Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ASTHENIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources
PubMed1999

Phase II study of raltitrexed (Tomudex) in chemotherapy-pretreated patients with advanced colorectal cancer. Tomudex Cooperative Study Group.

Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). This phase II study was conducted to evaluate the anti-timor efficacy and tolerability of raltitrexed in patients with advanced CRC who had received one previous chemotherapy regimen. Raltitrexed was administered at a dose of 3.0 mg/m2 i.v. over 15 min once every 3 weeks. Of 43 eligible patients, 53% had colon cancer and 47% rectal cancer. Objective responses were observed in 16% of patients [95% confidence interval (CI): 7-31%; seven partial responses). The median duration of response was 101 days (range: 45-239 days), the median overall duration of response was 145 days (range: 104-302 days) and the median survival was 11.6 months (95% CI: 9.4-14.7 months). Liver metastases showed a 17% (three of 18) response rate and lung metastases a 12% (three of 25) response rate. Adverse events of grade 3 or 4 reported for more than 5% of patients were neutropenia (23%), leukopenia (9%), reversible SGPT increase (7%) nausea/vomiting (19%), anorexia (14%), asthenia (9%) and hypotension (7%). Grade 3 or 4 diarrhea, stomatitis and alopecia were not observed. In summary, raltitrexed had an acceptable toxicity profile and promising anti-tumor activity against advanced CRC in patients who had received prior chemotherapy. Further clinical trials of combination chemotherapy using raltitrexed are warranted.

Adult↗
PubMed1999

Phase II study of raltitrexed ('Tomudex') for patients with advanced soft tissue sarcomas refractory to doxorubicin-containing regimens.

Advanced soft tissue sarcomas (ASTS) refractory to therapy with doxorubicin and/or ifosfamide are highly resistant to therapy with other cytotoxic agents. The efficacy and safety of raltitrexed ('Tomudex') was assessed in patients with ASTS refractory to one or two doxorubicin- and/or ifosfamide-containing regimens in eight centers of the EORTC STBSG group. Raltitrexed was given at 3 mg/m2 as a 15 min i.v. infusion once every 3 weeks. Among the 23 patients [mean age 54 (range 25-73) years] included, 22 patients (15 males and seven females) were eligible and evaluable for response to therapy and 21 were evaluable for toxicity. Patients had previously received chemotherapy in metastatic phase (n=16), as adjuvant treatment (n=5) or both (n=1). The primary tumor was located in the trunk (n=11), in the limbs (n=8) or in the head and neck (n=3). Most patients (n=13) received two courses of raltitrexed (range 1-8). The best response was stable disease in five (23%) patients, while disease progression was noted in 17 patients (77%); the median time to disease progression was 6 weeks. The treatment was well tolerated with only one patient experiencing grade 4 neutropenia and thrombocytopenia, one patient experiencing grade 3 nausea, one lethargy, one headache, and one asthenia. Only one patient experienced febrile neutropenia. Raltitrexed as monotherapy is not an effective treatment for patients with ASTS who failed conventional chemotherapy with doxorubicin and ifosfamide.

Adult↗
PubMed2003

Increasing-dose gemcitabine plus low-dose cisplatin in metastatic non-small cell lung cancer.

UNLABELLED: Gemcitabine, a pyrimidine analog active in non-small cell lung cancer (NSCLC), is widely used with cisplatin. The potential activity of the combination has not been fully assessed: gemcitabine is not used at its maximum tolerated dose (MTD) and cisplatin shows a clearly dose-related toxicity. This trial was designed to assess the MTD and dose-limiting toxicity (DLT) of low-dose cisplatin and increasing gemcitabine dose. CHEMOTHERAPY: cisplatin 50 mg/m2 on day 1, gemcitabine starting at 1400 mg/m on days 1 and 8 every 21 days. Subsequent levels were increased by 200 mg/m2. Forty-two patients with metastatic NSCLC were enrolled (37 males; median age 61 years; squamous cell carcinoma 19 patients; performance status 2, in 13 patients; 18 patients had significant weight loss). MTD was found to be 2600 mg/m2 because of DLT in three of six patients: two neutropenic fever and one massive bleeding. Overall toxicity was generally mild consisting mainly of neutropenia. Asthenia was the most common non-hematological effect. Overall response rate was 19 out of 41 patients (46.3%) and median survival was 31 weeks. We conclude that the recommended dose for a phase II dose is gemcitabine 2400 mg/m2 days 1 and 8 as a 30-min infusion when given with cisplatin 50 mg/m2.

