Laparoscopic Ablative and Reconstructive Surgeries in Genitourinary Tuberculosis

Background and Objectives:

Laparoscopy is the present standard of care for urologic diseases. Laparoscopy in renal tuberculosis (genitourinary tuberculosis) is difficult because of inflammation and fibrosis associated with the disease. We present the outcome of our experience of laparoscopy in genitourinary tuberculosis, both ablative and reconstructive.

Methods:

The detailed data of patients with genitourinary tuberculosis who underwent laparoscopic surgeries between January 2011 and September 2012 were reviewed. Indications, type of surgery, duration, blood loss, intraoperative problems, postoperative outcomes, and follow-up details were noted.

Results:

Overall, 7 laparoscopic procedures were performed: 5 nephrectomies, 1 ureteric reimplantation with psoas hitch, and 1 combined nephrectomy and laparoscopy-assisted Mainz II pouch reconstruction. The mean operative time was 192 minutes for nephrectomy, 210 minutes for ureteric reimplantation, and 480 minutes for nephrectomy with Mainz II pouch reconstruction. There were no conversions to open surgery. The mean amount of blood loss was 70 mL for the nephrectomies, 100 mL for ureteric reimplantation, and 200 mL for nephrectomy with Mainz II pouch reconstruction. In 5 of 6 patients who underwent nephrectomy, there was severe perinephric and peripelvic fibrosis posing difficulty in dissection. However, the renal vessels could be controlled individually. The mean postoperative hospital stay was 3 days for the nephrectomies, 5 days for the ureteric reimplantation, and 10 days for the nephrectomy with Mainz II pouch reconstruction. In all cases the recovery was uneventful.

Conclusions:

Laparoscopy, though technically more demanding, is a feasible and safe option for ablative and complex reconstructive procedures in genitourinary tuberculosis. It offers the benefits of minimally invasive surgery. The difficulty with this procedure is mostly because of peripelvic and perinephric fibrosis, whereas the lower ureter and bladder are relatively easier to dissect.     

Effects of Surgical Stress on Early Nonspecific Immune Response in Children

Surgery alters the body’s homeostatic balance and defense mechanisms. In adults transient postoperative cellular and humoral immunosuppression after different degrees of operative stress has been reported. In children the immunologic consequences of operations are not elaborated. This study investigates the effect of minor and major surgery on early nonspecific immune response in terms of neutrophil counts and function. Forty-three children undergoing minor and major elective procedures were studied. Blood samples were collected before, immediately after, and 72 h after surgery. Total white cell count, differential neutrophil count, and neutrophil phagocytic function were studied using nitroblue tetrazolium test. Children were divided into two groups—group 1 underwent minor surgery and group 2 major surgery. In group 1 there was a significant drop in total counts after surgery, but in group 2 total counts were not affected. In both groups, the percentage of neutrophils increased immediately after surgery but fell to near or less than preoperative levels 72 h after surgery. However, the assessment of neutrophil functions by nitroblue tetrazolium test in both unstimulated and stimulated forms revealed it to be unchanged in group 1. In group 2 the unstimulated neutrophil function was elevated 72 h after surgery, whereas stimulated function was elevated immediately after surgery. Minor surgery does not alter the early nonspecific immune response. However, major surgery seems to induce a transient increase in neutrophil phagocytic activity.     

Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons

Dysregulation of the glutamatergic system and its receptors in medial prefrontal cortex (mPFC) has been implicated in major depressive disorder. Recent preclinical studies have shown that enhancing NMDA receptor (NMDAR) activity can exert rapid antidepressant-like effects. AGN-241751, an NMDAR positive allosteric modulator (PAM), is currently being tested as an antidepressant in clinical trials, but the mechanism and NMDAR subunit(s) mediating its antidepressant-like effects are unknown. We therefore used molecular, biochemical, and electrophysiological approaches to examine the cell-type-specific role of GluN2B-containing NMDAR in mediating antidepressant-like behavioral effects of AGN-241751. We demonstrate that AGN-241751 exerts antidepressant-like effects and reverses behavioral deficits induced by chronic unpredictable stress in mice. AGN-241751 treatment enhances NMDAR activity of excitatory and parvalbumin-inhibitory neurons in mPFC, activates Akt/mTOR signaling, and increases levels of synaptic proteins crucial for synaptic plasticity in the prefrontal cortex. Furthermore, cell-type-specific knockdown of GluN2B-containing NMDARs in mPFC demonstrates that GluN2B subunits on excitatory, but not inhibitory, neurons are necessary for antidepressant-like effects of AGN-241751. Together, these results demonstrate antidepressant-like actions of the NMDAR PAM AGN-241751 and identify GluN2B on excitatory neurons of mPFC as initial cellular trigger underlying these behavioral effects.Subject terms: Cellular neuroscience, Prefrontal cortex     

