A comparative study of the utility of two superdisintegrants in microcrystalline cellulose pellets prepared by extrusion-spheronization.

This study evaluated the utility of including superdisintegrants (croscarmellose sodium or sodium starch glycolate) in microcrystalline cellulose extrusion-spheronization pellets as a means of increasing the dissolution rate of poorly water-soluble drugs. The model drug was hydrochlorothiazide, with water or water/ethanol as wetting agent for pellet preparation. Neither disintegrant had significant effects on pellet morphology, flow properties or mechanical resistance. Neither disintegrant caused disintegration of the pellet in drug dissolution medium. Nevertheless, the disintegrants afforded a modest increase in drug dissolution rate, attributable to the observed increase in pellet micropore volume. Drug dissolution rate was slightly higher in pellets prepared with sodium starch glycolate, probably because of this disintegrant's higher swelling capacity.     

Prevention of central venous catheter-related bloodstream infections using non-technologic strategies.

OBJECTIVE: To evaluate the incidence of nosocomial bacteremias related to the use of non-impregnated central venous catheters (CVCs) when only non-technologic strategies were used to prevent them. DESIGN: This was a prospective study of infectious complications of CVCs placed in intensive care unit (ICU) patients from April 1997 to December 2001. SETTING: The medical-surgical ICU of a tertiary-care, university-affiliated hospital in Argentina. METHODS: We studied all patients admitted to the ICU using non-impregnated CVCs. Maximal sterile barrier precautions (ie, use of cap, mask, sterile gown, sterile gloves, and large sterile drape), strict handwashing, preparation of the patients' skin with antiseptic solutions, insertion and management of catheters by trained personnel, and continuing quality improvement programs aimed at appropriate insertion and maintenance of catheters were employed. RESULTS: During the study period, 2,525 patients were admitted to the ICU. Eight hundred sixty-eight patients had 1,037 CVCs inserted. The number of CVC-related bloodstream infections (BSIs), acquired in the ICU, was 2.7 per 1,000 CVC-days (13 nosocomial CVC-related BSIs during 4,770 days of CVC use). Microorganisms isolated included methicillin-susceptible Staphylococcus aureus (n = 6), methicillin-resistant S. aureus (n = 2), coagulase-negative methicillin-resistant Staphylococcus (n = 2), Escherichia coli (n = 1), Klebsiella pneumoniae (n = 1), and Enterobacter cloacae (n = 1). CONCLUSIONS: A low rate of catheter-related BSI was achieved without antimicrobial-impregnated catheters. The incidence of CVC-associated bacteremias corresponded to the 10th to 20th percentile range of the National Nosocomial Infections Surveillance System hospitals for the same type of ICU.     

Breast-feeding in a woman with cystic fibrosis undergoing antibiotic intravenous treatment.

We report the case of a 30-year-old woman with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa who delivered and breast-fed a healthy boy. While breast-feeding the woman had to undergo an i.v. antibiotic course with tobramycin, due to pulmonary exacerbation. Tobramycin was not detected in her milk and lactation could be continued. This is the first time that the presence of tobramycin in the milk of a CF woman during i.v. administration has been investigated.     

Flavonoids and breast cancer risk in Italy.

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.     

Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph).

BACKGROUND: The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. METHODS: Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. RESULTS: In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1452). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking (> or = 36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. CONCLUSIONS: Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results.     

Dietary folate and risk of prostate cancer in Italy.

