Efficacy and safety of mometasone furoate nasal spray in nasal polyposis

BACKGROUND: Studies have suggested that topical corticosteroids are effective in the treatment of nasal polyps; however, this has yet to be confirmed in a large, robust clinical trial. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate nasal spray (MFNS) for nasal polyposis. METHODS: A total of 354 subjects with bilateral nasal polyps and clinically significant congestion/obstruction participated in this multinational, randomized, double-blind, placebo-controlled study. Subjects received MFNS 200 microg once or twice daily or placebo for 4 months. Coprimary endpoints were (1) change from baseline to last assessment in physician-evaluated bilateral polyp grade score and (2) change from baseline averaged over month 1 in subject-assessed nasal congestion/obstruction. ANOVA was used for all efficacy endpoints, except for change in bilateral polyp grade score, for which baseline polyp grade was added as a covariate. RESULTS: Compared with placebo, MFNS 200 microg administered once or twice daily produced significantly greater reductions in bilateral polyp grade score (P < .001, P = .010, respectively) and congestion/obstruction (P = .001, P < .001), as well as improvement in loss of smell (P < .001, P = .036), anterior rhinorrhea (P < .001 for both), and postnasal drip (P < .001, P = .001) over month 1. MFNS 200 microg twice daily was superior to MFNS 200 microg once daily in reducing congestion/obstruction (P = .039), and there were more improvers in the MFNS 200 microg twice daily group (P = .035). MFNS was well tolerated in both groups. CONCLUSION: MFNS 200 mug, once or twice daily, was safe and significantly superior to placebo in reducing polyp grade (size and extent) and improving congestion/obstruction and return of sense of smell. MFNS is an effective medical treatment for nasal polyposis and may reduce or delay the need for surgery.     

The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

Background

We aimed to determine the reliability and validity of a hepatitis symptom inventory and to identify predictors of hepatitis C (HCV) treatment initiation in a cohort of HIV-infected patients.

Methods

Prospective clinic based study that enrolled patients referred for HCV therapy consideration. A hepatitis symptom inventory and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to HIV/HCV individuals. The symptom inventory was factor analyzed and subscale reliability estimated with Cronbach's alpha. Predictive validity was evaluated using generalized estimating equations (GEE). Predictors of HCV treatment were identified using logistic regression.

Results

Between April 2008 to July 2010, 126 HIV/HCV co-infected patients were enrolled in the study. Factor analysis using data from 126 patients yielded a three-factor structure explaining 60% of the variance for the inventory. Factor 1 (neuropsychiatric symptoms) had 14 items, factor 2 (somatic symptoms) had eleven items, and factor 3 (sleep symptoms) had two items, explaining 28%, 22% and 11% of the variance, respectively. The three factor subscales demonstrated high intrinsic consistency reliability. GEE modeling of the 32 patients who initiated HCV therapy showed that patients developed worsening neuropsychiatric and somatic symptoms following HCV therapy with stable sleep symptoms. Bivariate analyses identified the following as predictors of HCV therapy initiation: lower HIV log₁₀ RNA, lower scores for neuropsychiatric, somatic and sleep symptoms, lower CES-D scores and white ethnicity. In stepwise multiple logistic regression analysis, low neuropsychiatric symptom score was the strongest independent predictor of HCV therapy initiation and HIV log₁₀ RNA was inversely associated with a decision to initiate HCV treatment.

Conclusions

A 41-item hepatitis-related symptom inventory was found to have a clinically meaningful 3-factor structure with excellent internal consistency reliability and predictive validity. In adjusted analysis, low neuropsychiatric symptom scores and controlled HIV infection were independent predictors of HCV treatment initiation. The usefulness of the HCV symptom inventory in monitoring HCV treatment should be evaluated prospectively.     

Lymphotoxin-α and galectin-2 SNPs are not associated with myocardial infarction in two different German populations

Recent data provided strong evidence for the association of single nucleotide polymorphisms (SNPs) in the lymphotoxin-alpha (LTA) and galectin-2 (LGALS2) genes with myocardial infarction (MI) in a Japanese population. For populations of other genetic background, the relevance of these polymorphisms in the pathogenesis of MI remains controversial. We aimed to define the role of LTA and LGALS2 SNPs in two German MI populations with markedly different ascertainment strategies. Two different MI populations were studied. In the first population, MI patients were ascertained by a strong family history of MI (n = 1214). Controls were unrelated disease-free participants of the study (n = 1080). The second population included patients suffering from sporadic (nonfamilial) MI from the German KORA register (n = 607). The control group consisted of participants of the WHO MONICA survey in Germany (n = 1492). TaqMan assays were used to determine the genotypes of 4 SNPs in the LTA genomic region and 1 SNP in the LGALS2 gene. Single SNPs in both genomic regions as well as haplotypes in the LTA genomic region were tested for association in various models of inheritance. No association with MI could be found for any of the examined SNPs in the LTA genomic region and LGALS2 gene, or for haplotypes spanning the LTA genomic region. In two MI populations of European descent with markedly different ascertainment strategies, we were not able to identify a significant association of SNPs in the LTA genomic region or the LGALS2 gene with MI. These variants are unlikely to play a significant role in populations of European origin.     

Coronary artery aneurysm and type-A aortic dissection demonstrated by retrospectively ECG-gated multislice spiral CT

The case of a 40-year-old male patient with a coronary aneurysm of the proximal left descending artery (LAD) combined with circumferential type-A dissection of the ascending aorta is reported. Computed tomography angiography of the coronary arteries was performed using multislice spiral computed tomography (MSCT) with retrospective ECG gating. Anatomical relations of the LAD aneurysm as well as the origin of the left coronary artery from the false lumen of the dissection were well depicted for planning of the surgical intervention using this new noninvasive imaging modality.     

