Effects of temporal fine structure preservation on spatial hearing in bilateral cochlear implant users.

Typically, the coding strategies of cochlear implant audio processors discard acoustic temporal fine structure information (TFS), which may be related to the poor perception of interaural time differences (ITDs) and the resulting reduced spatial hearing capabilities compared to normal-hearing individuals. This study aimed to investigate to what extent bilateral cochlear implant (BiCI) recipients can exploit ITD cues provided by a TFS preserving coding strategy (FS4) in a series of sound field spatial hearing tests. As a baseline, we assessed the sensitivity to ITDs and binaural beats of 12 BiCI subjects with a coding strategy disregarding fine structure (HDCIS) and the FS4 strategy. For 250 Hz pure-tone stimuli but not for broadband noise, the BiCI users had significantly improved ITD discrimination using the FS4 strategy. In the binaural beat detection task and the broadband sound localization, spatial discrimination, and tracking tasks, no significant differences between the two tested coding strategies were observed. These results suggest that ITD sensitivity did not generalize to broadband stimuli or sound field spatial hearing tests, suggesting that it would not be useful for real-world listening.

Current practice in nutrition after allogeneic hematopoietic stem cell transplantation - Results from a survey among hematopoietic stem cell transplant centers.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is frequently associated with impaired oral intake and malnutrition, which potentially increases morbidity and mortality. Therefore, nutrition is one of the major challenges in the post-transplant period. METHODS: To document the current clinical approach in nutritional treatment, we designed a questionnaire concerning the current practice in nutrition after alloHSCT and distributed it to German speaking centers performing alloHSCT in Germany, Austria and Switzerland between November 2018 and March 2020. Twenty-eight (39%) of 72 contacted centers completed the survey, 23 from Germany, two from Austria and three from Switzerland, representing 50% of alloHSCT activity within the participating countries in 2018. RESULTS: All centers reported having nutritional guidelines for patients undergoing alloHSCT, whereby 86% (n = 24) provided a low-microbial diet during the neutropenic phase. The criteria to start parenteral nutrition (PN) directly after alloHSCT seemed to be consistent, 75% (n = 21) of the corresponding centers started PN if the oral nutritional intake or the bodyweight dropped below a certain limit. In the setting of intestinal graft-versus-host disease (GvHD) the current practice appeared to be more heterogenous. About 64% (n = 18) of the centers followed a special diet, added food stepwise modulated by GvHD symptoms, while only four centers regularly stopped oral intake completely (intestinal GvHD grade >1). Half of the centers (54%, n = 15) applied a lactose-free diet, followed by 43% (n = 12) which provided fat- and 18% (n = 5) gluten-free food in patients with intestinal GvHD. Supplementation of micronutrients in acute intestinal GvHD patients was performed by 54% (n = 15) of the centers, whereas vitamin D (89%, n = 25) and vitamin B12 (68%, n = 19) was added regularly independently of the presence of GvHD. Only 5 (18%) participating centers ever observed a food-associated infection during hospitalization, whereas food-associated infections were reported to occur more often in the outpatient setting (64%, n = 18). CONCLUSION: The survey documented a general consensus about the need for nutritional guidelines for patients undergoing alloHSCT. However, the nutritional treatment in clinical practice (i.e. lactose-, gluten- or fat-free in intestinal GvHD) as well as the use of food supplements was very heterogeneous. In line with current general recommendations the centers seemed to focus on safe food handling practice rather than providing a strict neutropenic diet. More high-quality data are required to provide evidence-based nutrition to patients during and after alloHSCT.

[Postoperative physiotherapy in acute care--when, what and how much?]. / Postoperative Physiotherapie im Akutbereich--wann, welche und wieviel?

This article documents the role of early musculoskeletal rehabilitation in acute care after orthopaedic surgery involving the hip, knee or spine. It discusses the open questions of the type, time and intensity of physiotherapeutic intervention. The role of standardized quality management to define clinical pathways is discussed.

Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus.

