Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative colitis with budesonide MMX 9 mg: pooled analysis of two phase 3 studies.

BACKGROUND: Conventional oral corticosteroids are effective at reducing inflammation associated with ulcerative colitis (UC); however, systemic adverse effects limit their use. Budesonide MMX is an extended-release, second-generation corticosteroid that targets delivery of budesonide to the entire colon. AIM: To analyse efficacy and safety outcomes from two phase 3 studies of budesonide MMX in patients with mild-to-moderate active UC. METHODS: Patients were assigned to budesonide MMX 9 mg, budesonide MMX 6 mg, or placebo once daily in two randomised, double-blind, placebo-controlled, 8-week studies (CORE I and II). Pooled data were analysed for pre-defined primary (combined clinical and colonoscopic remission), secondary and exploratory endpoints. Primary endpoint data were analysed to evaluate the potential influence of demographical and baseline disease characteristics on remission. RESULTS: Modified intent-to-treat population (histological evidence of baseline inflammation) had 232, 230 and 210 patients in budesonide MMX 9 mg, budesonide MMX 6 mg and placebo groups respectively. Combined clinical and colonoscopic remission rates were significantly greater than placebo (6.2%) for the budesonide MMX 9 mg group (17.7%; P = 0.0002), but not the budesonide MMX 6 mg group (10.9%). The primary endpoint of remission with budesonide MMX 9 mg was significantly greater than placebo in most subgroups analysed. Symptom resolution and colonoscopic improvement rates were significantly greater with budesonide MMX 9 mg vs. placebo. Budesonide MMX was safe and well tolerated. CONCLUSION: This pooled analysis showed that budesonide MMX 9 mg is efficacious, safe and well tolerated for inducing remission of mild-to-moderate UC.

Comparison of the effects of immediate-release omeprazole oral suspension, delayed-release lansoprazole capsules and delayed-release esomeprazole capsules on nocturnal gastric acidity after bedtime dosing in patients with night-time GERD symptoms.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) patients on proton pump inhibitors before breakfast or dinner have acid recovery at night. Bedtime immediate-release omeprazole (IR-OME) demonstrated better control of nocturnal pH than pantoprazole before dinner. AIM: To compare repeated once daily bedtime dosing of IR-OME, lansoprazole and esomeprazole on nocturnal gastric acidity. METHODS: Open-label, randomized, crossover study enrolling 54 patients with nocturnal GERD symptoms comparing IR-OME, lansoprazole and esomeprazole at steady state for nocturnal acid breakthrough (NAB), percentage of time with gastric pH > 4 and median gastric pH. RESULTS: Onset of nocturnal acid control with IR-OME was rapid. During the first half of the night, percentage of time with gastric pH > 4 and median gastric pH were significantly higher after IR-OME compared to esomeprazole or lansoprazole (P < 0.001, both comparisons). Over the 8-h night-time period, acid control with IR-OME was significantly better than lansoprazole (P < 0.001), and comparable to esomeprazole. IR-OME reduced NAB compared with esomeprazole and lansoprazole (61% vs. 92% and 92%; P < 0.001, both comparisons). CONCLUSIONS: Bedtime IR-OME provided more rapid control of night-time gastric pH and decreased NAB compared with esomeprazole and lansoprazole. Nocturnal acid control with IR-OME was superior to lansoprazole and comparable to esomeprazole. Bedtime dosing with IR-OME may be effective for patients with night-time heartburn.

Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal acid breakthrough in patients with symptomatic gastro-oesophageal reflux disease.

