Serotonergic agents in the treatment of acute neuroleptic-induced akathisia: open-label study of buspirone and mianserin

It has been suggested that dopamine/serotonin (5-HT) imbalance, with relative enhancement of serotonergic activity, might be one of the possible pathophysiological mechanisms underlying neuroleptic-induced akathisia. On the basis of preclinical data, which imply that the partial 5-HT1A agonist buspirone possesses anti-5-HT activity, in the present open-label study we examined the putative antiakathitic effect of buspirone in 10 neuroleptic-treated patients with acute neuroleptic-induced akathisia. Buspirone (up to 30 mg/day in divided doses) was administered for a trial period of 4 days (first part of the study). No significant changes in neuroleptic-induced akathisia as rated using the Barnes Akathisia Scale were detected during buspirone treatment. Buspirone was effective in only two neuroleptic-induced akathisia patients and caused worsening of akathisia in the other two patients. According to the study design, eight buspirone non-responders were switched to the 5-HT2A/2C antagonist mianserin (15 mg/day) for the other 4 days of treatment (second part of the study). Seven mianserin-treated patients improved and five revealed complete disappearance of neuroleptic-induced akathisia. It seems that the 5-HT1A partial agonist buspirone is of limited value in the treatment of acute neuroleptic-induced akathisia. It contrast, it appears that low-dose mianserin is therapeutically effective in acute neuroleptic-induced akathisia.     

Beneficial effect of renal transplantation on cognitive brain function

Cognitive brain dysfunction is a common complication of end-stage renal disease. To investigate the cerebral effect of renal transplantation, we studied P300 event-related potentials--an objective marker of cognitive brain function--trailmaking test and Mini-mental state in 15 chronic hemodialysis patients and 45 matched healthy subjects. Before transplantation, patients showed prolonged P300 latency (364 vs. 337 ms, P < 0.01), smaller amplitude (15.2 vs. 19.1 microV) and scored lower (P < 0.05) in trailmaking test and Mini-mental state as compared to healthy subjects. Following renal transplantation (14 months), P300 latency decreased (337 ms, P < 0.01 vs. before) and amplitude increased (17.4 microV, P < 0.05 vs. before), indicating improved cognitive brain function. The trailmaking test and Mini-mental state tended to improve. Following transplantation, P300 findings, trailmaking test and Mini-mental state were not different from healthy subjects. Additional studies following erythropoietin treatment in 6 of the 15 hemodialysis patients revealed decreased (improved) P300 latency (351 vs. 379 ms before, P < 0.05) with further decrease following transplantation (341 ms, P = 0.06). Our findings indicate that cognitive brain dysfunction in hemodialysis patients may be fully reversed by successful renal transplantation.     

Beneficial effect of alpha-blocker on hemorheology in patients with essential hypertension

BACKGROUND: An increased prevalence of allergic diseases and atopic sensitization as assessed by skin-prick testing in children in West compared with East Germany has been reported. OBJECTIVES: This study was designed to evaluate whether such a difference is also present in adults, and if this can be shown when using a serological test for allergic sensitization. METHODS: Two large samples representative for all adults between 25 and 69 years of age were drawn in West (1991, n = 5313) and East Germany (1992, n = 2617). A serological test screening for IgE-antibodies to common aeroallergens (SX1) was performed. A questionnaire was used to assess the presence of clinical respiratory allergy, known possible risk factors for allergies and confounding variables. RESULTS: Allergic sensitization decreased with age. Significantly more subjects < 45 years of age had a positive allergy test in West as compared to East Germany. The prevalence of clinical allergy was also higher in West Germany. This difference was significant in younger adults and was independent of other risk factors identified. These additional risk factors encompassed younger age, higher educational level, male sex, and living in a community with more than 100,000 inhabitants. CONCLUSION: Sensitization to common aeroallergens as determined by a multiple allergen RAST test in adults below 45 years of age living in West Germany is increased compared to East Germany. This increase cannot be explained by genetic differences and is similar to the West to East decreasing gradient in allergies reported from studies in children employing skin-prick tests.     