Adenocarcinoma↗
PubMed2003

A review of phase II studies of ZD9331 treatment for relapsed or refractory solid tumours.

BACKGROUND: Non-small cell lung cancer (NSCLC), ovarian and breast cancers, especially in advanced stages, are difficult to treat using chemotherapy, and novel treatments are required to improve the outcome for the large numbers of patients who relapse after receiving the most effective first- and second-line treatments currently available. This paper reviews the results from three trials of ZD9331, a novel, direct-acting antifolate, in patients with relapsed or refractory solid tumours. PATIENTS AND METHODS: Patients with relapsed or refractory NSCLC, ovarian or breast cancer were included in these three open-label, multicentre trials. All three trials included an i.v. arm of ZD9331 at a dose of 130 mg/m2; the ovarian study also included a 65 mg/m2 i.v. treatment arm and the breast cancer trial included a 3 mg oral treatment arm. Patients received ZD9331 as a 30-min i.v. infusion once weekly for 2 weeks followed by 1 week without treatment (3-week cycle). Oral ZD9331 was given once daily for 28 consecutive days and repeated every 6 weeks. RESULTS: One hundred and eighty-nine patients were included in the three trials (NSCLC: n = 46; ovarian: n = 80; breast: n = 63). Neutropenia (45-59%), asthenia (25-42%) and nausea (41-59%) were amongst the most common adverse events observed in all three trials; however, in the oral treatment group of the breast cancer trial anaemia (58%) and increased alanine aminotransferase (45%) or aspartate aminotransferase (39%) were also frequent. There were no objective responses seen in the NSCLC trial; 20 of 46 patients (43.5%) experienced a best overall response of stable disease. Objective response rates (ORRs) in the ovarian trial were 2.5% (one patient) and 10% (four patients) in the 65 and 130 mg/m2 treatment arms, respectively. In the breast cancer trial ORRs were 9.7% (three patients) and 12.5% (four patients) in the oral and i.v. groups, respectively. CONCLUSIONS: ZD9331 has a manageable toxicity profile, and shows some evidence of activity in patients with relapsed or refractory NSCLC, ovarian and breast cancer.

Adolescent↗
PubMed2003

Oxaliplatin and 5-fluorouracil for heavily pretreated metastatic breast cancer: a preliminary phase II study.

UNLABELLED: Oxaliplatin shows in vitro and in vivo synergism with 5-fluorouracil (5-FU). In this study we evaluate the clinical efficacy of oxaliplatin and 5-FU in heavily pretreated metastatic breast cancer. Eligible patients had to be pretreated with both anthracyclines and taxanes. Pretreatment with capecitabine was recommended but not mandatory. Chemotherapy: oxaliplatin 85 mg/m2/2 h day 1, folinic acid 400 mg/m2/2 h day 1, 5-FU 400 mg/m2 i.v. push day 1, 5-FU 2400 mg/m2 continuous infusion/48 h day 1, q2w. Fourteen patients were included: one male and 13 females; age: median 53 years (38-62); ECOG 0: three patients, 1: nine patients, 2: two patients; all patients were pretreated with anthracyclines and taxanes, capecitabine: nine patients, vinorelbine: six patients, trastuzumab: four patients, hormonal therapy: 12 patients; lines of prior palliative chemotherapy: 0: one patient, 1: three patients, 2: one patient, 3: three patients, 4: four patients, 5: two patients. RESULTS: median number of cycles: 8 (range 1-17). Toxicity (14 patients evaluable; no. of patients with Common Toxicity Criteria grade 3/4): asthenia: 2/-, paraesthesia 3/-, leuko/neutropenia: 1/2, no neutropenic fever, other (alopecia, skin): 2/-. Response (12 patients evaluable, all with bidimensionally measurable disease): complete remission: no patients, partial remission: four patients (33%, all confirmed), stable disease: five patients, progressive disease: three patients. We conclude that despite the small number of patients, the combination of 5-FU and oxaliplatin shows promising efficacy in this heavily pretreated population.

