Comparative pharmacokinetics of azithromycin in serum and white blood cells of healthy subjects receiving a single-dose extended-release regimen versus a 3-day immediate-release regimen

The pharmacokinetic profiles of azithromycin given as a single-dose regimen (2.0-g extended-release microspheres) were characterized in serum and white blood cells (WBC) and compared with those of a 3-day regimen (a 500-mg immediate-release tablet once daily; total dose, 1.5 g) in an open-label, randomized, parallel-group study of 24 healthy adult subjects. Serial blood samples were collected up to 5 days after the start of dosing for both regimens. Safety assessments were conducted throughout the study. A single 2.0-g dose of azithromycin microspheres achieved significantly higher exposures in serum and WBC during the first 24 h after the start of dosing than a 3-day regimen: an approximately threefold higher area under the curve from time zero to 24 h postdose (AUC(0-24)) and an approximately twofold higher mean peak concentration on day 1. The single-dose regimen provided total azithromycin exposures in serum and WBC similar to those of the 3-day regimen, as evidenced by the similar AUC(0-120) and trough azithromycin concentrations in serum and WBC (mononuclear leukocytes [MNL] and polymorphonuclear leukocytes [PMNL]). For both regimens, the average total azithromycin exposures in MNL and PMNL were approximately 300- and 600-fold higher than those in serum. Azithromycin concentrations in MNL and PMNL remained above 10 microg/ml for at least 5 days after the start of dosing for both regimens. This "front-loading" of the dose on day 1 is safely achieved by the extended-release microsphere formulation, which maximizes the drug exposure at the time when the bacterial burden is likely to be highest.     

Clinical profile and outcome of swine flu in Indian children

Objective  

To describe the clinical characteristics and outcome of Indian children infected with 2009 H1N1 influenza virus.     

A comparison between epidural and IV tramadol for painless labor and effect on perinatal outcome

Objectives

To compare the efficacy of epidural and I/V Tramadol for painless labor and effect on perinatal outcome.

Material and methods

Atotal of 90 parturients admitted in S.N.Medical College, Agra were selected for study. Thirty parturients received intravenous tramadol, thirty received epidural tramadol and thirty were kept as controls by the method of randomization. In the intravenous group, tramadol in doses of 1mg/Kg body weight IV bolus and 100mg in 500ml Ringer lactate at the rate of 8–24 drops/min was given. In the epidural group tramadol 1mg/kg body weight with 8–10 ml of 0.25% bupivacaine was given.

Results

In the epidural group, pain relief was excellent in 36.67%, good in 50% and average in 13.33%. In intravenous group, pain relief was excellent in 10%, good in 26.67% and average in 63.33%. In both the groups there was no significant effect on duration of 1st & 3rd stage of labor. Second stage of labor was prolonged in the control group. There were no significant changes in APGAR scoring.

Conclusion

Epidural tramadol is a safe and effective method for labor pain relief better than I/V tramadol.     

Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer

IntroductionCKLF like MARVEL transmembrane domain containing 6 (CMTM6) has been described as a programmed death ligand 1 (PD-L1) regulator at the protein level by modulating stability through ubiquitination. In this study, we describe the patterns of CMTM6 expression and assess its association with response to programmed cell death 1 pathway blockade in NSCLC.MethodsWe used multiplexed quantitative immunofluorescence to determine the expression of CMTM6 and PD-L1 in 438 NSCLCs represented in tissue microarrays, including in two independent retrospective cohorts of immunotherapy-treated (n = 69) and non–immunotherapy-treated (n = 258) patients and a third collection of EGFR- and KRAS-genotyped tumors (n = 111).ResultsTumor and stromal CMTM6 expression was detected in approximately 70% of NSCLCs. CMTM6 expression was not associated with clinical features or EGFR/KRAS mutational status and showed a modest correlation with T-cell infiltration (R² < 0.40). We found a significant correlation between CMTM6 and PD-L1, which was higher in the stroma (R² = 0.51) than in tumor cells (R² = 0.35). In our retrospective NSCLC cohort, neither CMTM6 nor PD-L1 expression alone significantly predicted immunotherapy outcomes. However, high CMTM6 and PD-L1 coexpression in the stromal and CD68 compartments (adjusted hazard ratio = 0.38, p = 0.03), but not in tumor cells (p = 0.15), was significantly associated with longer overall survival in treated patients but was not observed in the absence of immunotherapy.ConclusionThis study supports the mechanistic role for CMTM6 in stabilization of PD-L1 in patient tumors and suggests that high coexpression of CMTM6 and PD-L1, particularly in stromal immune cells (macrophages), might identify the greatest benefit from programmed cell death 1 axis blockade in NSCLC.     

Clinical Correlates of Measured and Predicted Resting Energy Expenditure in Patients with Anorexia Nervosa: A Retrospective Cohort Study

Resting energy expenditure (REE; i.e., the calorie amount required for 24 h during a non-active period) is an important parameter in nutritional rehabilitation of patients with anorexia nervosa (AN). This study determined whether age, body mass index, AN duration/subtype/specific symptoms/clinical severity, cognitive function alterations, and psychiatric comorbidities influenced REE or the difference between the calculated and estimated REE. Patients with AN who were followed at a daycare treatment facility between May 2017 and January 2020 (n = 138) underwent a complete assessment that included the MINI, Eating Disorder Examination Questionnaire, d2 test of attention, body fat composition by bioelectrical impedance analysis (BIA) and REE measurement by indirect calorimetry (REE_IC). AN subtype (N = 66 for restrictive subtype and N = 69 for non-restrictive subtype; p = 0.005), free-fat mass (<0.001), and fat mass (<0.001) were associated with REE_IC. Age (p < 0.001), height (p = 0.003), and AN duration (N = 46 for <3 years and N = 82 for ≥3 years; p = 0.012) were associated with the difference between estimated REE (using the Schebendach equation) and measured REE_IC. Therefore, the Schebendach equation was adjusted differently in the two patients’ subgroups (AN duration ≤ or >3 years). Overall, REE was higher in patients with restrictive than non-restrictive AN. In the absence of BIA measures, REE-estimating equations should take into account AN duration.     

Cadaver dissection for oculoplastic procedures: A beginner’s guide

The purpose of this article is to form a basic guide for beginning the cadaver dissection training programs focused on oculoplastic surgical procedures. Ours was a collaborative study between the departments of Ophthalmology and Anatomy in a tertiary care teaching institute. We formed a step-wise approach to begin the cadaver dissection focused on the oculoplastic surgical procedures. The basics of cadaver procurement, processing, and preparation for dissections were described. The operative requirements of trainees, surgical handling of cadavers, and basic oculoplastic surgical steps were discussed. The types of embalming (cadaver preservation process) and steps have been described in detail. We have emphasized the preoperative discussion about the proposed dissections using standard teachings and skull models for easier understanding. Additional helping tools like soft embalming and injectable substances for better intra-dissection understanding (intra-arterial, intravenous and orbital injections) have been described. Post-dissection cadaver handing and soft-tissue disposal protocols have also been described. Overall, the cadaver dissections provide holistic surgical learning for the residents, specialty trainees, and practitioners. This article may act as a basic step-wise guide for starting the cadaver-based oculoplastics lab dissection in various institutes and workshops.