Studies on drug interactions between esomeprazole, amoxicillin and clarithromycin in healthy subjects

OBJECTIVE: A combination of esomeprazole, amoxicillin and clarithromycin may be used for Helicobacter pylori eradication. We explored the potential for interactions between these drugs. METHODS: In 2 randomized, 4-way crossover studies, healthy CYP2C19 extensive metabolizers (EMs) received esomeprazole 40 mg once daily (n = 20) or 20 mg twice daily (b.i.d.) (n = 20), clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d. or the combination of the 3 drugs for 7 days. In a third randomized, 2-way, crossover study, 6 healthy CYP2C 19 poor metabolizers (PMs) received esomeprazole 40 mg once daily with and without clarithromycin 500 mg b.i.d. for 1 week. RESULTS: Triple therapy with esomeprazole 40 mg increased the area under the plasma concentration-time curve during the dosing interval (AUCtau) from 13.31 micromol x h/l (11.12-15.93) for esomeprazole alone to 22.69 micromol x h/l (18.94-27.17) for triple treatment. Respective AUCtau values with esomeprazole 20 mg b.i.d. were 4.97 micromol.h/l (3.97-6.21) and 11.29 micromol x h/l (9.03-14.12). Clarithromycin and amoxicillin plasma levels were largely unchanged by combination therapy. In PMs, the esomeprazole AUC also approximately doubled when administered in combination with clarithromycin. All treatments were well tolerated. CONCLUSION: Clarithromycin decreases the metabolism rate of esomeprazole, leading to approximately doubled AUC values, both in EMs and PMs.     

Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma

PURPOSE: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy (RT) alone. The goal of this study was to update our experience of high-dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT), for such patients. METHODS AND MATERIALS: Between 1984 and 2003, 38 patients with Stage I and Stage II adenocarcinoma of the endometrium considered high operative risk received RT as the primary treatment. The median age was 74.1 years. Before 1996, the local extent of the disease was assessed by an examination under anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter. Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy, typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was 42 Gy. RESULTS: At a median follow-up of 57.5 months for patients at risk, 11 patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%) distantly, and 1 patient (3%) locally and distantly. Local failure was established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and higher grade were both associated with increased failure rate. The 15-year disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42% for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade II and III combined (p = 0.0254). Patients with Stage I disease established by MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of 100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3 Grade III or IV. CONCLUSION: Medically inoperable Stage I endometrial carcinoma may be safely and effectively treated with HDRB as the primary therapy. In selected Stage I patients, our results are equivalent to that of surgery. We believe that the alternative option of HDRB as the primary therapy for selected Stage I endometrial carcinoma, even in patients with low operative risks, needs further evaluation.     

Isolated intradural lumbosacral tailgut cyst with carcinoid features

Tailgut cysts are developmental cysts that arise from remnants of the embryonic postanal gut and are typically located within the presacral, retrorectal space. Isolated cases of aberrant locations, including prerectal, perirenal, perianal, retrovesical, and subcutaneous locations, have been reported. Malignant transformations with the presence of adenocarcinomas or carcinoids have been recognized within these entities. It is well recognized that anterior sacrococcygeal abnormalities are present and are frequently caused by the slow-growing nature of the tailgut cysts and related mass effect; however, the authors are aware of no reports in the literature of isolated tailgut cysts within the thecal sac in direct contact with neural elements, without extension into the peritoneal cavity. In this case, a 28-year-old woman presented with progressive back pain, frequent urinary tract infections, and bowel dysfunction. She was found to have a purely intradural tailgut cyst with malignant transformation consistent with carcinoid. No peritoneal extension of her disease was found. The authors hypothesize that this is a rare developmental aberration that has not been commonly recognized and potentially has implications for embryological development.     

Cotton leaf curl Multan betasatellite as a plant gene delivery vector trans-activated by taxonomically diverse geminiviruses

Cotton leaf curl Multan betasatellite (CLCuMB) replicates in tobacco, tomato and datura plants in the presence of the helper viruses tomato leaf curl virus-Australia, Iranian isolates of tomato yellow leaf curl virus, tomato leaf curl Karnataka virus, and beet severe curly top virus (BSCTV). Infectious recombinant CLCuMB constructs were made in which segments of either the CaMV 35S or the petunia ChsA promoter replaced the CLCuMB βC1 ORF, and these were designated pBinβΔC1-35S and pBinβΔC1-ChsA, respectively. Inoculation of tobacco plants containing a functional 35S-GUS transgene with pBinβΔC1-35S, and normal petunia plants with pBinβΔC1-ChsA, in the presence of helper viruses resulted in silencing of GUS and ChsA activities in transgenic tobacco and non-transgenic petunia plants, respectively. Replication of CLCuMB with different geminiviruses, especially BSCTV, a curtovirus with a broad host range, makes it a valuable gene delivery vector to the large number of host plant species of geminiviruses that support CLCuMB.     

Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance

Background

Metabolic syndrome over the years have structured definitions to classify an individual with the disease. Literature review suggests insulin résistance is hallmark of these metabolic clustering. While measuring insulin resistance directly or indirectly remains technically difficult in general practice, along with multiple stability issues for insulin, various indirect measures have been suggested by authorities. Fasting triglycerides-glucose (TyG) index is one such marker, which is recently been suggested as a useful diagnostic marker to predict metabolic syndrome. However, limited data is available on the subject with almost no literature from our region on the subject.

Objective

1. To correlate TyG index with insulin resistance, anthropometric indices, small dense LDLc, HbA1c and nephropathy. 2. To evaluate TyG index as a marker to diagnose metabolic syndrome in comparison to other available markers.

Design-cross-sectional analysis

Place and duration of study-From Jun-2016 to July-2017 at PSS HAFEEZ hospital Islamabad.

Subjects and methods

From a finally selected sample size of 227 male and female subjects we evaluated their anthropometric data, HbA1c, lipid profile including calculated sdLDLc, urine albumin creatinine raito(UACR) and insulin resistance (HOMAIR). TyG index was calculated using formula of Simental-Mendía LE et al. Aforementioned parameters were correlated with TyG index, differences between subjects with and without metabolic syndrome were calculated using Independent sample t-test. Finally ROC curve analysis was carried out to measure AUC for candidate parameters including TyG Index for comparison.

Results

TyG index in comparison to other markers like fasting triglycerides, HOMAIR, HDLc and non-HDLc demonstrated higher positive linear correlation with BMI, atherogenic dyslipidemia (sdLDLc), nephropathy (UACR), HbA1c and insulin resistance. TyG index showed significant differences between various markers among subjects with and without metabolic syndrome as per IDF criteria. AUC (Area Under Curve) demonstrated highest AUC for TyG as [(0.764, 95% CI 0.700–0.828, p-value?≤?0.001)] followed by fasting triglycerides [(0.724, 95% CI 0.656–0.791, p-value?≤?0.001)], sdLDLc [(0.695, 95% CI 0.626–0.763, p-value?≤?0.001)], fasting plasma glucose [(0.686, 95% CI 0.616–0.756, p-value?≤?0.001)], Non-HDLc [(0.640, 95% CI 0.626–0.763, p-value?≤?0.001)] and HOMAIR [(0.619, 95% CI 0.545–0.694, p-value?≤?0.001)].

Conclusion

TyG index, having the highest AUC in comparison to fasting glucose, triglycerides, sdLDLc, non-HDLc and HOMAIR can act as better marker for diagnosing metabolic syndrome.