Adult↗
PubMed2003

Fatal pulmonary toxicity in a patient treated with gefitinib for non-small cell lung cancer after previous hemolytic-uremic syndrome due to gemcitabine.

Gefitinib is a low-molecular-weight epidermal growth factor receptor tyrosine kinase inhibitor. To date, gefitinib has been administered to over 65,000 people worldwide. The most commonly reported adverse events were diarrhea, acne-like skin rash, nausea, vomiting and asthenia. Most of them were transient and mild in severity. Interstitial lung disease in patients who have been treated with gefitinib is uncommon and has recently been described with an estimated incidence rate of around 1%. We present here a case of fatal drug-induced pulmonary toxicity after therapy with gefitinib for metastatic non-small cell lung cancer. The patient had been treated with gemcitabine and cisplatin, and developed drug-induced hemolytic-uremic syndrome 6 months before gefitinib use.

Aged↗
PubMed2005

Phase II trial of vinorelbine tartrate in patients with treatment-naive metastatic melanoma.

Metastatic melanoma carries a dismal prognosis and there is a need to develop new treatment strategies. Vinca alkaloids have shown consistent activity in melanoma patients, as monotherapy and as part of combination regimens. The current study evaluates the clinical activity and tolerability of vinorelbine as first-line monotherapy in patients with metastatic melanoma. Patients were eligible if they presented metastatic melanoma not amenable to curative resection, had received no prior systemic therapy for advanced disease and had an adequate performance status (ECOG 0-1). Patients received vinorelbine at a dose of 30 mg/m2 on days 1 and 8 of a 21-day cycle, on an outpatient basis. Thirteen patients were accrued into the study and received 64 cycles. All patients were assessable for response, toxicity and survival. No objective responses were documented, for an overall response rate of 0% [95% confidence interval (CI) 0-19%] and the trial was terminated in accordance to the predetermined early discontinuation rule. The median progression-free survival was 3.3 months (95% CI 2.3-4.3 months) and the estimated median overall survival was 8.1 months (95% CI 6.0-10.2 months). No life-threatening toxicities occurred. Neutropenia was the main hematologic toxicity, but none of the three episodes of grade 3-4 neutropenia were complicated by infection. The most common non-hematologic toxicities were asthenia, nausea, neuropathy and myalgia. We conclude that vinorelbine as a single agent on days 1 and 8 of a 21-day cycle has a favorable toxicity profile, but appears to have no relevant clinical activity in patients with metastatic melanoma.

Aged↗
PubMed2005

Biweekly docetaxel and vinorelbine with granulocyte colony-stimulating factor support for patients with anthracycline-resistant metastatic breast cancer.

This phase II trial evaluated the efficacy and toxicity of vinorelbine 25 mg/m2 plus docetaxel 60 mg2/m administered on day 1, every 2 weeks with granulocyte colony-stimulating factor support (G-CSF, 5 microg/kg/day, days 3-7) as primary prophylaxis in patients with histologically confirmed metastatic breast cancer (MBC) and previously treated with anthracyclines in the adjuvant or in the first-line setting. A total of 48 patients received 352 cycles (median 8, range 2-10). All patients were included in the efficacy and safety evaluation on an intent-to-treat analysis. Eight patients (17%) showed a complete response and 14 patients (29%) showed a partial response. Overall response rate was 46% [95% confidence interval (CI) 33-60]. The median duration of response was 10.0 months. With a median follow-up of 18.0 months, the median time to progression was 11.9 months and the median overall survival was 27.1 months. The most frequently reported grade 3/4 hematological toxicity was neutropenia (19% of patients, 4% of cycles). Febrile neutropenia was reported in six patients (13%) and 7 cycles (2%), but no toxic deaths were reported. The most common grade 3/4 non-hematological toxicity was asthenia (17% of patients, 6% of cycles) and nail toxicity (15% of patients, 3% of cycles). In conclusion, biweekly docetaxel plus vinorelbine with G-CSF support is active and well tolerated as chemotherapy for patients with MBC resistant to anthracyclines. G-CSF support is recommended for lowering the incidence and severity of neutropenia and febrile neutropenia.

