Deciphering the inflection points to achieve proficiency for each procedure step during training in laparoscopic appendicectomy.

BACKGROUND: Laparoscopic appendicectomy is a common procedure early in surgical training. A minimum number is usually required for certification in general surgery. However, data on proficiency are scarce. This study aimed to investigate steps towards proficiency in laparoscopic appendicectomy. METHODS: This was a prospective observational cohort study of laparoscopic appendicectomies performed by junior trainees under supervision scored on a six-point performance scale. Structured assessment was done within a defined programme. Procedures performed for uncomplicated appendicitis in adults were included. The procedures were evaluated with LOWESS graphs generated to investigate inflection points. Factors associated with proficiency rates were reported with odds ratios and 95 per cent confidence intervals. RESULTS: In total 142 laparoscopic procedures were included for 19 trainees (58 per cent female). The cumulative number of procedures during the study was a median of 20 (i.q.r. 8-33). For overall proficiency, an inflection point occurred at 30 procedures. Proficiency rate increased from 51 per cent for 30 or fewer procedures to 93 per cent for more than 30 procedures (odds ratio 11.9 (95 per cent c.i. 3.4 to 40.9); P < 0.001). Inflection points for proficiency for each procedure step varied considerably, with lowest numbers (fewer than 15 procedures) for removing the specimen, and highest for dividing the mesoappendix (more than 55 procedures). Operating time was significantly reduced by a median of 7 minutes after 30 procedures, from median 62 (i.q.r. 25-120) minutes to median 55 (i.q.r. 30-110) minutes for more than 30 procedures. CONCLUSION: For junior trainees, variation in proficiency is related to specific procedure steps. Targeted training on specific procedure skills may reduce numbers needed to achieve proficiency in laparoscopic appendicectomy during training.

Prediabetes: The Variation between HbA1c and Fasting Plasma Glucose.

PURPOSE: The prevalence of Diabetes Type 2 is on the rise internationally. Currently, Fasting Plasma Glucose (FPG) and HbA1c are both used to determine if an individual is diabetic or prediabetic. We aimed to describe the prevalence of diabetes, prediabetes, and glycemic control in a population-based sample of elderly Hispanic and non-Hispanic White participants in New Mexico. METHODS: To do this, we compared HbA1c with FPG using Chi-Square analysis across gender and ethnicity to provide information for future health care policy. We also performed non-parametric regression using a locally weighted smoothing technique to investigate the relationship between FPG and HbA1c levels. RESULTS: Our analysis identifies a large variation between the sensitivity of HbA1c and FPG in the identification of both prediabetes and diabetes. Interestingly, 95% of diabetics defined by FPG are also defined by HbA1c, representing overlap between the two measures. When comparing the prevalence of prediabetes between the two measures, the overlap of FPG with HbA1c was only 30% and HbA1c identifies more individuals as prediabetic than FPG. Prevalence of diabetes was also higher when defined by HbA1c compared to FPG and the overall agreement between HbA1c and FPG appears to be poor particularly by sex and ethnicity (K=0.22-0.34). Glycemic control was poor overall with Hispanics displaying a larger amount of uncontrolled diabetes. CONCLUSION: We compared HbA1c and FPG by gender and ethnicity and showed both measures of diabetes differ in their sensitivity across ethnic groups. Our results suggest that using HbA1c, rather than FPG, results in higher rates of prediabetes and diabetes, a finding with numerous implications for health care practice.

Health of adults living with a clinically significant haemoglobinopathy in New South Wales, Australia.

AIM: To comprehensively review the health needs of patients living with clinically significant haemoglobinopathies (thalassaemia and sickle-cell disease (SCD)) in New South Wales, Australia. METHODS: A survey-based health needs assessment was undertaken in outpatients cared for at five tertiary institutions in metropolitan and regional centres. Sixty-three of 121 adults (approximately 80-90% of adult patients with transfusion-requiring haemoglobinopathies in New South Wales) completed an in-house and commercial health-related quality assessment survey (SF-36v2). RESULTS: Subjects came from more than eight world regions, with those with SCD being more likely to be born outside of Australia than subjects with thalassaemia (P < 0.001, likelihood ratio 20.64) as well as more likely to have been refugees (26% vs 2%). The population contained socially disadvantaged subjects with 13 subjects (20.6%) having incomes below the Australian poverty line. Complications of thalassaemia were comparable to previous international reports although our subjects had a high rate of secondary amenorrhea (>12 months = 27%) and surgical splenectomy (55.6%). Use of hydroxyurea in SCD was less than expected with only 46.6% of subjects having prior use. Lack of universal access to magnetic resonance imaging-guided chelation (international best practice) was evident, although 65.5% had been able to access magnetic resonance imaging through clinical trial, or self-funding. CONCLUSIONS: Patients with SCD and thalassaemia experience considerable morbidity and mortality and require complex, multidisciplinary care. This study revealed both variance from international best practice and between specialist units. The results of this research may provide the impetus for the development of clinical and research networks to enable the uniform delivery of health services benchmarked against international standards.

