Patch testing with preservatives, antimicrobials and industrial biocides. Results from a multicentre study

Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Cells from NBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from ataxia telangiectasia. We describe the positional cloning of a gene encoding a novel protein, nibrin. It contains two modules found in cell cycle checkpoint proteins, a forkhead-associated domain adjacent to a breast cancer carboxy-terminal domain. A truncating 5 bp deletion was identified in the majority of NBS patients, carrying a conserved marker haplotype. Five further truncating mutations were identified in patients with other distinct haplotypes. The domains found in nibrin and the NBS phenotype suggest that this disorder is caused by defective responses to DNA double-strand breaks.     

Posatirelin in the treatment of vascular dementia: a double-blind multicentre study vs placebo

INTRODUCTION: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia. PATIENTS AND METHODS: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Br?ne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance. RESULTS: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good. CONCLUSIONS: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.     

Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo, and psychological panic management combined with exposure and of exposure in vivo alone

OBJECTIVE: The purpose of this comparative outcome study was to investigate whether the effects of exposure in vivo treatment for panic disorder with agoraphobia could be enhanced by adding interventions specifically for panic attacks before the start of exposure treatment. The additional effect of two types of treatment for panic attacks--pharmacological (fluvoxamine) and psychological (repeated hyperventilation provocations and respiratory training)--was examined. Thus, the combined treatment of panic interventions with exposure in vivo could be compared to exposure in vivo alone. METHOD: Ninety-six patients were randomly assigned to four treatment conditions: double-blind, placebo-controlled fluvoxamine followed by exposure in vivo, psychological panic management followed by exposure, and exposure in vivo alone. Outcome was assessed by self-report measures, a standardized multitask behavioral avoidance test, and continuous monitoring of panic attacks. Seventy-six patients completed the study. RESULTS: All four treatments were effective and resulted in a significant decrease of agoraphobic avoidance. Moreover, the combination of fluvoxamine and exposure in vivo demonstrated efficacy superior to that of the other treatments and had twice as large an effect size (difference between pre- and posttreatment scores) on self-reported agoraphobic avoidance. The other treatments did not differ among each other in effectiveness. CONCLUSIONS: Results of the study indicate that the short-term outcome of exposure in vivo treatment can be enhanced by adding fluvoxamine treatment. Psychological panic management combined with exposure was not superior to exposure alone of equal duration.     

rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo

SETTING: Low-dose recombinant human interleukin 2 (rhuIL-2) adjunctive immunotherapy in multidrug resistant tuberculosis (MDR-TB) patients. OBJECTIVE: Evaluation of the effects of daily versus pulse-administered rhuIL-2 compared to placebo. DESIGN: MDR-TB patients on best available antituberculous chemotherapy received rhuIL-2 for 30 consecutive days (daily therapy), or for 5 days followed by a 9-day 'rest', for three cycles (pulse therapy). Placebo control patients received diluent. The cumulative total dose of rhuIL-2 given to each patient in either rhuIL-2 treatment group was the same. Patient immunologic, microbiologic, and radiologic responses were compared. RESULTS: The three treatment schedules induced different results. Immune activation was documented in patients receiving daily rhuIL-2 therapy. Numbers of CD25+ and CD56+ cells in the peripheral blood were increased in these patients, but not in patients receiving pulse rhuIL-2 or placebo. In addition, 5/8 (62%) patients receiving daily rhuIL-2 demonstrated reduced or cleared sputum bacterial load while only 2/7 (28%) pulse rhuIL-2 treated and 2/8 (25%) controls showed bacillary clearance. Chest radiographs of 7/12 (58%) patients receiving daily rhuIL-2 indicated significant improvement over 6 weeks. Only 2/9 (22%) pulse rhuIL-2-treated patients and 5/12(42%) placebo controls showed radiologic improvement. CONCLUSION: Daily low dose rhuIL-2 adjunctive treatment stimulates immune activation and may enhance the antimicrobial response in MDR-TB.     

Compulsive exhibitionism successfully treated with fluvoxamine: a controlled case study

BACKGROUND: Paraphilias are psychosexual disorders that are usually conceptualized as deviant in nature. Yet in some cases, paraphilia can be conceptualized as an obsessive compulsive disorder. METHOD: We describe an exhibitionist treated under partial single-blind conditions (patient was blind to placebo but was aware he was receiving desipramine and fluvoxamine) with the serotonin selective reuptake inhibitor fluvoxamine, followed by desipramine and a placebo that looked like fluvoxamine, in an ABACA design. He was serially assessed with the Yale-Brown Obsessive Compulsive Scale. RESULTS: Fluvoxamine eliminated the undesired impulse and behavior without affecting sexual desire. Desipramine and single-blind fluvoxamine-placebo treatment were both associated with relapses. CONCLUSION: A subset of paraphiliacs may be suffering from obsessive-compulsive-related disorders and may benefit from serotonergic agents.     