Adult↗
PubMed2006

Weekly paclitaxel, 5-fluorouracil and folinic acid with granulocyte colony-stimulating factor support in metastatic breast cancer patients: a phase II study.

We conducted a phase II study to determine the activity and tolerability of weekly paclitaxel, 5-fluorouracil (5-FU) and folinic acid plus granulocyte colony-stimulating factor (G-CSF) support in anthracycline-pre-treated or -resistant metastatic breast cancer patients. The phase II study was designed following the Simon optimal-two stage method. Patients received paclitaxel 80 mg/m, folinic acid 10 mg/m and bolus infusion of 5-FU 300 mg/m every week plus G-CSF on day 3 for 24 consecutive weeks in the absence of disease progression. From May 1998 to May 2000, 51 patients entered the study. Patients received a median relative dose intensity of 97.5% (range 81-100%). No severe toxicities were observed. Seven patients (14%) experienced neutropenia grade 2. Seven patients (14%) experienced grade 2 anemia. Two patients (4%) experienced severe asthenia. Three out of 50 evaluable patients [6%, 95% confidence interval (CI) 2-12.6%] showed a complete response, whereas 23 (46%, 95% CI 32.2-59.8%) had a partial response, with an overall response rate of 52% (95% CI 38.2-65.8%). In addition, eight patients (15.7%) had stable disease. In the 13 patients untreated for metastatic disease, the overall response rate was 92.3% (CI 77.8-100), with one complete response and 11 partial responses (84.6% CI 65-100%). In the whole group, the median time to progression and overall survival were 8 (range 1-18) and 14 months (95% CI 11-17), respectively. Thus, in metastatic breast cancer patients pre-treated with anthracyclines, the weekly administration of paclitaxel, 5-FU and folinic acid with G-CSF support seems to be extremely tolerable and active.

Adult↗
PubMed1999

Ritonavir and saquinavir combination therapy for the treatment of HIV infection.

OBJECTIVE: To evaluate the safety and antiretroviral activity of ritonavir (Norvir) and saquinavir (Invirase) combination therapy in patients with HIV infection. DESIGN: A multicenter, randomized, open-label clinical trial. SETTING: Seven HIV research units in the USA and Canada. PATIENTS: A group of 141 adults with HIV infection, CD4 T lymphocyte counts of 100-500 x 10(6) cells/l, whether treated previously or not with reverse transcriptase inhibitor therapy, but without previous HIV protease inhibitor drug therapy. INTERVENTIONS: After discontinuation of prior therapy for 2 weeks, group I patients were randomized to receive either combination (A) ritonavir 400 mg and saquinavir 400 mg twice daily or (B) ritonavir 600 mg and saquinavir 400 mg twice daily. After an initial safety assessment of group I patients, group II patients were randomized to receive either (C) ritonavir 400 mg and saquinavir 400 mg three times daily or (D) ritonavir 600 mg and saquinavir 600 mg twice daily. Investigators were allowed to add up to two reverse transcriptase inhibitors (including at least one with which the patient had not been previously treated) to a patient's regimen after week 12 for failure to achieve or maintain an HIV RNA level < or = 200 copies/ml documented on two consecutive occasions. MEASUREMENTS: Plasma HIV RNA levels and CD4+ T-lymphocyte counts were measured at baseline, every 2 weeks for 2 months, and monthly thereafter. Safety was assessed through the reporting of adverse events, physical examinations, and the monitoring of routine laboratory tests. RESULTS: The 48 weeks of study treatment was completed by 75% (106/141) of the patients. Over 80% of the patients on treatment at week 48 had an HIV RNA level < or = 200 copies/ml. In addition, intent-to-treat and on-treatment analyses revealed comparable results. Suppression of plasma HIV RNA levels was similar for all treatment arms (mean areas under the curve minus baseline through 48 weeks were-1.9, -2.0, -1.6, -1.8 log10 copies/ml in ritonavir-saquinavir 400-400 mg twice daily, 600-400 mg twice daily, 400-400 mg three times daily, and 600-600 mg twice daily, respectively). Median CD4 T-lymphocyte count rose by 128 x 10(6) cells/l from baseline, with an interquartile range (IQR) of 82-221 x 10(6) cells/l. The most common adverse events were diarrhea, circumoral paresthesia, asthenia, and nausea. Reversible elevation of serum transaminases (> 5 x upper limit of normal) occurred in 10% (14/141) of the patients enrolled in this study and was associated with baseline abnormalities in liver function tests, baseline hepatitis B surface antigen positivity, or hepatitis C antibody positivity (relative risk, 5.0; 95% confidence interval 1.5-16.9). Most moderate or severe elevations in liver function tests occurred in patients treated with ritonavir-saquinavir 600-600 mg twice daily. CONCLUSIONS: Ritonavir 400 mg combined with saquinavir 400 mg twice daily with the selective addition of reverse transcriptase inhibitors was the best-tolerated regimen of four dose-ranging regimens and was equally as active as the higher dose combinations in HIV-positive patients without previous protease inhibitor treatment.

