Mechanism of Alternariol monomethyl ether-induced mitochondrial apoptosis in human colon carcinoma cells

Alternariol monomethyl ether (AME) is a major mycotoxin produced by fungi of the genus Alternaria and a common contaminant of food products such as fruits and cereals worldwide. AME can cause serious health problems for animals as well as for humans. In this study, human colon carcinoma cells (HCT116) were used to explore the mechanisms of cell death induced by AME. Exposure of HCT116 cells to AME resulted in significant cytotoxicity manifested by a loss in cell viability mainly mediated by activation of apoptotic process. AME activated the mitochondrial apoptotic pathway evidenced by the opening of the mitochondrial permeability transition pore (PTP), loss of the mitochondrial transmembrane potential (ΔΨm) downstream generation of O(2)(-), cytochrome c release and caspase 9 and 3 activation. Experiments conducted on isolated organelles indicated that AME does not directly target mitochondria to induce PTP-dependent permeabilization of mitochondrial membranes. Moreover, no difference was observed in Bax-KO cells in comparison to parental cells, suggesting that the pro-apoptotic protein Bax is not involved in AME-induced mitochondrial apoptosis. Our findings demonstrate for the first time that AME induces cell death in human colon carcinoma cells by activating the mitochondrial pathway of apoptosis.     

Effects of dermal sub-chronic exposure of pubescent male rats to permethrin (PRMT) on the histological structures of genital tract, testosterone and lipoperoxidation

Short-term effects of pyrethroids on human health are better and well identified, whereas long-term risk’s estimation remains difficult, especially those affecting the reproductive function. The present study, carried out in male rats, is a contribution to explore some effects underlying permethrin (PRMT) toxicity. The aim of the present work was to investigate the effect of different subcutaneous treatments with PRMT low doses on testes and epididymides histopathology, testosterone and oxidative stress in pubescent male rats. Groups of six animals were treated with a dermal daily dose of 0.013, 0.13, or 1.3 mg/kg b.w/day of PRMT in 70% ethanol for 30, 45, and 60 days, respectively.Macroscopic studies showed an influence of PRMT on the testes, the epididymides and body weight. The pyrethroid induces a testis disturbance traduced by a deregulation of spermatogenesis and an epididymis dysfunction by the appearance of strong deformations into the microstructure of the epididymides. A hormonal disruption was evidenced by the measurement of the plasma testosterone concentrations. The findings of the present investigation mentioned a significant increase (p≤0.05) in lipoperoxidation, after 45 or 60 days, when we measured the plasma malondialdehyde (MDA) concentrations.In conclusion the study shows that subcutaneous PRMT treatment causes an arrest of spermatogenesis, and a significant disharmony in testosterone concentration and MDA levels. These effects are related to dose, length of treatment and to the lipid peroxidation, which may be one of the molecular mechanisms involved in PRMT-induced gonads and epididymides toxicity.     

Durée de l’antibiothérapie lors du traitement des pneumopathies acquises sous ventilation mécanique : comparaison entre sept jours et dix jours. Étude pilote

Objective

To compare the efficiency of a 7-day antibiotics regimen with a 10-day regimen for ventilator-associated pneumonia (VAP).

Study design

Prospective randomized study.

Patients and methods

Adults patients ventilated for more than 48 hours in the intensive care unit (ICU) with a clinical diagnosis of VAP documented by positive quantitative cultures of tracheal aspiration were included in this study. All included patients were randomized in two groups. Ten-day group: 10 days antibiotic therapy, and 7-day group: 7 days antibiotic therapy. Primary judgment criteria were 14- and 28-day mortality, the number of days without antibiotics. Secondary judgments criteria were rate of recurrent pulmonary infection, the evolution of the clinical pulmonary infection scores (CPIS), the length of ICU stay and the length of mechanical ventilation.

