Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy

OBJECTIVE: This study aimed to assess glycemic response to a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro (Mix 75/25) BID plus metformin versus insulin glargine QD plus metformin in patients with type 2 diabetes mellitus (DM). METHODS: Adults new to insulin therapy were enrolled in a multicenter, randomized, prospective, open-label, crossover study with 16 weeks on each treatment. Variables included glycosylated hemoglobin (HbA(1c)), hypoglycemia rate, fasting blood glucose (FBG), 2-hour postprandial blood glucose (ppBG), and rise in blood glucose after meals. RESULTS: One hundred five patients (mean age, 55 years) were randomized. There was no difference in baseline mean values for either treatment sequence group for body mass index, duration of DM, or HbA(1c). Ninety-five patients completed the study and 67 were included in the efficacy analysis. Mix 75/25 was associated with lower mean (SD) HbA(1c) at end point (7.4% [1.1%] vs 7.8% [1.1%]; P = 0.002). More patients using Mix 75/25 achieved target HbA(1c) < or =7.0% (42% [30/71] vs 18% [13/71]; P < 0.001). With Mix 75/25, the mean (SD) 2-hour ppBG was similar after lunch but lower after breakfast (156.4 [43.6] vs 171.1 [44.9] mg/dL; P = 0.012) and dinner (164.8 [42.5] mg/dL vs 193.8 [51.0] mg/dL; P < 0.001), although FBG was higher (139.3 [36.6] mg/dL vs 123.9 [34.9] mg/dL; P < 0.001). Rise in ppBG was lower with Mix 75/25 after breakfast (16.9 [47.0] mg/dL vs 47.4 [34.8] mg/dL; P < 0.001) and dinner (14.2 [44.1] mg/dL vs 45.9 [41.3] mg/dL; P < 0.001). Gain in mean (SD) body weight was greater with Mix 75/25 than insulin glargine (2.3 [4.0] kg vs 1.6 [4.0] kg; P = 0.006). For all randomized patients, mean (SD) hypoglycemia rates were lower with insulin glargine (0.68 [1.38] vs 0.39 [1.24] episodes/patient per 30 days; P = 0.041), although nocturnal hypoglycemia was similar. CONCLUSION: In this study population, Mix 75/25 plus metformin was associated with lower HbA(1c) than insulin glargine plus metformin, smaller rise in ppBG after breakfast and dinner, and higher proportion of patients achieving HbA(1c) < or =7.0%, with a slight increase in overall (but not nocturnal) hypoglycemia.     

Multiparametric analysis of peripheral blood in the normal pediatric population by flow cytometry

Lymphocyte subset analysis was performed on 114 healthy children and 84 healthy adults. Samples were prepared by a whole blood lysis technique and analyzed by flow cytometry. The percentage and total number of CD3+, CD4+, CD8+, and CD19+ lymphocytes were calculated for each of six age groups. A direct correlation with age was seen in the percentages of CD3+, CD4+, and CD8+ lymphocytes. The absolute number and percentage of total lymphocytes, the percentage and absolute number of CD19+ lymphocytes, and the absolute number of CD3+ lymphocytes decreased with age. No significant correlation with age was observed for white blood cells, the absolute number of CD4+ and CD8+ lymphocytes, and the CD4+/CD8+ ratio.     

The gene for synapsin III and attention-deficit hyperactivity disorder

OBJECTIVE: Recent studies have implicated the involvement of proteins regulating neurotransmitter release in the etiology of attention deficit hyperactivity disorder. On the basis of the role of synapsin III in the modulation of neurotransmitter release, we tested this gene as a candidate contributing to the genetic susceptibility of attention deficit hyperactivity disorder. METHOD: In this study, we genotyped five markers across the gene on 177 small, nuclear families consisting of an attention deficit hyperactivity disorder proband, their parents, and 43 affected siblings. We examined the transmission of the alleles at each one of these sites and the haplotypes of the polymorphisms using the transmission disequilibrium test. RESULT: Our observations did not yield any evidence of biased transmission of the alleles at any polymorphism or haplotype. On the basis of the evidence for synapsins in learning and memory from animal models, we also investigated the relationship of this gene to verbal short-term and working memory as measured by digit span forward and backwards. No evidence was found for an association of this gene to these traits. CONCLUSION: Our findings with this particular sample do not support the synapsin III locus as a major susceptibility locus contributing to attention deficit hyperactivity disorder.     

