Doppler tissue imaging reveals systolic dysfunction in patients with hypertension and apparent "isolated" diastolic dysfunction.

The purpose of this study was to examine left ventricular systolic longitudinal contraction in patients with essential hypertension with normal ejection fraction and fractional shortening. We used tissue tracking and strain rate Doppler echocardiography to evaluate left ventricular longitudinal contraction in 40 patients with hypertension and 30 age-matched control patients. Tissue tracking and peak systolic strain rate were significantly decreased in patients with hypertension and diastolic dysfunction compared with patients with hypertension and normal diastolic function or with control patients. In conclusion, patients with hypertension who, earlier, were considered to have isolated diastolic dysfunction were demonstrated to have reduced left ventricular systolic longitudinal function.     

Utility of activated partial thromboplastin time waveform analysis for identification of sepsis and overt disseminated intravascular coagulation in patients admitted to a surgical intensive care unit

OBJECTIVE: An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described in association with overt disseminated intravascular coagulation. This abnormality, a biphasic waveform, is caused by the in vitro formation of Ca2+-induced complexes between very low density lipoprotein and C-reactive protein. We have evaluated the diagnostic utility of aPTT waveform analysis for identifying patients with overt disseminated intravascular coagulation and sepsis. DESIGN: Observational study investigating the predictive value of biphasic waveform for the diagnosis of sepsis and overt disseminated intravascular coagulation. SETTING: Surgical intensive care unit of a university hospital. SUBJECTS: We studied 331 consecutive patients admitted to the intensive care unit during a period of 6 months. INTERVENTIONS: Laboratory analyses, including prothrombin time, aPTT, aPTT waveform analysis, fibrinogen, D-dimer antigen, and platelet count. MEASUREMENTS AND MAIN RESULTS: At the most sensitive threshold value of the waveform variable for detection of the biphasic waveform (slope_1 = -0.05 %T/sec), this abnormality was detected in 54 of 331 patients (16.3%) at admission and 95 of 331 patients (28.7%) during the entire course of intensive care unit treatment. At this threshold, 59.3% of patients with a biphasic waveform on admission and 45.3% with a biphasic waveform during the total intensive care unit course were diagnosed with sepsis. Depending on the threshold value of slope_1, the sensitivity of aPTT waveform analysis for detection of sepsis varied between 22% and 55% at admission and between 48% and 74% during the entire intensive care unit stay. The specificity for sepsis varied between 92% and 98% and between 81% and 94%, for admission and total intensive care unit course, respectively. Biphasic waveform showed a comparable specificity for the diagnosis of overt disseminated intravascular coagulation, albeit at a lower sensitivity. CONCLUSIONS: As an adjunct to routine coagulation testing in intensive care unit patients, aPTT waveform analysis is an elegant means for the rapid and highly specific identification of patients with sepsis.     

Activation of coagulation during alimentary lipemia under real-life conditions

High intake of saturated fat is a predictor of coronary heart disease mortality. The phenomenon of postprandial angina pectoris has been described many years ago. Although earlier studies have demonstrated postprandial activation of coagulation factors VII and XII, platelets and monocytes, conclusive evidence for intravascular fibrin formation after a fat-rich meal has not been reported yet. The present study included 33 healthy physicians (7 females, 26 males) with a mean age of 42 years (range 27-62 years), and 27 coronary heart disease patients (8 females, 19 males) with a mean age of 63 years (range 47-81 years). Of the coronary heart disease patients, 26/27 were treated with acetylsalicylic acid and 25/27 with lipid-lowering drugs simvastatin or atorvastatin. Blood samples were drawn 30-60 min before and 30-60 min after a dinner consisting of rye bread with liversausage and black pudding as hors d'oeuvre, lettuce with smoked bacon in a lard dressing, stuffed fried goose with red cabbage, potato dumplings and sweet chestnuts, and white and brown mousse au chocolat. Average intake per person was 3760 kcal, with 125.9 g protein, 238.0 g fat and 268.9 g carbohydrate. We measured a significant postprandial increase in fibrinopeptide A (FpA) levels from 1.14+/-1.23 microg/l to 4.18+/-2.86 microg/l (p<0.0001) in healthy probands, and 4.66+/-13.61 microg/l to 12.80+/-15.04 microg/l (p<0.0001) in coronary heart disease patients. Triglycerides increased from 137.6+/-60.5 to 201.5+/-75.0 mg/dl in healthy probands and from 211.9+/-94.6 to 273.6+/-122.5 mg/dl in coronary heart disease patients. Fat-rich meals may cause procoagulant episodes, which may promote vascular complications such as myocardial infarction, transient ischemia attacks in susceptible persons.     