BACKGROUND: Many patients treated with a proton-pump inhibitor for gastro-oesophageal reflux disease or erosive oesophagitis still have substantial night-time gastric acidity. A previous trial of a new immediate-release omeprazole oral suspension suggested that nocturnal gastric acidity could be more effectively controlled with a bedtime dose of immediate-release omeprazole than with a delayed-release proton-pump inhibitor administered before dinner or at bedtime. AIM: To compare the ability of immediate-release omeprazole with pantoprazole to control nocturnal gastric acidity, when they were dosed once daily and twice daily. METHODS: Thirty-six patients with nocturnal gastro-oesophageal reflux disease symptoms received immediate-release omeprazole and pantoprazole in this open-label, randomized-crossover trial. Median gastric pH, the percentage of time with gastric pH > 4 and the percentage of patients with nocturnal acid breakthrough, were evaluated with 24-h pH monitoring. RESULTS: Repeated once daily (bedtime) dosing with immediate-release omeprazole suspension produced significantly better nocturnal gastric acid control than repeated once daily (predinner) or twice daily (prebreakfast and bedtime) dosing with pantoprazole delayed-release tablets (median pH: 4.7 vs. 2.0 and 1.7; percentage of time pH > 4: 55 vs. 27 and 34; nocturnal acid breakthrough: 53 vs. 78 and 75). Twice daily dosing (prebreakfast and bedtime) with immediate-release omeprazole 20 and 40 mg achieved the best night-time control of gastric acidity. Repeated once daily bedtime dosing with immediate-release omeprazole 40 mg and twice daily dosing with pantoprazole 40 mg gave similar 24-h pH control. No safety issues were associated with either drug in this trial. CONCLUSIONS: Dosed once daily at bedtime, immediate-release omeprazole reduced nocturnal gastric acidity to a degree not observed with once daily dosing of delayed-release proton-pump inhibitors.

High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease: long-term follow-up in 128 patients.

BACKGROUND: There is little long-term follow-up information after autologous transplantation for Hodgkin's disease. We evaluated the influence of various prognostic factors and examined the outcome in 128 such patients. PATIENTS AND METHODS: Patients received high dose cyclophosphamide, carmustine, and etoposide followed by autologous hematopoietic rescue. RESULTS: Patients have been observed between 50-130 months (median 77 months) following transplantation. Overall survival at four years is estimated as 45 percent, and failure-free survival as 25 percent. The best results were seen in patients with a good performance status, who had failed at most one prior chemotherapy regimen. Failure-free survival at four years is estimated as 53 percent for this group. Relapses more than 24 months after transplantation were seen in 11 patients. Five patients developed myelodysplastic syndromes. Three patients became pregnant after the transplant. CONCLUSIONS: Prolonged failure-free survival may be observed following high dose chemotherapy and autologous hematopoietic rescue in patients with Hodgkin's disease. Superior results were seen in patients without extensive prior chemotherapy and in those with a good performance status. Late relapses and deaths from secondary myelodysplastic syndromes mandate prolonged follow-up after autologous transplantation for Hodgkin's disease.

Electrocardiographic changes in pericardial effusion.

OBJECTIVE: To investigate the association between ECG changes and the presence of pericardial effusion. BACKGROUND: The ECG changes associated with pericardial effusion described in textbooks are based only on small series of human cases and data from animals. These changes include low QRS voltage, electrical alternans, P wave changes, and T wave inversion. METHODS: All patients who had undergone 2 temporally separate echocardiographic and ECG examinations, with 1 echocardiographic examination indicating the presence and the other indicating the absence of pericardial effusion were identified (n = 46). These patients were age- and sex-matched to 46 patients without effusion (control subjects). Pericardial effusion was classified echocardiographically as small (n = 28), moderate (n = 13), and large (n = 5). The ECG variables were independently measured by two investigators blinded to effusion status. RESULTS: When 2 temporally separate ECGs for 46 patients were obtained in a repeated-measures fashion (1 obtained during the absence and the other during the presence of effusion; median time interval, 1.24 months), only the mean heart rate in patients with sinus rhythm (98 beats per minute increasing to 106 beats per minute) and the percentage of patients with QRS voltage of less than 0.5 mV (10 percent increasing to 22 percent) were associated with the development of effusion. A weak correlation (r = 0.296) was noted between QRS voltage and effusion size. Electrical alternans occurred only in one of the five patients with a large effusion but in no others. In addition, when the ECGs indicating effusion from the 46 patients were compared with the ECGs from their age- and sex-matched control subjects, differences in heart rate (106 beats per minute vs 80 beats per minute, respectively) and small changes in QRS voltage were associated with effusion status. No ECG variable was sensitive for the detection of pericardial effusion. CONCLUSIONS: In both repeated-measures and case-control comparisons, ECG findings are two few, subtle, insensitive, and nonspecific to be useful as indicators of the presence of pericardial effusion.