Automated spectral EEG analyses of premature infants during the first three days of life correlated with developmental outcomes at 24 months.

BACKGROUND: Spectral EEG analysis using automated quantification of total absolute band power (tABP) for long-term brain monitoring is reliable. We hypothesised that tABP during the first critical days of life could be a useful tool for predicting later developmental outcomes. OBJECTIVE: To determine whether measuring EEG background activity in premature infants with automated tABP quantification during the first 3 days of life correlated with their developmental outcomes at 24 months. METHODS: Preterm infants (group 1, gestational age, GA 24-28 weeks and group 2, GA 28-31 weeks) were continuously monitored by EEG for 3 days after birth. Their developmental outcomes were assessed using the Bayley-II and Peabody-2 developmental tests at 24 months. Their respective indices were calculated. Normal (index ≥85) and abnormal (index <85) outcomes were correlated with the tABP. RESULTS: In group 1, the tABP was significantly lower in the abnormal infants than in the normal infants. The specificity and negative predictive value were also high for all of the tests that were applied in this group. In group 2, there was no correlation between the tABP and developmental outcome. CONCLUSION: This study found that extremely premature infants with poor developmental outcomes had significantly lower tABP values in their first days of life compared to infants from the same group with normal outcomes. This method may be useful in predicting later outcomes in extremely premature infants and has the advantage of being automated.

Platelet function and constituents of platelet rich plasma.

Platelet Rich Plasma (PRP) therapies require blood to be processed prior to application, however, the full assessment of the output of platelet sequestration devices is lacking. In this study the products of the Autologous Fluid Concentrator (Circle BiologicsTM, Minneapolis, MN) and the Gravitational Platelet Separation System (GPS, Biomet, Warsaw, IN, USA) were evaluated in terms of platelet viability and PRP constituents. The AFC and GPS produced 6.4 (±1.0) ml and 6.3 (±0.4) ml of PRP, with platelet recovery of 46.4% (±14.7%) and 59.8% (±24.2%) producing fold increases of platelets of 4.19 (±1.62) and 5.19 (±1.62), respectively. Fibrinogen concentration was increased above baseline PPP produced with the AFC. pH was lower for both of the processed samples than for whole blood. White Blood Cell count was increased around 5 fold. Functional tests showed preserved viability with both devices. This represents essential knowledge that every treating physician should have before they can confidently administer PRP therapy produced by any method. These are the first published results of platelet function for the GPS system and the first performance results of the AFC system. The PRP produced is classified according to broad classifications as Leukocyte-PRP (L-PRP) for both devices.

Australian guidelines for the assessment of iron overload and iron chelation in transfusion-dependent thalassaemia major, sickle cell disease and other congenital anaemias.

Iron overload is the most important cause of mortality in patients with thalassaemia major. Iron chelation is therefore a critical issue in the management of these patients and others with transfusion-dependent haemoglobinopathies and congenital anaemias. In recent years, significant developments have been made in the assessment of iron overload, including the use of magnetic resonance imaging for measuring liver and cardiac iron. Advances in the modalities available for iron chelation, with the advent of oral iron chelators including deferiprone and deferasirox in addition to parenteral desferrioxamine, have expanded treatment options. A group of Australian haematologists has convened to formulate guidelines for managing iron overload on the basis of available evidence, and to describe best consensus practice as undertaken in major Australian Haemoglobinopathy units. The results of their discussions are described in this article, with the aim of providing guidance in the management of iron overload in these patients.

The role of glycogen synthase kinase-3beta in normal haematopoiesis, angiogenesis and leukaemia.