Adult↗
PubMedDate not supplied

Phase 1 study of the intravesical administration of recombinant human interleukin-12 in patients with recurrent superficial transitional cell carcinoma of the bladder.

Superficial transitional cell carcinoma (STCC) of the bladder is usually managed with intravesical bacille Calmette-Guerin. Recombinant human interleukin-12 (rhIL-12) is a heterodimeric cytokine that induces T-cell and natural killer cell proliferation/activation and production of IFNgamma. It has demonstrated preclinical in vivo bladder antitumor activity and no systemic toxicity. This phase 1 study evaluated intravesical rhIL-12 administration in patients with STCC (Tis, Ta, or T1) who had failed at least one prior intravesical therapy or had at least two recurrences of low-grade tumors. Eligible patients had adequate hematologic, renal, and hepatic function and Karnofsky performance status at least 70%. Cohorts of three patients received 5, 20, 50, 100, and 200 microg rhIL-12 (treated n = 15). Each patient received intravesical rhIL-12 weekly for 6 weeks, with a 2-hour bladder dwell. No patient experienced moderate, severe, or life-threatening systemic toxicity. Treatment-related adverse events included dysuria, urinary frequency, urinary urgency, asthenia, pain, hematuria, bladder spasms, and chills. Specific AE incidences were not dose-related. Among 12 patients without visible pretreatment lesions, 7 remained disease-free and 5 experienced recurrence of STCC within the 4-week follow-up period. Three patients with pretreatment Tis or Ta/T1 lesions had persistent disease at posttreatment follow-up. No patients with persistent tumor manifested antitumor response to rhIL-12. Two-hour dwell urine samples and 24- to 30-hour postdose serum samples showed negligible induction of IFNgamma. In summary, intravesical rhIL-12 was well tolerated by patients with recurrent STCC but showed no clinically relevant evidence of antitumor or immunologic effects.

Administration, Intravesical↗
PubMed2001

Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.

OBJECTIVE: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study. METHOD: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method. RESULTS: Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p < .05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p < .05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia. CONCLUSIONS: Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD.

Adolescent↗
PubMedDate not supplied

Superior mesenteric artery syndrome in scoliosis surgery: weight percentile for height as an indicator of risk.

A retrospective analysis of charts identified cases of superior mesenteric artery (SMA) syndrome occurring after scoliosis surgery over a 23-year period. Despite numerous reports on this potentially fatal complication of scoliosis surgery, no method exists to stratify patients for risk of developing disease after spine surgery. A study of charts was performed to identify all cases of SMA syndrome occurring after scoliosis surgery from 1972 to 1995. An upper gastrointestinal study with findings specific for the syndrome was requisite for inclusion. Patients' weight and height at the time of diagnosis of SMA syndrome were recorded. Based on standard national data tables, a percentile for weight, percentile for height, and a weight percentile for height were derived for each patient. The syndrome occurred after posterior spinal fusion in six patients (three boys, three girls). The average weight percentile for height, available in five of the six patients, was 3%, significantly different from both age-matched controls in the general population and from age-matched controls undergoing posterior spinal fusion for adolescent idiopathic scoliosis. This study, the largest reported from a single institution, suggests that a weight percentile for height of 5% is the degree of asthenia that allows compromise of the duodenum. The percentile identifies patients at risk for SMA syndrome for the purposes of increasing postoperative vigilance for gastrointestinal complaints, decreasing the threshold for diagnostic workup, and guiding perioperative dietary supplementation.

