Combined Procedures with Laparoscopic Cholecystectomy

With advancement in laparoscopic surgery a number of surgical procedures can be performed combined with laparoscopic cholecystectomy in a single surgery. We evaluate the safety & efficacy of such surgeries. A retrospective review of all patients who had undergone combined procedures with laparoscopic cholecystectomy during January 2005 to June 2009 was performed. 3144 laparoscopic cholecystectomies were performed in the period from January 2005 to June 2009. Of these, 401 cases were combined with another procedure. The mean operative time was 80 min (range 50–270 min). The mean hospital stay was 3.2 days (range 1–5 days). The mean no. of days injectable analgesics was required was 2 days (range 1 day–4 days). Combined procedures provide patients with all the benefits of minimal invasive surgery and also give the benefit of single time anaesthesia without adding to post operative morbidity & hospital stay.     

Preclinical (1)H-MRS neurochemical profiling in neurological and psychiatric disorders

The ongoing development of animal models of neurological and psychiatric disorders in combination with the development of advanced nuclear magnetic resonance (NMR) techniques and instrumentation has led to increased use of in vivo proton NMR spectroscopy ((1)H-MRS) for neurochemical analyses. (1)H-MRS is one of only a few analytical methods that can assay in vivo and longitudinal neurochemical changes associated with neurological and psychiatric diseases, with the added advantage of being a technique that can be utilized in both preclinical and clinical studies. In this review, recent progress in the use of (1)H-MRS to investigate animal models of neurological and psychiatric disorders is summarized with examples from the literature and our own work.     

Does the association with diabetes say more about schizophrenia and its treatment?--the GLUT hypothesis

All effective anti psychotic drugs block glucose transporter proteins (GLUTs), peripherally and in the brain. These drugs are implicated in hyperglycaemia as demonstrated in mouse and human studies. Clozapine is the strongest blocker, with Haloperidol the weakest.The GLUT hypothesis suggests that schizophrenia is partly due to poor functioning of brain glucose transporters (GLUT 1 and 3). Neuronal glucose malnutrition could result in excessive neuronal pruning (so called Crow’s Type 2 with a predominance of negative symptoms) or result in recurrent/ineffective pruning (Type 1 with positive symptoms).GLUT blockade by anti psychotic agents could assist Type 1 patients to complete the pruning process by deactivating already damaged neurones and circuits, but will make Type 2 patients more cognitively impaired.Future treatment options are discussed in line with the above formulation.     

儿童腹部囊性肿块CT分析

目的分析儿童腹部囊性肿块CT特征。方法分类统计临床病理证实的101例儿童腹部囊性肿块,总结其CT特征。结果①真性囊肿30例（29．7％）,其CT表现相似。②假性囊肿14例（13．8％）,其中胰腺假性囊肿11例、脑脊液假性囊肿3例,CT表现各异。③囊性畸形26例（25．7％）,其中肠系膜囊肿8例,网膜囊肿4例,胃肠道重复畸形3例,胆总管囊肿9例,脐尿管囊肿2例,其CT表现多呈光滑的囊性肿块。④囊性肿瘤24例（23．8％）,其中囊性畸胎瘤13例,多发生在腹膜后、卵巢和骶尾部;浆液性和粘液性囊腺瘤各4例,发生在卵巢和胰腺,4例浆液性囊腺瘤CT呈微腔肿瘤,4例粘液性囊腺瘤CT呈大囊病灶;2例肝脏间充质错构瘤,CT呈低密度多房性肿块;1例多房性囊性肾瘤,CT呈边界清楚、厚度不均的多分隔肿块。⑤腔道积水、积脓7例（6．9％）,其中单侧肾积水5例,阑尾脓肿2例。结论儿童腹部最常见囊性肿块是真性囊肿,其次是囊性畸形、囊性肿瘤和假性囊肿,其CT表现各有特征。     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Smarter screening for prostate cancer: for the few, not the many? A stratified approach based on baseline risk

Evaluation of: van Leeuwen PJ, Connolly D, Tammela TLJ et al. Balancing the harms and benefits of early detection of prostate cancer. Cancer 116(20), 4857-4865 (2010). Prostate cancer screening remains controversial, with different countries taking different views on its value. We review the study by van Leeuwen and colleagues, evaluating the risk-benefit ratio for screening from the European Randomized study of Screening for Prostate Cancer (ERSPC) stratified by age and serum prostate-specific antigen level at study entry. Though the overall results from the ERSPC demonstrated a 20% relative reduction in prostate cancer mortality in the screened arm, the current study demonstrated that the benefit was minimal for men aged 55-74 years with a serum prostate-specific antigen <4 ng/ml and came at the expense of significant overdiagnosis and overtreatment. This study adds to the growing body of evidence that prostate cancer screening works, but not for everyone, and suggests a smarter strategy of targeted screening to those most at risk from prostate cancer mortality.     

HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in the cysteine-rich domain and block extracellular Tat efficiently

Tat, an important regulatory protein of HIV-1, has been implicated in HIV-related pathogenesis. Immune responses to Tat, although underrepresented, confer protection against disease progression, in natural infection and experimental immunization, making Tat an attractive vaccine candidate. Information on immune responses to Tat from India which has the second largest HIV incidence has been lacking. Here we report a cross-sectional study evaluating the humoral response to Tat from a large number of samples from two southern states of India. 14% of the seropositive (63/447) and 4.6% of seronegative samples (7/150) harbored Tat-reactive antibodies. A significant number of the seropositive samples contained high levels of anti-Tat antibodies (31/447) which demonstrated class-switch to IgG1 and bound to Tat with high avidity. Cross-reactivity analysis showed that these antibodies interacted with Tat from different clades with variable degree withthe highest interaction with subtype-AE and the least with subtype-B Tat. Importantly, a B-cell epitope in the cysteine-rich domain was found to be the most immunodominant one and antibodies interacting with this epitope blocked extracellular Tat efficiently. To the best of our knowledge this is the first report on immune responses to Tat from Indian populations and the data presented here could significantly contribute to HIV Tat vaccine design.