A new method for evaluating antiarrhythmic drug efficacy

To develop standards for distinguishing antiarrhythmic drug effect from spontaneous variability of premature ventricular complexes (PVCs), 21 males (mean age 56 +/- 8 years) with chronic ischemic heart disease and PVCs underwent symptom-limited treadmill exercise testing and 24-hour ambulatory monitoring before and after 2 weeks of placebo medication. Linear regression analysis was used to describe the relationship between baseline and placebo PVC frequency for various indexes of ventricular ectopic activity and to establish 95% and 99% one-tailed confidence intervals for this relationship within the group of 21 patients. The lower limit of baseline PVC frequency for which the procedure could distinguish a placebo from a true drug response, termed the "sensitivity threshold," was an average frequency of 2.2 PVCs/hour for ambulatory electrocardiographic monitoring and 1.2 PVCs/min for treadmill exercise testing. All patients exceeded the sensitivity threshold on baseline ambulatory ECGs, but only 38% of patients did so on baseline treadmill exercise tests. To establish antiarrhythmic efficacy with 95% confidence, the minimal percent reduction of PVCs between baseline and placebo visits was 68% for treadmill exercise testing and 65% for ambulatory electrocardiography. Although these standards were developed in patients with chronic ischemic heart disease, the model can be used to establish antiarrhythmic drug efficacy in any patient group.     

The drug prophylaxis of peptic ulcer exacerbations

453 patients with ulcer located in the duodenal bulb and pyloric part of the stomach in the presence of Helicobacter pylori were examined before and followed up after hospital treatment of the ulcer. The authors findings support the importance of maintenance with current antisecretory drugs and on-demand therapy as well as of combined antibacterial therapy against Helicobacter pylori. Adequate chemotherapy in the ulcer exacerbation was able to reduce the number of recurrences and complications.     

The impact of Helicobacter pylori eradication on peptic ulcer healing

OBJECTIVE: Current literature was reviewed analyzing the outcome of peptic ulcer healing in relation to the results of the posttherapeutic Helicobacter pylori (HP) status. METHODS: Literature was reviewed along with an analysis of 60 studies, comprising a total of 4329 patients. RESULTS: Successful Helicobacter pylori eradication was found to induce a better response in peptic ulcer healing, regardless of diagnosis: gastric ulcer 88% vs 73% (odds ratio [OR] 2.7, p < 0.01), duodenal ulcer 95% vs 76% (OR 5.6, p < 0.0001), and peptic ulcer 95% vs 76% (OR 6.6, p < 0.0001), for patients having their HP infection successfully cured versus those remaining HP-positive, respectively (Fisher's exact test). For all evaluated time points (< or = 6, 7-8, and 10-12 wk after beginning treatment), HP-negative patients had higher healing rates than HP-positive patients (95% vs 82%, 94% vs 69%, and 96% vs 78% with corresponding OR of 4.2, 6.5, and 7.4, all p < 0.0001, Fisher's exact test). The use of concomitant acid suppression therapy during initial HP eradication provided a benefit on peptic ulcer healing only for patients with persistent HP infection (improved healing rates of 78% vs 67%; otherwise rates were 94-96%). Likewise, prolonged acid inhibition in HP treatment failures after the initial HP treatment phase resulted in 7-20% improved healing rates, whereas patients becoming HP-negative did not profit. CONCLUSION: Successful HP eradication therapy accelerates peptic ulcer healing even without concomitant acid suppression.     

