The preventative analgesic effect of preincisional peritonsillar infiltration of two low doses of ketamine for postoperative pain relief in children following adenotonsillectomy. A randomized, double-blind, placebo-controlled study

Background:  In literature, the use of ketamine for the preventative analgesia in the management of postoperative pain is controversial. The purpose of the present study was the clinical assessment of the efficacy of preincisional peritonsillar infiltration of two doses of ketamine on postoperative pain relief compared with peritonsillar saline in children undergoing adenotonsillectomy.
Methods/materials:  Seventy-five ASA physical status I and II patients, aged 3–12 years, scheduled for adenotonsillectomy were enrolled in this randomized, double-blind, placebo-controlled study. Patients were divided into three groups of 25 each and received a local peritonsillar infiltration of 0.9% saline (group S), ketamine 0.5 mg·kg⁻¹ (group K1), or ketamine 1 mg·kg⁻¹ (group K2). All medications were 2 ml in volume which was applied 1 ml per tonsil 3 min prior to tonsillectomy. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale were used to evaluate pain levels and sedative conditions, respectively.
Results:  Group S had significantly higher CHEOPS scores than group K1 and K2. Both K1 and K2 groups had comparable scores, which were not statistically significant ( P  > 0.05). During 24 h after surgery, 16 patients in group S and no patients in groups K1 or K2 needed analgesics ( P  <   0.001).
Conclusions:  A 0.5 or 1 mg·kg⁻¹ dose of ketamine given at approximately 3 min before surgery by peritonsillar infiltration provides efficient pain relief during 24 h after surgery without side-effects in children undergoing adenotonsillectomy.     

Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.     

Patient suitability and outcome in short-term individual psychotherapy

The effects of short-term (time-limited), dynamically oriented individual therapy and the patient characteristic quality of object relations (QOR) were studied in a controlled clinical trial involving 8 experienced therapists and 144 psychiatric outpatients. A comprehensive set of outcome scores was monitored at 5-month intervals including a follow-up assessment. A strong treatment effect that was maintained at follow-up was found. The effect was evident in terms of statistical significance, effect size, and clinical significance. Evidence for an additive effect of the combination of treatment and QOR was also found. The best results were attained by high QOR therapy patients, and the worst results were attained by low QOR control patients. The results were suggestive of an optimal match between type of patient and type of therapy.     

Injecting drug users in Bangladesh: prevalence of syphilis, hepatitis, HIV and HIV subtypes.

Injecting drug users (IDU) were enrolled from two detoxification clinics and two needle/syringe exchange programmes (NEP) in central and northwest Bangladesh. Syphilis, hepatitis C and HIV rates were highest in IDU from the NEP of central Bangladesh (23, 66.5 and 1.4%, respectively), whereas current hepatitis B infection rates were highest in IDU from the NEP of northwest Bangladesh (12%). Five HIV strains were subtype C and one E/B. The 32 base pair (bp) deletion of the CCR5 gene was not detected.     

Dppa2 and Dppa4 are closely linked SAP motif genes restricted to pluripotent cells and the germ line

Despite the enormous medical potential of ESCs, the molecular mechanisms conferring the ability to differentiate into all cell types of the embryo remain elusive. We used an in silico approach to identify genes expressed exclusively in mouse preimplantation embryos and pluripotent cell lines. Two of these genes were developmental pluripotency-associated gene 2 (Dppa2) and Dppa4, which we show are closely linked genes encoding putative nuclear SAP domain proteins expressed in human and mouse pluripotent stem cells and germ cell tumor-derived embryonal carcinoma cells. In the mouse, these genes are transcribed in germinal vesicle-stage oocytes and throughout the cleavage stages of embryogenesis. They then become restricted to the pluripotent inner cell mass of blastocysts and are subsequently downregulated. After gastrulation, Dppa2 and Dppa4 are expressed only in the developing germ line, showing that these genes mark cells of the pluripotent cycle. In the germ line, both genes are downregulated as the germ cells commit to the oogenic pathway or soon after commitment to the spermatogenic pathway. We have observed similar germ line expression profiles for other pluripotent markers, and these results are consistent with the hypothesis that pluripotent markers must be downregulated during fetal germ line development, a process that may be required to facilitate appropriate germ line differentiation. The study of expression and function of pluripotent markers such as Dppa2 and Dppa4 is likely to unveil new aspects of the regulation of pluripotency and germ line development in mammals.     

Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer

Background: Resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether the benefit is consistent for BRAF V600E mutant (MT) and wild type (WT) mCRC. This retrospective analysis explores the influence of BRAF MT on survival after metastasectomy. Methods: Overall survival (OS) and recurrence-free survival (RFS) for BRAF MT and WT mCRC were evaluated. Survival was also analyzed in the cohort of BRAF MT with or without metastasectomy. Results: Five hundred and thirteen patients who had undergone metastasectomy were identified, 6% were BRAF-MT. Median age 63. Median OS in BRAF MT vs WT: 25.7 vs 48.5 months (hazard ratio [HR] 1.95; 1.18-3.22). However, difference was not significant in a multivariate model. Right primary tumor, intact primary, >1 metastatic site, non-R0 resection, peritoneal metastasis, and synchronous metastasis were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 vs 19 months, p=0.09). In another cohort of 158 BRAF-MT patients, OS was significantly better after metastasectomy compared to “no metastasectomy” (HR 0.34; 0.18-0.65, P= 0.001). Proficient mismatch repair status showed a trend toward worse survival after metastasectomy in BRAF MT (HR 1.71, P = 0.08). Conclusion: OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Median OS was >2 years in this study after metastasectomy among BRAFV600E MT patients suggesting a survival benefit of metastasectomy in this group where systemic therapeutic options are limited. Metastasectomy may be considered in carefully selected BRAF-MT patients.