Immunomagnetic enrichment and detection of micrometastases in colorectal cancer: correlation with established clinical parameters.

PURPOSE: Micrometastatic disease in bone marrow is of prognostic significance in colorectal cancer patients. However, detection rates of standard immunocytology are relatively low. We used magnetic activated cell sorting (MACS), a highly sensitive method, to increase detection rates and correlated the presence of cytokeratin (CK)-expressing cells with clinical parameters. PATIENTS AND METHODS: Bone marrow was obtained from 51 consecutive patients with newly diagnosed colorectal adenocarcinoma who underwent primary surgery and 18 control subjects. International Union Against Cancer (UICC) stage I disease was diagnosed in 11 patients, stage II disease was diagnosed in 14 patients, stage III disease was diagnosed in 12 patients, and stage IV disease was diagnosed in 14 patients. CK-positive cells were enriched and stained with magnetically labeled CAM 5.2 antibodies directed to CK 7 and 8. RESULTS: CK-positive cells were found in 33 (65%) patients and were absent in 18 (35%). Four of 11 (36%) patients with UICC stage I disease, nine of 14 (64%) with stage II diease, eight of 12 (67%) with stage III disease, and 12 of 14 (86%) with stage IV disease were CK-positive. Epithelial cells were more frequently found in pT3/4 (72%) than in pT1/2 (36%) tumors (P =.026), but there was no difference for lymph node status. CK-positive patients had a higher chance for elevated carcinoembryonic antigen (85% v 15%, P = NS) and CA 19-9 levels (92% v 8%, P =.019). There were no significant differences in CA 72-4, sex, age, tumor grading, or tumor localization regarding the presence of CK-positive cells. All control subjects were CK-negative. CONCLUSION: In searching for micrometastases in colorectal cancer patients, we have achieved high detection rates by using MACS. The presence of these cells correlated significantly with tumor stage, tumor extension, and the tumor marker CA 19-9.     

Gallium-67 scans in renal tumors

The role of gallium-67 is limited in the genitourinary tract [1]. The rare occurrence of increased⁶⁷Ga uptake in renal carcinoma and other tumors is notable because of a lack of documentation in the literature [2]. This report is of such cases found in the last year. Gallium-67 scanning has been performed at our institution since 1972 with an average of 200 cases per year.     

Phase II trial of gemcitabine/irinotecan in refractory or relapsed small-cell lung cancer

BACKGROUND: Gemcitabine and irinotecan have shown a broad range of activity in solid tumors, including small-cell lung cancer (SCLC), with a synergistic effect on SCLC cell lines. The objective of this phase II trial was to evaluate the activity of gemcitabine/irinotecan in patients with relapsed SCLC. PATIENTS AND METHODS: Thirty-five patients (15 with refractory disease and 20 with sensitive disease) who had experienced treatment failure with 1 previous chemotherapy regimen were recruited. Treatment consisted of gemcitabine 1,000 mg/m(2) and irinotecan 100 mg/m(2) on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and signed informed consent. RESULTS: All 35 patients were assessable for response, survival, and toxicity. Best objective responses exhibited were as follows: complete response in 2 patients (6%), partial response in 4 (11%; 95% confidence interval [CI], 21%-61%), stable disease in 7 (20%; 95% CI, 9%-45%), and progressive disease in 22 (63%; 95% CI, 17%-57%). Median time to disease progression was 3.4 months and median survival was 5.8 months. The 1-year survival rate was 34%. Toxicity was mainly hematologic. Grade 3/4 nausea and vomiting occurred in 9% of patients, neuropathy occurred in 2.8%, and diarrhea occurred in 14.3%. Survival was not significantly different for patients with refractory versus sensitive disease. CONCLUSION: The combination of gemcitabine/irinotecan was shown to be active as second-line chemotherapy, especially in patients with refractory disease.     

Detection of anticoagulant residues by a new HPLC method in specimens of poisoned animals and a poison control case study

Poisonings of domestic and wildlife animals are frequently caused by anticoagulants. Between 1996 and 2003, 70% of all suspected animal poisoning cases were confirmed in this laboratory following analysis of a variety of specimens. Thirty-nine percent of all animal poisonings detected in this laboratory were caused by anticoagulants. Suspicious veterinarians and pet owners involved with animal poisonings ask for toxicological analyses. With respect to these demands, a new high-performance liquid chromatography (HPLC) method (system-I, reversed-phase C-18 column, methanol/ammonium acetate) combined with specific extraction procedures was developed for the sensitive detection of nine substances with anticoagulative properties. This method yields high recoveries of the analytes, which can simultaneously be detected. In addition, another HPLC (system-II, acetonitrile/potassium phosphate) was used to confirm and separate chromatographic peaks, which could not be resolved by HPLC system-I. The reliable method has good reproducibility and is most suitable for forensic analyses. Using these analytical procedures, concentrations of eight organic anticoagulants were determined in more than 100 aliquots of animal liver, blood, bait, gastric content, bloody intestinal content, and water. Over the last eight years, dogs and wild birds were the most frequently poisoned species. Interestingly, lethally poisoned birds had lower anticoagulant residues in their organs than mammals.     

The route of administration (oral vs intravenous) does not influence dose or outcome in Graves’ disease and unifocal autonomy

Purpose In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome.Methods Fifty-four patients suffering from Graves disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test.Results No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%.Conclusion The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this.