Treatment of peptic ulcer

AIMS: To establish whether MIB-1 and p53 staining are useful for differentiating pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas. This study was restricted to children and young adults under 30 years of age because of the differences in p53 mutations between paediatric and adult astrocytomas. METHODS AND RESULTS: Forty-five astrocytic tumours, including 18 pilocytic astrocytomas, 14 astrocytomas, four anaplastic astrocytomas and nine glioblastomas, from 45 children and young adults, between 1 and 29 years (mean 11 years) of age, were examined pathologically, and sections from paraffin-embedded blocks were used for MIB-1 and p53 immunostaining. The MIB-1 labelling index and the frequency and intensity of p53 staining in both the pilocytic astrocytoma and the astrocytoma group were significantly lower than in the anaplastic astrocytoma plus glioblastoma group (P < 0.001). In 11.1% (two of 18) of pilocytic astrocytomas and 42.9% (six of 14) of astrocytomas, immunoreactivity of either MIB-1 or p53 staining was of almost the same intensity as that of anaplastic astrocytomas and glioblastomas. However, in these cases, results using both MIB-1 and p53 stain differed from those for anaplastic astrocytomas and glioblastomas. CONCLUSIONS: MIB-1 and p53 co-staining is very useful for differentiating pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas. However, MIB-1 or p53 staining alone cannot differentiate pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas.     

Therapy of peptic ulcer

After a historical review of therapeutic methods of peptic ulcer the author discusses contemporary views on therapy. As a basis he uses the idea that Helicobacter pylori is the decisive factor for the development of peptic ulcers. Therefore the basis of treatment should be its eradication by bismuth salts. Despite this at present the basis of treatment are antagonists of H2 receptors. Economic aspects are important. In repeatedly relapsing ulcers with evidence of Helicobacter pylori the author recommends eradication by a combination of drugs.     

Recurrence of peptic ulcer

In the paper, the causes, clinic and treatment in 15 patients with recurrent peptic ulcer after repeated operative procedures for duodenal ulcer are described. The main causes of the recurrence were as follows: the remaining of the mucous membrane of the antral gastric portion in Finsterer gastric resection for ulcer exclusion (5) and Zollinger-Ellison syndrome (10). The surgical therapy consisted in resection of the antral portion and repeated gastric resection (the first group) or in subtotal gastrectomy associated with trunk vagotomy (the second group).     

The principles of administering drug and non-drug treatment methods in peptic ulcer

As the result of the study optimal schemes of the ulcer disease treatment were elaborated. They include microwave resonance therapy, immunomodulatory and antibacterial drugs with regard to localisation, depth and size of the ulcerous lesion, exacerbation rate, degree of secondary immune disorders and seeding of gastric mucosa with Helicobacter pylori. The treatment suggested allows to shorten the terms of ulcer cicatrization, reduces exacerbation rate and ensures clinico-endoscopic remission in most patients with ulcer disease.     

In vitro drug assays and statistical analysis

The development of in vitro drug tests to assess the efficacy of drugs against Pneumocystis carinii has been hindered by the lack of efficient methods for continuous cultivation of the microorganism. However, different short-term culture systems have been proposed by many teams. In the present contribution an in vitro microplate drug assay and two statistical programs allowing the analysis of results are presented.     

A comparison of omeprazole and placebo for bleeding peptic ulcer

BACKGROUND: The role of medical treatment for patients with bleeding peptic ulcers is uncertain. METHODS: We conducted a double-blind, placebo-controlled trial in 220 patients with duodenal, gastric, or stomal ulcers and signs of recent bleeding, as confirmed by endoscopy. In 26 patients the ulcers showed arterial spurting, in 34 there was active oozing, in 35 there were nonbleeding, visible vessels, and in 125 there were adherent clots. The patients were randomly assigned to receive omeprazole (40 mg given orally every 12 hours for five days) or placebo. The outcome measures studied were further bleeding, surgery, and death. RESULTS: Twelve of the 110 patients treated with omeprazole (10.9 percent) had continued bleeding or further bleeding, as compared with 40 of the 110 patients who received placebo (36.4 percent) (P<0.001). Eight patients in the omeprazole group and 26 in the placebo group required surgery to control their bleeding (P<0.001). Two patients in the omeprazole group and six in the placebo group died. Thirty-two patients in the omeprazole group (29.1 percent) and 78 in the placebo group (70.9 percent) received transfusions (P<0.001). A subgroup analysis showed that omeprazole was associated with significant reductions in recurrent bleeding and surgery in patients with nonbleeding, visible vessels or adherent clots, but not in those with arterial spurting or oozing. CONCLUSIONS: In patients with bleeding peptic ulcers and signs of recent bleeding, treatment with omeprazole decreases the rate of further bleeding and the need for surgery.     

