5 months. No statistically significant differences were found between the two groups in percentage of recurrences (43.4% KLH-53.9% etoglucid), recurrence rate (4.4 KLH-3.9 etoglucid), mean disease-free interval (12.1 months KLH-13.6 months etoglucid) or progression rate (6.5% KLH-9.4% etoglucid).

Role of glucocorticoids in the cholinergic degeneration in rat hippocampus induced by ethylcholine aziridinium (AF64A).

Glucocorticoids potentiate hippocampal damage induced by various noxious insults in vivo and in vitro and are implicated in age-related loss of neurons in the hippocampus of various species. The cholinergic innervation of the hippocampus appears to be especially prone to the endangering effect of glucocorticoids, since corticosterone, like acute stress or ACTH, induces a rapid activation of the cholinergic septo-hippocampal pathway. We now report the influence of glucocorticoids on the degeneration of this pathway induced by the cholinergic neurotoxin ethylcholine aziridinium (AF64A). The toxic effect of a submaximal dose of AF64A on cholinergic neurons was evaluated in rats during exposure to glucocorticoids or vehicle as well as in adrenalectomized or sham-operated rats. Daily treatment with either corticosterone or dexamethasone, starting 7 d before the bilateral intracerebroventricular injection of AF64A (1 nmol/ventricle), significantly increased the AF64A-induced loss of ChAT activity in the whole hippocampus, whereas bilateral adrenalectomy 7 d prior to AF64A-injection attenuated the effect of AF64A. Short-term exposure to corticosterone starting 24 hr before AF64A was as effective as the 7 d pretreatment. Dexamethasone exacerbated the AF64A-induced cholinergic lesion in the hippocampal subregions CA1, CA3, and dentate gyrus, and adrenalectomy protected all subregions against the action of AF64A. Along the longitudinal axis of the hippocampus a comparable influence was seen in the dorsal and ventral parts. The subregional pattern in the response to glucocorticoid suggests the involvement of mineralocorticoid type I receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Interferon-alpha stimulates the hypothalamic-pituitary-adrenal axis in vivo and in vitro.

The successful therapeutic use of interferon-alpha (IFN-alpha) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-alpha therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-alpha a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-alpha therapy, no significant stimulation of the HPA axis occurred after administration of IFN-alpha. IFN-alpha-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-alpha treatment for 3 weeks. To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-alpha at concentrations of 5 x 10(-8) M or 10(-7) M respectively. In contrast, no direct IFN-alpha effect on pituitary ACTH secretion could be observed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of carotid endarterectomy on various neuropsychologic parameters. A neuropsychologic longitudinal study]. / Einflüsse der Karotisendarterektomie auf verschiedene Hirnleistungsparameter. Eine neuropsychologische Längsschnittstudie.

Carotid endarterectomy was performed in 25 patients with symptomatic cerebrovascular disease. All patients underwent detailed neuropsychological investigations immediately before surgery, immediately after surgery, and again after a follow-up period of 14 months. Immediately after surgery the flicker fusion frequency was temporarily reduced, indicating an impairment of global cognitive functioning. Postoperatively, verbal attention was found to be improved, particularly in younger patients, in patients with TIA, and in patients with left-sided operation. Finally, visual retention (Benton) was improved at the end of the observation period, especially in older patients and in patients with left-sided operation. Considering the complexity of pathologic brain perfusion, the effects of carotid endarterectomy can only be explained if a multidimensional approach is adopted.