Subjective side effects of mianserin in relation to plasma concentrations of mianserin and desmethylmianserin

The main purpose of the present study was to examine the possibility that plasma concentrations of mianserin and its metabolite, desmethylmianserin, might be predicted by recording subjective side effects. In 44 depressed patients, subjective side effects during 3 weeks of treatment with 30 mg of mianserin were evaluated by the UKU Side Effect Rating Scale, and their relationships to plasma concentrations of mianserin and desmethylmianserin were analyzed. There was no significant relationship between plasma concentrations of these compounds and the occurrence of mianserin-induced side effects, except for dryness of mouth during week one. Our study, therefore, suggests that it is difficult to predict plasma concentrations of mianserin and desmethylmianserin based on the occurrence of subjective side effects.     

Beneficial effect of proteases on allograft arteriosclerosis in a rat aortic model

PURPOSE: Our goal was to describe the CT findings in patients with an apparent mass at the thoracic inlet on barium swallow and to further explore its etiology by making appropriate measurements on CT. METHOD: Barium swallows and CT scans of five patients with esophageal pseudomass were reviewed and compared with CT scans of 65 controls. Anteroposterior (AP) diameters of the thoracic inlet were measured, and the relationships of the esophagus to the trachea were determined on CT. RESULTS: Absence of a demonstrable mass on CT in patients with an extrinsic impression on barium swallow was associated with narrowed AP diameter of the thoracic inlet (< 5 cm) and the esophagus to the left of the trachea. A significant correlation was observed between the AP diameter of the inlet and the position of the esophagus in relation to the trachea in control subjects (r = 0.52, p < 0.001); with diminished diameter, the esophagus is more frequently located to the left side of the trachea. CONCLUSION: An apparent mass is simulated by lateral deviation of the lower cervical esophagus, due to diminished available space between the trachea and the esophagus in subjects with a narrow (< 5 cm) AP diameter of the thoracic inlet.     

Beneficial effects of nitrogen Atomization on an Austenitic Stainless Steel

Metallurgical and Materials Transactions A - Fully dense nitrogenated austenitic stainless steels were produced by gas atomization and HIP consolidation. The base alloy, 304L, contained about 0.15...     

Beneficial effects of nitrogen atomization on an austenitic stainless steel

Fully dense nitrogenated austenitic stainless steels were produced by gas atomization and HIP consolidation. The base alloy, 304L, contained about 0.15 wt pct nitrogen when melted under a nitrogen atmosphere, and a modified version of 304L with 23 wt pct Cr contained 0.21 wt pct nitrogen. A series of experiments using various combinations of N₂ and Ar as the melt chamber backfill gas and atomizing gas demonstrated that the nitrogen content of the powder was largely controlled by the backfill gas and that the fraction of hollow particles was determined by the atomization gas. The hollow powder particles, which are common in inert-gas atomized materials, were virtually eliminated in the nitrogen atomized powders. Additional atomizing experiments using copper and a nickel-base superalloy indicate that low gas solubility in the metal leads to gas entrapment. Hardness and compression behavior (yield strength and flow stress) are substantially improved with the addition of nitrogen. The results of this study suggest that the properties of nitrogenated stainless steels fabricated in this manner are comparable to other high nitrogen austenitic alloys. G.M. JANOWSKI, formerly NRC/NIST Postdoctoral Research Associate, National Institute of Standards and Technology.     

Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis

BACKGROUND: Recently we observed that ursodeoxycholic acid (UDCA) ameliorates an experimental small intestinal inflammation induced by indomethacin in the rat. In this study, we have tested whether ursodeoxycholic acid also reduces mucosal damage in the bile-independent trinitrobenzene sulphonic acid (TNB) model of experimental colitis. METHODS: Intestinal inflammation (colitis) was induced in male Sprague-Dawley rats (250-300 g) by intracolonic administration of TNB (30 mg in 50% ethanol). Rats were treated with UDCA (10 mg/kg) either for 3 days starting with the administration of TNB for an acute inflammation (n = 11) or for 8 days starting one day after induction of colitis related to a more acute/chronic inflammation (n = 11). Rats were sacrificed at day 3 or day 9, respectively. Healing of induced colitis was assessed by macroscopic and blinded microscopic analysis as well as by measurement of bowel wet weight, daily body weight, and myeloperoxidase activity. All examinations were separately performed in three colon segments (S1 3-5 cm, S2 5.5-8 cm and S3 8.5-11 cm from anus). RESULTS: UDCA treatment significantly reduced macroscopically and microscopically detectable injury in acute inflammation in segments 1 and 2. The colitis-rats with acute/chronic inflammation had less marked mucosal damage. Nevertheless, UDCA treatment led to a significant decrease of visible injury parameters which was seen exclusively at the area of maximal ulceration (S2). Furthermore, a significant increase in body weight of UDCA-treated TNB rats compared to controls from day 5 on was found. CONCLUSION: Ursodeoxycholic acid attenuates the severity of acute inflammation and inhibits the development of acute/chronic inflammation predominantly around the area of maximal ulceration in TNB-induced colitis. In addition to our previous studies and results in indomethacin induced enteritis, these data may provide a rationale for studying how UDCA modulates functions of immune cells in the colonic mucosa.     

Beneficial effect of fluorocarbon emulsion media on the function of neuromuscular preparations in vitro

The effects of liquid fluorocarbons as bathing media were determined by use of in vitro neuromuscular preparations. Rat hemidiaphragms were bathed in either oxygenated fluorocarbon (FC) emulsion or standard oxygenated Krebs solution. Contractile force in response to simple supramaximal nerve stimuli as well as to high frequency stimulation was greater, while twitch:tetanus ratio was smaller in FC emulsion. With such medium, post-tetanic potentiation of contraction was also more consistently observed. Indirectly stimulated diaphragms survived longer in FC emulsion. After cessation of oxygenation, oxygen tension (rhoO(2)) of the medium declined more rapidly with Krebs than with FC emulsion; rhoO(2) directly correlated with force of contraction. Similarly, in the chick biventer cervicis preparation, FC emulsion enhanced nerve-stimulated force of contraction; returning the preparation to standard Krebs solution reversed this phenomenon. Dose-resonse curves of muscle contraction in response to acetycholine and KCl administration were shifted upward during FC emulsion superfusion. Frequency of miniature endplate potentials was lower in FC emulsion than that observed in Krebs solution, measured from the same cell of the rat diaphragm. Resting membrane potentials were also greater in muscle cells sampled from FC emulsion-bathed preparations. These data suggest that FC emulsion is superior to standard Krebs solution as a bathing medium for in vitro neuromuscular preparations by virtue of the high solubility of oxygen in it.     

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia

Study of the solubilization of commercial grades of soya phosphatidylcholine (SPC) with different purities by bile salts (BS) indicated that only highly pure grades of SPC are suitable for the preparation of clear solutions of BS/SPC-mixed micelles (BS/SPC-MM). The solubilizing capacity of different BS towards SPC increased in the following order; Sodium cholate (SC) < sodium deoxycholate (SDC) < sodium glycocholate (SGC). Moreover, egg phosphatidylcholine (EPC) was solubilized to a higher extent than SPC. Furthermore, the solubility study of different drugs in the prepared MM showed substantial enhancement of solubility, the extent of which is essentially affected by the chemical nature of the drug and the composition of MM. Benzodiazepine drugs such as clonazepam, tetrazepam, diazepam, and lorazepam displayed higher affinity for MM compared with BS alone, whereas steroidal drugs, such as estradiol, prednisolone and progesterone, compared with benzodiazepines, displayed relatively higher affinity for BS alone. The solubilizing capacity of MM for the different drugs was increased to different degrees by the addition of benzyl alcohol which was comparable to the solubility of the drug in pure benzyl alcohol. The interaction between benzyl alcohol and the drug in MM could be proved by NMR.     