Mutational analysis of the RB1 gene in Indian patients with retinoblastoma

Twenty-one probands, twelve with bilateral and nine with unilateral retinoblastoma, were screened for mutations in the RB1 gene using genomic DNA from peripheral blood leukocytes as well as tumors. Amplification of individual exons and flanking regions of the RB1 gene were carried out, followed by direct sequencing of the amplified products. Sequences of affected individuals were compared with those of controls. Mutations were identified in seven patients, five with bilateral and two with unilateral retinoblastoma. Six out of seven mutations involved the formation of premature termination codons by means of single base substitutions (2), frameshifts due to splice-site mutations (2), or deletion and duplication (2). One missense mutation was identified. Of the remaining fourteen patients, seven with bilateral disease had no mutations in peripheral blood (7 cases) or tumors (3/7 cases). Analysis of the peripheral blood of seven patients with unilateral disease also showed no mutations. Mutations were detected in about one-third of the cases, suggesting that hemizygous deletions at the RB1 locus or mutations outside the coding regions of RB1 may be responsible for the disease in the remaining patients.     

Evaluation of a novel shape-based computational filter for lead evolution: application to thrombin inhibitors

A novel shape-feature-based computational method is described and used to rapidly filter compound libraries. The computational model, built using three-dimensional conformations of active and inactive molecules, consists of a collection of whole molecule shapes and chemical feature positions that are ranked according to their correlation with activity. A small ensemble of these shapes and features is used to filter virtual compound libraries. The method is applied to two thrombin data sets and is shown to be efficient in identifying novel scaffolds with enhanced hit rates.     

Improving basic health service delivery in low-income countries: 'voice' to the poor

Public social services, such as basic health care, represent the effective option for the poor, especially in the rural areas of low-income countries. The quality of such services are at present extremely deficient, largely due to resource constraints and lack of political will to make them function effectively. The state can no longer provide the comprehensive services it has in the past and which were highly successful in a number of 'high-achieving' developing countries. Yet, the state must turn priority attention to providing public services for the poor, in order to close the widening gap between rich and poor. It needs to do this in partnership with the population it aims to reach, through effective linkage with grass-roots organizations and with the support of non-governmental organizations. Giving 'voice' and participation to the population can not only increase the resource base for public services, but can also significantly improve the accountability of providers and lead to a cost-effective option for the poor.     

Brain biopsy in Creutzfeldt-Jakob disease: evolution of pathological changes by prion protein immunohistochemistry

The formation of protease-resistant prion protein (PrPsc) is considered to be an early event in the pathogenesis of Creutzfeldt-Jakob disease (CJD) and hence its demonstration in brain biopsies by immunohistochemistry is considered diagnostic. We analysed eight brain biopsies from the frontal cortex collected from different parts of India from cases diagnosed as CJD on clinical and pathological grounds for the expression of prion protein (PrP). The duration of illness in these cases varied from 2 months to 1 year. Immunohistochemistry was carried out on paraffin sections using two different clones (KG9 and 3F4) of monoclonal antibodies to PrP. Although all eight cases showed classical features of spongiform encephalopathy of varying severity, only five of the eight cases revealed PrP(sc) in the brain tissue. The immunolabelling was focal and all areas with spongiform change were not labelled. A temporal evolution in the staining pattern was evident - particulate diffuse labelling (synaptic type) in early stages (2 months), perivacuolar deposits in intermediate stages (5-6 months), and dense plaques in late stages (12 months).     

Effective and Sustainable Multimedia Education for Children With Asthma: A Randomized Controlled Trial

Traditional asthma education has been found to be time-consuming and limited in terms of availability. Our goal was to improve asthma care by meeting special needs of children with asthma and by building on their skills in using new technologies. Multimedia asthma education occurred through the viewing of short, animated vignettes on an exam room computer. Evaluation of 228 children showed significant improvement in days of asthma symptoms (p ??.01), in emergency room visits (p ??.05), in school days missed (p ??.05), and in days of activity limitation from baseline to the year-end follow-up (p ??.05). Effective multimedia education, if integrated into pediatric practice to supplement existing asthma care, can improve clinical outcomes.