Routine application of the proton-pump inhibitor pantoprazole in patients with gastric lymphoma undergoing chemotherapy

Objective. The stomach is the most common site of origin for extranodal lymphomas. While resection has played a major part in the management of such patients in the past, in recent years there has been a change towards organ-conserving therapies. However, the risk of perforation and bleeding in patients undergoing organ-conserving therapy has been used as an argument against primary application of chemotherapy. In this article, we present our experience with the prophylactic use of oral pantoprazole. Material and methods. All patients undergoing chemotherapy for gastric lymphoma at our institution were prophylactically given oral pantoprazole (2×40 mg) for the duration of chemotherapy. Compliance with intake of the proton-pump inhibitor (PPI) was assessed at every visit for application of chemotherapy and at routine blood counts taken 10–14 days after each cycle of treatment by direct questioning of the patient. Results. A total of 82 patients (median age 69 years, range 33–93) received chemotherapy for gastric lymphoma: 51 had diffuse large B-cell lymphoma (DLBCL), 24 had mucosa-associated lymphoid tissue (MALT) lymphoma and 7 had DLBCL?+?MALT lymphoma. Compliance with intake of the PPI was excellent, as only two patients reported irregular intake and only one patient refused regular medication with pantoprazople. All patients responded to chemotherapy, with 74 (90%) achieving complete remission and 8 (10%) partial remission. After a median follow-up time of 50 months (range: 9–84 months) only one of these 82 patients (1.22%), the patient who discontinued intake of pantoprazole, died from gastric perforation, while none of the other patients had gastrointestinal bleeding or perforation. Conclusions. Judging from these data, continuous PPI intake is feasible and has a high rate of compliance. In the absence of randomized trials, routine application of oral pantoprazole in patients given chemotherapy for gastric lymphoma, especially DLBCL, appears to be a reasonable approach.     

Structural polymorphism of glycophorins demonstrated by immunoblotting techniques

We have explored the polymorphism of the glycophorin system in the human erythrocyte membrane using the immunoblotting techniques and examining 52 individuals selected without prior bias as to their serologic state and ten documented serologic variants of M, N, S, s blood group system. Polyclonal antisera to alpha glycophorin and to alpha glycophorin CNBr carboxyl terminal fragment C (residues 82-131) and M and N specific monoclonal antibodies (MoAbs) were used. The first two reagents detect specific regions of the alpha glycophorin molecule and all electrophoretically resolved species of glycophorins immunologically related to alpha and delta glycophorins (delta glycophorin, [alpha-delta] hybrids and other glycophorins with an alteration in the carboxyl terminal segment); the M and N MoAbs identified the glycophorin species containing or lacking the M or N determinant in the amino terminal octapeptide structures. We find that immunoblotting confirmed in all cases the serologically determined phenotype; we also find that polymorphic forms of the glycophorin system are relatively infrequent; immunoblotting, independent from serologic testing, was capable of detecting five mutants, two most likely S-s-U-phenotypes; a new glycophorin species was detected in normal red cells with both antiglycophorin and antipeptide C sera, which is not evident with MoAbs; immunoblots of known glycophorin variants (En(a-), U-, Mg, Mi I, II, III, V, and Sta) confirmed but also extended our knowledge of the abnormal glycophorins involved; and the He+ and Wrb(-) cells showed normal patterns.     

Cardiogenic shock: a summary of the randomized SHOCK trial

Cardiogenic shock is the most common cause of death for patients hospitalized with acute myocardial infarction. The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial randomly assigned 302 patients with predominant left ventricular failure following an acute myocardial infarction to a strategy of emergency revascularization or initial medical stabilization. Emergency revascularization by either coronary artery bypass grafting or angioplasty was required within 6 hours of randomization. Patients assigned to initial medical stabilization could undergo delayed revascularization at a minimum of 54 hours post-randomization. The primary end point of the study was 30-day all-cause mortality. Overall survival at 30 days did not differ significantly between the emergency revascularization and initial medical stabilization groups (53% vs. 44%; p=0.109). However, at the 6- and 12-month follow-up, there was a significant survival benefit with early revascularization (50% vs. 37%; p=0.027 and 47% vs. 34%; p=0.025, respectively). The benefit appeared to be greatest for those less than 75 years of age, with 20 lives saved at 6 months per 100 patients treated. According to the results of the SHOCK trial, the American College of Cardiology/American Heart Association guidelines for myocardial infarction now recommend emergency revascularization for patients younger than 75 years with cardiogenic shock.     

Antipsychotic Augmentation of Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: An Update Meta-Analysis of Double-Blind,Randomized, Placebo-Controlled Trials

Background:

Many patients with obsessive-compulsive disorder do not respond adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic drugs can be beneficial in this regard. However, since new relevant randomized controlled trials evaluating new antipsychotics were conducted, a recalculation of the effect sizes appears necessary.

Methods:

We meta-analyzed all double-blind, randomized, placebo-controlled trials comparing augmentation of serotonin reuptake inhibitors with antipsychotics to placebo supplementation in treatment-resistant obsessive-compulsive disorder. The primary outcome was mean change in the Yale-Brown Obsessive–Compulsive Scale total score. Secondary outcomes were obsessions, compulsions, response rates, and attrition rates. The data collection process was conducted independently by 2 authors. Hedges’s g and risks ratios were calculated as effect sizes. In preplanned meta-regressions, subgroup analyses, and sensitivity analyses, we examined the robustness of the results and explored reasons for potential heterogeneity.

Results:

Altogether, 14 double-blind, randomized, placebo-controlled trials (n=491) investigating quetiapine (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were incorporated. Augmentation with antipsychotics was significantly more efficacious than placebo in Yale-Brown Obsessive–Compulsive Scale total reduction (N=14, n=478; Hedges’s g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges’s g=-1.35), haloperidol (Hedges’s g=-0.82), and risperidone (Hedges’s g=-0.59) significantly outperformed placebo. Antipsychotics were superior to placebo in treating obsessions, compulsions, and achieving response. There was no between-group difference concerning all-cause discontinuation. The nonsignificant meta-regressions suggest no influence of the antipsychotic dose or baseline symptom severity on the meta-analytic results.

Conclusions:

According to our findings, antipsychotic augmentation of serotonin reuptake inhibitors can be regarded as an evidence-based measure in treatment-resistant obsessive-compulsive disorder.     

Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.