Prolactin circulates predominantly as a 23-kDa monomer, and a high-molecular-weight form largely consisting of a complex of prolactin and an anti-prolactin IgG autoantibody, called macroprolactin. This cross-reacts with conventional laboratory assays for prolactin. We here describe how quantitative adjustment for this may assist patient management.In a consecutive series of 218 patients with prolactin elevated to 400 mu/L or more in men (normal range≤180)(n=79, 36.2% of sample) and 1 000 mu/L or more in women (normal range≤500)(n=139, 63.8%) a macroprolactin screen was performed using PEG precipitation.Where present, median macroprolactin as a proportion of total prolactin was in women 13%(percentile25-percentile75: 7-25%) and in men 15%(7-30%).The distribution of macroprolactin as a proportion of total prolactin was markedly skewed to the left with 69.7% of women and 62.9% of men having macroprolactin proportion of 20% or less. There was no relation between %macroprolactin and total measured prolactin, age or gender.Of relevance to clinical management, in 24% of men and 20.5% of women, correction for estimated macroprolactin gave an adjusted monomeric prolactin level below the agreed threshold for further investigation, potentially avoiding unnecessarily referral.In our clinical series, quotation of an adjusted monomeric prolactin would have resulted in unnecessary further investigation being avoided in a number of cases.Screening for macroprolactin is a key element of laboratory assessment for hyperprolactinaemia.In cases where measured total prolactin is significantly raised, quantitative reporting of estimated monomeric prolactin instead of just ‘macroprolactin positive' can avoid unnecessary investigations.

OBJECTIVE: Diet and exercise reduce the incidence of diabetes in high-risk individuals as does Metformin, although less dramatically. Here we evaluated if lifestyle and pharmacological intervention, for people at risk of diabetes, resulted in an improvement in their cardiometabolic risk profile. RESEARCH DESIGN/METHODS: In a primary care based study, 92 individuals screened opportunistically and identified to have impaired glucose handling were offered detailed lifestyle advice, at 6 monthly intervals, with targeting of cardiovascular risk factors. Duration of follow-up was 4years. The relation between fasting and 2h glucose with different cardio-metabolic risk factors over time was assessed using multi-level modeling. RESULTS: There was no significant weight reduction. At 24months, mean fasting glucose level (6.4mmol/L (95% CI 6.0-6.8)) was slightly lower than at baseline (6.6mM (95% CI: 6.4-6.9), F=3.67; p<0.001). For men and women combined, systolic blood pressure (mean difference=-6mmHg, p=0.013), total cholesterol (-0.66mmol/L, p<0.0001) and triglycerides (-0.13mmol/L, p=0.133) fell, whilst HDL-cholesterol (0.12mmol/L, p=0.047) rose. Diabetes developed in 18/92 participants during follow-up (up to 4years). Five per cent of participants were started on Metformin, 88.5% on lipid lowering agents and 85.4% on anti-hypertensive agents. After adjusting for age, sex and BMI, 2h glucose was independently and negatively associated with HDL-cholesterol (β=-2.17, p=0.041), and positively with systolic BP (β=0.24, p=0.004, per 5mmHg). CONCLUSIONS: Targeted intervention had an effective role in improving lipid and BP profile in individuals with impaired glucose handling, with limited impact on glycaemia and no impact on weight. More work needs be done to evaluate the potential benefit of insulin sensitizing agents in this setting.

AIMS: In the context of changes in the last 10 years in treatment strategies for type 1 diabetes we evaluated longitudinal trends in cardiometabolic risk factor profiles in a population from North-West England. METHODS: We retrospectively examined longitudinal case records for the period for 291 adult patients followed up between 2004 and 2009 (age range 16-85). Data search was performed through the EMIS(®) software provider using data held in primary care. RESULTS: Longitudinal analysis of individually followed patients indicated a mean 0.4% reduction in HbA1c from 8.3%(67mmol/mol) at baseline (p=0.002). The proportion of patients with an HbA1c ≥10%(86mmol/mol) at baseline had a significant reduction over time from 14.0% to 9.5%(χ(2)=9.4, p=0.002). BMI remained unchanged (28.3 vs 28.4kg/m(2)). However total cholesterol fell by 12.5% from 4.8mM to 4.2mM,(p<0.0001) with a corresponding 23% reduction in LDL-cholesterol from 3.0mm to 2.3mM (p<0.0001). There was a significant fall in diastolic BP (78-74mmHg, p=0.0016). In a mixed longitudinal regression model, HbA1c was associated with LDL-C (β=0.28, p<0.001) and age (β=0.02, p=0.001), independent of BMI, gender and systolic BP. DISCUSSION: In spite of intensive work to improve glycaemic control in type 1 diabetes, mean HbA1c remains above target for many people in our area, highlighting the difficulty of achieving glycaemic targets in type 1 diabetes. The significant reduction in diastolic BP, LDL and total cholesterol may have long-term benefit in cardiovascular event rate reduction.