Glycogen synthase kinase 3 beta (GSK-3beta) was one of the first kinases identified and studied, initially for its role in the regulation of glycogen synthesis. Over the past decade, interest in GSK-3beta has grown far beyond glycogen metabolism, and this is due in large measure to the critical role that GSK-3beta plays in the regulation of many other cellular processes, particularly cell proliferation and apoptosis. GSK-3beta has been shown to regulate the proteolysis and sub-cellular compartmentalization of a number of proteins directly involved in the regulation of cell cycling, proliferation, differentiation and apoptosis. GSK-3beta also regulates the degradation of proteins that regulate gene expression and thus affects a variety of important cell functions. Specifically, GSK-3beta controls the degradation of beta-catenin, the main effector of Wnt that regulates haematopoiesis and stem cell function. In this case GSK-3beta is a negative regulator of Wnt. In contrast, GSK-3beta positively regulates NF-kappaB, another important biochemical pathway also involved in the regulation of multiple aspects of normal and aberrant haematopoiesis. GSK-3beta regulates degradation of IkappaB, a central inhibitor of NF-kappaB. In this way, GSK-3beta acts to control the resistance of leukaemic cells to chemotherapy through the modulation of NF-kappaB, a critical factor in maintaining leukaemic cell growth. In addition, GSK-3beta regulates the pro-inflammatory activity of NF-kappaB. As GSK-3beta is a pleiotropic regulator, inhibitors may increase the range of novel anti-leukaemic and anti-inflammatory drugs that control immune response.

Rituximab treatment of mild haemophilia A with inhibitors: a proposed treatment protocol.

Inhibitors are an uncommon complication of mild haemophilia A but represent a severe disease, typically with high titre inhibitors and an associated high rate of bleeding. We present data from three patients with MHAI who were successfully treated with Rituximab alone and unequivocally prove that such inhibitors respond to this agent. A treatment protocol is suggested.

Gene therapy in plastic and reconstructive surgery.

Gene therapy has been investigated in many aspects of plastic and reconstructive surgery. These areas ultimately involve various forms of tissue healing and the manipulation of bony and soft tissues to reconstruct defects secondary to neoplastic and congenital disorders and trauma. Most research has been limited to animal studies with the exception of clinical trials on the use of gene therapy in lower leg ulcer healing and as an adjunct to advanced recurrent squamous cell carcinoma of the head and neck. Overall, these preliminary studies have produced optimistic results. With the development of more efficient and safer delivery systems, the application of gene therapy in plastic surgery could become more widespread, especially in combination with tissue engineering technology.

Synthesis and release of human (pro)insulin in human BM progenitor cells.

BACKGROUND: Pancreatic insulin-producing g-cells are permanently destroyed in Type I diabetic patients, leading to hypoglycemica. Various somatic cells have been studied for their ability to deliver insulin as an alternative source of pancreatic g-cells. We investigated the potential of human BM progenitor cells for this purpose. METHODS: Two BM-derived hematopoietic cell lines, Tf-1 (CD34+) and K562 (CD34m) cell and primary human BM stromal cells were transduced with the human preproinsulin cDNA, and the ability of these cells to synthesize, store and release insulin was analyzed. RESULTS: All cells produce and released (pro)insulin at 116-295 wU/10(6) cells/day respectively. No storage of insulin was detected in either cell line or in stromal cells. DISCUSSION: We conclude that human BM-derived progenitor cells can be induced to produce and release basal levels of (pro)insulin.

Longitudinal study of fasting serum glucose concentrations in healthy elderly. The New Mexico Aging Process Study.

BACKGROUND: The American Diabetes Association s Expert Committee on the Diagnosis and Classification of Diabetes Mellitus has made the recommendation that all individuals over the age of 45 years should be screened for diabetes every 3 years. OBJECTIVE: This study was designed to determine the necessity for screening healthy elderly (> 65 years) this frequently using fasting serum glucose (FSG) determinations. DESIGN: This is a longitudinal study of initially healthy, upper middle class, community-based volunteers, mostly age 65 years and older at entry into the study. Participants were followed longitudinally with annual FSG concentrations and body mass indices (BMI) for periods up to 18 years (mean 12.4 years). RESULTS: Only 4 of 299 individuals with entry FSG < 126 mg/dl (mean + S.D. age at entry 71.6 + 4.8 years) and 6 or more annual visits have subsequently met the Expert Committee criteria for the diagnosis of diabetes (two consecutive FSGs > 126 mg/dl unless under treatment). When one examines the slopes of FSGs plotted over time (years) for each individual, more participants had a negative slope (220) than positive slope (79), i.e., their FSGs tended to decrease with age. None of the 68 individuals entered age > 75 years subsequently developed diabetes or a significantly positive slope. CONCLUSIONS: It does not appear necessary to screen non-obese elders (excluding minorities) age >65 years with a FSG < 100 mg/dl, or those age >75 years every 3 years as recommended.

Vascular endothelial growth factor gene therapy in ischaemic rat skin flaps.

