Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.     

Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET.

The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. METHODS: Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. RESULTS: PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.     

Effects of long-term moderate food restriction on growth, serum factors, lipogenic enzymes and adipocyte glucose metabolism in lean and obese Zucker rats

The effects of long-term moderate food restriction were assessed in lean and obese male Zucker rats. A 30% reduction in food intake from 5 to 68 wk of age resulted in parallel lowering of body weight in both lean and obese rats compared to their respective ad libitum-fed control groups. In lean rats, epididymal and retroperitoneal fat pad weights and cell size were lowered by food restriction. In obese rats there was an effect of food restriction on growth of the epididymal pad but not the retroperitoneal pad. Hyperinsulinemia, hyperlipidemia and elevated serum albumin levels, as well as higher activity of lipogenic enzymes, were also not affected by food restriction in the obese rat. In a second experiment, long-term food restriction resulted in greater glucose conversion to CO2 in response to insulin in adipocytes from lean rats but not obese rats compared to their respective control groups. These results indicate that food restriction throughout the first year of life in the obese Zucker rat does not alter the development of hyperplastic obesity and insulin resistance.     

CASPER, a Computer ASsisted PERicardial puncture system: first clinical results.

Pericardial puncture is the percutaneous insertion of a needle into the pericardial space to drain a pathological pericardial effusion. The challenge for the operating surgeon is to reach percutaneously a target zone in the vicinity of the mobile heart, in a soft-tissue environment. The surgeon's ability to accomplish this depends on his own mental picture of the effusion. CASPER is a navigation software using an optical localizer which assists the surgeon by enhancing the representation of the effusion and guiding the needle's progress. Using a localized and calibrated echographic probe, the surgeon acquires a set of images in the region of interest. This zone is then manually segmented on each image, a common zone is computed, and the surgeon defines a trajectory for the needle. During the puncture procedure, the surgeon follows the position of the localized needle on a computer monitor. After initial validation on an experimental phantom, a feasibility study was performed using canine and porcine models. The optical localization device was changed from an Optotrak to a Polaris device for easier use in the clinical setting. Prior to clinical application, various tests were performed concerning the mobility of the thoracic cage, the reproducibility of the thoracic position over several apneas, and the stability of anatomic structures relative to the thoracic cage. Finally, a first clinical application was successfully performed using this system. The present paper reports on these last two stages.     

Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n=10), GHRH and GHRP-2 (n=10), GHRP-2 and GHRH+GHRP-2 (n=10), GHRH+GHRP-2 and GHRH+GHRP-2+TRH (n=10). The GHRH and GHRP-2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS Critically ill patients presented a striking GH response to GHRP-2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients; P=0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P=0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response < ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P=0.007). GHRP-2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05). CONCLUSIONS The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.     

Behavioural pharmacology of the serenic, eltoprazine

In this paper the effects of serenics (eltoprazine and fluprazine) are described in several animal models for offensive agonistic, defensive agonistic and predatory behaviour. They are compared with the effects of a number of other putative anti-aggressive compounds or drugs used clinically in order to ameliorate aggressive behaviour of psychiatric patients. In isolation-induced offensive aggression in mice, eltoprazine has a marked and potent anti-aggressive activity, although numerous other psychoactive drugs also exert anti-aggressive effects. The behavioural specificity of this anti-aggressive profile was investigated using an ethologically derived animal model, social interaction in male mice. In this model, eltoprazine has a very specific anti-aggressive (serenic) profile, inhibiting aggression while social interaction and exploration are not decreased but even enhanced; inactivity, a measure for sedation, is not affected. Such a profile contrasts sharply with that of neuroleptics (chlorpromazine, haloperidol), psychostimulants (d-amphetamine) or benzodiazepines (chlordiazepoxide), which exert severe sedation (neuroleptics) or even aggression-enhancing effects (BDZ). After subchronic treatment no tolerance for the anti-aggressive effects of eltoprazine occurred. The specific anti-aggressive effects of eltoprazine were also found in rat models of offensive agonistic behaviour. In one such model - resident-intruder aggression - eltoprazine reduced offensive behaviour specifically, leaving social interactions and exploration intact, and did not induce sedation or other unwanted side-effects. The neuroleptic haloperidol was very sedative in this model, as was the 5-HT1A-agonist buspirone. Benzodiazepines (chlordiazepoxide) have a biphasic effect in this paradigm, enhancing offence at low doses and decreasing it at higher doses, due to muscle relaxation. In another offensive model, colony-aggression, in which a dominant and subordinate male in a colony are confronted with a male intruder, eltoprazine reduced offensive behaviour of both the dominant and the subordinate against the intruder. In contrast, chlordiazepoxide enhanced aggression, at least at lower doses, whereas alcohol had, up to very high doses, no effect on the offensive behaviour. In a brain-stimulation induced offensive model--hypothalamically-induced aggression in rats--eltoprazine specifically reduces offence. Locomotion, a measure for sedation, was either unaffected or even somewhat enhanced, indicating the absence of any sedatory activity of this serenic compound. In contrast, haloperidol heavily sedated animals, making them incapable of aggression.(ABSTRACT TRUNCATED AT 400 WORDS)