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.     

Breast tumour imaging using incomplete circular orbit pinhole SPET: a phantom study

Improvements in 99Tcm-sestamibi breast lesion visualization using single photon emission tomography (SPET) may help define the clinical role of this technique alongside X-ray mammography in the diagnosis and management of breast cancer. Pinhole SPET offers the advantages of high resolution and sensitivity when compared to conventional parallel-beam collimation for sources located near the pinhole aperture. In this work, the potential of incomplete (180 degrees) circular orbit (ICO) SPET with pinhole collimation is investigated as a means to visualize small (6.4 and 9.6 mm diameter) spherical simulated tumours, at clinical count densities and tumour-to-background ratios, in a breast phantom. ICO pinhole SPET is compared to complete circular orbit (CCO) pinhole SPET for reference, and planar breast imaging (scintimammography) using parallel-beam and pinhole collimators. A prototype box-shaped pinhole collimator with a 4 mm diameter circular aperture was used to acquire projections of an 890 ml breast phantom both in isolation and mounted on a cylinder filled with a mixture of 99Tcm-pertechnetate and water. A heart phantom containing 99Tcm activity in the myocardium was placed in the cylinder. Simulated tumours containing 99Tcm were placed in the breast phantom and scanned at clinically relevant count densities and scan times with tumour-to-normal tissue concentration ratios of 5.0:1 (9.6 mm sphere) and 7.7:1 (6.4 mm sphere). Phantom data were reconstructed using pinhole filtered backprojection (FBP) and maximum likelihood-expectation maximization (ML-EM). The tumours were not visualized with scintimammography, in which lesion contrast and signal-to-noise were estimated from region of interest analysis to be < 2% and 0.01, respectively. Average (over lesion size and scan time) contrast and signal-to-noise in the ICO (CCO) SPET images were 33% and 1.72 (34% and 1.3), respectively. These values indicate that ICO pinhole SPET has the potential to improve visualization of small (< 10 mm) breast tumours when compared with scintimammography, which may be beneficial for the early classification of cancers of the breast.     

Fusaproliferin production by Fusarium subglutinans and its toxicity to Artemia salina, SF-9 insect cells, and IARC/LCL 171 human B lymphocytes

Fusarium subglutinans is an important pathogen of maize and other commodities worldwide. We examined MRC-115 and 71 other F. subglutinans strains from various geographic areas for their ability to synthesize fusaproliferin, a novel toxic sesterterpene recently isolated from F. proliferatum. Fusaproliferin production ranged from 30 to 1,500 micrograms/g of dried ground substrate, with 33 strains producing more than 500 micrograms/g. In particular, strain MRC-115 produced as much as 1,100 to 1,300 micrograms/g. In toxicity studies of two invertebrate models, fusaproliferin was toxic to Artemia salina (50% lethal dose, 53.4 microM) and to the lepidopteran cell line SF-9 (50% cytotoxic concentration, approximately 70 microM, after a 48-h exposure). Fusaproliferin was also toxic to the human nonneoplastic B-lymphocyte cell line IARC/LCL 171 (50% cytotoxic concentration, approximately 55 microM in culture in stationary phase after a 48-h exposure). Experiments performed will cells exposed at seeding suggested a possible cytostatic effect at subtoxic concentrations.     

Accelerated radiotherapy, carbogen and nicotinamide (ARCON) in locally advanced head and neck cancer: a feasibility study

BACKGROUND AND PURPOSE: ARCON (Accelerated Radiotherapy, CarbOgen, Nicotinamide) achieves a large therapeutic gain in rodents. A phase I/II study was therefore undertaken to determine its feasibility in patients with locally advanced head and neck cancer. MATERIALS AND METHODS: The accelerated regime CHART was used in 35 patients given carbogen and/or nicotinamide with 11 small volume fractions. Eight patients received carbogen, 12 received nicotinamide and 15 were treated with ARCON. Treatment compliance, side-effects and acute mucositis were monitored in all cases. RESULTS: All patients underwent CHART as intended. In the 23 patients receiving carbogen, two failed to complete treatment. Compliance with nicotinamide was much lower. Out of 25 patients, only 52% received 10-11 doses of the 80 mg/kg/day of the drug. The most common side-effect was nausea and vomiting, which responded to standard anti-emetics in almost half of the patients. Historical comparisons with the CHART head and neck trials indicate that there was no increase in the severity of acute mucositis in any of these patients. Although the observation period is not sufficiently long to be definitive (median 20 months) there is no evidence of an increase in late normal tissue reactions. CONCLUSIONS: ARCON using CHART as the radiotherapy protocol is feasible in patients with advanced head and neck cancer. However, we are concerned about the low compliance rate in our patients, which is far lower than that reported elsewhere. The implications are discussed together with identifying strategies for increasing compliance.     