The effect of an alphanumeric paging system on patient compliance with medicinal regimens

There are numerous actual and potential impediments to patient compliance with medicinal regimens. The implications of poor compliance include worsening disease states or symptoms, with resultant increased costs of care. Using a population of hospice patients at high risk for noncompliance, this study evaluated the use of an alphanumeric paging system as a memory prosthetic, finding that compliance rose from a mean of 56 percent to 96 percent when the system was used. We conclude that such a program is of use in this setting, and that these findings warrant study and suggest applications in other populations.     

Lack of immunosuppressive effect of low-dose oral methotrexate on lymphocytes in rheumatoid arthritis

Whether methotrexate (MTX) is effective in rheumatoid arthritis (RA) because of immunosuppressive and/or anti-inflammatory mechanisms of action is controversial. Many lines of investigation point to the latter. We evaluated DNA synthesis in peripheral blood lymphocytes (PBL) from 33 RA patients on oral MTX (7.5-15 mg/wk) and in 30 healthy controls by flow cytometric cell cycle analysis (CCA). DNA synthesis was also evaluated with a thymidilate synthetase activity assay (TSA) (3H-deoxyuridine incorporation) in 12 patients and 21 controls (12 on MTX and NSAID, and 9 healthy subjects). The patients had taken MTX for at least 3 months and were in different stages of clinical activity. There were no significant differences in TSA or in the cell cycle phase distributions (especially the S phase) between treated RA patients and controls. These data suggest that low-dose oral MTX does not inhibit DNA synthesis and therefore does not have an immunosuppressive effect on lymphocytes from patients with RA.     

Beneficial effect of intranasal desmopressin for nocturnal polyuria in Parkinson's disease

Patients with Parkinson's disease (PD) are known to experience autonomic nervous system dysfunction: this disruptive symptomatology includes urinary urgency, frequency, and nocturnal polyuria. Anticholinergic and tricyclic medications can be beneficial in controlling these urinary symptoms, but have unpleasant side effects in some patients. Desmopressin has been used to treat nocturnal polyuria successfully in a number of conditions, such as central diabetes insipidus, enuresis, and autonomic failure. The purpose of the present study was to assess the efficacy of desmopressin in patients with PD with significant nocturia. Eight patients were recruited into the study. They were first asked to establish a baseline of number of nocturnal voids; the patients were then prescribed the intranasal form of desmopressin and asked to continue to record the number of nocturnal voids. The five patients who completed the trial demonstrated clinically and statistically significant reductions in the frequency of nocturnal voids. One patient became hyponatremic and confused during desmopressin administration; his symptoms resolved soon after the desmopressin was discontinued. Two patients failed to complete the trial due to compliance problems. Thus, desmopressin appears to be a safe and effective medication for nocturnal polyuria in PD.     

Biphasic effects of typical antidepressants and mianserin, an atypical antidepressant, on aggressive behavior in socially isolated mice

Effects of several typical antidepressants and of an atypical antidepressant, mianserin, on the aggressive behavior (AGB) in long-term isolated mice were examined. IP administration of maprotiline (2.5 and 5 mg/kg), amitriptyline (5 and 10 mg/kg), clomipramine (2.5 and 5 mg/kg), and mianserin (5 mg/kg) significantly increased the duration of AGB. However, at higher doses (maprotiline, 10 mg/kg; amitriptyline, 20 mg/kg; clomipramine, 10 and 20 mg/kg; mianserin, 10 and 20 mg/kg) these antidepressants either did not affect AGB or inhibited it. Amitriptyline (20 mg/kg) and mianserin (10 mg/kg) but not maprotiline (10 mg/kg) or clomipramine (20 mg/kg) decreased spontaneous motor activity in isolated mice. Yohimbine (0.5 mg/kg, IP), an alpha 2-antagonist, changed the antidepressant-induced enhancement of AGB into inhibition without affecting the basal aggressive responses. Prazosin (0.3 mg/kg, IP), an alpha 1-antagonist, did not affect either maprotiline- or clomipramine-induced enhancement of AGB, but it changed the mianserin-induced enhancement of AGB into inhibition. These results indicate that antidepressants that inhibit noradrenaline uptake and/or stimulate noradrenaline output from nerve terminals have biphasic effects on AGB in isolated mice and that the antidepressant-induced enhancement of AGB is mediated by noradrenergic stimulation of alpha 2-adrenoceptors, whereas the antidepressant-induced inhibition of AGB may be mediated by non-alpha 2-adrenoceptors or by nonadrenergic system(s).     

