Nerve growth factor serum levels in treatment-resistant schizophrenic patients following electroconvulsive therapy.

BACKGROUND: Electroconvulsive Therapy (ECT) has been widely applied to treat schizophrenia (SCZ) in the presence of resistance to pharmacotherapy. The mechanism of action of ECT in schizophrenia has not been fully clarified, though its intrinsic mechanism presents analogies with some neurobiological processes mediated by nerve growth factor (NGF). OBJECTIVES: The aim of this study was to investigate in patients with treatment-resistant schizophrenia (TRS) the effect of ECT on acute and long-term NGF serum levels and the association with the clinical outcomes. METHODS: Twelve male inpatients with TRS underwent eight sessions of ECT. Blood samples were collected during the first and the eighth ECT at the following time points: 5 minutes before the induction of seizure and then at 0, 5, 15 and 30 minutes after seizure. RESULTS: Following ECT treatment, a substantial clinical improvement in symptom severity was indicated by a significant reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscales scores. Even though the baseline NGF levels showed an increase over time, there were no statistical differences in NGF at time 0 at the first and the eighth ECT session. Furthermore, no correlation was observed between the severity of schizophrenic symptoms and NGF levels. CONCLUSIONS: This is the first study addressing peripheral NGF during ECT treatment in TRS, as well as the first study in which NGF has been evaluated in different ECT sessions at various time points. These findings may potentiate the knowledge about the neurotrophic effects of ECT and the role of NGF in synaptic plasticity related to possible mechanisms of schizophrenia treatment.

Effect of Camellia sinensis teas on left ventricular hypertrophy and insulin resistance in dyslipidemic mice.

The control of dyslipidemia using plants is an important subject of studies since it has numerous benefits in cardiovascular protection. The objective of this study was to evaluate the effect of three Camellia sinensis L. teas (green, red, and white) on left ventricular hypertrophy and insulin resistance in low-density lipoprotein receptor knockout (LDLr-/-) mice fed a high-fat diet. The LDLr-/- mice were divided into four experimental groups: Group C: standard feed; Group CT: standard feed and three teas, Group HL: high-fat feed; HLT Group: high-fat feed and three teas. The three types of tea (green, red, and white) originated from different processing of the Camellia sinensis L. plant, and were administered associated once a day at a dose of 25 mg/kg by gavage for 60 days. The teas partially prevented hyperlipidemia, the decrease of the serum levels of high-density lipoproteins (HDL), insulin resistance, and increased C-reactive protein (CRP) levels, and completely prevented left ventricular hypertrophy in LDLr -/- mice of the HLT group. In conclusion, the three Camellia sinensis L. teas used to control genetic dyslipidemia associated with a high-fat diet can be used as an auxiliary treatment associated with the control of lipid intake, thus promoting cardiac protection against hyperlipidemia.

Effect of Camellia sinensis teas on left ventricular hypertrophy and insulin resistance in dyslipidemic mice

The control of dyslipidemia using plants is an important subject of studies since it has numerous benefits in cardiovascular protection. The objective of this study was to evaluate the effect of three Camellia sinensis L. teas (green, red, and white) on left ventricular hypertrophy and insulin resistance in low-density lipoprotein receptor knockout (LDLr-/-) mice fed a high-fat diet. The LDLr-/- mice were divided into four experimental groups: Group C: standard feed; Group CT: standard feed and three teas, Group HL: high-fat feed; HLT Group: high-fat feed and three teas. The three types of tea (green, red, and white) originated from different processing of the Camellia sinensis L. plant, and were administered associated once a day at a dose of 25 mg/kg by gavage for 60 days. The teas partially prevented hyperlipidemia, the decrease of the serum levels of high-density lipoproteins (HDL), insulin resistance, and increased C-reactive protein (CRP) levels, and completely prevented left ventricular hypertrophy in LDLr -/- mice of the HLT group. In conclusion, the three Camellia sinensis L. teas used to control genetic dyslipidemia associated with a high-fat diet can be used as an auxiliary treatment associated with the control of lipid intake, thus promoting cardiac protection against hyperlipidemia.