Results

Thirty patients were included in this study (16 in the 10-day group and 14 in the 7-day group). The demographic and clinical characteristics of the groups assigned to receive antibiotic therapy for 7 or 10 days were generally similar. The 14-day and 28-day mortality rate following VAP onset were 31.2 and 37.5% in the 10-day group and 7.1 and 35.7% in the 7-day group. The difference was not significant. The number of day without antibiotics and without mechanical ventilation turned out: 1.75 and 2.06 days versus 4.14 and 3.43 days in the 10-day group and 7-day group respectively, the recurrent rate of pulmonary infection (12.5% versus 14.3%, p = 0.6), the length of stay in the ICU (27.7 days versus 26.0 days, p = 0.8) and the evolution of the CPIS were no different in the two groups.

Conclusion

In patients with microbiologically confirmed VAP who received appropriate empirical antibiotic therapy, a 7-day antibiotic regimen was as efficient clinically and microbiologically as a 10-day antibiotic regimen with a reduction of antibiotic use.     

Juvenile myasthenia gravis

Juvenile myasthenia gravis shares a similar pathophysiologic origin with adult myasthenia gravis, but there are important differences, mostly relating to epidemiology, presentation, and therapeutic decision making. Gender ratios and the proportion of seropositive patients differ in the pre‐ and postpubertal age groups. The diagnostic evaluation is similar to that in adults, although special techniques are sometimes necessary to perform single‐fiber electromyography in younger patients. Therapeutic decisions in affected children and adolescents are complicated by the greater long‐term consequences of using steroids, and thus other interventions, such as intravenous immunoglobulin (IVIg) and plasmapheresis, may play a greater therapeutic role in this population than in adults. Steroid‐sparing agents may contribute to the management of refractory cases, but they should be used with caution due to the risk of malignancy. Muscle Nerve, 2008     

Is Patients’ Preferred Involvement in Health Decisions Related to Outcomes for Patients with HIV?

BACKGROUND Previous studies suggest that patients who are more involved in their medical care have better outcomes. OBJECTIVES We sought to compare health care processes and outcomes for patients with HIV based on their preferred level of involvement in health decisions. DESIGN Cross-sectional analysis of audio computer-assisted interviews with patients at an urban HIV clinic. PATIENTS One thousand and twenty-seven patients awaiting an appointment with their primary care provider. MEASURES Patients were asked how they preferred to be involved in decisions (doctor makes most or all decisions, doctor and patient share decisions, patient makes all decisions). We also asked patients to rate the quality of communication with their HIV provider, and their self-reported receipt of and adherence to HAART. RESULTS Overall, 23% patients preferred that their doctor make all or most decisions, 63% preferred to share decisions with their doctor, and 13% preferred to make all final decisions alone. Compared to patients who prefer to share decisions with their HIV provider, patients who prefer that their provider make all/most decisions were significantly less likely to adhere to HAART (OR [odds ratio] 0.57, 95% CI 0.38–0.86) and patients who preferred to make decisions alone were significantly less likely to receive HAART or to have undetectable HIV RNA in unadjusted analyses (OR 0.52, 95% CI 0.31–0.87 for receipt of HAART; OR 0.64, 95% CI 0.44–0.95 for undetectable HIV RNA). After controlling for potentially confounding patient characteristics and differences in patient ratings of communication quality, patients who preferred that their provider make all/most decisions remained significantly less likely to adhere to HAART (OR 0.58, 95% CI 0.38–0.89); however, the associations with receipt of HAART and undetectable HIV RNA were no longer significant (OR 0.60, 95% CI 0.34–1.05 for receipt of HAART; OR 0.80, 95% C.I 0.53–1.20 for undetectable HIV RNA). CONCLUSIONS Although previous research suggests that more patient involvement in health care decisions is better, this benefit may be reduced when the patient wants to make decisions alone. Future research should explore the extent to which this preference is modifiable so as to improve outcomes.     

