Management of difficult airway by retrograde tracheal intubation

A case of difficult intubation is presented in a patient of adenoid cystic carcinoma with a large right-sided facial defect. She was managed with radiotherapy and a myocutaneous flap reconstruction was done with retrograde tracheal intubation     

Neural coding of nociceptive stimuli—from rat spinal neurones to human perception

Translational studies are key to furthering our understanding of nociceptive signalling and bridging the gaps between molecules and pathways to the patients. This requires use of appropriate preclinical models that accurately depict outcome measures used in humans. Whereas behavioural animal studies classically involve reports related to nociceptive thresholds of, for example, withdrawal, electrophysiological recordings of spinal neurones that receive convergent input from primary afferents permits investigation of suprathreshold events and exploration of the full-range coding of different stimuli. We explored the central processing of nociceptive inputs in a novel parallel investigation between rats and humans. Using radiant laser pulses, we first compared the electrophysiological responses of deep wide dynamic range and superficial nociceptive-specific neurones in the rat dorsal horn with human psychophysics and cortical responses. Secondly, we explored the effects of spatial summation using laser pulses of identical energy and different size. We observed 3 main findings. Firstly, both rodent and human data confirmed that neodymium–yttrium aluminium perovskite laser stimulation is a nociceptive-selective stimulus that never activates Aβ afferents. Secondly, graded laser stimulation elicited similarly graded electrophysiological and behavioural responses in both species. Thirdly, there was a significant degree of spatial summation of laser nociceptive input. The remarkable similarity in rodent and human coding indicates that responses of rat dorsal horn neurones can translate to human nociceptive processing. These findings suggest that recordings of spinal neuronal activity elicited by laser stimuli could be a valuable predictive measure of human pain perception.     

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Levels and Its Association with Renal Allograft Rejection

Background: CCL2 is a chemoattractant for monocytes/macrophages, T cells, and natural killer cells. It is shown to be involved in the immunological responses against renal allograft. This study was conducted to access the role of urinary CCL2 expression in predicting the rejection episodes in renal transplant patients.

Method: A total of 409 urine samples included in this study. The samples were consisted of (a) biopsy-proven graft rejection (n = 165); (b) non-rejection (n = 93); (c) non-biopsy stable-graft (n = 42), and (d) healthy renal donors (n = 109). The samples were quantified for the CCL2 using the MCP-1/CCL2 ELISA kit. The data were analyzed using the Statistical Package for Social Sciences (SPSS^®) and MedCalc^® statistical software.

Results: Results showed that the CCL2 levels were significantly increased in rejection group when compared with the non-rejection, stable-graft, and control, P < 0.05. The receiver operating curve’s characteristics illustrated that the urinary CCL2 level is a good predictor for graft rejection, with an area under the curve of 0.81 ± 0.03 with optimum sensitivity and specificity of 87% and 62%, respectively, at a cut-off value of 198 pg/mL. Kaplan–Meier curve also showed better cumulative rejection-free graft survival time in group with less than 198 pg/mL of CCL2 as compared to those with expression levels of more than 198 pg/mL (30 weeks vs. 3 weeks; log-rank test, P < 0.001).

Conclusion: In our study, noninvasive investigation of CCL2 levels in urine has showed potential to predict rejection episodes. It is suggested that the CCL2, with others markers, may help in early detection and monitoring of graft rejection episodes.     

Carcinogenesis of PIK3CA

PIK3CA is the most frequently mutated oncogene in human cancers. PIK3CA is phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha. It controls cell growth, proliferation, motility, survival, differentiation and intracellular trafficking. In most of human cancer alteration occurred frequently in the alpha isoform of phosphatidylinositol 3 kinase. PIK3CA mutations were most frequent in endometrial, ovarian, colorectal, breast, cervical, squamous cell cancer of the head and neck, chondroma, thyroid carcinoma and in cancer family syndrome. Inhibition of PI3K signaling can diminish cell proliferation, and in some circumstances, promote cell death. Consequently, components of this pathway present attractive targets for cancer therapeutics. A number of PI3K pathway inhibitors have been developed and used. PI3K inhibitors (both pan-PI3K and isoform-specific PI3K inhibitors), dual PI3K-mTOR inhibitors that are catalytic site inhibitors of the p110 isoforms and mTOR (the kinase component of both mTORC1 and mTORC2), mTOR catalytic site inhibitors, and AKT inhibitors are the most advanced in the clinic. They are approved for the treatment of several carcinomas.     

Pharmacological effects of Artocarpus lakoocha methanol extract on inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway

ContextArtocarpus lakoocha Roxb. (Moraceae) is reported to possess antioxidant, anti-inflammatory, and anti-skin ageing agents.ObjectiveThis study evaluates the pharmacological effects of A. lakoocha leaves methanol extract on enzymes involved in the cholesterol synthesis pathway in high-fat diet-induced hyperlipidemic rats.Materials and methodsTwenty-four male Wistar rats, weighing approximately 180–220 g, were divided into four groups: control, diseased (hyperlipidemic), A. lakoocha leaves extract treated, and simvastatin treated. The rats were fed with high-fat diet for 2 months to induce hyperlipidaemia, afterward, experimental groups received A. lakoocha leaves methanol extract (250 mg/kg) and simvastatin (10 mg/kg) orally until the 89^th day of the experiment, while the diseased group continued to receive high-fat diet along with normal saline.ResultsIt was found that A. lakoocha extract significantly lowered the serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) levels, while effectively increasing serum high-density lipoprotein (HDL) levels as compared to the diseased group (p ≤ 0.05). The mRNA expression levels of squalene synthase and HMG-CoA reductase were found to be effectively down-regulated after the treatment with A. lakoocha leaves extract (17.45 ± 2.48 vs. 31.91 ± 5.292 and 5.85 ± 3.164 vs. 37.37 ± 6.492) and simvastatin (7.148 ± 0.76 vs. 31.91 ± 5.292, and 3.098 ± 2.09 vs. 37.37 ± 6.492) as compared to the diseased group.Discussion and ConclusionsThe results suggested that A. lakoocha leaves extract have observable beneficial effects on inhibition of enzymes involved in cholesterol synthesis pathway and improve lipid profile analogous to simvastatin.     

The hidden burden of HIV in the undocumented immigrant population of the United States

In the United States, approximately 1.1 million people have HIV, and 15% of them are unaware of their disease. The United States has one of the larger populations of undocumented residents in the world. These undocumented residents pose an equal risk of HIV infection and transmission as U.S. citizens. Migration status, strict policies, fear of deportation, and low-income status prevents these individuals from seeking HIV screening and treatment options.For the United States to achieve robust HIV prevention and treatment, more organizations and services are needed to address HIV infections and transmissions among undocumented residents.     

A survey of infection control practices of consultant anaesthesiologists in teaching hospitals of pakistan

Objective: To determine the infection control practices of Anaesthesiologist in the teaching hospitals of Pakistan. Study Design: Cross-sectional survey. Place and Duration of Study: The survey was conducted from January 2002 to December 2002 in Combined Military Hospital Quetta. The survey was closed after allowing 6 months for return of the replies. Subjects and Methods: A questionnaire was distributed to 170 consultant anaesthesiologist randomly selected from all over Pakistan. Out of these, 90 (53%) were returned and analyzed. To reduce self-report bias, the forms were filled anonymously. Results: Thirty four percent of the respondents always used masks, and only 9% used gloves in their every day practice. Only 18% of respondents stated that they always washed their hands after every patient contact and 54% reported that they always used aseptic technique for placing an indwelling cannula. Most respondents had a good knowledge of universal precautions for prevention of occupational transmission of infection. Five percent of the anaesthetists reported frequently or always reusing syringes for more than one patient. The practice of reusing syringes was significantly greater when the same consultants were anaesthetizing patients in private clinics rather than in their primary institutions (p < 0.01). On a scale of 0 - 10 (10 = high), anaesthesiologist rated their potential for contributing to transmission of infection as>5, in 58% of cases. Conclusion: Whereas most responding anaesthesiologist exhibit appropriate infection control behaviour, there are several potentially hazardous practices that continue unabated.     

Brain death and related issues

Concerns about the erroneous diagnosis of death and premature burial have been expressed from times immemorial. Patients with brain stem death have absolutely no chance of recovery. brain death is considered at par with death in most of the countries. General public in most parts of the world shows reluctance to accept this concept due to different social, cultural and religious backgrounds and state of literacy and awareness. The criteria for the diagnosis of brain death have been established which include certain pre-conditions, exclusions and tests of the brain stem function. These criteria are universally accepted. The criteria in children are somewhat different from the adults. The subject is intimately related with organ transplantation. If the patient is registered as organ donor or the family consents, organs can be harvested from brain dead patients for transplantation. Pakistan is amongst the few countries where no legislation exists to accept brain death as being at par with death of an individual, and to facilitate and regulate, cadaveric organ donation and transplantation.     

PTPRJ haplotypes and colorectal cancer risk

Recent studies from mouse mapping studies for cancer susceptibility have successfully led to the identification of a handful of susceptibility genes. Ptprj was identified as a strong candidate gene for mouse locus susceptibility to colorectal cancer 1, and one variant, rs1566734, showed evidence of preferential allelic imbalance in human colorectal tumors. Haplotypes in human PTPRJ have also been associated with protective effects for breast cancer risk. To determine if variants or haplotype in PTPRJ confer protective or risk effects for colorectal cancer (CRC), we genotyped rs1566734 and six additional PTPRJ haplotype tagging single nucleotide polymorphisms (SNP) in CRC cases and controls from the Molecular Epidemiology of Colorectal Cancer study. There was no evidence for cancer risk with rs1566734 in 1,897 cases and 1,954 controls with a homozygote odds ratio of 1.09 and 95% confidence interval of 0.85 to 1.39. The 6 tagging SNPs resulted in 6 main haplotypes (frequencies, >1%). None of the six tagSNPs individually showed significant evidence for risk; however, rs1503185 showed a nonsignificant protective effect. One haplotype was overrepresented in cases compared with controls, corresponding to a 34% increase in risk CRC, but there was no significant difference overall in haplotype frequencies between cases and controls (global test P statistic=0.19). From this study, we observe no significant increase in risk for human CRC with variants or haplotypes in PTPRJ. Additional studies are warranted to study possible PTPRJ-interacting loci, which are observed with Scc1 in the mouse models for CRC susceptibility.