Pituitary dysfunction and association with fatigue in stroke and other acute brain injury.

BACKGROUND: Poststroke fatigue (PSF) is a highly prevalent and debilitating condition. However, the etiology remains incompletely understood. Literature suggests the co-prevalence of pituitary dysfunction (PD) with stroke, and the question raises whether this could be a contributing factor to the development of PSF. This study reviews the prevalence of PD after stroke and other acquired brain injuries and its association with fatigue. SUMMARY: We performed a bibliographic literature search of MEDLINE and EMBASE databases for English language studies on PD in adult patients with stroke, traumatic brain injury (TBI) or aneurysmatic subarachnoid hemorrhage (aSAH). Forty-two articles were selected for review. Up to 82% of patients were found to have any degree of PD after stroke. Growth hormone deficiency was most commonly found. In aSAH and TBI, prevalences up to 49.3% were reported. However, data differed widely between studies, mostly due to methodological differences including the diagnostic methods used to define PD and the focus on the acute or chronic phase. Data on PD and outcome after stroke, aSAH and TBI are conflicting. No studies were found investigating the association between PD and PSF. Data on the association between PD and fatigue after aSAH and TBI were scarce and conflicting, and fatigue is rarely been investigated as a primary end point. KEY MESSAGES: Data according to the prevalence of PD after stroke and other acquired brain injury suggest a high prevalence of PD after these conditions. However, the clinical relevance and especially the association with fatigue need to be established.

Psychiatric co-morbidity is highly prevalent in idiopathic cervical dystonia and significantly influences health-related quality of life: Results of a controlled study.

INTRODUCTION: The aim of this study was to systematically investigate the prevalence of psychiatric disorders and factors influencing health-related quality of life (HR-QoL) in cervical dystonia (CD) patients, in the context of objective dystonia motor severity. METHODS: We studied 50 CD patients and 50 matched healthy controls. Psychiatric assessment included the MINI-PLUS interview and quantitative questionnaires. Dystonia motor severity (based on video evaluation), pain and disability were determined with the TWSTRS rating scale. In addition, severity of tremor and jerks was evaluated with the 7-point CGI-S scale. HR-QoL was determined with the RAND-36 item Health Survey and predictors of HR-QoL were assessed using multiple regression analysis. RESULTS: In CD patients, the MINI-PLUS revealed a significantly higher prevalence of psychiatric disorders (64% vs. 28%, p = 0.001), with substantially more depression (32% vs. 14%) and anxiety disorders (42% vs. 8%). This was confirmed by the quantitative rating scales. Disease characteristics did not differ between patients with and without a psychiatric diagnosis. HR-QoL in dystonia patients was significantly lowered. The most important predictors of HR-QoL appeared severity of depressive symptoms, pain and disability, but not severity of motor symptoms. CONCLUSION: Psychiatric co-morbidity is highly prevalent and is an important predictor of HR-QoL in CD patients, rather than dystonia motor severity. Our findings support the theory of a shared neurobiology for motor and non-motor features and highlight the need for systematic research into psychiatric disorders in dystonia. Adequate treatment of psychiatric symptoms could significantly contribute to better overall quality of life of CD patients.

Treatment with intravenous insulin followed by continuous subcutaneous insulin infusion improves glycaemic control in severely resistant Type 2 diabetic patients.

AIMS: Despite high-dose s.c. insulin therapy, some Type 2 diabetes mellitus (DM) patients remain in poor metabolic control. We investigated whether a period of euglycaemia using i.v. insulin, followed by continuous subcutaneous insulin infusion (CSII), would ameliorate the deleterious effects of hyperglycaemia on insulin sensitivity and result in sustained, improved metabolic control. METHODS: In a prospective observational study, eight Type 2 DM patients with severe insulin resistance (insulin dose 1.92 +/- 0.66 U/kg per day (mean +/-sd)), in poor metabolic control (HbA(1c) 12.0 +/- 1.7%), were treated with i.v. insulin for 31 +/- 10 days aimed at euglycaemia, followed by CSII therapy for 12 months, using insulin lispro. Before and after 28 +/- 6 days of i.v. insulin treatment, insulin sensitivity was measured by a hyperinsulinaemic euglycaemic clamp. RESULTS: Euglycaemia was reached after 12 +/- 6 days of i.v. insulin treatment. Subsequently, the i.v. insulin dose required to maintain euglycaemia decreased from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg per day (P < 0.005). Whole body glucose uptake increased from 12.7 +/- 5.7 to 22.4 +/- 8.8 micromol/kg per min (P < 0.0005). HbA(1c) decreased to 8.9 +/- 1.2% after 28 +/- 6 days, to 7.1 +/- 0.6% after 6 months and to 8.3 +/- 1.4% after 12 months (P < 0.001 vs. pretreatment, for all). Lipid profile improved and plasminogen activator inhibitor type 1 levels decreased significantly. Mean body weight did not change. CONCLUSIONS: In Type 2 diabetic patients, who are poorly controlled despite high-dose s.c. insulin treatment, a period of 2 weeks of euglycaemia achieved by i.v. insulin reverses hyperglycaemia-induced insulin resistance and substantially improves metabolic control. Subsequent CSII treatment, using insulin analogues, appears to maintain improved metabolic control for at least 1 year. This approach is promising but needs further evaluation.

