Detection of novel mitochondrial mutations in cytochrome C oxidase subunit 1 (COX1) in patients with familial adenomatous polyposis (FAP)

Familial adenomatous polyposis (FAP) is an Autosomal dominant inherited disorder and a rare form‌ of colorectal cancer (CRC) that is characterized by     

Linguoaxial wall and cervicoincisal dimension of anterior crown preparation: effect on retention

This study sought to evaluate the effect of the linguoaxial wall, a lingual auxiliary groove, and the cervicoincisal dimension of the anterior tooth preparation on retention. A simulated maxillary central incisor was prepared following "ideal" guidelines. The linguoaxial wall of these preparations was modified and the samples were divided into three groups: preparations with a linguoaxial wall (Group 1), preparations with a linguoaxial wall and groove (Group 2), and preparations with no linguoaxial wall (Group 3). Ten metal dies and crowns were fabricated from each preparation group. A universal testing machine subjected cemented crowns to force along the long axis of the dies and load-to-dislodgement was measured. All preparations were shortened by 3.0 mm and crowns for the reduced-height groups were fabricated, cemented, and subjected to similar force. The preparations with the groove produced higher mean retention than the other groups. Among the reduced-height groups, the preparations with the groove also produced higher mean retention than the other groups. There were no differences in mean retention for the short and long preparation heights of each group.     

Parechovirus Genotype 3 Outbreak among Infants,New South Wales,Australia, 2013–2014

From October 2013 through February 2014, human parechovirus genotype 3 infection was identified in 183 infants in New South Wales, Australia. Of those infants, 57% were male and 95% required hospitalization. Common signs and symptoms were fever >38°C (86%), irritability (80%), tachycardia (68%), and rash (62%). Compared with affected infants in the Northern Hemisphere, infants in New South Wales were slightly older, both sexes were affected more equally, and rash occurred with considerably higher frequency. The New South Wales syndromic surveillance system, which uses near real-time emergency department and ambulance data, was useful for monitoring the outbreak. An alert distributed to clinicians reduced unnecessary hospitalization for patients with suspected sepsis.     

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin

AIM: To assess the efficacy and safety of a 24-week treatment with sitagliptin, a highly selective once-daily oral dipeptidyl peptidase-4 (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and or=4 mg/day) monotherapy and 229 were on glimepiride (>or=4 mg/day) plus metformin (>or=1,500 mg/day) combination therapy. Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy (pioglitazone) until study end. The primary efficacy analysis evaluated the change in HbA(1c) from baseline to Week 24. Secondary efficacy endpoints included fasting plasma glucose (FPG), 2-h post-meal glucose and lipid measurements. RESULTS: Mean baseline HbA(1c) was 8.34% in the sitagliptin and placebo groups. After 24 weeks, sitagliptin reduced HbA(1c) by 0.74% (p < 0.001) relative to placebo. In the subset of patients on glimepiride plus metformin, sitagliptin reduced HbA(1c) by 0.89% relative to placebo, compared with a reduction of 0.57% in the subset of patients on glimepiride alone. The addition of sitagliptin reduced FPG by 20.1 mg/dl (p < 0.001) and increased homeostasis model assessment-beta, a marker of beta-cell function, by 12% (p < 0.05) relative to placebo. In patients who underwent a meal tolerance test (n = 134), sitagliptin decreased 2-h post-prandial glucose (PPG) by 36.1 mg/dl (p < 0.001) relative to placebo. The addition of sitagliptin was generally well tolerated, although there was a higher incidence of overall (60 vs. 47%) and drug-related adverse experiences (AEs) (15 vs. 7%) in the sitagliptin group than in the placebo group. This was largely because of a higher incidence of hypoglycaemia AEs (12 vs. 2%, respectively) in the sitagliptin group compared with the placebo group. Body weight modestly increased with sitagliptin relative to placebo (+0.8 vs. -0.4 kg; p < 0.001). CONCLUSIONS: Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy. The addition of sitagliptin was generally well tolerated, with a modest increase in hypoglycaemia and body weight, consistent with glimepiride therapy and the observed degree of glycaemic improvement.     

Coinfection with Giardia lamblia and Clostridium difficile after use of ranitidine

A 49-year-old man presented with a 3-week history of vomiting and diarrhea. He reported foamy stools but no blood or melena and had crampy epigastric pain. He denied usage of antibiotics. He had been taking ranitidine for intermittent epigastric pain for the last few months and noted an 11-pound weight loss during the 3 weeks before admission. Stool was positive for Clostridium difficile toxin and Giardia lamblia antigen. Cultures and occult blood tests were negative. Oral metronidazole, 500 mg 3 times a day, was administered, and the patient was hydrated. The diarrhea resolved, and patient was discharged on the fourth hospital day. Prior antibiotic therapy is the most common risk factor for C difficile colitis. This patient developed concomitant infection with C difficile and G lamblia while he used ranitidine. He had no other risk factors for these infections. Hence, we propose that ranitidine-induced hypochlorhydria predisposed this patient to the enteric infections.     