AIM: There is increasing awareness of hypogonadism in men with type 2 diabetes but limited data from Primary Care. SUBJECTS AND METHODS: The anonymised records of 6457 male patients aged 18-80 years with diabetes were accessed. Within the last 2 years 391 men (6.0% of total) underwent measurement of serum testosterone. Data search was performed through the centralised data facility afforded by EMIS(®), the majority GP systems provider in Cheshire. RESULTS: 4.4% of type 2 diabetes men screened were frankly hypogonadal with a serum total testosterone of less than 8.0nmol/l. For borderline hypogonadism (serum total testosterone 8-11.99nmol/l) the proportion of type 2 diabetes men rose to 32.1%. Age adjusted mean (geometric) testosterone was lower in men with type 2 diabetes (13.6nmol/l 95%CI: 13.1-14.2) vs type 1 diabetes (17.9nmol/l; 95%CI 15.2-21.0), F=10.3; p=0.0014. For those screened age adjusted body mass index (BMI) was greater in type 2 diabetes at 30.7 (30.1-31.3) vs 28.4 (26.1-30.6)kg/m(2) in type 1 diabetes (F=4.3; p=0.04). Multiple linear regression analysis indicated that there was a statistically significant interaction (P=0.014) between BMI and diabetes type in their relation with log testosterone. For persons with type 1 DM and type 2 DM, testosterone can be expected to decrease by 6%(P=0.002) and by 1%(P=0.002) respectively, for every one unit increment in BMI. CONCLUSIONS: There is manifestly a subset of men with diabetes and androgen deficiency who could benefit from testosterone replacement. BMI has an independent influence on androgen status.

Ensuring that trainees receive appropriate clinical supervision is one proven method for improving patient safety outcomes. Yet, supervision is difficult to monitor, even more so during advanced levels of training. The manner in which trainees' perceived failures of supervision influenced patient safety practices across disciplines and various levels of training was investigated. A brief, open-ended questionnaire, administered to 334 newly hired interns, residents, and fellows, asked for descriptions of situations in which they witnessed a failure of supervision and their corresponding response. Of the 265 trainees completing the survey, 73 (27.5%) indicated having witnessed a failure of supervision. The analysis of these responses revealed three types of supervision failures-monitoring, guidance, and feedback. The necessity of adequate supervision and its accompanying consequences were also highlighted in the participants responses. The findings of this study identify two primary sources of failures of supervision: supervisors' failure to respond to trainees' seeking of guidance or clinical support and trainees' failure to seek such support. The findings suggest that the learning environment's influence was sufficient to cause trainees to value their appearance to superiors more than safe patient care, suggesting that trainees' feelings may supersede patients' needs and jeopardize optimal treatment. The literature on the impact of disruptive behavior on patient care may also improve understanding of how intimidating and abusive behavior stifles effective communication and trainees' ability to provide optimal patient care. Improved supervision and communication within the medical hierarchy should not only create more productive learning environments but also improve patient safety.