Inappropriate prescribing in a large community-dwelling older population: a focus on prevalence and how it relates to patient and physician characteristics.

WHAT IS KNOWN AND OBJECTIVE: The prescription of potentially inappropriate medications (PIMs) for older adults is a well-known population health concern. Updated country-specific estimates of inappropriate prescribing in older adults using germane explicit criteria are needed to facilitate physician-tailored quality improvement strategies. Therefore, we sought to determine the prevalence of PIMs for older adults in Emilia-Romagna, Italy, using the updated Maio criteria. We also evaluated patient and general practitioner (GP) characteristics related to inappropriate prescribing. METHODS: Older adults (≥ 65) in 2012 were evaluated in a one-year retrospective study using administrative health care data. The 2011 Maio criteria includes 25 medications reimbursed by the Italian National Formulary, in the following categories in terms of severity: 16 medications that 'should always be avoided,' 3 that are 'rarely appropriate,' and 6 that have 'some indications although they are often misused.' To evaluate the extent of associations between patient and GP related characteristics, we used generalized estimating equations with an exchangeable covariance design to fit robust logistic regression models. RESULTS AND DISCUSSION: A total of 865,354 older adults were in the cohort and 28% had at least one PIM. Of the entire cohort, 8%, 10%, and 14% of individuals were prescribed at least one medication that 'should always be avoided,' is 'rarely appropriate,' and has 'some indications but are often misused,' respectively. Older patients (≥ 75) and females were more likely to be exposed to PIMs. 2,923 GPs were identified in the region, each having prescribed at least one PIM, of which older GPs (≥ 56), male GPs, and solo practice GPs were more likely to prescribe PIMs to their older patients. WHAT IS NEW AND CONCLUSION: The high prevalence of PIM exposure among older adults is a substantial issue in the region. Knowing how patient and GP characteristics relate to PIMs exposure may improve the design and targeting of initiatives for improving prescribing safety in this population.

Body composition, eating behavior, food-body concerns and eating disorders in adolescent girls.

AIMS: Dieting is a behavioral phenomenon which is becoming more frequent among adolescents and the search for weight loss, through dieting, may result in an unbalanced nutrition both quantitatively and qualitatively. Our study intended to look at the eating habits and behavior on a cohort of adolescent girls to verify the presence of unbalanced diets and the prevalence of eating disorders with particular attention to the partial syndromes (EDNOS). METHODS: A cross-sectional double-stage study was carried out on a group of schoolgirls in the suburbs of Naples. We assessed anthropometrical measures, body composition (skinfolds and bioimpedance analysis), dietary intake by means of 3-day food records and we administered the Eating Disorder Inventory 2 and Psychosocial Factor Risk Questionnaire. A multidisciplinary and double-stage approach had been used to get a better diagnosis of eating disorders in our sample. RESULTS: 156 adolescent girls, 14-18 years old, took part in our study. Height, weight, and BMI were 160.38 cm, 58 kg and 22.6, respectively. Analysis of food intake showed that all the values reported, with the exception of lipids and sodium, were below the recommendations by LARN. We observed a prevalence of 1.28% of bulimia nervosa, 1.28% of binge eating, and 10.25% of eating disorders not otherwise specified. EDI 2 and PRFQ confirmed how important drive for thinness and body dissatisfaction dimensions are when we deal with adolescent girls and with the phenomenon of dieting. The study confirmed the validity of the PRFQ questionnaire to evaluate mass media influence on body perception and eating behavior of adolescents. CONCLUSION: Multidisciplinary and well-designed studies are needed to systematically and accurately study eating habits and behavior of adolescents to tackle more efficiently the increasing spread of eating disorders and obesity.

Interdisciplinary treatment of a female outpatient population. Organizational model and preliminary results.