Laparoscopic surgery in the rat. Beneficial effect on body weight and tumor take

INTRODUCTION: Epithelioid hemangioendothelioma is an uncommon vascular neoplasm, one of intermediate-grade malignancy. Cutaneous epithelioid hemangioendothelioma is rare and often associated with multiple site involvement. CASES: Three patients with cutaneous EHE without systemic involvement in one case, with skin, liver and lung tumoral lesions in two others cases are reported. One patient is in complete remission after one year. The second patient is stable without treatment after ten years. In the third patient, alpha interferon given for one year don't produce effective results and the lesions do not progress without treatment after eight years of follow-up. DISCUSSION: Cutaneous presentation of EHE is quite variable. After the diagnosis is done, systemic involvement must be detected specially in bone, liver or lung. Metastatic spread or mulitcentric origin of the tumor are a matter of controversy. The pathobiologic behavior of EHE is not clearly recognized. Little data are available regarding the results of treatment with alpha interferon.     

Beneficial effect of risperidone on sleep disturbance and psychosis following traumatic brain injury

Severe disturbances of sleep architecture and circadian rhythms are common in traumatic brain injured patients; however, complete absence of the rapid eye movement sleep stage is very rare. We describe a brain injured patient with cognitive disturbances who developed severe alterations of sleep architecture, accompanied by paranoid and jealousy delusions. Following several trials with conventional antipsychotics his psychotic state stabilized but he continued to complain of insomnia and daytime fatigue. When treated with risperidone 2 mg/day, both his sleep and the delusional thoughts improved markedly and his daytime alertness increased. Severe deterioration of his support system brought about discontinuation of treatment with re-emergence of all symptoms.     

Beneficial effect of raxofelast, an hydrophilic vitamin E analogue, in the rat heart after ischemia and reperfusion injury

Several studies report that among the antioxidant agents used to reduce injury after myocardial ischemia/reperfusion, analogues of vitamin E (VE) seem to have a significant efficacy. Raxofelast is a potent antioxidant agent under investigation, structurally related to VE, having an excellent bioavailability and favourable physicochemical properties. We assessed raxofelast in a rat model of myocardial damage induced by 1 h of left coronary artery occlusion followed by 6 h of reperfusion. Myocardial ischemia/reperfusion produced: wide tissue necrosis (50.3+/-10.3%); membrane peroxidation, evaluated by assessing cardiac malondialdehyde (MAL) (87.8+/-15.8 nmol/g tissuev 9.53+/-2.4 nmol/g tissue) and plasma conjugated dienes (CD) (8.73+/-1.86 DeltaABS/mlv 1.61+/-0.45 DeltaABS/ml); endogenous antioxidant wasting [cardiac VE=23.5+/-10.2 nmol/g tissuev 61.4+/-13.4 nmol/g tissue, cardiac reduced glutatione (GSH)=2.15+/-1.23 micromol/g proteinv 7.34+/-0.92 micromol/g protein and cardiac superoxide dismutase (SOD)=8.9+/-4.1 U/mg proteinv 17. 5+/-4.2 U/mg protein]; depressed mean arterial blood pressure (MAP) (61.4+/-5.8 mmHgv 85.3+/-6.2 mmHg); heart rate (HR) (275+/-35 beats/minv 368+/-34 beats/min) and left-ventricular derivative developed force (LV dP/dtmax) (1050+/-187 mmHg/sv 2520+/-194 mmHg/s); and cardiac neutrophil accumulation, evaluated by assessing cardiac myeloperoxidase (MPO) (9.23+/-2.1 U/g tissuev 0.92+/-0.12 U/g tissue). Administration of raxofelast (25, 50 and 100 mg/kg i.p. 5 min after occlusion) limited myocardial necrosis (22.3+/-14.8%P<0. 005, following the highest dose), reduced lipid peroxidation (MAL=43. 5+/-14.7 nmol/g tissueP<0.001 and CD=4.01+/-2.21 DeltaABS/mlP<0.001, following the highest dose), restored the endogenous antioxidants VE (52.8+/-14.2 nmol/g tissueP<0.001, following the highest dose), SOD (14.2+/-2.7 U/mg proteinP<0.001, following the highest dose) and GSH (4.92+/-1.33 micromol/g proteinP<0.005, following the highest dose), improved hemodynamic parameters (MAP=68.1+/-5.3 mmHgP<0.05, HR=317+/-27 beats/minP<0.05, LV dP/dtmax=1427+/-143 mmHg/sP<0.05, following the highest dose) and reduced myocardial neutrophil infiltration (MPO=5.1+/-1.5 U/g tissueP<0.001, following the highest dose). These data suggest that raxofelast could be considered a useful drug to reduce myocardial infarction.     