Acute therapy of episodic and chronic cluster headache with sumatriptan s.c. Results of a one-year long-term study

Breast cancer is the commonest malignancy to affect women. The malignant process may present clinicians with problems in establishing the diagnosis expeditiously, accurately staging the disease and assessing tumour response to primary systemic chemotherapy. Considerable recent interest has focused on the application of imaging techniques that utilize tumour-specific gamma-ray-emitting radiopharmaceuticals to resolve these problems. The wide availability of gamma camera systems makes single photon-imaging techniques, using radiopharmaceuticals incorporating conventional isotopes, attractive options. However, results concerning the detection of the primary breast cancer and the staging of axillary lymph nodes suggest that these techniques would appear to offer no significant advantages, when compared with those obtained using standard diagnostic methods. Dual gamma-ray-emission imaging by positron emission tomography (PET) may offer an alternative solution. Studies performed show that PET can accurately detect primary breast cancers, stage locoregional lymph nodes and visualize distant tumour metastases. Furthermore, PET may be able to monitor early tumour response to chemotherapy agents. It would appear, therefore, that dual gamma emission might have an important role to play in the management of patients with breast cancer.     

One week triple therapy for Helicobacter pylori: a multicentre comparative study. Lansoprazole Helicobacter Study Group

BACKGROUND: Eradication of Helicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis. AIM: To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori. PATIENTS: Men or women with H pylori positive duodenal ulceration or gastritis, or both. METHODS: A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pylori status. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment. RESULTS: H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. CONCLUSIONS: All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.     

A comparison of fluvoxamine and fluoxetine in the treatment of major depression

Two monoclonal antibodies (MAbs) to human placenta laminin (pl-LAM), 1D8 (IgG1) and 6G5 (IgG2b) were generated and shown by ELISA and immunoblot analysis to recognize only native pl-LAM, but not denatured, reduced pl-LAM or mouse EHS laminin. Intact pl-LAM was easily isolated and purified in large scale from human placenta by 1D8-conjugated affinity chromatography. Electrophoretic analysis of the purified pl-LAM revealed the presence of a major 750-kDa component composed of 320-, 220-, and 200-kDa polypeptides and a minor 800-kDa component composed of 320-, 240-, and 220-kDa polypeptides. Neither molecule had a 400-kDa component corresponding to the A chain. It has already been shown that the 320-kDa polypeptide is identical to the M chain of human merosin (Hori et al. J. Biochem. 1994;116:1212-1219). Electron microscopy revealed that isolated merosin was composed of three short arms and one long arm. By immunohistochemistry, MAbs showed positive staining in human adult kidney and liver. These results indicate that these MAbs recognize only native merosin and can be used to study merosin structure and function by rapid purification of native merosin and by immunohistochemical analysis.     

Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy

Lipoid proteinosis is a rare autosomal recessive disorder with a chronic, benign course. There is no generally accepted systemic therapy apart from the experimental oral use of dimethyl sulphoxide (DMSO) and etretinate in two single cases. We treated two sisters and an unrelated man with lipoid proteinosis with longterm oral DMSO (60 mg/kg/d). At the end of an average treatment time of 3 years, DMSO was withdrawn because it produced no beneficial effects with regard to their skin, mucosal lesions or hoarseness. Additionally, one patient showed progression of her disease with worsening hoarseness and onset of dyspnea, requiring surgical removal of vocal cord infiltrates. Three patients with lipoid proteinosis failed to show any beneficial response to long term treatment with DMSO.     

Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study

We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.     

Stepwise therapy of community-acquired pneumonia. Results of cefuroxime and cefuroxime axetil study

The efficacy of a 7-day switch therapy with parenteral cefuroxime in a dose of 750 mg for 3-5 days followed by the use of oral cefuroxime axetil in a dose of 500 mg every 12 hours was compared with that of a 7-day therapy with parenteral cefuroxime in a dose of 750 mg every 8 hours in hospitalized patients with community-acquired pneumonia. The clinical and bacteriological efficacies and pharmacokinetic properties of both the dosage forms were estimated. It was shown that the clinical and bacteriological effects did not significantly differ in the patients under the parenteral regimen with cefuroxime and under the parenteral-to-oral regimen with cefuroxime and cefuroxime axetil: the cure in 75 and 83 per cent of the patients and the bacteriological response in 100 and 86 per cent of the cases respectively. The results indicated that the cost of the switch therapy was much lower while the efficacy did not decrease.     

Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group

BACKGROUND: Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. METHODS: 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. FINDINGS: The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. INTERPRETATION: Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.     

Acceptance and commitment therapy for smoking cessation: A preliminary study of its effectiveness in comparison with cognitive behavioral therapy.