Adolescent↗
PubMed1998

The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group.

This 12-week, double-blind, placebo-controlled study evaluated the efficacy and safety of venlafaxine as first-line therapy for the treatment of major depression and major depression associated with anxiety in 384 adult outpatients. Fixed total daily dosages of 75, 150, and 200 mg of venlafaxine were administered in a twice-a-day regimen. Primary efficacy parameters were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D Depressed Mood Item, the Montgomery-Asberg Depression Rating Scale total score, and the Clinical Global Impressions Scale. Overall, a higher percentage of patients responded to venlafaxine than to placebo. Efficacy data indicated a dose-related response, most evident in the onset of clinical improvement; statistically significant improvements in some primary parameters were seen as early as 1 to 2 weeks after initiation of treatment, especially in the 150-and 200-mg/day groups. These dose-related clinical improvements continued through week 12. Venlafaxine-treated patients who had depression associated with anxiety showed significant dose-related improvements compared with placebo-treated patients; improvement was noted by scores on the HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor. Few clinically significant changes were observed in laboratory values, vital signs, or electrocardiogram tracings. Venlafaxine was generally well tolerated at all dosages. The most common study events included nausea, dizziness, somnolence, insomnia, dry mouth, and asthenia, which are consistent with findings of previous studies. The current study demonstrated that 75 to 200 mg/day of venlafaxine twice daily produced a dose-related improvement in the primary efficacy parameters and in the onset of significant antidepressant effects, which was noted at weeks 1 to 2 with the highest dosage tested (200 mg/day). The study also demonstrated that these dosages of venlafaxine were safe and effective as first-line therapy for major depression and depression associated with anxiety.

Adult↗
PubMed2000

Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter study. European Valproate Mania Study Group.

To compare the efficacy of sodium valproate administered as adjunct to neuroleptic medication for patients with acute mania with the efficacy of neuroleptics alone, the authors conducted a 21-day, randomized, double-blind, parallel-group, placebo-controlled trial. The study design closely reflected a clinical psychiatric setting in Europe where patients with acute mania commonly receive neuroleptic medication. In this trial, 136 hospitalized patients met the ICD-10 criteria for acute manic episodes; these patients received a fixed dose of 20 mg/kg of body weight of sodium valproate (Orfiril, Desitin Arzneimittel GmbH, Hamburg, Germany) orally, in addition to basic neuroleptic medication, preferably haloperidol and/or perazine. The primary outcome measure was the mean dose of neuroleptic medication (after conversion into haloperidol-equivalents) for the 21-day study period. Severity of symptoms was measured using the Young Mania Rating Scale (YMRS), the Global Assessment Scale, and the Clinical Global Impression Scale. Intent-to-treat analysis was based on 69 patients treated with valproate and 67 patients who received placebo. Groups were comparable with regard to demographic and clinical baseline data. Premature discontinuations occurred in only 13% of the patients. The mean neuroleptic dose declined continuously in the valproate group, whereas only slight variations were observed in the placebo group; the difference was statistically significant (p = 0.0007) for study weeks 2 and 3. The combination of neuroleptic and valproate proved superior to neuroleptics in attempts to alleviate manic symptoms. The proportion of responders (a 50% improvement rate shown on the YMRS) was higher for the combination with valproate than for the group receiving only neuroleptics (70% vs. 46%; p = 0.005). Adverse events consisted of those known for valproate or neuroleptics; the only adverse event was asthenia, which occurred more frequently with the combination therapy. Valproate represents a useful adjunct medication for the treatment of acute manic symptoms. Valproate is beneficial because it allows the administration of fewer neuroleptic medications and produces improved and quicker remission of manic symptoms.