OBJECTIVE: To compare the efficacy of diet alone vs interdisciplinary therapy. METHOD: 256 women were divided into an interdisciplinary therapy group composed of 102 subjects and a control group composed of 154 subjects treated by means of diet alone. RESULTS: 21.56% of the interdisciplinary group did not come for the 2 check-ups compared with 49.35% of the diet group (p < 0.001). A weight loss of 5.88 kg and 4.18 kg for the interdisciplinary and the diet group was recorded 8 weeks after the start of the programme (second check-up). DISCUSSION: Interdisciplinary therapy is necessary to personalize treatment and satisfy the patient's desire and need for appropriate and effective management.

Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon.

Laxatives abuse has been associated with an increased risk for colon cancer. However, little is known about laxatives long-term carcinogenic potential in experimental studies. The present study was designed to investigate the effects of bisacodyl (4.3 and 43 mg/kg) and cascara (140 and 420 mg/kg) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors. Animals, divided in 10 groups were treated with AOM and laxatives (alone or in combination) for 13 weeks. At the end of treatment animals were killed and the colon removed and analysed for the determination of ACF and tumors. Bisacodyl (4.3 and 43 mg/kg), given alone, did not induce the development of colonic ACF and tumors. Bisacodyl (4.3 mg/kg) coupled with AOM increased the number of crypt per focus, but not the number of tumors. Bisacodyl (43 mg/kg) significantly increased the number of crypt per focus and tumors. Cascara (140 and 420 mg/kg) did not induce the development of colonic ACF and tumors and did not modify the number of AOM-induced ACF and tumors. The results of the present study indicate a possible promoting effect of bisacodyl on rat colon carcinogenesis (especially at higher doses) and absence of any promoting or initiating activity of a laxative and diarrhoeal dose of cascara.

Long-acting octreotide is effective in controlling rebleeding angiodysplasia of the gastrointestinal tract.

BACKGROUND: Management of bleeding angiodysplasia of the gastrointestinal tract is often a major clinical problem. Lesions are frequently multiple, not detectable or missed during conventional endoscopy and patients are sometimes at high risk for complications because of advanced age and serious concomitant disorders. AIMS: To determine the efficacy of a new formulation of somatostatin analogue (octreotide long-acting) in management of recurrent bleeding angiodysplasia in patients resistant to endoscopic treatment and not suitable for surgery. PATIENTS AND METHODS: Three patients with recurrent bleeding angiodysplasia of gastrointestinal tract were treated with long-acting octreotide administered intramuscularly 20 mg monthly to each individual. The number of admissions for acute bleeding, hospital stay and number of blood units transfused before and after treatment (followup: 15-17 months) were regularly monitored. RESULTS: In each patient, a relevant decrease in number of hospital admissions, duration of hospital stay, number of administered blood units was seen and mean haemoglobin values significantly increased in all of them after introducing long-acting octreotide therapy. CONCLUSIONS: This is the first report on use of long-acting octreotide in bleeding angiodysplasia of gastrointestinal tract. Data suggest that long-acting octreotide is a safe drug and is successful in controlling recurrent gastrointestinal bleeding due to angiodysplasia in elderly patients not eligible for surgical or endoscopic therapy.

A randomized 4-arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone.

To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n = 139) received 3 million units (MU) IFN-alpha2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P =.04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P =.03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30%, group 4 = 35%, P = NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if re-treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 year. Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive.

N-acetyl-cysteine reduces neointimal thickening and procoagulant activity after balloon-induced injury in abdominal aortae of New Zealand white rabbits.