This controlled preliminary trial determined the feasibility and initial effectiveness of a promising behavioral intervention for smoking: Acceptance and Commitment Therapy (ACT). In a quasi-experimental design, the ACT intervention condition used metaphors and experiential exercises focused on personal values to motivate quitting smoking and enhancing the willingness to experience internal cues to smoke (e.g., urges) and abstinence-related internal distress. The comparison condition was cognitive behavioral therapy (CBT)—the current standard in behavioral intervention for smoking cessation. Each treatment was delivered in seven weekly 90-min sessions in a group format to 81 (43 in ACT; 38 in CBT) adult smokers. Results show that the ACT treatment was as feasible as the CBT treatment. They also demonstrate promising evidence of ACT’s effectiveness: 30.2% intent-to-treat biochemically-supported 30-day point prevalence at twelve month follow-up, compared with 13.2% in the CBT condition (odds ratio = 5.13; p = .02). Replication in a well-powered, randomized, controlled trial is now needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sulbactam/ampicillin in comparison with cefuroxime for infections of the lower respiratory tract. Results of a prospective, randomized comparative study

Gallbladder removal using laparoscopic techniques has rapidly been adopted by surgeons around the world. Questions have been raised concerning laparoscopic cholecystectomy, including the safety of the operation, its implications for management of common bile duct stones, and the means by which surgeons should be trained. In the present series, 424 patients were referred to a single surgeon for cholecystectomy during a 22-month period. A traditional open cholecystectomy was performed in 9 patients (2.1%) because of presumed contraindications to laparoscopic cholecystectomy. Laparoscopic cholecystectomy was attempted in the remaining 415 patients (97.9%). On the basis of preoperative investigations, 19 patients (4.6%) underwent endoscopic retrograde cholangiopancreatography. Endoscopic sphincterotomy and stone extraction were performed in the 13 patients (3.1%) demonstrating choledocholithiasis. Laparoscopic cholecystectomy was converted to an open operation in 8 patients (1.9%) owing to dense adhesions, obscure anatomy, or cholangiographic abnormalities. Laparoscopic cholecystectomy was successfully performed in 407 patients (96%) in 95 +/- 2 minutes (mean +/- SEM). Surgical trainees were involved in all operations and performed 68% of the procedures under supervision. Cystic duct cholangiograms were obtained selectively in 129 patients (30.4%). Intraoperative complications occurred in 3 patients, including 1 patient with a minor injury to the common bile duct (0.2%). There was no perioperative mortality, and major complications occurred in 6 patients (1.4%). Minor complications were seen in 12 others (2.8%), and one patient required reoperation for a trocar injury to the jejunum. Prolonged follow-up has revealed one case of asymptomatic retained common bile duct stones (0.2%). Laparoscopic cholecystectomy can therefore be performed in more than 95% of patients with no mortality and minimal morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of non-proven therapy among patients treated in Norwegian oncological departments. A cross-sectional national multicentre study

A national multicentre study was performed to investigate the prevalent use of "alternative medicine", here called "non-proven therapies (NPT)", applied among Norwegian cancer patients. Of 911 patients invited to take part in the study, 642 were included in the analysis. Demographic characteristics were collected for all patients. The participating physicians gave information about the patients' clinical characteristics. Among 630 evaluable patients, 20% had been or were present users of NPTs for their oncological disease. The preferred methods were healing by hand and faith healing. Herbs, vitamins, diets and Iscador were other popular methods. As many as 40% of the users of NPTs had used NPTs earlier for non-malignant diseases. Elderly patients were less likely to use NPTs. Use was high in the northern part of Norway.     

Epidemiology of encephalitis in children. A prospective multicentre study

We found 175 cases with acute encephalitis in a population of 791,712 children aged 1 month-15 years during a 2-year surveillance period in 1993-1994. The overall incidence was 10.5/100,000 child-years with the highest figure in children < 1 year of age, 18.4/100,000 child-years. The microbial diagnosis was considered proven or suggested in 110 cases (63%); varicella zoster, respiratory and enteroviruses comprised 61% of these, and adeno, Epstein Barr-, herpes simplex and rota viruses comprised 5% each. A clearcut change seems to have occurred in the aetiology of encephalitis. Mumps, measles, and rubella virus associated encephalitides have been almost eliminated. Varicella zoster, respiratory, and enteroviruses have increased in frequency and occur in younger age groups. New causes were identified, especially Chlamydia pneumoniae and HHV-6. Our data should assist in making a specific diagnosis and defining appropriate antimicrobial therapy. CONCLUSIONS: The spectrum of encephalitis in children has changed due to vaccination programs. The incidence, however, appears to be about the same due to increasing frequency of other associated old and new microbes.     

Magnesium in migraine. Results of a multicenter pilot study

BACKGROUND: Numerous experiments and clinical observations have credited magnesium with a positive influence on the incidence of migraine attacks. METHODS: With the aim of testing this hypothesis, a doubleblind, cross-over multicenter pilot study was initiated. The study contained 43 migraine patients who met the criteria of the international Headache Society. INTERVENTIONS: Administration of 600 mg magnesium/day in the form of trimagnesium dieitrate for prophylaxis. RESULTS: Under this medication, a significant reduction in the incidence of migraine attacks was observed. Although the level of effectiveness of the regimen does not appear to be as high as that of presently approved migraine prophylactic substances, a very low rate of side effects can be expected. CONCLUSION: The working hypothesis to the effect that magnesium may be useful in the prevention of migraine attacks has been confirmed by the pilot study. Further studies aimed at determining dosage and enabling a further differentiation of patient material are in preparation.