Gene therapy with the complementary DNA (cDNA) of the angiogenic cytokine vascular endothelial growth factor (VEGF) has emerged as a promising strategy in the treatment of myocardial and lower-limb ischaemia. The objective of this study was to determine whether these principles could be applied to a recognised model of skin-flap ischaemia. Plasmid vectors including the cDNA of green fluorescent protein (GFP) and one of three VEGF isoforms (A165, B167 or B186) were constructed, and their base sequences confirmed. GFP expression was used as a marker of successful in vitro transfection of human endothelial cells with each plasmid. The plasmids were then administered subcutaneously to rat abdominal skin flaps surgically rendered ischaemic, and the percentage of viable tissue was assessed at 1 week. Angiograms of the flaps and histological preparations of flap tissue were assessed for evidence of angiogenesis. The survival of flaps treated with VEGF A165 or B167 cDNA was significantly greater than that of controls (P < 0.05). The survival of flaps treated with VEGF B186 cDNA was greater than that of controls, but statistical significance was not reached. Angiograms and microvessel density counts failed to produce evidence of angiogenesis. With improved delivery strategies, VEGF may have a role in the management of surgical ischaemia.

A biethnic community survey of cognition in participants with type 2 diabetes, impaired glucose tolerance, and normal glucose tolerance: the New Mexico Elder Health Survey.

OBJECTIVE: To determine whether elderly individuals with type 2 diabetes or impaired glucose tolerance are at increased risk for cognitive impairment compared with individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: Elderly Hispanic individuals (n = 414) and non-Hispanic white individuals (n = 469) aged > or =65 years, randomly selected from the Medicare rolls of Bernalillo County (Albuquerque), NM, were recruited for an interview/examination that included an evaluation of glucose tolerance. Information on nine tests of cognitive function and two measures of depression allowed comparisons between diabetic status and these functions. Comparisons also were made between glycosolated hemoglobin concentrations and these cognitive tests in the 188 participants with diabetes. RESULTS: None of the mean scores on the tests of cognitive function was significantly lower in the participants with diabetes compared with those participants with normal glucose tolerance after adjustments for ethnicity, sex, age, level of education, and presence of depression, with or without elimination of those with dementia (Mini-Mental State Exam <18). Interestingly, participants with impaired glucose tolerance tended to score higher than those with normal glucose tolerance. No significant associations were found between glycosolated hemoglobin concentrations and cognitive test scores in participants with diabetes. CONCLUSIONS: We could not show any increased risk for cognitive impairment in participants with diabetes compared with those with normal glucose tolerance after adjustments for ethnicity, sex, age, education, and presence of depression, before or after elimination of dementia in this random sample from a biethnic population of predominantly community-dwelling elders.

CD80 (B7-1) expression on human acute myeloid leukaemic cells cultured with GM-CSF, IL-3 and IL-6.

Acute myeloid leukaemia (AML) blasts rarely express the B7 family of co-stimulatory molecules and do not elicit a clinically significant autologous T-lymphocyte anti-tumour response. The aim of this study was the in vitro modification of AML blasts to an antigen-presenting cell phenotype characterised by upregulated expression of the co-stimulatory molecule CD80 (B7-1). Circulating AML cells were induced to undergo partial differentiation in culture with the cytokines IL-3, IL-6 and GM-CSF; they exhibited variable upregulation of CD80 and continued to express MHC class I and II. These cells remained viable to day 20, in contrast with normal peripheral blood mononuclear cells (PBMNC), which did not survive under the culture conditions. In contrast to unmanipulated blasts, cultured leukaemic cells expressed B7-1. Where initial cytogenetic abnormalities were present, they were also seen in flow-sorted CD80-expressing cells after culture in cytokines, indicating their malignant origin. The immunogenic potential of these cultured cells was highlighted by allogeneic and autologous mixed lymphocyte reactions, in which both differentiated, but not unmanipulated, blasts produced expansion of T-lymphocyte numbers. Autologous cytotoxic T-lymphocyte (CTL) assays indicated specific killing of B7-1+ leukaemic cells, which was greatly enhanced after priming of the T-lymphocytes by B7-1+ blasts prior to the CTL assay, then enabling the CTL to lyse both unmanipulated and differentiated leukaemic cells.

Prevalence of self-reported illnesses in elderly Hispanic and non-Hispanic Whites in New Mexico.