BACKGROUND: Procoagulant activity and oxidative stress generated by balloon injury to normal vessels promote the migration of medial smooth muscle cells and their proliferation in the intima. We hypothesised that administering levo N-acetyl-cysteine (NAC) i.v. at the time of injury, and s.c. before and after injury would reduce neointimal formation 4 weeks later and would regulate procoagulant activity in vessels with neointima undergoing ballooning a second time. METHODS AND RESULTS: at the time of injury rabbits received: NAC, unfractionated heparin (HEP) or both (NAC + HEP). Neointimal thickening at 28 days, calculated as the ratio between the intimal and medial area, was attenuated after NAC, HEP and NAC+HEP by 39%, 30% and 47% respectively when compared to untreated injured animals (CONTROLS) (p <0.05). At 28 days, bound thrombin activity and platelet adhesion 1 h after a repeated balloon injury decreased in animals receiving NAC, HEP and NAC+HEP bv 54%, 63% and 64% for thrombin activity (p <0.05 vs CONTROLS), and by 56%, 66% and 75% respectively for 111Indium-platelet deposition (p <0.05 vs CONTROLS). CONCLUSIONS: NAC in-vivo was effective in reducing neointimal thickening and procoagulant response after balloon injury.

The three-factor eating questionnaire in the evaluation of eating behaviour in subjects seeking participation in a dietotherapy programme.

AIM: To evaluate the eating behaviour in normal-weight, overweight, and obese women seeking participation in a diet-based programme of weight reduction or achievement of ideal body weight. METHODS: Thirty-seven obese, 42 overweight, and 14 normal-weight subjects, seen at an Italian university outpatient clinic, were asked to complete the Stunkard and Messick three-factor eating questionnaire (TFEQ). The TFEQ is designed to evaluate three different factors in eating behaviour: restraint, disinhibition, and hunger. Forty-eight mothers of children attending public primary schools (25 normal weight and 23 overweight) served as controls. RESULTS: Significantly altered scores of cognitive restraint were observed both in normal-weight and in overweight subjects of the outpatient clinic as compared with normal-weight and overweight control women. Outpatient clinic overweight women scored significantly higher in terms of disinhibition as compared with overweight control subjects. Among outpatient clinic subjects, overweight women showed higher scores of disinhibition but similar values of cognitive restraint as compared with outpatient clinic normal-weight subjects. In obese patients, the scores of disinhibition and hunger were higher than those observed in outpatient clinic normal-weight subjects, whereas values of cognitive restraint were significantly lower. As compared with outpatient clinic overweight women, obese subjects showed significantly lower values of cognitive restraint. CONCLUSIONS: Alterations in TFEQ results are a frequent feature in subjects seeking participation in programmes of weight reduction or ideal body weight achievement. This may reflect a possible impairment in eating behaviour.

Evaluation of flutamide genotoxicity in rats and in primary human hepatocytes.

Flutamide, an effective competitive inhibitor of the androgen receptor used orally for palliative treatment of prostatic carcinoma and regulation of prostatic hyperplasia was evaluated for its genotoxic effects in the intact rat and in primary cultures of human hepatocytes. Negative responses were obtained in all the in vivo assays as well as in the in vitro assay. In rats given a single oral dose of 500 mg/kg flutamide, fragmentation and repair of liver DNA were absent, and no increase was observed in the frequency of micronucleated hepatocytes. In the liver of rats given flutamide as initiating agent at the dose of 500 mg/kg/week for 6 successive weeks, gamma-glutamyltraspeptidase-positive foci were detected only in 3 of 10 rats. There was no evidence of a promoting effect on the development of aberrant crypt foci in rats given 100 mg/kg flutamide on alternate days for 8 successive weeks. In primary cultures of human hepatocytes from one male and one female donor DNA fragmentation as measured by the Comet assays, and DNA repair synthesis as revealed by quantitative autoradiography, were absent after a 20 hr exposure to flutamide concentrations ranging from 18 to 56 microM. Taken as a whole, our results seem to indicate that flutamide is a non-genotoxic drug.

The Eating Disorder Inventory in evaluation of impaired eating behaviour in subjects requesting nutritional consultation.