Prognostic significance of clinical and pathologic features in diffuse large B-cell lymphoma.

BACKGROUND AND METHODS: The diffuse large cell non-Hodgkin lymphomas are a heterogeneous group of neoplasms that are potentially curable. To identify important predictors of clinical outcome, the authors evaluated the clinical and pathologic features of 114 patients with newly diagnosed diffuse large B-cell lymphoma who were uniformly staged and treated with curative intent. The authors were particularly interested in determining whether any pathologic features added to the ability of the clinical features to predict patient survival. RESULTS: Several clinical and pathologic features were found to be associated with survival by univariate analysis. However, multivariate analysis disclosed that only the stage of disease and the symptom status were significantly associated with survival. Low stage and lack of B symptoms were favorable indicators of overall survival and failure-free survival. CONCLUSIONS: The authors suggest that the evaluation of pathologic features in diffuse large B-cell lymphoma has little prognostic utility and recommend that the pathology evaluation be limited to features that are useful for diagnostic purposes.

Effect of exercise level on the diagnostic accuracy of thallium-201 SPECT scintigraphy.

The sensitivity of electrocardiographic ST analysis for detecting coronary artery disease is markedly decreased in patients unable to exercise vigorously. To determine the diagnostic accuracy of Thallium-201 SPECT scintigraphy at various exercise levels, we evaluated 179 patients without evidence of prior myocardial infarction or other confounding factors who performed symptom-limited exercise with Thallium-201 SPECT scintigraphy. Sensitivity decreased from 89% in those patients achieving greater than or equal to 85% of maximal heart rate to 63% in those achieving less than 65%. Like ST segment analysis, Thallium 201 SPECT scintigraphy has decreased diagnostic yield at low levels of exertion.

Association of serum iron, serum transferrin saturation, and serum ferritin with survival in acute lymphocytic leukemia.

The present investigation was motivated from the consideration that a host environment rich in iron, represented by high serum transferrin saturation (TS) and high serum iron and serum ferritin levels might offer favorable growth conditions for leukemic cells in addition to infection, thus affecting survival. Serum measurements were obtained on 113 pediatric patients with acute lymphoblastic leukemia (ALL), seen at Memorial Sloan-Kettering Cancer Center between May 20, 1981 and August 8, 1983. A significant difference (p less than 0.001) was found between the survival of patients according to whether their first measured TS was greater than 36% or less than 36%, with fewer deaths in the group with TS less than 36. The relationship between TS and survival was still observed when patients were stratified according to length of time from diagnosis, risk group, French-American-British (FAB) classification, or presence of organomegaly at diagnosis (p less than 0.001). Similar differences were observed between survival of patients grouped according to their first measured serum ferritin. These results independently confirm and extend observations presented earlier and support the consideration that motivated this study. The value of serum iron-related measurements as prognostic variables cannot be established from this type of study; however, these findings suggest the need for a prospective study.

Tumor marker expression in breast carcinomas and relationship to prognosis. An immunohistochemical study.

A collaborative immunohistochemical study was carried out to examine the expression and prognostic significance of tumor markers in a retrospective series of 233 invasive breast carcinomas. The patterns of tumor marker expression in 94 patients with short remission duration (recurrence within five years) were compared with 50 patients with intermediate (at five to ten years) and 89 patients with long (no recurrence at ten years or longer) remission durations. The antigens examined were carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), placental lactogen, alpha-lactalbumin, and pregnancy-specific beta-1 glycoprotein. Carcino-embryonic antigen was the most frequently expressed antigen, whereas HCG was demonstrated least frequently. Also, the ABH isoantigen status was examined using monoclonal antibodies; isoantigen expression was observed in a subset of breast carcinomas, contrary to previous reports of total deletion in breast cancer. Two of the markers, CEA and HCG, were examined by both laboratories, each with two different antisera and also with both PAP and ABC immunohistochemical technics. Meticulous efforts were taken to provide quality control and ensure reproducibility of results. These included the use of serial sections of duplicate pathologic material by both institutions, standardization of experimental conditions and interpretation criteria, double-blind evaluation of exchanged slides, and use of standardized data sheets to record staining extent and intensity. No significant disagreements were observed between data obtained through the different approaches. The steps that were taken to minimize interobserver and interinstitutional differences in this study are presented as a model for collaborative immunohistochemical studies. The expression of tumor markers, alone or in combination, was not found to bear any significant relationship to prognostic indicators, such as the likelihood of recurrence, interval before recurrence, or presence of metastasis.