OBJECTIVE: To report on the prevalences of self-reported illnesses from the New Mexico Elder Health Survey. DESIGN: Randomized community-based cross-sectional survey of elderly (> or = 65 years of age) Hispanics and non-Hispanic Whites. METHOD: Analysis of data from the 883 participants in the New Mexico Elder Health Survey. RESULTS: Complete data on 848 subjects were available for this analysis: Hispanic males, 212; Hispanic females, 189; non-Hispanic White males, 236; non-Hispanic White females, 211. The mean age was 74 years (age range 65-98). Hispanics had fewer years of school and lower income. Hispanics reported a significantly (P<.05) higher prevalence of type 2 diabetes; leg ulcers/pressure sores; and Parkinson's Disease. Non-Hispanic Whites reported a significantly (P<.05) higher prevalence of asthma; circulatory problems; stomach (not ulcers), intestinal or gallbladder disease; urinary tract disorders (other than kidney disease); and cancer. Prevalence odds ratios and confidence intervals were calculated. Hispanic males reported a higher prevalence of type 2 diabetes (OR 1.88, CI 1.10-3.26, P = .02), and lower prevalences of asthma (OR 0.43, CI 0.18-0.93, P = .04); urinary tract disorders, other than kidney disease (OR 0.59, CI 0.38-0.91, P = .01); and cancer (OR 0.31, CI 0.13-0.68, P = .005). Hispanic females reported a higher prevalence of diabetes (OR 3.01, CI 1.48-6.50, P = .003), and a lower prevalence of glaucoma (OR 0.48, CI 0.22-1.00, P = .05). These differences remained significant after adjustment for age, education, income, and language. CONCLUSION: There are significant differences in the prevalences of self-reported illnesses between Hispanic and non-Hispanic White elderly.

A review of therapeutic angiogenesis and consideration of its potential applications to plastic and reconstructive surgery.

The use of exogenous agents to stimulate the growth of new blood vessels into ischaemic tissue is a potentially revolutionary therapy in a wide variety of clinical specialties. Therapeutic angiogenesis research has been mostly confined to ischaemia of the heart and the lower limb. There has been relatively little research into the potential applications of the technique to plastic, reconstructive and burns surgery. In this paper, relevant published work is reviewed and potential applications of therapeutic angiogenesis to our specialty are considered.

Adenoviral mediated interleukin-2 gene transfer to human long-term bone marrow stromal cultures.

Human long-term bone marrow stromal cultures (LTBMC) have been transduced to express the immunostimulatory cytokine interleukin-2 (IL-2). LTBMC were established from normal bone marrow and characterized by gross morphology, immunohistochemistry, immunophenotyping, and immunofluorescent staining. A stromal marrow cell (SMC) population expressing the markers CD68, CD29, CD13, and CD54 was identified. These cells were successfully transduced with an adenoviral vector containing the human IL-2 gene. Production of IL-2 was demonstrated for at least 13 days post-transduction and was maximal on day 10 at 19,350 pg (or 38 IU) of IL-2/10(6) cells/24 h. IL-2 expressed by the transduced SMC was demonstrated to be biologically active, resulting in the proliferation of autologous T lymphocytes in a mixed lymphocyte reaction. Autologous human LTBMC can be obtained and manipulated with relative ease and may be a useful vehicle for sustained local cytokine delivery.

Prevalence of mild impairment in renal function in a random sample of elders from a biethnic community survey.

The purpose of this study was to compare the prevalences of renal impairment, notably an elevation in serum urea nitrogen and/or serum creatinine concentration, in a randomly selected, biethnic population of Hispanic and non-Hispanic white men and women, and to determine the associations with coronary heart disease and its risk factors (diabetes, hypertension, and dyslipidemia). A survey of health and health-related issues was conducted on 883 volunteers, mean age 74.1 years, randomly selected from the Medicare rolls of Bernalillo County (Albuquerque), New Mexico. Equal numbers of Hispanic and non-Hispanic white men and women were selected and recruited. A fasting serum creatinine and serum urea nitrogen was included in the battery of laboratory tests. Mild elevations of SUN and serum creatinine concentrations are common (9.2%) in an aging, randomly selected population (mean age 74.1 years). Males were more commonly affected than females. There were no differences between Hispanics and non-Hispanic whites, even though diabetes was twice as prevalent in Hispanics. Mild elevations of SUN and serum creatinine were more common in participants with coronary heart disease and its risk factors (diabetes, hypertension, and dyslipidemia). All participants with mild renal impairment had either increased total cholesterol or decreased HDL-cholesterol. One cannot determine from a cross-sectional study whether the dyslipidemia consistently associated with mild renal impairment was a cause of the renal impairment or a result of the renal impairment; however, biological explanations do exist to explain how the dyslipidemias can lead to progressive glomerulosclerosis.