Folate status may affect cancer risk through its role in both methylation and nucleotide synthesis of DNA. A low dietary intake of folate has been linked to risk of several cancers, but epidemiologic studies with reference to prostate cancer are scanty. We therefore analyzed data from a case-control study of prostate cancer conducted between 1991 and 2002 in various areas of Italy. Cases were 1,294 patients with incident, histologically confirmed prostate cancer and controls were 1,451 patients admitted to the same network of hospitals of cases for acute, nonneoplastic conditions. All subjects were < 75 years old. Intake of folate and other nutrients was computed from a validated food frequency questionnaire. We adjusted for energy intake using the residual method, and calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression. The OR of prostate cancer was 0.66 (95% CI, 0.51-0.85) for the highest versus the lowest quintile of folate intake. The relation between dietary folate and prostate cancer was consistent across strata of age, methionine, vitamin B6, and alcohol intake, and did not vary substantially according to Gleason score of prostate cancer. The combined OR for high-folate and low-alcohol intake versus low-folate and high-alcohol intake was 0.46 (95% CI, 0.29-0.75). Therefore, this study supports a favorable role of dietary folate on prostate cancer risk.     

Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors study.

PURPOSE: Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. PATIENTS AND METHODS: Patients > or = 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. RESULTS: By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. CONCLUSION: Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.     

FGFR3 and Tp53 mutations in T1G3 transitional bladder carcinomas: independent distribution and lack of association with prognosis.

FGFR3 and Tp53 mutations have been proposed as defining two alternative pathways in the pathogenesis of transitional bladder cancer. FGFR3 mutations are associated with low-grade tumors and a favorable prognosis. Tp53 alterations are associated with advanced tumors and, possibly, with a poor prognosis. We focus here on the subgroup of T1G3 superficial tumors because they are a major clinical challenge. Patients (n = 119) were identified from a prospective study of 1,356 cases. Mutations in FGFR3 (exons 7, 10, and 15) and Tp53 (exons 4-9) were analyzed using PCR and direct sequencing. All cases were followed for recurrence and death. Survival was analyzed using Kaplan-Meier curves and multivariable Cox regression. FGFR3 mutations were detected in 20 (16.8%) tumors; 100 mutations in Tp53 were found in tumors from 78 (65.5%) cases. Multiple alterations in Tp53 were present in 19 tumors (16%). Inactivating mutations were present in 58% of tumors. The combined mutation distribution (FGFR3/Tp53) was: wt/wt (34.5%), mut/wt (7.6%), wt/mut (48.7%), and mut/mut (9.2%), indicating that the presence of either mutation did not depend on the other (P value = 0.767). FGFR3 and Tp53 mutations were not associated with clinicopathologic characteristics of patients and did not predict, alone or in combination, recurrence or survival. Taking the risk of the wt/wt group as reference, the mutation-associated risks of cancer-specific mortality were: mut/wt 1.42 (0.15-13.75), wt/mut 0.67 (0.19-2.31), mut/mut 1.62 (0.27-9.59). These molecular features support the notion that T1G3 tumors are at the crossroads of the two main molecular pathways proposed for bladder cancer development and progression.     

Assessment of chitosan derivatives as buccal and vaginal penetration enhancers.

The aim of the present work was to evaluate the mucoadhesive and penetration enhancement properties via the buccal and vaginal mucosae of four different chitosan derivatives: 5-methyl-pyrrolidinone chitosan (MPC), two low molecular weight chitosans (DC1 and DC2) and a partially reacetylated chitosan (RC). Chitosan HCl was used as a reference. Polymer solutions (4% w/w) were prepared in media simulating the buccal (pH 6.4 buffer or water) and the vaginal (pH 5.0 buffer) environments and subjected to rheological characterization. Acyclovir was added to the polymer solutions at 5% (w/w) concentration. The mucoadhesive properties of the polymer solutions were measured using excised porcine cheek or vaginal mucosa and mucin dispersions to simulate the buccal or vaginal environments, respectively. Drug permeation and penetration tests were carried out using porcine cheek and vaginal mucosae as model membranes. Acyclovir aqueous suspensions prepared in pH 6.4 and 5.0 buffers were used as blanks. Drug release measurements were also carried out in the same conditions employed for the permeation and penetration tests. Methyl-pyrrolidinone chitosan shows the best mucoadhesive and penetration enhancement properties in both buccal and vaginal environments. The capability to enhance the permeation/penetration of acyclovir was decreased by partial depolymerization of chitosan and disappeared after partial reacetylation.