Multiple sleep latency measures in narcolepsy and behaviourally induced insufficient sleep syndrome

BackgroundShort mean latencies to the first epoch of non-rapid eye movement sleep stage 1 (NREM1) and the presence of ?2 sleep onset REM (SOREM) periods on multiple sleep latency test (MSLT) occur in both narcolepsy–cataplexy (NC) and behaviourally induced insufficient sleep syndrome (BIISS). It is not known whether specific MSLT findings help differentiate the two disorders.MethodsWe analyzed MSLT data including sleep latencies to and between different sleep stages of 60 age-, gender- and body mass index (BMI)-matched subjects (hypocretin-deficient NC, actigraphy-confirmed BIISS, healthy controls: each 20).ResultsMean latency (in minutes) to NREM1 sleep was significantly shorter in NC (1.8 ± 1.5) than in BIISS (4.7 ± 2.1, p < 0.001) and controls (11.4 ± 3.3, p < 0.001). Mean latency to NREM2 sleep was similar in NC (8.6 ± 4.7) and BIISS (8.1 ± 2.7, p = 0.64); latency to either NREM2 or rapid eye movement (REM) sleep (i.e., the sum of the sleep latency to NREM1 and the duration of the first NREM1 sleep sequence), however, was shorter in NC (4.4 ± 2.9) than in BIISS (7.9 ± 3.5, p < 0.001). Referring to all naps with SOREM periods, the sequence NREM1–REM–NREM2 was more common (71%) in NC than in BIISS (15%, p < 0.001), reflecting the shorter latency from NREM1 to NREM2 in BIISS (3.7 ± 2.5) than in NC (6.1 ± 5.9, p < 0.001).ConclusionsOur findings show that both sleepiness (as measured by NREM1 sleep latency) and REM sleep propensity are higher in NC than in BIISS. Furthermore, our finding of frequent REM sleep prior to NREM2 sleep in NC is in line with the recent assumption of an insufficient NREM sleep intensity in NC. Together with detailed clinical interviews, sleep logs, actigraphy, and nocturnal polysomnography, mean sleep latencies to NREM1 ?2.5 min, the presence of multiple SOREM periods, and the sequence NREM1–REM–NREM2 may be the best MSLT measures to discriminate NC from BIISS.     

Pretransplant hepatitis C virus infection and its effect on the post-transplant course of living renal allograft recipients

BACKGROUND: Hepatitis C virus infection (HCV) is a main health problem in end-stage renal disease (ESRD) patients. The effect of pretransplant HCV infection on survival among ESRD patients who have undergone renal transplantation is controversial. We report the results of a large monocenter study that evaluated the effect of hepatitis C on the patient, and on graft survival in renal-transplanted patients who received living donated allograft. METHODS: A historical cohort study, we investigated all 1006 patients who received a living kidney transplant at Baghiatollah Medical Center in Tehran, Iran, between March 1995 and October 2001 (up to 85 months follow up). Patients' sera had been routinely assayed for anti-HCV antibodies and hepatitis B surface antigen (HBsAg) at the time of transplantation. The HBsAg-positive patients were excluded from the survival analysis. Survivals were examined using Kaplan-Meier analysis and compared using the log-rank test. Multivariate analysis was performed using Cox's model. RESULTS: Forty-five patients (4.5%) were anti-HCV-antibody positive. Anti-HCV-antibody-positive patients spent a longer time on dialysis and had a higher rate of retransplantation. There were no differences in recipients' sex and age and donors' age between the two groups. The 7-year patient survival rate was 89.9% in the anti-HCV-antibody-positive group and 95.5% in the HCV-negative group (P = 0.74). Seven-year graft survival was 82.0% and 75.0% in the anti-HCV-antibody-positive and HCV-negative groups, respectively (P = 0.39). In the multivariate analysis, age was the only significant parameter correlated with patient survival (P = 0.02). CONCLUSIONS: HCV infection does not seem to influence patient and graft survival within a medium-time follow up in living allograft recipients, and anti-HCV-antibody positive status (alone) is not a contraindication for renal transplantation. However, further studies are needed to better define the role of HCV infection in long-term prognosis.