Comparison of acute toxicity and mortality after two different dosing regimens of high-dose interleukin-2 for patients with metastatic melanoma

We compared acute toxicity, drug exposure, in-hospital mortality, and inpatient length of stay between two currently recommended dosing protocols (from the National Comprehensive Cancer Network Guidelines) of high-dose interleukin-2 (IL-2) treatment for patients with metastatic melanoma. Patients with metastatic melanoma who received high-dose IL-2 treatment between 2003 and 2010 were identified. Chemotherapy orders, electronic medical records, paper medical charts, and patient discharge summaries were reviewed retrospectively. We identified 13 patients who had received 600,000 units/kilogram (kg)/dose and 15 patients who had received 720,000 units/kg/dose. Patients in the 720,000 units/kg/dose group had a higher rate of grade 3 and 4 bilirubin elevations (34 vs. 12 %), weight gain (any grade, 96 vs. 89 %), and thrombocytopenia (any grade, 75 vs. 65 %). Patients receiving the higher dose also experienced more dose-limiting neurotoxicity (45 vs. 23 %), large-volume diarrhea (15 vs. 0 %), and hepatotoxicity (7 vs. 0 %). There was no in-hospital mortality during treatment in either group. The average length of stay was similar between both groups (5 days, SD?=?1 for both groups), and the median cumulative IL-2 exposure was similar between both groups for the first course (10.1 vs.10.5 million units/kg) and for all courses (approximately 11–12 million units/kg). Both high-dose IL-2 protocols had comparable in-hospital mortality and cumulative IL-2 exposure. The 720,000 units/kg/dose dosing scheme did not shorten the length of stay but did lead to greater acute toxicity. Therefore, as a result, we recommend 600,000 units/kg/dose when deciding between the two regimens.     

Decreased Intrinsic Factor Secretion in AIDS: Relation to Parietal Cell Acid Secretory Capacity and Vitamin B12 Malabsorption

AIDS-associated gastric secretory failure has been characterized by decreased secretion of acid, pepsin, and gastric juice volume. To determine whether decreased intrinsic factor secretion and vitamin B12 malabsorption occur in this entity, we performed prospective measurements of maximal acid output, intrinsic factor output, vitamin B12 absorption, serum vitamin B12, and holotranscobalamin II in 10 consecutive AIDS patients. Four of 10 patients had low maximal acid output, i.e., < or = 1.5 mEq/h (control = 12.8 +/- 9.0, range 2.5-25 mEq/h). Four patients had low intrinsic factor output, i.e., < or = 1.1 microgram/h (control = 8.2 +/- 6.9, range 3.1-19.4 micrograms/h). One patient with low intrinsic factor output had low serum vitamin B12 and a Schilling test consistent with pernicious anemia. A second patient with very low intrinsic factor output (0.16 micrograms/h) had low parts I and II Schilling tests; malabsorption most likely resulted from both low intrinsic factor secretion and ileal disease. One of three vitamin B12 malabsorbing patients, with normal serum vitamin B12, had low holotranscobalamin II, 25 pg/ml (control holotranscobalamin II = 76 +/- 44, range 44-152 pg/ml). Maximal acid output and intrinsic factor output did not correlate in AIDS (r = 0.36, p = 0.30) in contrast to the expected correlation in controls (r = 0.91, p = 0.03). We conclude that low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption. Decreased parietal cell secretion of intrinsic factor and acid may occur independently in human immunodeficiency virus-associated gastric secretory failure. Low holotranscobalamin II, an early manifestation of vitamin B12 malabsorption, results in decreased delivery to vitamin B12-dependent tissues prior to depletion of serum vitamin B12. Regular supplementation with vitamin B12 may therefore be warranted in patients with advanced HIV infection.     

Co-existence of primary biliary cirrhosis and primary sclerosing cholangitis: a rare overlap syndrome put in perspective

Overlap syndromes between autoimmune hepatitis and both primary biliary cirrhosis and primary sclerosing cholangitis are well described, but overlap between primary biliary cirrhosis and primary sclerosing cholangitis is not recognized. We present two cases of an unusual autoimmune liver disease, both of which included an overlap between primary biliary cirrhosis and primary sclerosing cholangitis, while one had features of all three conditions. The diagnoses were based on clinical, biochemical, serological, histological and cholangiographic findings. The two cases were identified from a consecutive cohort of 261 patients with autoimmune liver disease followed prospectively in secondary care over a 20-year period, which gives perspective to this uncommon overlap syndrome.     