Acute Disease↗
PubMed1996

Antimitochondrial antibody-negative chronic nonsuppurative destructive cholangitis. Atypical primary biliary cirrhosis or autoimmune cholangitis?

We investigated whether autoimmune cholangitis (AC) has specific features that constitute an entity other than primary biliary cirrhosis (PBC). We compared clinical, laboratory, and liver biopsy features; response to treatment; and the follow-up of two groups of patients. The first group comprised seven patients with AC criteria-PBC with negative antimitochondrial antibodies (AMAs) and positive antinuclear antibodies (ANAs)-termed the PBC AMA-negative group; the second was made up of another seven PBC patients with positive AMA, labeled the PBC AMA-positive group. We found that the PBC AMA-negative group had, besides negative AMAs and positive ANAs, a significantly higher incidence of asthenia, a higher and earlier incidence of liver failure, and higher ANA titers and serum immunoglobulin G levels than the PBC AMA-positive group. There were no significant differences in the other laboratory tests, although the PBC AMA-negative group showed higher serum bilirubin and aminotransferase and lower serum alkaline phosphatase and immunoglobulin M levels. Liver histological data were similar in both groups. Patients in the PBC AMA-negative group, with more markedly abnormal liver tests, responded to immunosuppressive therapy. We concluded that patients with criteria for PBC but with negative AMAs and positive ANAs have a few specific features that fall between PBC and autoimmune chronic hepatitis. This finding suggests that these patients have a different disease, for which autoimmune cholangitis seems to be an appropriate name.

Adult↗
PubMed1990

A tolerance study of single and multiple dosing of the selective dopamine uptake inhibitor GBR 12909 in healthy subjects.

GBR 12909 selectively blocks dopamine uptake and its biochemical and pharmacological profiles suggest that it may possess antidepressant activity and be of value in treatment of Parkinson's disease. The tolerance, pharmacokinetics and influence on psychomotor performance of GBR 12909 were investigated in a randomized placebo-controlled double-blind study. Four healthy subjects were administered oral single doses of 100, 200 and 300 mg GBR 12909 and placebo, and four other healthy subjects received, 50, 100 and 150 mg GBR 12909 and placebo once daily for 7 days. The intermediate and highest doses resulted in mild to moderate side-effects such as difficulties in concentrating, asthenia, feeling of drug influence and palpitations. No changes were observed in haematological and clinico-chemical parameters. A dose-related effect on ECG was observed with a slight reduction of the T-wave amplitude. No signs of arrhythmia or decompensation during exercise until exhaustion were observed. Psychomotor performance indicated dose-related sedation in the single-dose study. Only minor deviations from first order kinetics were observed. Elimination half-life was estimated at 1-2 days. Steady-state serum concentrations of GBR 12909 appeared to be attained within 1 week. Based on the results of this study, the estimated therapeutic doses are expected to be well-tolerated in patients.

Adult↗
PubMed1993

A placebo-controlled double-blind multicenter trial of two doses of ipsapirone versus diazepam in generalized anxiety disorder.

Ipsapirone is a partial 5-HT1A agonist which appears promising for the pharmacologic treatment of anxiety. In this four-week, double-blind, 19-center study, 249 outpatients with generalized anxiety disorder were randomized to one of four treatments: ipsapirone, 5 or 10 mg t.i.d., diazepam 5 mg t.i.d., or placebo. Both active treatments were significantly superior to placebo in reducing anxiety symptoms, although response to ipsapirone was not significant until week 2 while diazepam had a more rapid onset. Five mg t.i.d. was the optimal ipsapirone dose. At 10 mg t.i.d. adverse experiences prompted more patients to discontinue treatment. Adverse experiences that were reported significantly more often for ipsapirone than placebo included asthenia, nausea, dizziness, paresthesias and sweating. Sedation was the most common diazepam-related side effect. The results of this study when combined with others suggest that 5 mg t.i.d. of ipsapirone is an effective and well-tolerated anxiolytic without many of the risks of benzodiazepine therapy. Dosage escalation by patients is unlikely because of an increased risk of side effects.

Ambulatory Care↗