Genetic and environmental influences on the rate of progression to alcohol dependence in young women

Background: The development of alcohol dependence (AD) involves transitions through multiple stages of drinking behaviors and is shaped by both heritable and environmental influences. We attempted to capture this dynamic process by characterizing genetic and environmental contributions to the rate at which women progressed through 3 significant transitions along the pathway to AD: nonuse to initiation, initiation to onset of first alcohol‐related problem, and first problem to onset of AD. Methods: The sample consisted of 3,546 female twins from the Missouri Adolescent Female Twin Study. Participants ranged in age from 18 to 29 years. Retrospective reports of alcohol use histories were collected by telephone diagnostic interview and transition times between drinking milestones were coded ordinally. Standard genetic analyses were conducted in Mx to derive a trivariate model that provided estimates of genetic and environmental influences that were common as well as specific to the 3 transition times. Results: Heritable influences were found for rate of progression across all 3 transitions, accounting for 30 to 47% of the variance in transition times. Shared environmental contributions were evident only in rate of progression from nonuse to initiation (i.e., age at first drink). Heritable contributions to the rate of movement through successive drinking milestones were attributable to a common factor, whereas environmental influences were transition‐specific. Conclusions: The current study is unique in its use of a genetically informative design to document the rate of movement between drinking milestones in a female sample and to examine genetic contributions to multiple transition times over the course of AD development. Results indicate that an earlier report of heritability for males in rate of progression from regular drinking to AD generalizes to women and to other alcohol stage transitions. Findings also suggest the need to consider stage‐specific environmental contributions to alcohol outcomes in developing interventions.     

Orbital apex osteodural fistula - An unusual surgical access

Dural arteriovenous fistulas (DAVFs) are fistulas connecting the branches of dural arteries to dural veins or a venous sinus. Osteodural fistulas are a rare subset of this group of diseases. We wish to report a rare case of an osteodural arteriovenous fistula at the foot of the superior ophthalmic vein (SOV), treatment of which required an unusual surgical approach via the orbit and SOV. Though access for endovascular treatment via the SOV for treatment of caroticocavernous fistulas is reported, the external approach is relatively infrequently performed, outside Europe and the Americas, with this being the first reported procedure from the Indian subcontinent. We wish to explain the steps of this unusual surgical access and highlight the salient precautions and pitfalls in the technique.     

Safety and efficacy of Ahmed glaucoma valve implantation in refractory glaucomas in Northern Indian eyes

Purpose

To evaluate the safety and efficacy of Ahmed glaucoma valve (AGV) implantation in refractory glaucoma in Northern Indian eyes.

Background

The success rate of trabeculectomy remains low in cases of refractory glaucoma even with the use of antifibrotics. Glaucoma drainage devices have proven to be more efficacious in reducing intraocular pressure (IOP) in these glaucomas.

Methods

Retrospective records of 55 consecutive patients who underwent AGV implantation at Dr. Shroff’s Charity Eye Hospital, New Delhi, India from January 2003 to December 2012 were reviewed. Pre-operative data included age, gender, eye laterality, specific diagnosis, number of anti-glaucoma medications, number of prior incisional surgeries, visual acuity and IOP on medical treatment. Postoperative data included visual acuity and IOP on day one, 1 week, 1 month, 3 months, 6 months, 1 year and yearly thereafter, number of anti-glaucoma medications, any complication or additional surgical intervention required. Success was defined as IOP >5 and <22 mmHg with or without treatment.

Results

Mean IOP decreased from 39.71 ± 8.99 pre-operatively to 17.52 ± 5.72 mmHg at last follow-up (p < 0.001) and number of medications reduced from 3.27 ± 0.84 to 1.25 ± 0.88 (p < 0.001). Visual acuity remained within one Snellen line or improved at last follow-up in 47 cases (85.4%). The cumulative probability of success was 85.45% at 1 year and 79.63% at 3 years. The incidence of post-operative complications was 25.45%.

Conclusion

AGV implantation has proven to be safe and is effective in controlling IOP in refractory glaucoma in Northern Indian eyes.     

Foreign body in ocular coats causing a pseudo optic nerve head shadow

Small intraocular foreign body in the outer coats of the eye may be wrongly interpreted as optic nerve head on ultrasound imaging. Such errors can be avoided by performing multiple sonography scans in different axes.     

In vitro Cytotoxicity of Methanol Extract from Aerial Parts of Aralia cachemirica and Purified Continentalic Acid

The present study was designed to evaluate the in vitro cytotoxic effect of methanol extract of aerial parts including stems, leaves and twigs of Aralia cachemirica and purified continentalic acid isolated from this extract against a panel of human cancer cell lines of varied tissues. Percentage of growth inhibition was evaluated by sulphorhodamine B assay. Purified continentalic acid showed moderate cytotoxicity against all the cell lines used. In contrast, the extract exhibited significant concentration dependant cytotoxicity against A-549 (lung), THP-1 (leukemia) and MCF-7 (breast) cell lines. This work highlights cytotoxic potential of this extract, which can further be explored for different constituents for their possible use autonomously or in combined manner in cancer therapy. The detailed analysis of their cytotoxicity has been presented in this paper.     

Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor

OBJECTIVE: The aim of this study was to assess the rate of upper gastrointestinal (UGI) ulcer complications (bleeding, perforation, or gastric outlet obstruction) associated with celecoxib, a specific COX-2 inhibitor, compared with the rate associated with nonspecific, nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: A pooled analysis was conducted of 14 multicenter, double-blind, randomized, controlled trials (RCTs) and a separate analysis of one long-term open label trial that assessed the efficacy and safety of celecoxib for symptomatic treatment of arthritis. The RCTs enrolled 11,008 patients with osteoarthritis or rheumatoid arthritis treated for 2-24 wk; the long-term open label trial enrolled 5,155 patients receiving celecoxib for a maximum of 2 yr. In the RCTs, patients were randomly assigned to receive placebo (n = 1,864; 208 patient-years), celecoxib 25-400 mg b.i.d. (n = 6,376; 1,020 patient-years), or a comparator NSAID (n = 2,768; 535 patient-years); NSAIDs were naproxen 500 mg b.i.d., diclofenac 50 or 75 mg b.i.d., or ibuprofen 800 mg t.i.d.). In the long-term, open-label trial, patients received celecoxib 100-400 mg b.i.d. for up to 2 yr (n = 5,155; 5,002 patient-years). The principal outcome measure of this analysis was development of a UGI ulcer complication, which was prospectively defined as bleeding, perforation, or gastric outlet obstruction. Ulcer complications were assessed and adjudicated by persons blinded to the patient's treatment assignment or the study in which the patient participated. RESULTS: In the RCTs, UGI ulcer complications occurred in no placebo patients (0 of 1,864 patients), in 2 of 6,376 celecoxib patients (0.03%), and in 9 of 2,768 patients receiving an NSAID (0.33%), corresponding to annual incidences of 0.20% for celecoxib (p > 0.05 vs placebo) and 1.68% for NSAIDs (p = 0.002 vs celecoxib and placebo). In the long-term open-label trial, nine UGI ulcer complications occurred, for an incidence of 0.17% and an annualized incidence of 0.18%. CONCLUSIONS: The incidence of UGI ulcer complications associated with celecoxib was 8-fold lower than with nonspecific NSAIDs. The incidence of ulcer complications observed in celecoxib-treated patients was similar to that in patients receiving placebo in the RCTs, and to that in non-NSAID users reported in the literature.     

Prevalent phenotypes and antibiotic resistance in Escherichia coli and Klebsiella pneumoniae at an Indian tertiary care hospital: plasmid-mediated cefoxitin resistance.

BACKGROUND: The beta-lactam antibiotics, in combination with aminoglycosides, are among the most widely prescribed antibiotics. However, because of extensive and unnecessary use, resistance to these drugs continues to increase. In recent years, resistance in the Indian bacterial population has increased markedly, the majority showing complex mechanisms. Due to increased transcontinental movement of the human population, it would be wise to know the prevalence and resistance complexity of these strains, well in advance, in order to formulate a policy for empirical therapy. METHODS: One hundred and eighty-one isolates of Escherichia coli and 61 isolates of Klebsiella pneumoniae obtained from 2655 non-repeat samples of pus (912) and urine (1743) were studied, and their resistance rates and patterns were noted. The isolates were analyzed for prevalent aminoglycoside and cephalosporin resistance phenotypes and for the presence of extended spectrum beta-lactamase (ESBL) and AmpC enzymes by spot-inoculation and modified three-dimensional tests developed in our laboratory. Fourteen isolates of E. coli and six of K. pneumoniae, resistant to all of the antibiotics tested, were selected for plasmid screening, curing, and transconjugation experiments, and for comparative evaluation of the double disk synergy test (DDST) and modified three-dimensional test (TDT) for detection of beta-lactamases. RESULTS: Urinary E. coli isolates showed maximum susceptibility to amikacin (57.1%), followed by tobramycin (38.5%) and gentamicin (31.9%). Eighteen (19.8%) isolates were susceptible to cefotaxime, whereas 11 (12.1%) were susceptible to ceftriaxone. The K. pneumoniae isolates from urine samples showed maximum susceptibility to tobramycin (63.6%) followed by amikacin (54.5%). Of the K. pneumoniae isolates, 31.8% were susceptible to cefotaxime and 13.6% were susceptible to ceftriaxone. A more or less similar trend of antibiotic susceptibility was noted in E. coli and K. pneumoniae isolates from pus samples. Twenty-six (14.4%) E. coli and 15 (24.6%) K. pneumoniae isolates were found to be ESBL-producers by NCCLS-ESBL phenotypic confirmatory test. Eighteen (9.9%) E. coli and 19 (31.1%) K. pneumoniae isolates were found to be AmpC enzyme-producers by our modified TDT. The simultaneous occurrence of ESBL and AmpC enzymes was noted in 7.7% and 9.8% isolates of E. coli and K. pneumoniae, respectively. CONCLUSIONS: The prevalence of multidrug-resistant bacterial isolates is quite high in our bacterial population. On comparative evaluation of DDST and TDT in resistant isolates, TDT was found to be the better method, detecting ESBLs in 80% of isolates compared to 15% with DDST. A 19.9-kb plasmid was consistently present in all the screened isolates of E. coli and K. pneumoniae, and was inferred to encode cefoxitin and tetracycline resistance based on curing and transconjugation experiments.