The effect of the PREMIER interventions on insulin sensitivity

OBJECTIVE: This ancillary study of PREMIER sought to determine the effects on insulin sensitivity of a comprehensive behavioral intervention for hypertension with and without the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. RESEARCH DESIGN AND METHODS: Participants were assigned to one of three nonpharmacologic interventions for blood pressure (group A, advice only; group B, established; and group C, established plus DASH). The established intervention included weight loss, reduced sodium intake, increased physical activity, and moderate alcohol intake; the DASH dietary pattern was added to the established intervention for those in group C. The DASH dietary pattern is high in fruits, vegetables, and low-fat dairy products while being lower in total fat, saturated fat, and cholesterol. It is abundant in nutrients such as magnesium, calcium, and protein, which have been associated with improved insulin sensitivity. Insulin sensitivity was measured at baseline and at 6 months using the frequently sampled intravenous glucose tolerance test with minimal model analysis. RESULTS: Both intervention groups decreased total calories, percentage of calories from fat, and sodium intake to similar levels, with similar amounts of energy expenditure and weight loss. Covariate differences seen only in group C included increased intake of protein, potassium, calcium, and magnesium. Compared with control subjects, insulin sensitivity improved significantly only in group C, from 1.96 to 2.95 (P = 0.047). Group B did have a significant decrease in fasting insulin and glucose, but the changes in insulin sensitivity did not reach statistical significance when compared with control subjects. CONCLUSIONS: These results suggest that including the DASH dietary pattern as part of a comprehensive intervention for blood pressure control enhances insulin action beyond the effects of a comprehensive intervention that does not include DASH.     

Population genetic implications from DNA polymorphism in random human genomic sequences

Denaturing high performance liquid chromatography (DHPLC) in combination with dye-terminator sequencing was used to survey 516 random genomic sequence tagged sites (STSs) for biallelic polymorphisms in 24 representatives of the major ethnic groups residing in the United States. Of the 301 polymorphic STSs (58.3%), 172 contained a single simple sequence polymorphism (SSP), while 78, 35, and 16 contained 2, 3, and 4-6 SSPs, respectively. Of the 541 SSPs identified, 342 (63%), 152 (28%), and 47 (9%) were transitions, transversions, and insertions or deletions, respectively. Only 21% of the STSs contained SSPs with a minor-allele frequency >20%. The nucleotide diversity estimate for random genomic sequences theta = 8.23 x 10(-4) was on average 50% higher than that for intragenic non-coding regions of the human genome ( theta = 5.52 x 10(-4). The discrepancy in Tajima's D statistic between 22 autosomal genes (D=-1.304+/-0.622, mean+/-SD) and random STSs (D=-0.27) suggests that, in the absence of significant mutation rate heterogeneity, the more negative values for genes are a consequence of directional selection rather than population growth.     

Pancreatectomy with islet autotransplantation for the treatment of severe chronic pancreatitis: the first 40 patients at the leicester general hospital

BACKGROUND: Surgical resection of the pancreas is considered a final resort in the treatment of chronic pancreatitis. However, the opportunity to perform an islet autotransplant at the same time provides the potential to prevent the onset of diabetes. METHODS: Pancreatectomy together with islet autotransplantation has been offered in our center since 1994. A total of 40 patients have now undergone this procedure. The follow-up times range from 6 months to 7 years. The data presented here include the annual postoperative oral glucose tolerance test and glycosylated hemoglobin (HbA(1c)) results, together with insulin and opiate requirements. RESULTS: Nineteen male and 21 female patients (median age 44, range 21-65) have been transplanted. Pancreatitis was related to alcohol in 45% and was idiopathic in 40%. A median of 130108 (24332-1, 165538) islet equivalent (IEQ) were transplanted, which related to 2020 (320-23311) IEQ per kilogram of body weight. At 2 years posttransplant, 18 patients had a median HbA(1c) of 6.6% (5.2-19.3%), fasting C-peptide of 0.66 ng/mL (0.26-2.65 ng/mL), and required a median of 12 (0-45) units of insulin per day. At 6 years, these figures were 8% (6.1-11.1%), 1.68 ng/mL (0.9-2.78 ng/ml) and 43 U/day (6-86 U/day), respectively. The majority of patients no longer require opiate analgesia, 68% have been able to return to work, and one patient has had a baby. CONCLUSIONS: Islet autotransplantation offers a valuable addition to surgical resection of the pancreas, as a treatment for chronic pancreatitis; and even in cases in which insulin independence is not achieved, the potential beneficial effects of C-peptide make the procedure worthwhile.     