BACKGROUND: Obesity is closely related to type 2 diabetes and long-term weight reduction is an important part of the care delivered to obese persons with diabetes. OBJECTIVES: To assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. SEARCH STRATEGY: Computerized searches were performed of MEDLINE (January 1966 to May 2004), EMBASE (January 1974 to May 2004, Web of Science (January 1981 to May 2004, and other electronic bibliographic databases, supplemented with hand searches of reference lists and selected journals. SELECTION CRITERIA: Randomized, controlled trials were included where pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished literature in any language and with any study design was included. DATA COLLECTION AND ANALYSIS: Two reviewers abstracted data and the quality of included studies was evaluated by assessing potential attrition, as well as selection and measurement bias, and a Jadad score was obtained. Effects were combined using a random effects model. MAIN RESULTS: A sufficient number of studies were available for a quantitative synthesis for fluoxetine, orlistat, and sibutramine. Twenty two randomized controlled trials were included in the review, with a total of 296 participants for fluoxitine, 2036 for orlistat, and 1047 for sibutramine. Pharmacotherapy produced modest reductions in weight for fluoxetine (5.1 kg (95% confidence interval [CI], 3.3 - 6.9) at 24 to 26 weeks follow up; orlistat 2.0 kg (CI, 1.3 - 2.8) at 12 to 57 weeks follow-up, and sibutramine 5.1 kg (CI, 3.2 - 7.0) at 12 to 52 weeks follow-up. Glycated hemoglobin also modestly and significantly reduced for fluoxetine and orlistat. Gastrointestinal side effects were common with orlistat; tremor, somnolence and sweating with fluoxetine; and palpitations with sibutramine. Some studies, using a variety of study designs, were available on other drugs and a significant decrease in weight was noted in three studies of mazindol, one of phenmetrazine, two of phentermine. No studies were identified that fit inclusion criteria for pseudophedrine, ephedra, sertraline, yohimbine, amphetamine or its derivatives, bupropion, topiramate, benzocaine, threachlorocitric acid, sertraline, and bromocriptine. AUTHORS' CONCLUSIONS: Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.

Antitrypanosomal and antiplasmodial activity of medicinal plants from Côte d'Ivoire.

The antitrypanosomal activity of 101 crude ethanol extracts derived from 88 medicinal plants from Côte d'Ivoire was determined in vitro using Trypanosoma brucei rhodesiense. Of those extracts 8 showed good activity (IC50 values < or =8 microg/ml), 37 revealed a weak activity (IC50 values between 25 and 8.1 microg/ml) and 56 did not show any activity at all (IC50 values >25 microg/ml). The extracts of Enantia polycarpa (Annonaceae) and Trichilia emetica (Meliaceae) were the most promising ones. Their IC50 values were 0.5 and 0.04 microg/ml, respectively, and the selectivity index 616 and 209, respectively. This is the first report of in vitro antitrypanosomal activity of these two plants. Their high activities render them candidates for the isolation of compounds which could develop into new lead structures for drug development programs against African trypanosomiasis. Seven of the tested extracts exhibited an antiplasmodial activity against K1 strain of Plasmodium falciparum with IC50 values below 4 microg/ml. The highest activity was found for Enantia polycarpa stem bark with an IC50 value of 0.126 microg/ml.

Insulin-like growth factor (IGF) I down-regulates type 1 IGF receptor (IGF 1R) and reduces the IGF I response in A549 non-small-cell lung cancer and Saos-2/B-10 osteoblastic osteosarcoma cells.

The insulin-like growth factor type 1 receptor (IGF 1R) mediates the acute metabolic effects of IGF I as well as IGF I-stimulated cell proliferation and protection from apoptosis. IGF binding proteins (IGFBPs) can modulate these responses. We, therefore, investigated whether intrinsic IGFBPs interfere with IGF I-induced regulation of IGF 1R expression and with the biological response to IGF I in two human tumor cell lines, the non-small-cell lung cancer cell line A549 and the osteoblastic osteosarcoma cell line Saos-2/B-10. We compared the growth rates, IGFBP production, IGF I binding characteristics, IGF 1R protein and mRNA levels, and the acute IGF I response (stimulation of glycogen synthesis) after pretreatment of the cells in serum-free medium with or without added IGF I or medium supplemented with 5% fetal calf serum (FCS). In contrast to A549 cells, which produce IGF I and significant amounts of IGFBPs, survival and proliferation of Saos-2/B-10 cells, which do not produce IGF I or significant amounts of IGFBPs, depended on the addition of exogenous IGF I. IGF I increased the concentration of IGFBP-2 and -3 and decreased the concentration of IGFBP-4 in the medium of A549 cells. As compared to FCS, IGF I pretreatment in both cell lines decreased the number of specific IGF I binding sites, down-regulated total and membrane IGF 1R protein, and largely reduced or abolished the acute IGF I response without affecting IGF 1R mRNA levels. The data suggest that the IGF 1R protein of the two cell lines is translationally and/or posttranslationally down-regulated by its ligand in the presence and in the absence of locally produced IGFBPs and that the cell lines have retained this negative feedback to counteract IGF I stimulation.