Combined Insulin Pump Therapy with Real-Time Continuous Glucose Monitoring Significantly Improves Glycemic Control Compared to Multiple Daily Injection Therapy in Pump Na?ve Patients with Type 1 Diabetes; Single Center Pilot Study Experience

Objectives

This study assessed the safety and clinical effectiveness of the training protocol for initiating insulin pump therapy with real-time continuous glucose monitoring (MiniMed Paradigm REAL-Time System) in a stepwise approach on pump naive subjects with type 1 diabetes compared to a control group who remained on multiple daily injection (MDI) therapy.

Methods

This was a 15-week treat-to-target pilot study of 16 adult subjects (n = 50% male, age 45.9 ± 16 years) with type 1 diabetes (duration of diabetes 21.9 ± 11 years) on MDI therapy with hemoglobin A1c levels at or above 7.5% at baseline. Subjects were randomized to either the study arm (using a combined insulin pump and real-time continuous glucose monitoring system) or the control arm [which continued on MDI therapy with self-monitored blood glucose (SMBG) only]. All subjects dosed insulin according to results of SMBG by finger stick and uploaded data into the CareLink data management software.

Results

Significant improvements in glycemic control were observed from baseline in both study groups—study arm: pre-A1c 9.45 ± 0.55 and post-A1c 7.4 ± 0.66 (p = 0.00037); control arm: pre-A1c 8.58 ± 1.30 and post-A1c 7.5 ±1.01 (p = 0.04). Both arms had no incidence of severe hypoglycemia.

Conclusion

In this pilot study, the Paradigm REAL-Time System was initiated safely and effectively in type 1 diabetes patients who were pump naïve using a stepwise educational protocol.     

Internal fixation in compound type III fractures presenting after golden period

Objective:

Patients often reach the hospital late after passage of golden hours (initial 6 hours) after sustaining high-velocity injuries. The decision of internal fixation in Gustilo''s Type IIIA and IIIB fractures becomes a formidable challenge in patients reaching late. The purpose of the present study was to find out if internal fixation could be safely undertaken in these patients.

Materials and Methods:

Sixty-three patients, having 70 compound fractures (46 Type IIIA and 24 IIIB), which were internally fixed after 6h but within 24h after injury, were included in the present analysis. Follow-up ranged from 18 to 48 months with mean of 28 months.

Result:

Overall infection rate noted was (n = 11) 15.71% (8.7% in IIIA, and 29.16% in IIIB). The difference in deep infection rate between Type IIIA and Type IIIB was found to be statistically significant (P value < 0.01). Nonunion was seen in five fractures. Functional evaluation using Katenjian''s criteria, showed 62.85% (44 fractures of 70) good to excellent results.

Conclusion:

Satisfactory results may be obtained in Gustilo''s Type IIIA and IIIB fractures even if fixed after the golden period, provided strict protocol such as aggressive debridement, prophylactic antibiotic coverage, early soft tissue reconstruction and timely bone grafting is followed. The primary coverage of the wound is discouraged.     

Endoscopic management of recurrent primary bile duct stones

Background: The management of recurrent choledocholithiasis today remains as challenging as in the pre‐endoscopic era. Between 2 and 7% of affected patients have historically required surgical intervention for the treatment of recurrent or retained choledocholithiasis and of these, as many as 24% develop biliary complications. To avoid surgery, repeated endoscopic management of the problem has been suggested. In this study, we evaluate our policy of repeated endoscopic management of recurrent primary bile duct stones. Methods: This study examined a cohort of nine patients identified from a prospective database with recurrent choledocholithiasis. Demographic, clinical and investigative details were recorded and data were analysed. Complications were determined from a review of the patient’s file. Results: There were nine patients and 66 procedures were carried out. Mean age at time of first endoscopy was 70.1 years (36–91 years). Three patients were of male sex (33.3%). The mean number of endoscopies carried out per patient was 7.3 (3‐13). Failure to completely clear the duct occurred in 36.4% of all endoscopies. There were no periprocedural complications. Conclusion: Repeated endoscopic stone extraction by endoscopic retrograde cholangiopancreatography when required is a safe policy. However, this technique will only provide temporary relief from primary duct stones and repeated endoscopic treatment, again safe, will be required.