The present study evaluated impaired eating behaviour in women seeking participation in a diet-based programme of weight reduction or achievement of ideal body weight. Forty-seven obese, 42 overweight and 14 normal-weight subjects, attending an Italian university outpatient clinic completed the Eating Disorder Inventory (EDI). Forty-eight mothers of primary school children (25 normal-weight and 23 overweight) were used as controls. The EDI consists of 8 subscales, 3 evaluating psychopathology related to eating disorders (drive for thinness, bulimia, body dissatisfaction) and 5 evaluating general psychopathology (intereoceptive awareness, ineffectiveness, maturity fears, perfectionism, interpersonal distrust). Significantly altered scores in the first three subscales were observed both in normal-weight and overweight outpatients compared to the controls. The overweight outpatients scored higher than the obese patients in terms of drive for thinness and bulimia and higher than the normal-weight women for terms of bulimia, body dissatisfaction and drive for thinness. The overweight controls scored significantly higher than the normal-weight controls in the first three subscales in the remaining subscales, mean values were also higher in the overweight group, though significance was only reached in the interpersonal distrust and interoceptive awareness subscales. Impaired eating behaviour is frequent in subjects seeking participation in weight reduction or ideal body weight achievement programmes.

Does senna extract promote growth of aberrant crypt foci and malignant tumors in rat colon?

Current evidence suggests that aberrant crypt foci (ACF) can be used to evaluate agents for their potential colon carcinogenic activity. The aim of the present study was to determine whether senna pod extract (SE) itself induces ACF and tumors in the rat colon or increases the development of ACF and tumors induced by azoxymethane (AOM). A daily administration of SE 10 mg/kg by mouth for 13-28 weeks produced a weak laxative effect but did not itself cause the appearance of ACF or tumors. The numbers of ACF and tumors induced by AOM were, however, increased by a dose of SE (100 mg/kg) able to induce chronic diarrhea over three months. These results suggest that SE does not cause the appearance of ACF or tumors in the rat colon nor does it have a promoting effect when given to rats at a dose that produces laxation (10 mg/kg), whereas a diarrhogenic dose (100 mg/kg) increases the appearance of tumors induced by AOM.

Induction of micronuclei and of enzyme-altered foci in the liver of female rats exposed to progesterone and three synthetic progestins.

Progesterone (PG) and three structurally similar synthetic progestins-norethisterone (NE), allylestrenol (AE), and dydrogesterone (DG)-have been compared for their ability to induce the formation of micronuclei and of enzyme-altered foci in the liver of female rats. In the micronucleus assay, carried out in rats given a single p.o. dose of 100 mg kg-1 3 days before partial hepatectomy and sacrificed for cell sampling 2 days later, the frequency of micronucleated hepatocytes was 3.5-fold higher than in controls with PG, 2.8-fold with DG, 2.2-fold with NE and 2.1-fold with AE, but the increase was statistically significant only for PG. In the liver foci assay, performed to evaluate the tumor initiating activity of p. o. dosing with 100 mg kg-1 once a week for 6 successive weeks, the values of the number and area of gamma-glutamyltranspeptidase-positive foci were, as compared to controls, 15.9- and 100-fold higher with NE, and 13.9- and 52-fold higher with AE, but only the increase of area produced by NE was statistically significant; PG and DG did not display in this test any activities. Considered together with previous findings, these results suggest that NE might be biotransformed in the liver into reactive species and thus behave as a weak genotoxic agent.

[Rupture of the diaphragm caused by closed thoraco-abdominal trauma. Case contribution and anatomo-clinical considerations]. / Rottura del diaframma da trauma chiuso toraco-addominale. Contributo casistico e considerazioni anatomo-cliniche.

Diaphragmatic rupture is a potentially severe complication of blunt trauma which can easily be overlooked during initial emergency department evaluation. Delayed diagnosis is due to severe concurrent injuries and lack of specific clinical features and instrumental procedures. Clinical features of diaphragmatic herniation, in the early presentation, include respiratory symptoms, while abdominal symptoms and signs are late. Plain chest radiography repeated, if negative, is the main help in the diagnosis: especially in patients managed with intermittent positive-pressure ventilation. Experience in five cases of diaphragmatic hernia is reported.

Efficacy of nefopam for the prevention and treatment of amphotericin B-induced shivering.

