Kinetics of removal and reappearance of non-transferrin-bound plasma iron with deferoxamine therapy

The rapidity and duration of the response of non-transferrin-bound iron (NTBPI) to chelation therapy are largely unknown and have important implications for the design of optimal chelation regimens. Methodology was developed to measure simultaneously NTBPI, deferoxamine (DFO), and its major metabolite. NTBPI was present in all but 2 of 28 thalassaemia major (TM) patients who had received conventional subcutaneous DFO the previous night, suggesting a short duration of NTBPI clearance by DFO. The detailed kinetics of NTBPI were therefore studied in response to intravenous DFO at 50 mg/kg/27 h for 48 hours and compared in 17 regularly transfused TM and 8 untransfused thalassaemia intermedia (TI) patients to determine the influence of hypertransfusion and iron overload on NTBPI response. Before DFO infusion, NTBPI was present in all patients and was significantly higher in TI (4.52 +/- 0.53 mumol/L) than TM (2.92 +/- 0.03 mumol/L; P = .03). NTBPI values in TM correlated with transferrin saturation (r = .6, P = .03) but not with serum ferritin. Removal of NTBPI by intravenous DFO is in a biphasic manner. The initial rapid rate constant (alpha) was similar in TI (1.5 hour-1) and TM (1.6 hour-1), but the subsequent beta phase was slower (0.04 hour-1) in TI when compared with TM (0.4 hour-1, P = .002). Detectable NTBPI persisted during the beta phase, particularly in TI, despite an excess of plasma DFO also being present (steady state 8 mumol/L). On cessation of DFO infusion, NTBPI reappearance was rapid; the kinetics also being biphasic. The rapid initial rate constant (alpha = 2.5 hour- 1) lasted less than 30 minutes and was approximately equal to the summation of the initial rate constant for removal of DFO (1.8 hour-1) and its major metabolite (0.6 hour-1). This was followed by a slower return to pretreatment levels, usually between 6 and 12 hours, which was faster in TI than in TM. This marked NTBPI lability supports the use of continuous rather than intermittent DFO in high risk patients.     

Chronic Psychological Stress and Racial Disparities in Body Mass Index Change Between Black and White Girls Aged 10–19

Background

One of the largest health disparities in the USA is in obesity rates between Black and White females.

Purpose

The objective of this study was to test the hypothesis that the stress–obesity link is stronger in Black females than in White females aged 10–19.

Methods

Multilevel modeling captured the dynamic of acute (1 month) and chronic (10 years) stress and body mass index (BMI; weight in kilograms divided by height in meters squared) change in the National Heart, Lung, and Blood Institute Growth and Health Study, which consists of 2,379 Black and White girls across a span of socioeconomic status. The girls were assessed longitudinally from ages 10 to 19.

Results

Higher levels of stress during the 10 years predicted significantly greater increases in BMI over time compared to lower levels of stress. This relationship was significantly stronger for Black compared to White girls.

Conclusion

Psychological stress is a modifiable risk factor that may moderate early racial disparities in BMI.     

Impact of Lifestyle Intervention and Metformin on Health-Related Quality of Life: the Diabetes Prevention Program Randomized Trial

BACKGROUND

Adults at high risk for diabetes may have reduced health-related quality of life (HRQoL).

OBJECTIVE

To assess changes in HRQoL after interventions aimed at diabetes risk reduction.

DESIGN, SETTING, AND PARTICIPANTS

A randomized clinical trial, the Diabetes Prevention Program, was conducted in 27 centers in the United States, in 3,234 non-diabetic persons with elevated fasting and post-load plasma glucose, mean age 51?years, mean BMI 34 Kg/m2; 68 % women, and 45 % members of minority groups.

INTERVENTIONS

Intensive lifestyle (ILS) program with the goals of at least 7 % weight loss and 150 min of physical activity per week, metformin (MET) 850?mg twice daily, or placebo (PLB).

MEASUREMENTS

HRQoL using the 36-Item Short-Form (SF-36) health survey to evaluate health utility index (SF-6D), physical component summaries (PCS) and mental component summaries (MCS). A minimally important difference (MID) was met when the mean of HRQoL scores between groups differed by at least 3?%.