GDM (gestational diabetes mellitus) is associated with later adverse cardiovascular risk. The present study examined the relationship between glycaemia during pregnancy and small artery function and structures approx. 2 years postpartum. Women were originally enrolled in the HAPO (Hyperglycaemia and Adverse Pregnancy Outcome) study from which they were classified by their glycaemic distribution during pregnancy as controls (in the lower half of the distribution), UQ (upper quartile; in the UQ of the glycaemic distribution) or having had overt GDM. Subcutaneous arteries from a gluteal fat biopsy taken at follow-up 2 years later were examined using wire myography. Small artery structure, stiffness and vasoconstrictor responses were similar across groups. Maximal endothelium-dependent dilation in response to carbachol was impaired in arteries from both GDM (43.3%, n=8 and P=0.01) and UQ (51.7%, n=13 and P=0.04) women despite generally 'normal' current glycaemia (controls, 72.7% and n=8). Inhibition of NOS (nitric oxide synthase) significantly reduced maximum endothelium-dependent dilation in controls but had no effect on arteries from UQ and GDM women, suggesting impaired NOS activity in these groups. Endothelium-independent dilation was unaffected in arteries from previous GDM and UQ women when compared with the control group. Multiple regression analysis suggested that BMI (body mass index) at biopsy was the most potent factor independently associated with small artery function, with no effect of current glycaemia. Overweight women with either GDM or marginally raised glycaemia during pregnancy (our UQ group) had normal vascular structure and stiffness, but clearly detectable progressively impaired endothelium-dependent function at 2 years follow-up. These results suggest that vascular pathology, which may still be reversible, is detectable very early in women at risk of decline into Type 2 diabetes mellitus.

Context: Adiponectin, high-density lipoprotein cholesterol (HDL-C) and insulin concentrations may be important in the pathophysiology of cardiovascular disease. Objective: We tested the hypothesis that serum adiponectin rather than insulin differs from early life, between South Asians and Europeans, with a potentially key role in excess cardiovascular risk characteristic of adult South Asians. Design and Participants: We conducted a longitudinal study of 215 British-born children of European (n = 138) and South Asian (n = 77) origin, from birth to 3 yr. Main Outcome Measure: Serum adiponectin, insulin, proinsulin and HDL-C concentrations were assessed in relation to ethnic group and growth in anthropometric variables from 0-3 yr of age. Results: Serum adiponectin was lower in South Asian children, despite their smaller size, notable at age 3-6 months (9.5 vs. 11.8 mg/liter; P = 0.04), with no ethnic differences in serum lipids or insulin or proinsulin. In mixed-effects longitudinal models for HDL-C, determinants were adiponectin (P = 0.034), age (P < 0.001), and body mass index (P < 0.001) but not ethnicity. None of these or growth variables affected either insulin or proinsulin. In a fully adjusted mixed-effects longitudinal model including age, sex, insulin, and proinsulin, the independent determinants of serum adiponectin were height [21.3 (95% confidence interval = 31.7-10.8 cm lower, for every 1 mmol/liter increase in adiponectin, P < 0.001], HDL-C [2.8 (1.3-4.2) mmol/liter higher, P < 0.0001], body mass index (lower, P = 0.03), and South Asian ethnicity (lower, P = 0.01). Conclusions: These British South Asian-origin infants have lower serum adiponectin but no differences in HDL-C or insulin molecules. In South Asians, factors affecting adiponectin metabolism in early life, rather than insulin resistance, likely determine later excess cardiovascular risk.

OBJECTIVES: To determine the population distribution of cardiovascular risk in eight low- and middle-income countries and compare the cost of drug treatment based on cardiovascular risk (cardiovascular risk thresholds ≥30%/≥40%) with single risk factor cutoff levels. STUDY DESIGN AND SETTING: Using World Health Organization (WHO) and the International Society of Hypertension risk prediction charts, cardiovascular risk was categorized in a cross-sectional study of 8,625 randomly selected people aged 40-80 years (mean age, 54.6 years) from defined geographic regions of Nigeria, Iran, China, Pakistan, Georgia, Nepal, Cuba, and Sri Lanka. Cost estimates for drug therapy were calculated for three countries. RESULTS: A large fraction (90.0-98.9%) of the study population has a 10-year cardiovascular risk <20%. Only 0.2-4.8% are in the high-risk categories (≥30%). Adopting a total risk approach and WHO guidelines recommendations would restrict unnecessary drug treatment and reduce the drug costs significantly. CONCLUSION: Adopting a total cardiovascular risk approach instead of a single risk factor approach reduces health care expenditure by reducing drug costs. Therefore, limited resources can be more efficiently used to target high-risk people who will benefit the most. This strategy needs to be complemented with population-wide measures to shift the cardiovascular risk distribution of the whole population.

We demonstrate a compact hyperdispersion stretcher and compressor pair that permit chirped-pulse amplification in Nd:YAG. We generate 750 mJ, 0.2 nm FWHM, 10 Hz pulses recompressed to an 8 ps near-transform-limited duration. The dispersion-matched pulse compressor and stretcher impart a chirp of 7300 ps/nm, in a 3 m x 1 m footprint.