Repeated administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) modulates neuroinflammation and amyloid plaque load in mice bearing amyloid precursor protein and presenilin-1 mutant transgenes

Background

Data indicates anti-oxidant, anti-inflammatory and pro-cognitive properties of noradrenaline and analyses of post-mortem brain of Alzheimer's disease (AD) patients reveal major neuronal loss in the noradrenergic locus coeruleus (LC), the main source of CNS noradrenaline (NA). The LC has projections to brain regions vulnerable to amyloid deposition and lack of LC derived NA could play a role in the progression of neuroinflammation in AD. Previous studies reveal that intraperitoneal (IP) injection of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) can modulate neuroinflammation in amyloid over-expressing mice and in one study, DSP-4 exacerbated existing neurodegeneration.

Methods

TASTPM mice over-express human APP and beta amyloid protein and show age related cognitive decline and neuroinflammation. In the present studies, 5 month old C57/BL6 and TASTPM mice were injected once monthly for 6 months with a low dose of DSP-4 (5 mg kg^-1) or vehicle. At 8 and 11 months of age, mice were tested for cognitive ability and brains were examined for amyloid load and neuroinflammation.

Results

At 8 months of age there was no difference in LC tyrosine hydroxylase (TH) across all groups and cortical NA levels of TASTPM/DSP-4, WT/Vehicle and WT/DSP-4 were similar. NA levels were lowest in TASTPM/Vehicle. Messenger ribonucleic acid (mRNA) for various inflammatory markers were significantly increased in TASTPM/Vehicle compared with WT/Vehicle and by 8 months of age DSP-4 treatment modified this by reducing the levels of some of these markers in TASTPM. TASTPM/Vehicle showed increased astrocytosis and a significantly larger area of cortical amyloid plaque compared with TASTPM/DSP-4. However, by 11 months, NA levels were lowest in TASTPM/DSP-4 and there was a significant reduction in LC TH of TASTPM/DSP-4 only. Both TASTPM groups had comparable levels of amyloid, microglial activation and astrocytosis and mRNA for inflammatory markers was similar except for interleukin-1 beta which was increased by DSP-4. TASTPM mice were cognitively impaired at 8 and 11 months but DSP-4 did not modify this.

Conclusion

These data reveal that a low dose of DSP-4 can have varied effects on the modulation of amyloid plaque deposition and neuroinflammation in TASTPM mice dependent on the duration of dosing.     

Anabolic steroid abuse: psychiatric and physical costs

The psychiatric effects of anabolic-androgenic steroids (i.e., testosterone and its derivatives) have been less well studied than their physical effects but are reported to include depression, mania, psychosis, and aggression. Dependence can also occur, with withdrawal involving psychiatric and physical symptoms. Adverse effects of steroid abuse should be managed by discontinuing the drugs-by tapering if necessary-and by treating the symptoms.     

Patients and nurses: a powerful force

Quality of care is of paramount importance to both patients and nurses. This article examines how the existing patient/nurse partnership is the result of a variety of clinical, political, and organisational power paradigm shifts over time. The significance of this partnership on the quality of care, particularly in terms of the necessary power base required, is then considered. Next the education, health care systems, and diversity issues found in the UK and the US are compared and contrasted. The conclusion focuses on a transatlantic vision for the future in the consolidation of the patient/nurse transaction for the achievement of negotiated, competent, compassionate care and as a continuing force for quality at policy, strategic, and operational levels.     

Implementation of a prechemotherapy educational intervention

Traditionally, patients have received chemotherapy education in the clinical setting during the first chemotherapy treatment. Nurses long have been aware that patients are anxious and overwhelmed on that first chemotherapy day and have noted a lack of retention of information. This article describes a prechemotherapy education project initiated at an urban cancer clinic in the midwestern United States. The project was created in an effort to alleviate some of the anxiety associated with the first chemotherapy experience.