Siponimod for the treatment of secondary progressive multiple sclerosis

Introduction: Multiple sclerosis (MS) is a chronic central nervous system immune-mediated disease with an important inflammatory component associated with focal demyelination and widespread neurodegeneration. In most cases, the clinical presentation is relapsing-remitting, followed by a secondary progressive phase, characterized by disability accrual unrelated to relapses. In a minority, the phenotype is progressive from the beginning. Major therapeutic achievements have been made concerning the relapsing phase but modifying the evolution of progressive MS remains an unmet need.

Areas covered: This review covers siponimod (BAF312), a new sphingosine 1-phosphate receptor modulator, and its role in the treatment of secondary progressive MS. The authors reviewed PubMed English literature using the keywords ‘siponimod’ or ‘BAF312’ and ‘multiple sclerosis.’ They also present the pharmacological profile of siponimod, as well as clinical efficacy and safety, with emphasis on the recently published results of a Phase III trial. Phase II data in relapsing MS are also summarized.

Expert opinion: Siponimod may reduce the activity of the disease and has a modest effect on the gradual disability accrual. If approved, it may become one of the few available therapy options for secondary progressive MS.     

The effects of a ‘pets as therapy’ dog on persons with dementia in a psychiatric ward

A pets as therapy (PAT) programme was initiated in a closed ward of a major psychiatric hospital. The effect of regular contact with a dog on a selected group of chronic ward-bound patients suffering from dementia was assessed over a 12 week period using a number of measures. These included global measures of daily functioning, physiological measures (blood pressure and heart rate) and a measure of general ward noise levels. A matched group from a similar closed ward was used as a control. Results indicated significant experimental group changes in heart rate and a substantial drop in noise levels in the experimental ward during the presence of the dog.     

Factors associated to persistence with hormonal therapy in women with breast cancer

OBJECTIVE

To analyze factors associated with persistence to breast cancer hormone therapy in order to contribute to the quality of care improvement.

METHODS

Retrospective longitudinal study, based on secondary data. A cohort of 5,861 women with breast cancer registered in different datasets of the Brazilian National Cancer Institute and the Brazilian Unified Health System were analyzed. All women were treated at this hospital, which provides free medication, and the follow-up period was from January 2004 to October 2010. Sociodemographic, behavioral, and clinical variables, as well as aspects of lifestyle and health care, were considered in the explanation of variations in the persistence to hormone therapy, applying the Kaplan-Meier method and the Cox proportional hazard model.

RESULTS

Overall persistence to hormone therapy was 79.0% at the end of the first year, and 31.0% in five years of treatment. The risk of discontinuing hormone therapy was higher among women under 35 years old, with more advanced disease (stages III and IV), alcohol drinkers, those undergoing chemotherapy, and for each additional hospitalization, exam performed, and month between diagnosis and beginning of treatment. In the opposite direction, the risk of discontinuity was lower among women who had at least finished high school, those with partner, with a family history of cancer, those who had undergone breast surgery, and who had outpatient visits to a Mastologist, and a Clinical Oncologist.

CONCLUSIONS

The majority of the women with breast cancer (69.0%) do not persist with hormone treatment for the five years recommended, increasing the risk of inadequate clinical results. The results show aspects of care that can provide better results.     

Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women

BACKGROUND: Bacterial intestinal glucosidases exert an important role in isoflavone absorption. Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and, hence, stimulate the absorption of these substances in subjects who may need isoflavone supplementation. OBJECTIVE: The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women. DESIGN: Twelve healthy postmenopausal women participated in a randomized, double-blind, crossover study. They consumed 40 mg of a conjugated form of soybean isoflavones (6 mg daidzein and 18 mg genistein as free form) with or without 3.66 g inulin twice daily in two 21-d experimental phases. Blood samples were collected 0, 1, 2, 3, 4, 6, 10, 12, and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase. Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector. RESULTS: Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein (38% and 91%, respectively) compared with the formulation without inulin. Furthermore, the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones, with or without inulin. However, the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin. CONCLUSIONS: Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women. The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin.