TP53 codon 72 polymorphism and type 2 diabetes: a case-control study in South Indian population.

TP53 functions primarily as a tumor suppressor, controlling a myriad of signalling pathways that prevent a cell from undergoing malignant transformation. This tumor suppressive function requires an activation and stabilization of TP53 in response to cell stressors. However, besides its cancer-preventive functions, TP53 is also known to be involved in diverse cellular processes including metabolism, reproduction, stem cell renewal and development. Indeed, several lines of evidence strongly suggest that TP53 plays crucial role in diabetes. A number of studies have evaluated the association of genetic alterations (single nucleotide variations) in TP53 gene with the development of diabetes. However, the results have not been consistent. The aim of this study was to evaluate whether the C/G polymorphism at codon 72 (Pro72/Arg72), located in exon 4 of TP53, is associated with type 2 diabetes in South Indian population. A total of 74 type 2 diabetic patients and 54 non-diabetic subjects were screened. None of the three genotypes, namely C/C (Pro/Pro), C/G (Pro/Arg), and G/G (Arg/Arg) was found to be significantly associated with type 2 diabetes in our study group. The findings of this study indicate that TP53 codon 72 polymorphism is not associated with increased risk of type 2 diabetes in South Indian population. Further studies with a large cohort size would be necessary to corroborate the observations of this study. Nevertheless, this study represents the first genetic analysis of TP53 variants in South Indian type 2 diabetic patients.

Association of insulin resistance and leptin receptor gene polymorphism in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired glucose metabolism and insulin resistance. The objectives of the study were to evaluate the pattern of leptin receptor gene polymorphism Gln223Arg in T2DM and to identify its association with the serum leptin and insulin levels as well as with insulin resistance in diabetes. METHODS: In this cross-sectional study, genotyping of leptin receptor was done for Gln223Arg alleles by PCR-restriction fragment length polymorphism in 39 patients with type 2 diabetes. Serum leptin and insulin levels were assayed using enzyme linked sorbent assay in 39 cases and 45 nondiabetic controls. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. Statistical analysis was performed with Graph pad Instat version 3. RESULTS: Hardy-Weinberg Equilibrium for the leptin receptor (LEPR) gene variants showed that alleles were in equilibrium. Leptin levels were insignificantly low in patients with diabetes compared to those in controls. Women in the control group showed significantly higher leptin levels (p < 0.05) compared with men. There was a significant difference in the serum insulin levels and insulin resistance (HOMA-IR) among patients with different genotypes (p = 0.04 and p = 0.0378, respectively). CONCLUSION: Leptin receptor gene polymorphism affected glucose metabolism by altering insulin resistance and pancreatic beta cells. Thus, single-nucleotide polymorphism of LEPR may affect the pathogenesis of T2DM.

How effective is our current Orthopaedic Prioritisation Tool for scoring patients for arthroplasty surgery?

AIM: To compare those patients who are being accepted onto the waiting list for total hip and knee arthroplasty surgery with those patients who are being declined surgery, using a validated functional questionnaire. METHOD: The clinic records from all patients seen for consideration of total hip or knee arthroplasty at Hawkes Bay Hospital during the preceding four months were reviewed. We sent the Oxford Hip and Knee Score questionnaire to all patients who had been put forward for consideration of surgery. RESULTS: Of the 150 patients we surveyed, 81 had been accepted onto the waiting list and received a date for surgery within the next four months and 69 had been declined surgery. Of the 81 patients who had been accepted onto the waiting list for surgery, 61 returned the Oxford questionnaire with an average score of 10.9. Of the 69 patients who had been declined surgery, 59 returned the Oxford questionnaire with an average score of 10.8. Thus the mean Oxford score was not statistically different between those patients being accepted onto the waiting list for surgery and those being declined surgery (p=0.925). CONCLUSION: No difference was found between those patients being accepted onto the waiting list for total hip or knee arthroplasty and those being declined surgery in Hawkes Bay after using the Oxford Hip and Knee Score as a measure of functional impairment. The average Oxford score indicates that patients being seen in Hawkes Bay Hospital for consideration of total hip or knee arthroplasty are severely functionally impaired as a result of their condition.

The impact of the 6-month waiting target for elective surgery: a patient record study.

AIM: To quantify the number of patients declined surgery due to scoring below the financial threshold, when presenting for total hip or total knee arthroplasty at two New Zealand District Health Boards (DHBs). METHOD: Data from patients presenting with hip or knee osteoarthritis at both Whangarei Base Hospital and Hawke's Bay Regional Hospital from June 2012 to June 2013 were reviewed. Data were taken from hospital codes and patient records. The outcome from clinic visits were recorded as well as the patient's New Zealand Orthopaedic Association (NZOA) prioritisation score. RESULTS: A total of 1202 patient records were reviewed: 393 from Whangarei Base Hospital and 809 from Hawke's Bay Regional Hospital. Of the 858 patients where surgery was both desired by the patient and deemed appropriate by the surgeon, 307 (36%) were declined for being below the financial threshold. These patients had a mean NZOA score of 66.42. At Whangarei Base Hospital, 300 patients were referred for surgery and 98 (33%) were declined for being below threshold. The mean NZOA score was significantly higher in the patients booked for surgery (M=70.62) compared with those declined below threshold (M=55.39, p<0.001). Of the 497 patients referred for arthroplasty at Hawke's Bay Regional Hospital, 205 (41%) were declined for being below threshold. The mean NZOA prioritisation scores were also significantly higher in the patients booked for surgery (M=76.96) compared to those declined (M=64.66; p less than or equal to 0.001). CONCLUSION: 36% of patients who were suitable for hip or knee arthroplasty were declined elective surgery for being below threshold. Many of these patients have significant pain and disability.

Laparoscopic ultrasound for the diagnosis of choledocholithiasis: quick, safe, and effective.

Visualization of the common bile duct during laparoscopic cholecystectomy is frequently required to confirm or exclude choledocholithiasis. Although on-table cholangiogram (OTC) is the traditional imaging technique, laparoscopic ultrasound (LUS) is increasingly deployed for this purpose. We are reporting a 31-month experience with an LUS, starting from the initial set up of the equipment. We retrospectively studied 70 patients who underwent LUS during their laparoscopic cholecystectomy operation over a period of 31 months. Data about preoperative investigation, intraoperative findings, and postoperative outcome were retrospectively collected and analyzed. LUS was found to be quick, safe, and effective in the intraoperative diagnosis of the common bile duct stones. It does not add significantly to the operative time and is inherently safer than intraoperative cholangiogram owing to the fact that it does not involve ionizing radiation. It is also more convenient, as there is no need to wear protective lead to avoid the side effects of ionizing radiation.

Early laparoscopic cholecystectomy in a district general hospital: is it safe and feasible?

BACKGROUND: Early laparoscopic cholecystectomy (ELC) is becoming the accepted treatment for the management of acute gallstone disease in specialist centres. It has also been achieved safely in the district general hospital (DGH) setting. We audited the management of acute gallstone disease in our DGH and set about to see if we could implement ELC safely and effectively. PATIENTS AND METHODS: A retrospective audit of 2 years of practice was performed using our hospital-computerised systems. Following this, departmental education regarding the benefits of early cholecystectomy was widely disseminated. Management guidelines were altered to promote and consider ELC for all suitable patients. A prospective audit of practice was then performed for 6 months. RESULTS: The first cycle revealed that only 10.42% of emergency patients admitted with gallstone-related disease had ELC. In the second cycle, 63 patients were admitted with acute gallstone disease. Three died from acute pancreatitis. Twenty-one (58%) of the 36, who were deemed suitable, had ELC. Fifteen (42%) had planned delayed laparoscopic cholecystectomy (DLC), with six (40%) being readmitted whilst waiting for their elective surgery (all undergoing ELC during their readmission). Conversion rates were similar between all groups. One of the patients having DLC had a bile leak, which settled following Endoscopic Retrograde Cholangiopancreatography and stent. CONCLUSION: We were able to increase ELC rates following the implementation of necessary changes. There did not appear to be any difference in conversion or morbidity rates between ELC and DLC. We conclude ELC is safe and feasible in the DGH setting.