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase‐1 (HO‐1), Nrf2, NF‐B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO‐1 gene and a significant increase in NF‐?β, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO‐1 and NOS enzymes, a significant increase in HO‐1, and Nrf2 gene expression, and a significant decrease in NF‐?β, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.     

Insuffisances cardiaques du sujet jeune : aspects épidémiologiques,cliniques et étiologiques au CHU Sylvanus Olympio de Lomé

Aims

The aim of the study was to analyze the epidemiologic, clinical and etiologic aspects of heart failures of the young age to 18 to 45 years.

Patients and method

It consisted of a cross-sectional study realized in hospitalization in the service of cardiologic of Teaching Hospital Sylvanus Olympio of Lomé on 35 months (January 2009 to November 2012). The completion of a Doppler echocardiography was necessary to include the patients in the study.

Results

The prevalence heart failure in the 45 years old young people to more was of 28.6%. The median age of the patients was of 36.5 ± 3 years with a sex ratio of 10.7. Heart failure was total among 268 patients (71.3%). The electrocardiogram found 88 patients (23.4%) in complete arrhythmia by auricular fibrillation. Cardiac echography found a dilation of the left ventricle among 271 patients (72.1%), a systolic dysfunction of left ventricle among 213 patients (56.6%) and an intracavitary thrombus among 37 patients (9.8%). The etiologies were: hypertension 161 cases (42.8%), heart valve diseases 68 cases (18.1%), the peripartum cardiomyopathy 58 cases (15.4%), dilated cardiomyopathy 22 cases (5.8%), the alcoholism 12 cases (3.1%), ischaemic heart diseases 10 cases (2.7%), congenital heart diseases 10 cases (2.7%), the chronic pulmonary heart 8 cases (2.1%), the cardiothyreosis 7 cases (1.8%), the pericardial tamponnade 4 cases (1.1%) and myocarditis with VIH 4 cases (1.1%). Hospital lethality was of 16.4% (62 patients).

Conclusion

Heart failure is a serious and frequent pathology in Africa. It affects young and active subjects. The causes are dominated by hypertension.     

Fatigue resistance and microleakage of CAD/CAM ceramic and composite molar crowns

Purpose: The aim of this study was to determine effect of compressive cyclic loading on fatigue resistance and microleakage of monolithic CAD/CAM molar ceramic and composite crowns. Materials and Methods: Thirty‐two extracted molars were prepared to receive CEREC crowns according to manufacturer's guidelines using a special paralleling device (Parallel‐A‐Prep). Sixteen feldspathic ceramic crowns (VITABLOCS Mark II) (VMII) and 16 resin‐composite crowns (Paradigm‐MZ100 blocks) (PMZ) were milled using a CEREC‐3D machine. Eight crowns of each group were cemented to their respective teeth using self‐etching resin cement (Panavia‐F‐2.0) (PAN), and eight were cemented using self‐adhesive resin cement (RelyX‐Unicem‐Clicker) (RXU). Following storage for 1 week in water, specimens were subjected to uniaxial compressive cyclic loading in an Instron testing machine at 12 Hz for 1,000,000 cycles. Load was applied at the central fossa, and the cycle range was 60–600 N. Specimens were then subjected to microleakage testing. Data were statistically analyzed using factorial ANOVA and Post Hoc (Tukey HSD) tests. Results: All composite crowns survived compressive cyclic loading without fracture, while three ceramic crowns from the subgroup cemented with RXU developed surface cracks at the center of occlusal surfaces, extending laterally. Microleakage scores of ceramic crowns cemented with PAN were significantly lower than those of the other three subgroups (p < 0.05). Conclusions: After 1,000,000 cycles of compressive cyclic loading, PMZ composite molar crowns were more fatigue‐resistant than VMII ceramic crowns. Cement type had a significant effect on fatigue resistance of the ceramic crowns but not the composite ones. Microleakage scores of ceramic crowns cemented with PAN were significantly lower than those of the other subgroups (p < 0.05).