RESULTS

After a mean follow-up of 3.2?years, there were significant improvements in the SF-6D (+0.008, p?=?0.04) and PCS (+1.57, p?<?0.0001) scores in ILS but not in MET participants (+0.002 and +0.15, respectively, p?=?0.6) compared to the PLB group. ILS participants showed improvements in general health (+3.2, p?<?0.001), physical function (+3.6, p?<?0.001), bodily pain (+1.9, p?=?0.01), and vitality (+2.1, p?=?0.01) domain scores. Treatment effects remained significant after adjusting sequentially for baseline demographic factors, and for medical and psychological comorbidities. Increased physical activity and weight reduction mediated these ILS treatment effects. Participants who experienced weight gain had significant worsening on the same HRQoL specific domains when compared to those that had treatment-related (ILS or MET) weight loss. No benefits with ILS or MET were observed in the MCS score.

CONCLUSION

Overweight/obese adults at high risk for diabetes show small improvement in most physical HRQoL and vitality scores through the weight loss and increased physical activity achieved with an ILS intervention.     

Portal Venous Thrombosis After Distal Pancreatectomy: Clinical Outcomes

Aim

Outcomes of patients developing portal vein (PV) thrombosis (PVT) after distal pancreatectomy (DP) are unknown. The goal of this study was to identify risk factors for PVT and describe the long-term outcomes in these patients.

Methods

Patients undergoing DP without repair or reconstruction of the PV between 2001 and 2011 were included. Patients that showed evidence of PVT on pre-operative imaging were excluded from the study. Location and extent of thrombosis was determined by post-operative computed tomography or ultrasound imaging in all patients. Evidence of systemic thrombosis (if present) in addition to PVT was also documented.

Results

In the study period, 991 patients underwent DP and 21 (2.1 %) patients were diagnosed with PVT. Pancreatic neoplasm was the most frequent indication for operation (n?=?11). Thrombus occurred in the main PV in 15 and the right branch of the PV in 8 patients. Complete PV occlusion occurred in nine patients with a median time to diagnosis of 16 days (range 5–85 days). Seventeen patients were anticoagulated for a median duration of 6 months (range 3.3–36 months) after the diagnosis of PVT. Over a median follow-up of 22 months, resolution of PVT occurred in seven patients. Predictors of non-resolution of PVT included anesthesia time >180 min (p?=?0.025), DM type II (p?=?0.03), BMI?>30 Kg/m² (p?=?0.03), occlusive PVT (p?<?0.001), or thrombus in a sectoral branch (p?=?0.02). Anticoagulation therapy did not influence the frequency of thrombus resolution and was complicated by gastrointestinal hemorrhage in four patients. There was no mortality as a direct result of PVT or anticoagulation.

Conclusion

PVT after distal pancreatectomy is a rare complication. Serious complications as a direct result of PVT in this setting are uncommon and are not dependent on thrombus resolution. Although anticoagulation does not appear to influence the rate of PVT resolution in this small retrospective series, we support the use of anticoagulation until larger, controlled studies define clear advantages or disadvantages.     

Relationship of Sodium and Magnesium Intakes to Hypertension Proven by 24‐Hour Urianalysis in a South Indian Population

The Healthy Eating Asians Remain Together (HEART) study was carried out to investigate the relationship between 24‐hour urine nutritional biomarkers and cardiometabolic risks in India. A total of 168 participants underwent health examination to assess body mass index, blood pressure, and 24‐hour urine samples. The participants were divided into normotensive and hypertensive. The average blood pressure, weight, and body mass index were significantly high in patients considered to be hypertensive, and 24‐hour urine biomarkers showed significant differences in sodium and magnesium/creatinine ratios in patients aged 40 and older. High sodium intake and reduction in magnesium consumption are associated with increased blood pressure in patients from India.     

Gene polymorphisms,tobacco exposure and oral cancer susceptibility: a study from Gujarat,West India

Polymorphic variability in the enzymes involved in biotransformation of tobacco‐related pro‐carcinogens plays an important role in modulating oral cancer susceptibility. CYP1A1*2A, CYP1A1*2C, GSTM1 and GSTT1 polymorphisms were determined in 122 oral carcinoma cases and 127 controls from Gujarat, West India using PCR‐based methods. The results revealed that the polymorphic variants of CYP1A1 gene did not show association towards oral cancer risk. The GSTM1 and GSTT1 null genotypes were found to be over‐represented in patients than controls, suggesting a moderate increase in risk of oral cancer. The oral cancer risk was significantly increased in the patients having either alone or concurrent deletion of GSTM1 and GSTT1. The results also suggested significant association between tobacco habits, especially chewing, variant genotypes of CYP1A1, GSTM1 and GSTT1 and oral cancer risk. Our data have provided evidence that GST polymorphism modified the susceptibility to oral cancer and individuals with variant genotypes of the three genes with tobacco habits are at significant risk of developing oral cancer.