Melarsoprol refractory T. b. gambiense from Omugo, north-western Uganda.

Culture adapted T. b. gambiense isolated from Northwest Uganda were exposed to 0.001-0.14 microg/ml melarsoprol or 1.56-100 microg/ml DL-alpha-difluoromethylornithine (DFMO). Minimum inhibitory concentrations (MICs) of each drug were scored for each isolate after a period of 10 days drug exposure. The results indicate that T. b. gambiense isolates from Northwest Uganda had elevated MIC values for melarsoprol ranging from 0.009 to 0.072 microg/ml as compared with T. b. gambiense isolates from Cote d'Ivoire with MIC values ranging from 0.001 to 0.018 microg/ml or with T. b. rhodesiense from Southeast Uganda with MIC values from 0.001 to 0.009 microg/ml. All MIC values obtained fell below expected peak melarsoprol concentrations in serum of treated patients. However, it may not be possible to maintain constant drug concentrations in serum of patients as was the case in our in vitro experiments. Importantly, the MIC of 0.072 microg/ml exhibited by one of the isolates from Northwest Uganda was above levels attainable in CSF indicating that this isolate would probably not be eliminated from CSF of treated patients. PCR amplification of the gene encoding the P2-like adenosine transporter followed by restriction digestion with Sfa NI enzyme revealed presence of fragments previously observed in a trypanosome clone with laboratory-induced arsenic resistance. From our findings it appears that reduced drug susceptibility may be one factor for the frequent relapses of sleeping sickness after melarsoprol treatment occurring in Northwest Uganda.

Phex cDNA cloning from rat bone and studies on phex mRNA expression: tissue-specificity, age-dependency, and regulation by insulin-like growth factor (IGF) I in vivo.

Phosphate regulating gene with homology to endopeptidases on the X chromosome (Phex) inactivating mutations cause X-linked hypophosphatemia (XLH). The disorder is characterized by decreased renal phosphate (Pi) reabsorption in both humans and mice, in the latter shown to be due to a reduction in mRNA and protein of type II sodium-dependent phosphate cotransporter (NadPi-II). To gain insight into the physiological role of Phex, we cloned the rat cDNA and examined tissue-specific and age-dependent mRNA expression. The rat full-length cDNA (2247 nucleotides) shares 96 and 90% identity with the mouse and human cDNA, respectively. We found 6.6 kb Phex transcripts in calvarial bone and lungs, and a weaker signal in liver of newborn rats. In adult animals, Phex mRNA signals were weaker in bone and lungs and absent in liver. Phex mRNA expression in bones and NadPi-I and -II cotransporter mRNA expression in kidney were also determined in hypophysectomized rats. These rats, which lack GH and IGF I, stop growing and exhibit decreased serum Pi levels. Treatment during 6 days with IGF I stimulated growth and increased serum Pi. Phex and NadPi-II cotransporter mRNA levels were higher in IGF I than in vehicle-treated animals, while mRNA expression of NadPi-I, 1alpha-hydroxylase and 24-hydroxylase and serum levels of calcitriol remained unaffected. Age-dependency of Phex expression suggests a role for Phex in Pi retention during growth. Moreover, our findings indicate that an increase in Phex expression in bones under the influence of IGF I may contribute to increased serum Pi by enhancing renal phosphate reabsorption. Because IGF I treatment increased NadPi-II mRNA expression and serum Pi, IGF I appears to act at least partially at pretranslational levels to increase NadPi-II mediated renal Pi retention in growing rats.

Safety of nifedipine in angina pectoris: a meta-analysis.