Dopamine fails to stimulate protein kinase C activity in renal proximal tubules of spontaneously hypertensive rats

We have previously reported that dopamine-1 receptor-mediated activation of phospholipase C is diminished in renal cortical slices of spontaneously hypertensive rats. The present study was carried out to examine the effect of dopamine on protein kinase C (PKC), which is one of the enzymes involved in the signal-transduction pathway leading to dopamine-induced inhibition of Na+/K(+)-ATPase in the renal proximal tubule. Renal proximal tubule suspensions were obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats of 10-12 weeks old. The tubules were incubated with dopamine in the presence or absence of DA-1 receptor antagonist SCH 23390. The PKC activity was measured by using a specific fluorescent peptide substrate (sequence, PKSRTLSVAAK). We found that dopamine produced a concentration-dependent increase in protein kinase C activity in the WKY rats, however, it failed to stimulate PKC activity in the SHR. Peak stimulation of 3.828 +/- 0.35 (ng/micrograms) protein in the WKY rats was observed at dopamine concentration of 1 microM, which was blocked in a concentration-dependent manner by SCH 23390 (0.25 microM). These results provide evidence that dopamine directly stimulates PKC activity via activation of DA-1 receptors in WKY rats. Furthermore, we discovered that dopamine fails to stimulate PKC activity in the SHR. This phenomenon may be responsible for the failure of dopamine to inhibit Na+/K(+)-ATPase activity in the hypertensive animals.     

The lack of predictive value of prostate specific antigen density in the detection of prostate cancer in patients with normal rectal examinations and intermediate prostate specific antigen levels

PURPOSE: The management of patients with a normal digital rectal examination and a prostate specific antigen (PSA) level of 4.0 to 10.0 ng./ml. remains controversial. To improve the specificity of cancer detection in this group, PSA density has been recommended with biopsies based on a PSA density of 0.15 or more. To evaluate PSA density as a discriminator of prostate cancer we enrolled patients in a prospective study. MATERIALS AND METHODS: A prospective evaluation was done of 44 consecutive patients with a palpably normal digital rectal examination and a serum PSA level of 4.0 to 10.0 ng./ml. enrolled during a 13-month period. All patients underwent transrectal ultrasound with sextant biopsies regardless of calculated PSA density. RESULTS: Overall, 8 of 44 men (18%) had prostate cancer. There was no significant difference in the mean PSA density between the patients with positive and negative biopsies (mean 0.12 and 0.15, respectively, p = 0.258). Also, there was no significant association between PSA or PSA density and a positive biopsy in multivariate analysis (p = 0.863). Receiver operating characteristic curves for PSA and PSA density failed to demonstrate any superior benefit for PSA density in this patient population. A PSA density of 0.15 was an unreliable indicator of cancer (sensitivity 12.5%, specificity 61.1% and positive predictive value 6.7%). CONCLUSIONS: In our study, PSA density did not discriminate between patients with positive and negative biopsies, and in fact most cancers would not have been detected if a PSA density of 0.15 or more had been used as the sole indication for biopsy. Therefore, we recommend systematic biopsies in these patients independent of calculated PSA density.     

Clinical and functional outcomes of internal fixation of displaced pilon fractures

The clinical and functional outcomes for patients treated with open reduction and plate fixation of displaced tibial pilon fractures were determined. A retrospective search of the authors' trauma database was conducted for AO and Orthopaedic Trauma Association Code 43 injuries (pilon fractures) in adults 18 years or older who were treated between December 1988 and December 1992. The group of 64 patients who required open reduction and internal fixation to treat their fractures make up the primary cohort for this analysis. Twenty of these cases required no fibular fixation; the remainder were mostly fixed with 1/3 tubular or 3.5-mm compression plates. Tibial fixation was done using most commonly 3.5-mm cloverleaf plates, 1/3 tubular plates, or both. Of the 64 patients treated with open reduction and internal replacement, four (5%) patients had deep infection develop. Two (7%) of 14 patients had open fractures, and two (4%) of 50 patients had closed fractures. Three of these four patients smoked tobacco products; one was also an intravenous drug abuser. Staphylococcus aureus was the organism in two cases; Enterobacter, in the other two. The infection was controlled with a free flap in two cases, with antibiotics and wound debridement in one and with an arthrodesis in one. Thirty of the 64 patients completed the Short Form-36; two of these patients had bilateral fractures. The study group had significant differences in general health perceptions, physical function, physical role function, emotional role function, social and mental function, and pain and energy levels when compared with age matched population data and patients with tibial plateau fractures. The effect of other injuries on these functional status results cannot be determined specifically.     

Adult head-banging and stereotypic movement disorders

Stereotypic movement disorders (SMD) such as head-banging, which are common among children with mental retardation or pervasive developmental disorders, may also occur in intellectually normal adults. We report a 27-year history of daily head-banging with self-injury in a 49-year-old man with normal cognition. The patient had no personal or family history of Tourette's syndrome, tic disorder, obsessive-compulsive disorder (OCD), or mental retardation. The frequency of his stereotypical head-banging increased with anxiety, loud noises with startle, and boredom. He reported a sense of pleasure from his head-banging, and the frequency of this behavior decreased when he was treated with the opioid antagonist naltrexone. Although not diagnostic, the self-stimulatory or pleasurable component of head-banging, body-rocking, thumb-sucking, and other SMD may help distinguish them from tics, Tourette's syndrome, OCD, and deliberate self-harming behavior. This report reviews the disorders associated with SMD and discusses the potential mechanisms for these behaviors. The treatment of SMD includes drugs that work through opioid, serotonergic, or dopaminergic systems.     

Hypophosphatemia-induced neuropathy: clinical and electrophysiologic findings

Severe hypophosphatemia has rarely been reported as a cause of acute paralysis. We present the clinical and electrophysiological findings on a patient who developed quadriparesis following several surgeries for complicated cholecystectomy. The paralysis was most likely the result of severe hypophosphatemia causing a neuropathy which improved readily after proper phosphate replacement. The possible pathogenic mechanisms of hypophosphatemic neuropathy are discussed.     

Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.