Short-term glucosamine infusion does not affect insulin sensitivity in humans.

Overactivity of the hexosamine biosynthetic pathway may underlie hyperglycemia-associated insulin resistance, but to date human studies are lacking. Hexosamine pathway activation can be mimicked by glucosamine (GlcN). In the present placebo-controlled study we determined whether GlcN infusion affects insulin resistance in vivo. In 18 healthy subjects, we applied the double forearm balance technique (infused arm vs. control arm) combined with the euglycemic hyperinsulinemic clamp (60 mU/m(2).min insulin) for at least 300 min. During the clamp, subjects received infusions in the brachial artery of 4 micromol/dL.min GlcN from 90-240 min (n = 6) or from 0-300 min (n = 6) or saline (placebo; n = 6). We studied the effects of GlcN on forearm glucose uptake (FGU; infused arm vs. control arm, and vs. placebo experiments) and on whole body glucose uptake. GlcN infusion raised the plasma GlcN concentration in the infusion arms to 0.42 +/- 0.14 and 0.81 +/- 0.46 mmol/L; plasma GlcN remained very low (< 0.07 mmol/L) in the control arms and in the placebo group. GlcN infusion did not change forearm blood flow. During insulin, FGU increased more than 10-fold. At all time points, FGU was similar in the GlcN-infused arm compared with the control arm and was not different from FGU in the placebo experiments. Similar results were obtained for forearm arteriovenous glucose differences or extraction and for whole body glucose uptake. Thus, despite relevant GlcN concentrations for 5 h in the infused forearm, GlcN had no effect on insulin-induced glucose uptake. These results do not support involvement of the hexosamine pathway in the regulation of insulin sensitivity in humans, at least not in the short-term setting.

Results of a collaborative study of the EDNAP group regarding the reproducibility and robustness of the Y-chromosome STRs DYS19, DYS389 I and II, DYS390 and DYS393 in a PCR pentaplex format.

A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in the frame work of the STADNAP program, i.e. standardization of DNA profiling in Europe, in order to evaluate the performance of a Y-chromosome STR pentaplex, which includes the loci DYS19, DYS389 I and II, DYS390 and DYS393 and to determine whether uniformity of results could be achieved among different European laboratories. Laboratories were asked to analyze the five Y-STRs using singleplex and multiplex conditions in three bloodstains and one mixed stain (95% female and 5% male). All the laboratories reported the same results even for the mixed stain included in the exercise. This demonstrates the reproducibility and robustness of Y-chromosome STR typing even with multiplex formats and proves the usefulness of Y-STR systems for analyzing mixed stains with a male component.A total of 930 male samples from 10 different populations from Europe were also analysed for all the loci included in the pentaplex. Eight of these ten populations also included haplotype data. As for single gene analysis, haplotype diversity was higher in Germany and Italy and lower in Western European countries and Finland. Pairwise haplotype analysis shows the Finnish departure from the rest of the populations and a relatively homogeneity in the other European populations with F(ST) estimates lower than 0.05.UPGMA analysis shows an association of Western European population (Ireland, UK, Portugal and Galicia) on the one hand and central European populations on the other.

Clostridium septicum sepsis and neutropenic enterocolitis in a patient treated with intensive chemotherapy for acute myeloid leukemia.

We report a case of neutropenic enterocolitis complicated by Clostridium septicum sepsis following intensive chemotherapy to induce remission of acute myeloid leukemia. With the trend towards more intensive chemotherapy, particularly using regimens that induce gastrointestinal toxicity, it is important to recognize the circumstances under which sepsis due to C. septicum is likely to occur, so that appropriate treatment can be instituted promptly.

Comparison of steady-state serum concentrations of digoxin in tablets (Lanoxin) and capsules (Lanoxicaps) in the elderly.

The bioavailability of digoxin in solution (Lanoxicaps, 90-100 percent) is superior to that of Lanoxin tablets (60-80 percent) in young healthy volunteers. The alleged bioequivalence of digoxin in tablets (Lanoxin 0.25, 0.125 mg) and capsules (Lanoxicaps 0.2, 0.1 mg) was studied in 20 elderly inpatients (14 women, 6 men, aged 84 +/- 5 years), treated with digoxin for atrial fibrillation. In a crossover design, steady-state digoxin concentrations were measured in 16 patients after once-daily administration of Lanoxin 0.125 mg or Lanoxicaps 0.1 mg, each for at least ten days. Four other patients took Lanoxin 0.25 mg and Lanoxicaps 0.2 mg successively. The steady-state digoxin concentrations were statistically significantly different, being 1.3 +/- 0.5 nmol/L for Lanoxin and 0.9 +/- 0.4 nmol/L for Lanoxicaps (p = 0.003). Whereas in young healthy volunteers the bioavailability of digoxin from Lanoxicaps (90-100 percent) exceeds that from Lanoxin (80 percent), in elderly patients the absorption appears to be similar. This suggests a lower than expected bioavailability of Lanoxicaps, which may result in subtherapeutic serum concentrations.