-Our objective was to compare cardiovascular event rates in patients with stable angina receiving nifedipine as monotherapy or combination therapy and in active drug controls. A MEDLARS search of published articles from 1966 to 1995 in English, French, German, Italian, or Spanish, supplemented by a manual search of bibliographies, identified 60 randomized controlled trials that met protocol criteria. Blinded articles were extracted by 2 physicians. The pooled risks of death, withdrawal, and cardiovascular event were computed and expressed as odds ratios (ORs) for all nifedipine formulations and relative to same study control drug regimens. Thirty cardiovascular events were reported in 2635 nifedipine exposures (1.14%) and 19 events in 2655 other active drug exposures (0.72%). Unadjusted ORs for nifedipine versus controls were 1.40 (95% CI, 0.56 to 3.49) for major events (death, nonfatal myocardial infarction, stroke, revascularization procedure), 1.75 (95% CI, 0.83 to 3.67) for increased angina, and 1.61 (95% CI, 0.91 to 2.87) for all events (major events plus increased angina). Episodes of increased angina were more frequent on immediate-release nifedipine (OR, 4.19 [95% CI, 1.41 to 12.49]) and on nifedipine monotherapy (OR, 2.61 [95% CI, 1.30 to 5.26]). The OR for immediate-release nifedipine was significantly higher than that for sustained-release/extended-release nifedipine (P=0.001), and the OR for nifedipine monotherapy was higher than that for nifedipine combination therapy (P=0.03). Increased risks of cardiovascular events in patients with stable angina on nifedipine were due primarily to more episodes of increased angina, confined to the immediate-release formulation and to nifedipine monotherapy.

Safety of nifedipine in patients with hypertension: a meta-analysis.

Our objective was to compare cardiovascular event rates in patients with mild or moderate hypertension who received nifedipine with active drug controls. We performed a MEDLARS search using the MeSH heading "hypertension" and the text word "nifedipine" to identify all articles that were published between 1966 and August 1995 in English, French, German, Italian, and Spanish languages and that involved human subjects. The computerized search was supplemented by a manual search of article bibliographies. Review of 1880 citations revealed 98 randomized controlled clinical trials that met protocol criteria. Articles were extracted independently by two doctors who were blinded for author, institution, and treatment regimen, using a structured, pretested extraction form. Differences of opinion were resolved by consensus. Fourteen events occurred in 5198 exposures (0.27%) to nifedipine and 24 events in 5402 exposures (0.44%) to other active drug controls. Unadjusted odds ratios for nifedipine versus controls were 0.49 (95% confidence interval [CI], 0.22-1.09) for definitive events (death, nonfatal myocardial infarction or stroke, revascularization procedure) and 0.61 (95% CI, 0.31-1.17) for all events (definitive plus increased angina). The odds ratio for nifedipine monotherapy (sustained- or extended-release in 91% of exposures) was nonsignificantly higher for definitive and all events (odds ratio, 1.40; 95% CI, 0.49-4.03 and odds ratio, 1.39; 95% CI, 0.59-3.32, respectively). The odds ratio for nifedipine in combination with another drug was significantly lower for definitive and all events (odds ratio, 0.09; 95% CI, 0.01-0.66 and odds ratio, 0.15; 95% CI, 0.03-0.65, respectively). Differences in odds ratio for nifedipine monotherapy and combined therapy were statistically significant (P=.02 for definitive events and P=.001 for all events). Results support the safety of sustained- and extended-release nifedipine in the treatment of mild or moderate hypertension when it is used in combination with other drugs.

Searching for signals: mortality and cardiovascular events in published randomized control trials of nifedipine in ischemic heart disease and hypertension.

UNLABELLED: META-ANALYSIS: A meta-analysis of published randomized control trials of nifedipine in hypertension and stable angina pectoris was performed. RESULTS: The results suggest a formulation-dependent increased risk of mortality and adverse cardiovascular outcomes for monotherapy use in patients with stable angina pectoris. No increased risk was seen in the hypertension studies.

(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA]: a purine analogue with trypanocidal activity in vitro and in vivo.

The unique features of purine salvage systems of pathogenic haemoflagellates render them selectively susceptible to the cytotoxic effects of purine analogues. A series of acyclic nucleoside phosphonates were evaluated for activity against pathogenic haemoflagellates in vitro. One of the phosphonylmethoxyalkylpurines, namely (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], was active in vitro against bloodstream forms of Trypanosoma brucei rhodesiense, T. b. gambiense, multidrug-resistant T. b. brucei, T. congolense and T. evansi, but not against intracellular T. cruzi or Leishmania donovani. Cytotoxic effects against mammalian cells were observed at 4900-27 300-fold higher concentrations than those necessary to inhibit T. b. rhodesiense. (S)-HPMPA was able to eliminate T. b. rhodesiense and multidrug-resistant T. b. brucei in an acute rodent model with two administrations of 10 mg/kg each.