Randomized trial comparing vindesine plus cisplatin with vinblastine plus cisplatin in patients with non-small cell lung cancer, with an analysis of methods of response assessment.

One hundred eight patients with stage III non-small cell lung cancer were randomly assigned to receive cisplatin (120 mg/m2) with either vindesine (3 mg/m2) or vinblastine (6 mg/m2). None had previously received chemotherapy. An additional goal was to determine if the observation of visible evaluable lesions was as accurate a method of response assessment as the observation of bidimensionally measurable lesions in non-small cell lung cancer. When vindesine plus cisplatin was compared to vinblastine plus cisplatin, response rates (33% vs 41%), median response durations (8.6 vs 5.6 months), and median survival times of responding patients (18.4 vs 16.2 months) were similar. Response rates, response durations, and survival times of responding patients determined through the observation of evaluable or measurable indicator lesions did not differ significantly. More patients receiving vinblastine plus cisplatin experienced wbc counts less than 2100/mm3 (P = 0.003). The two regimens demonstrated comparable response and survival data but clinically significant leukopenia was more common in vinblastine-treated patients. There was no difference in response data obtained through the study of patients with measurable and evaluable indicator lesions.

ABH blood group isoantigen expression in breast carcinomas--an immunohistochemical evaluation using monoclonal antibodies.

The ABH blood group isoantigen status of a retrospective series of 233 invasive breast carcinomas was examined, employing monoclonal antibodies (MCAB) against A, B, and H antigens with the avidin-biotin-peroxidase complex method. In addition, the H antigen was localized with Ulex Europeus Agglutinin I (UEAI) binding. The MCABs provided consistent and specific staining of erythrocytes and endothelium, as well as normal and neoplastic breast epithelium. The anti-H MCAB yielded cleaner background and less intense staining, but otherwise the staining distribution was comparable to the UEA I technique. Contrary to previous reports, deletion of isoantigen expression was not universal in all invasive carcinomas. Whereas 64%, 77%, and 73% of carcinomas from groups A, B, and AB patients, respectively, demonstrated total isoantigen loss, the remaining tumors exhibited variable degrees of isoantigen expression. Moreover, those carcinomas with complete loss of A and B determinants still displayed variable degrees of H immunoreactivity. Carcinomas from group O patients had different degrees of H antigen deletion, with only 12% showing total loss. Statistical analysis revealed that the isoantigen status bore no significant relationship to various epidemiologic, clinical, and pathologic parameters and did not serve as a useful prognostic determinant.

Ferritin in neuroblastoma. Impact of tumor load and blood transfusions.

Serial serum ferritin (SF) levels were measured in 36 patients with neuroblastoma seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between January 1981 and December 1982. The significance of the associations among SF, stage and extent of disease, number of blood transfusions, liver function, serum iron (Fe), total iron-binding capacity (TIBC), and transferrin saturation was investigated. Although a dominant statistical correlation was found between SF and number of blood transfusions, the results suggest that amount of disease contributes to increasing SF levels. Serum ferritin levels increased on average in a linear fashion with number of blood transfusions in patients free of disease or with minimal disease. In patients with bulky disease, this increase was exponential (p value less than 0.01). Application of a reverse hemolytic plaque assay to the analysis of ferritin secretion by cells demonstrates that tumor cells do secrete ferritin in vitro.