BACKGROUND: Shivering is experienced by up to 70% of patients undergoing amphotericin B therapy. Treatment with meperidine hydrochloride, currently the most widely used medication for controlling amphotericin B-induced shivering, was compared with nefopam hydrochloride, which has been successfully used to treat post-operative shivering. METHODS: Forty-five patients with cancer and systemic fungal infections randomly received nefopam hydrochloride, 0.3 mg/kg, meperidine hydrochloride, 0.7 mg/kg, or saline solution intravenously 15 minutes before the cessation of amphotericin B infusion (1 mg/kg for 45 minutes). If shivering persisted, patients in the control (saline solution) group received either nefopam hydrochloride, 0.3 mg/kg, or meperidine hydrochloride, 0.7 mg/kg. RESULTS: Occurrence of shivering 15 minutes after the cessation of amphotericin B infusion was significantly less frequent in the nefopam (6.6%) and meperidine (40%) groups compared with the control group (66.6%). The incidence of shivering in the nefopam group with respect to the meperidine group was also significantly reduced. Moreover, nefopam administration to 5 persistently shivering patients in the control group definitively stopped the shivering in all of them (100%) in a mean (+/- SD) time of 29.1 +/- 4.8 seconds, while meperidine terminated shivering in 4 (80%) of 5 patients in a mean (+/- SD) time of 200.0 +/- 30.2 seconds. The adverse reactions that can be ascribed to nefopam or meperidine use were nausea and sedation, respectively, and may be considered negligible. CONCLUSION: Nefopam seems to be more effective than meperidine in preventing and quickly suppressing amphotericin B-induced shivering.

Hepatic hydrothorax without diaphragmatic defect. An original surgical treatment.

A 58-year-old woman with a long history of well-compensated postnecrotic cirrhosis with acute massive ascites and right-sided pleural effusion was admitted. The injection of colorant and radioactive material into the peritoneal cavity didn't show up any passage through the diaphragm. After resuscitation therapy and insertion of abdominal and chest tube, effusions rapidly and massively re-accumulated. A LeVeen peritoneovenous shunt was inserted as an emergency measure owing to hepatorenal syndrome. Ascites completely resolved but pleural effosion was continuously and severely recharged. A Denver inverted shunt was subcutaneously inserted from pleural to peritoneal cavity. After operation CPAP was applied and pump device activated; pleural effusion gradually disappeared clearing completely the pleural space. The patient was discharged on the 10th postoperative day; her general condition and laboratory test have remained satisfactory up to one year without ascites and pleural effusion.

Control of post anaesthetic shivering with nefopam hydrochloride in mildly hypothermic patients after neurosurgery.

Postoperative shivering may be prevented by maintaining normothermia intraoperatively or it may be treated using specific drugs. The aim of this study was to compare the efficacy of nefopam hydrochloride (nefopam) to that of clonidine and meperidine in patients undergoing elective neurosurgical procedures. Three groups of patients were included in the study. Patients in group A (60) received i.v., at random, 20 mg of nefopam, 50 mg of meperidine or 150 micrograms of clonidine in the immediate postoperative period. The incidence of shivering and the time at which shivering ceased were noted, along with central temperature and main haemodynamic changes. Group B (20) received i.v., at random, either 10 mg of nefopam or saline before awakening from anaesthesia. The effects of nefopam on central temperature, oxygen consumption (Vo2), carbon dioxide production (VcO2), basal metabolic rate (BMR) and energy expenditure (EE) were investigated. Group C (10) received i.v. 20 mg of nefopam during surgery: cerebrospinal fluid pressure (CSFP), cerebral perfusion pressure (CPP) and electroencephalogram (EEG) were monitored. In group A nefopam stopped shivering in 95% of patients when compared to meperidine and clonidine, which were effective in 32% and 40% of patients respectively. In group B, only 10% of patients receiving nefopam had postoperative shivering, Vo2, VcO2 and EE were significantly lower in patients treated with nefopam than those in the control group. No changes in CSFP, CPP or EEG were observed in group C. In conclusion, nefopam seems to be more effective than clonidine or meperidine in quickly suppressing shivering, without producing significant adverse reactions.