Effects of controlled exposure of sunlight on plasma and skin levels of beta-carotene.

We conducted a randomized placebo-controlled double-blind study in 20 healthy young female students (skin type II + III, body mass index 18-22) in order to evaluate the efficacy of 10 weeks of moderate dose (30 mg/d) beta-carotene (BC) on plasma and skin beta-carotene levels during 12 days of time and intensity controlled sunlight exposure at sea level (30 degrees latitude, Red Sea, Eilath, Israel). After 12 days of controlled sun exposure (total UV dose of about 10.000J/cm2), plasma beta-carotene decreased in the placebo (p < 0.01) and beta-carotene group (not significant). In addition cutaneous beta-carotene decreased significantly in both groups. Plasma alpha-tocopherol decreased significantly (p < 0.01) during exposure time in both groups. In the supplemented group, however, the decrease of a-tocopherol was significantly greater (p < 0.01) than in the placebo group. We conclude that sunlight influences the beta-carotene and alpha-tocopherol content of blood and tissues.

Expression of sodium-dependent phosphate (NadPi) transport in Xenopus laevis oocytes induced by mRNA from 1 alpha, 25-dihydroxyvitamin D3-treated rat osteoblast-like cells.

Injection of messenger ribonucleic acid (mRNA) isolated from 1 alpha, 25-dihydroxyvitamin D3-treated osteoblast-like (PyMS) cells leads to an enhanced sodium-dependent phosphate (NadPi) transport in Xenopus laevis oocytes, when compared to untreated cells. After mRNA size fractionation, mRNA with an average size of 2.2-3.8 kilobases showed up to a 1.8-fold stimulation of NadPi transport encoding either directly a NadPi transporter(s) or proteins controlling their activity. No hybridization was observed in Northern blots with RNA from rat bone or PyMS cells with the recently cloned rat renal brush border NadPi transporter NaPi-2; hybrid depletion with a NaPi-2 antisense oligonucleotide did not abolish the PyMS mRNA-induced NadPi transport in oocytes. We present the first evidence for functional expression in Xenopus laevis oocytes of a new type of NadPi transport system in bone cells, which is different from the renal type.

[Outer retinitis as an early symptom of subacute sclerosing panencephalitis]. / Aussere Retinitis als Frühsymptom bei subakut sklerosierender Panencephalitis (SSPE).

BACKGROUND: A primary ocular manifestation of subacute sclerosing panencephalitis is known and can progress to severe visual deterioration. The rare occurrence of the disease makes diagnosis often difficult. CASE REPORT: The lethal clinical course of a patient with subacute sclerosing panencephalitis (SSPE) is presented. The disease manifested itself with severe ophthalmic symptoms preceding clinical and neurological signs and leading to bilateral blindness. The dramatic drop of visual acuity was due to a unilateral and later in the course bilateral pigmentepitheliopathy of the posterior pole. Inflammatory signs of retinal vasculature or inner retinal layers were detected neither clinically nor by fluoresceine angiography. A typical blockage of background fluorescence was demonstrated in fluoresceine and indocyanine angiography. Within two weeks after initial symptoms optic atrophy developed in both eyes. CONCLUSION: The primary lesion of retinal pigment epithelium and outer retinal layer were the prominent findings in this case. The presence of an outer retinitis of the posterior pole should alert the physician to the possibility of subacute sclerosing panencephalitis.

Safety, accuracy, and diagnostic yield of needle localization biopsy of the breast performed using local anesthesia.

