Azithromycin resistance and its molecular characteristics in Neisseria gonorrhoeae isolates from a tertiary care centre in North India

Treatment guidelines for management of uncomplicated gonorrhoeae have been recently modified owing to alarming upsurge in azithromycin resistance. This study investigated the prevalence and genetic determinants of gonococcal azithromycin resistance in India. Four (5.7%) of 70 gonococcal isolates were resistant to azithromycin. Of 16 isolates investigated for molecular mechanisms of resistance, 13 (81.3%) and 6 (37.5%) isolates exhibited mutations in coding and promoter regions of mtrR gene, respectively. However, ermA, ermB and ermC genes or mutations in rrl gene were absent in all isolates. Azithromycin resistance is low in India posing no immediate threat to use of dual-therapy for syndromic management.     

1,450 nm Long-Pulsed Diode Laser for Nonablative Skin Rejuvenation

Background:. There has been growing patient demand for laser technology to treat rhytids and to refine skin texture without the associated lifestyle hindrance common to ablative cutaneous procedures. Nonablative laser systems have been developed to meet this need and, in many instances, have replaced ablative lasers as the preferred treatment modality.
Objective:. To review long-pulsed diode laser technology in the treatment of a variety of cutaneous disorders.
Materials and Methods. All publications involving 1,450 nm long-pulsed diode laser technology were reviewed and discussed.
Results. The latest generation of nonablative lasers, in the midinfrared electromagnetic spectrum, selectively targets and heats dermal tissue to stimulate collagen remodeling while sparing the epidermis.
Conclusions. Demonstrating efficacy in the treatment of a wide range of cutaneous disorders, including facial rhytids, acne vulgaris, and atrophic scars, the 1,450 nm diode laser is a useful addition to the nonablative laser armamentarium.     

Laparoscopic total radical hysterectomy by the Pune technique: our experience of 248 cases

STUDY OBJECTIVE: To describe our experience and technique of total laparoscopic radical hysterectomy with pelvic lymphadenectomy, which is the largest single- institution study. DESIGN: Retrospective, nonrandomized study (Canadian Task Force classification II-2). SETTING: Private hospital. PATIENTS: Two hundred forty-eight patients with International Federation of Gynecology and Obstetrics stage IA2 (n = 32) and IB1 (n = 216) of cancer of the cervix. INTERVENTION: Total laparoscopic type III radical hysterectomy with bilateral pelvic lymphadenectomy was done. Simple repetitive steps were used to perform this surgery and develop an easily replicable technique. Harmonic Shears, bipolar coagulation, and vascular clips were used. Resection of the cardinal and uterosacral ligaments was performed with LigaSure (LigaSure Vessel Sealing System; Valleylab, Tyco Healthcare, Boulder, CO) or the Harmonic Shears (Ethicon Endo-Surgery, Inc., Cincinnati, OH). Pelvic lymph node dissection was done. MEASUREMENTS AND MAIN RESULTS: Histopathologically, there were 183 (73%) cases of squamous carcinoma, 52 (20%) adenocarcinomas, and 13 (5%) adenosquamous carcinomas. Four patients needing anterior exenteration because of bladder involvement were excluded from data analyses. The operation was performed entirely by laparoscopy in all patients and by the same surgical team. The patients' median age was 61 years. The median operative time was 92 minutes (range 65-120 minutes). The median number of resected pelvic nodes was 18. The median blood loss was 165 mL. The median length of stay was 3 days. All 15 intraoperative complications were tackled laparoscopically. No patients were converted to the open technique. There were no deaths in our series. Seventeen patients had complications within 2 months of surgery. Seven patients had recurrences after a median follow-up of 36 months. CONCLUSION: Our technique of total laparoscopic radical hysterectomy, developed over 248 cases, can be performed safely. It is an easily replicable technique. This procedure reduces the morbidity associated with abdominal radical hysterectomy. All of the complications can also be tackled laparoscopically, which does not further add to the morbidity.     

Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers

Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer surgery in humans remain speculative. Methods: We examined the expression of three estrogen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle. Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells and density. Results: We found no differences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as periovulatory versus perimenstrual. Conclusions: Our findings do not support a variation in c-erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.     

Antifungal potential of disulfiram.

Disulfiram, an alcohol antagonistic drug has been on the market since 1949 with 80% bioavailability and an established safety profile. Recently it has been reported as a P-glycoprotein efflux pump modulator. Herein we report its antifungal potential. The MIC50 and MIC90 of disulfiram for yeast isolates is 4 and 8 microg/ml, respectively, and the MIC range is 1-16 micro g/ml for both fluconazole sensitive and resistant strains. Interestingly, disulfiram also showed fungicidal activity on Aspergillus spp. with MIC50 and MIC90 of 2 and 8 microg/ml, respectively.     

Other genomic disorders and congenital heart disease

Congenital heart disease (CHD) is the common birth defect worldwide. Despite its recognized burden on public health, the etiology in the vast majority of individuals remains unknown. Chromosomal abnormality plays an important role, frequently observed as large cytogenetically visible rearrangement or small submicroscopic structural variation in the genome. Several genomic disorders are now recognized that are increasingly responsible for CHD with variable penetrance. Single gene disorders, epigenetic alterations, and environmental etiologies are also significant contributors. Our understanding of the genetic basis of CHD has increased exponentially with the escalating use of next generation sequencing to identify ever so small submicroscopic genomic imbalances at the level of coding exons in CHD. This review focuses on genomic disorders other than 22q11.2 deletion, that are major players in the etiology of human cardiac malformations.     

Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling.

Although Hedgehog (HH) signaling plays a critical role in patterning the ventral midbrain, its role in early midbrain specification is not known. We examined the midbrains of sonic hedgehog (Shh) and smoothened (Smo) mutant mice where HH signaling is respectively attenuated and eliminated. We show that some ventral (Evx1+) cell fates are specified in the Shh-/- mouse in a Ptc1- and Gli1-independent manner. HH-independent ventral midbrain induction was further confirmed by the presence of a Pax7-negative ventral midbrain territory in both Shh-/- and Smo-/- mice at and before embryonic day (E) 8.5. Midbrain signaling centers are severely disrupted in the Shh-/- mutant. Interestingly, dorsal markers are up-regulated (Wnt1, Gdf7, Pax7), down-regulated (Lfng), or otherwise altered (Zic1) in the Shh-/- midbrain. Together with the increased cell death seen specifically in Shh-/- dorsal midbrains (E8.5-E9), our results suggest specific regulation of dorsal patterning by SHH, rather than a simple deregulation due to its absence.