Citalopram in the treatment of obsessive-compulsive disorder: an open pilot study

PURPOSE: To evaluate QT dispersion in hypertensive patients, with and without left ventricular hypertrophy, and compare with normal persons. METHODS: Thirty eight patients (21 male and 17 female, age 55 +/- 15 years) underwent echocardiography and simultaneous 12 lead, vertically aligned, electrocardiogram at 50 mm/s speed. No patient was on antiarrhythmic therapy. There were 19 non-hypertensive patients that constituted the control group (G-I). Group II was constituted by the other 19 patients, who were hypertensives. This group was further divided in group II-A (9 patients without left ventricular hypertrophy) and group II-B (10 patients with left ventricular hypertrophy). QT dispersion was obtained by the difference between the longest and the shortest QT registered. RESULTS: QT dispersion was significantly increased on hypertensive patients, both with and without left ventricular hypertrophy, when compared to controls (G-I 31 +/- 9 ms, G-II 52 +/- 15 ms. P < 0.0001; G-IIa 46 +/- 10 ms and G-IIb 56 +/- 18 ms X G-I, p < 0.0005). In hypertensive patients, there was no statistically significant difference between group II-A and group II-B. CONCLUSION: We conclude that QT dispersion is significantly increased on hypertensive patients when compared to non-hypertensive individuals and that such increase, occurs before left ventricular hypertrophy develops. These findings suggest that, in hypertensive patients, electrical changes in left ventricular myocardium can precede structural and morphological abnormalities. Such findings offer new insights into the mechanisms related to enhanced mortality among hypertensive patients.     

Effective low-dose amiodarone therapy for ventricular tachycardia complicated with ischemic heart disease and poor left ventricular function in an elderly patient

A 71-year-old man who had ischemic heart disease with poor left ventricular function and ventricular tachycardia was admitted to hospital for evaluation. Cardiac catheterization was performed on August 19, 1996, and right coronary arteriography revealed total occlusion at segment 3. Left coronary arteriography revealed total occlusion at segment 6, and a lesion at segment 13 was 75% occluded. Partial collateral flow from the right ventricular branch to the left anterior descending artery was demonstrated, and the left ventricular ejection fraction was 24%. Recurrent ventricular tachycardia followed by pre-syncope occurred from August 23, 1996, and the patient underwent emergency coronary artery bypass surgery to the left anterior descending artery and circumflex artery using saphenous vein grafts. Ventricular tachycardia followed by pre-syncope occurred frequently after the bypass surgery, and antiarrhythmic agents (Vaughan Williams classification Ia and Ib groups) were ineffective. He received amiodarone (100 mg/day after a loading dose of 200 mg/day for 2 weeks) from September 6, 1996. His symptoms of arrhythmia decreased, and side effects have not been observed. Low-dose amiodarone was effective in this case of ischemic heart disease with left ventricular dysfunction and sustained ventricular tachycardia.