BACKGROUND: In changing our technique to performing needle localization breast biopsies (NLBB) using local anesthesia in an outpatient setting, we investigated whether or not our complication rates with local anesthesia were acceptable when compared with complications from a cohort of biopsies of the breast performed for palpable masses. We were also interested in determining whether or not our rate of missed biopsies was within acceptable ranges. STUDY DESIGN: Complications occurring in 283 patients who underwent 301 NLBB using local anesthesia between 1983 and 1991 were compared with complications occurring after excision of 249 palpable masses of the breast excised using local anesthesia during this period. RESULTS: Complications associated with NLBB were missed lesions, six (1.99 percent) of 301; hematoma, 12 (3.99 percent) of 301; abscess, three (0.99 percent) of 301; seroma, one (0.33 percent) of 301, and wound separation, two (0.66 percent) of 301, for a total of 24 complications (7.96 percent). These rates were not statistically different from the rates of complication after biopsies of palpable lesions using local anesthesia (p < 0.49). The 301 NLBB revealed 87 carcinomas (28.9 percent); 50 invasive and 37 in situ. Of the nonpalpable carcinomas, 43 percent were in situ. Only 11 percent carcinomas, 43 percent were in situ. Only 11 percent of the palpable lesions were in situ (p < 0.001). Forty-four patients with nonpalpable invasive carcinoma had a 25 percent rate of positive axillary lymph nodes. CONCLUSIONS: Needle localization breast biopsies can be performed using local anesthesia exclusively with less than a 2 percent chance of missed lesions and complication rates similar to those associated with biopsies of palpable lesions. The biology of these lesions varies. Although there is a high rate of in situ carcinoma, there is a significant rate of node positivity in the patients with nonpalpable invasive carcinoma.

Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats.

Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on bone and mineral metabolism of male rats treated with a high dose of dexamethasone. Dexamethasone was added to the drinking water in a concentration of 1 mg/l. After 30 days of dexamethasone treatment, recombinant human IGF-I (300 micrograms/day) or solvent was infused sc by osmotic minipumps for 21 days while dexamethasone was continued. Age-matched untreated male rats served as healthy controls. Dexamethasone-treated rats lost weight. Their IGF-I levels were decreased to 36% of healthy controls. Infusion of IGF-I resulted in an increase in IGF-I serum levels (582% compared to healthy controls) and allowed some weight gain. Osteocalcin and calcitriol levels were markedly decreased in dexamethasone-treated rats and were not influenced significantly by IGF-I infusion. In contrast, IGF-I treatment restored the free calcitriol concentration (molar ratio of calcitriol to vitamin D-binding protein) towards normal. Furthermore, infusion of IGF-I partially corrected the dexamethasone-induced hyperinsulinemia. Histomorphometric analysis revealed no difference in vertebral trabecular bone density (i.e. growth-independent bone remodeling) between the three groups. In contrast, mean trabecular bone density in tibial metaphyses was increased markedly by dexamethasone, presumably due to osteoclast inhibition. Insulin-like growth factor I infusion did not significantly influence these structural metaphyseal bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

[The value of inpatient withdrawal treatment of alcoholic patients within the scope of a combined rehabilitation plan]. / Zum Stellenwert der stationären Entziehungsbehandlung von Alkoholkranken im Rahmen eines Gesamtplanes.

The article describes a medium-term, i.e., 4-6 months, inpatient withdrawal programme for alcoholic men in a specialized clinic. A holistic therapy approach is applied, equally including the multiple etiologic aspects of alcoholism as well as underscoring the need for comprehensive diagnosis and individualized treatment in therapeutic respects. The therapeutic activities of a multidisciplinary team are set out, comprising medical doctors, social workers, psychologists, and Occupational Therapists. The treatment concept is based on a systemic/family-therapy view of the symptoms present. The focus hence is not confined to tracing possibilities for behavioural change to the alcoholic individual, but significant others are equally involved in the therapeutic process in order that the individual may newly define and experience his environment and frame of reference. In this process, abstinencé is a major prerequisite for self-reliant, contented life planning and future coping.

Two forms of cytochrome P-450(11 beta) in rat zona glomerulosa cells: a short review.

Aldosterone, the major mineralocorticoid hormone, is produced exclusively in the zona glomerulosa of the mammalian adrenal cortex. In the rat species, this zonal specificity of aldosterone biosynthesis appears to be due mainly to the existence of a second form of cytochrome P-450(11 beta), which differs from the major form of the enzyme (molecular weight 51,000) by (1) a lower molecular weight (49,000), (2) a broader range of catalytic activities, which include corticosterone methyl oxidation 1 and 2, (3) an exclusive occurrence in the zona glomerulosa, and (4) a crucial dependence on sodium and potassium intake. The 49K form of the enzyme can be induced by potassium ions in vivo (potassium repletion of potassium-deficient rats) or in vitro (primary cell culture). The biosynthesis of this protein is controlled most likely at the level of transcription. According to indirect evidence, ACTH induces only the 51K form of the enzyme in vitro. Prolonged treatment of rats with a high dose of ACTH has a repressive effect on the 49K form of the enzyme.