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study

High-dose therapy with peripheral blood stem cell (PBSC) support is a frequently used treatment option in younger patients with poor prognosis histologically indolent (low-grade) non-Hodgkin's lymphoma (NHL), usually at the time of second or subsequent response to conventional-dose therapy. We have undertaken PBSC collection in 57 patients with histologically indolent NHL mobilized with either cyclophosphamide 1.5 g/m2 or the ESHAP regimen, followed by daily G-CSF. Progenitor cell yields were determined by quantification of CD34+ cells and GM-CFC. Twelve patients (21%) failed to achieve the minimum progenitor cell requirements of 1 x 10(6)/kg CD34+ cells or 1 x 10(5)/kg GM-CFC in their pooled harvests and 40 patients (70%) failed to achieve the optimal harvest thresholds of 3.5 x 10(6)/kg CD34+ cells or 3.5 x 10(5)/kg GM-CFC. This high failure rate is significantly higher than that in patients with histologically aggressive NHL or Hodgkin's disease. A multivariate analysis was performed to identify factors contributing to the low stem cell yields in this group. This identified the time interval from the last chemotherapy to the priming chemotherapy as the most important predictive factor. With respect to CD34 and GM-CFC numbers, on the single harvest on the day the white cell count first exceeded 5 x 10(9)/l the P values were 0.0078 and 0.0065, respectively, and for the progenitor cell values on the pooled harvests the P values were 0.004 for CD34+ cells and 0.015 for GM-CFC. Progenitor cell yields may therefore be improved in patients with low grade lymphoma by harvesting at diagnosis if no marrow disease is present, or by delaying mobilization for 6 months post-chemotherapy in patients in first or subsequent remission.     

The clinical prognosis of the complication of peptic ulcer by acute hemorrhage

Clinical parameters have been studied in 45 peptic ulcer patients without and 47 ones with acute hemorrhage. Factors of acute hemorrhage risk in ulcer patients have been specified (old age, long history of the disease, previous hemorrhages, duodenal ulcer localization at the back and upper walls and gastric ulcer localization at the middle and upper thirds of the lesser curvature of the stomach, size of ulcer, penetration). Combined existence of the factors is conducive to acute hemorrhage.     

Eradication of Helicobacter pylori in peptic ulcer patients

The aim of this study was to compare in an open trial the efficacy of 2 x 500 mg clarithromycin + 2 x 1000 mg amoxicillin + 40 mg pantoprazole/day given for 7 days (I. group, 48 cases), with that of 2 x 500 mg clarithromycin + 2 x 400 mg ranitidine bismuth citrate/day given for 14 days (II. group, 51 cases). The diagnosis of peptic ulcer was established endoscopically. HP infection was confirmed the modified Giemsa stain and rapid urease test. After eradication all patients were given 2 x 150 mg ranitidine for one month. Controls were performed 4-6 weeks after eradication. Peptic ulcer healing was proven in the group I in 93.0% and in the group II in 91.6% (p > 0.05). On intention-to-treat basis, HP was eradicated in 80.3% (confidence interval, CI: 73-92.7%) in the I. and 80.3% (confidence interval: 76-95%) in the II. group (p > 0.05). Per protocol analysis revealed eradication rates of 88.3% (CI: 81-97.6%) and 85.4% (CI: 80-97%) (p > 0.05). Side effects were recorded in 9.5% and 14.5% of the cases. Both regimens were equally effective in the eradication of HP and healing of peptic ulcers.