Association and linkage of allelic variants of the dopamine transporter gene in ADHD

Previously, we had reported a genome-wide scan for attention-deficit/hyperactivity disorder (ADHD) in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 (parametric HLOD analysis under a dominant model) near the dopamine transporter gene (DAT1). We genotyped 30 single nucleotide polymorphisms (SNPs) in this candidate gene and its 5' region in 329 families (including the 102 initial families) with 523 affected offspring. We found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P=0.0046); (2) the global P-value for association of haplotypes was significant for block two upon correction for all (n=3) tested blocks (P=0.0048); (3) within block two we detected a nominal P=0.000034 for one specific marker combination. This CGC haplotype showed relative risks of 1.95 and 2.43 for heterozygous and homozygous carriers, respectively; and (4) finally, our linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains our linkage peak and that rs463379 (P<0.05) is the only SNP of the above haplotype that contributed to the linkage signal. In sum, we have accumulated evidence that genetic variation at the DAT1 locus underlies our ADHD linkage peak on chromosome 5; additionally solid association for a single SNP and a haplotype were shown. Future studies are required to assess if variation at this locus also explains other positive linkage results obtained for chromosome 5p.     

Allelic variants of <Emphasis Type="Italic">SNAP25</Emphasis> in a family-based sample of ADHD

Summary Altered neurotransmission has been suggested to be a crucial factor in the pathophysiology of attention-deficit/hyperactivity disorder ADHD. Subsequently genes encoding for synaptic proteins have been investigated in candidate gene studies. These proteins mediate the release of neurotransmitters into the synaptic cleft in the process of signal transduction by forming a transient complex, enabling the junction of vesicle and synaptic membrane. One of the core proteins of this complex is the synaptosomal-associated protein 25 (SNAP25). It is one of the most validated candidate genes in ADHD according to meta-analyses. However, differing results were observed in previous studies, some of which were not able to observe association with ADHD. In this study we aimed to investigate association of genetic variants of SNAP25 located in the putative promoter region of SNAP25 and a SNP in intron 8, previously reported to associated with ADHD. A family based design was applied to detect preferential transmission of genetic variants. In our German ADHD sample no preferential transmission of either variant could be observed. Further investigation considering sub-sample analysis regarding response to D-amphetamine could enlight the role of SNAP25 in ADHD. Correspondence: Tobias J. Renner, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany     

Purification of human plasma fibrinogen by chromatography on protamine-agarose

A study was performed to investigate if protamine covalently attached to CNBr-activated agarose is a useful tool for the purification of fibrinogen from human plasma samples. One chromatography step yielded a preparation with a clottability greater than 90% from platelet-poor plasma with a yield of 65-80% of fibrinogen applied. The preparation is free of plasminogen, immunoglobulins, fibronectin, albumin, antithrombin III, alpha 2-macroglobulin, and alpha 1-antitrypsin, as determined by immunological and functional methods. 6.5 mg of fibrinogen were adsorbed to 1.0 ml of protamine-agarose. Protamine-agarose chromatography can be applied to plasma samples as small as 200 microliters.     

A randomized controlled trial of two weight-reducing short-term group treatment programs for obesity with an 18—month follow—up

We found in an earlier study that participants in a short-term streatment program for obesity showed a good weight reduction (10.4 kg) 18 months after treatment terminated. The program included elements from cognitive therapy (CT) and psychoeducation. In the present study the efficacy of as light modification of the same treatment program (cognitive treatment group) was compared with a behavioral program that included moderate-intensity physical activity and behavioral techniques (the control treatment group) in a randomized controlled trial. The primary effect variable was weight change 18 months after the end of therapy. Both treatment programs lasted for 10 weeks (2 hr/week), and thereafter the participants were weighed periodically over an 18-month period. The participants were obese women employed outside the home. Twelve of the participants did not receive treatment after randomization. Eleven of these participants had been randomized to the cognitive program, whereas the remaining participant was randomized to the control program.The mean age for those that began the 2 programs was 48.5 years, and the mean body mass index (BMI) was 36.6. For those who completed the treatment programs and participated in the 18-month follow-up, the baseline BMI was 34.7. One participant in the cognitive treatment group (n = 16) and 6 in the control program (n = 26) dropped out during treatment. Both per-protocol and intention-to-treat analyses were performed on the data. Fifteen participants (94%) completed the cognitive program. Of these, 13 (87%) participated at the18-monthfollow-up.Their mean weight loss attreatment completion was 8.6kg(SD = 2.9) and 18 months later 5.9 kg (SD =5.4). Twenty participants (77%) completed the control program. Of these, 16 (80%) participated in the 18-month follow-up. Their mean weight lossatthe end of treatment was 0.7kg(SD=1.2), and 18 months later they showed an increase in weight of 0.3 kg (SD = 4.3) as compared with baseline weight. The weight differences between the 2 program groups were highly significant (p< .01-.001) at all posttreatment weighings. In the intention-to-treat analysis, all participants who started the cognitive treatment (n=16) or control program(n=26) were included. The last observation carried forward was used for those who dropped out from therapy or from follow-up. Eighteen months after the end of therapy, the mean weight loss was 5.5 kg (SD = 5.5) in the cognitive group, whereas the control group evidenced a weight loss of 0.6 kg (SD = 5.5). The weight change differences between the 2 groups were highly significant at all follow-up weighings (p < .001). The low drop-out rate during the treatment period demonstrates that the participants found the 2 programs acceptable. The long-term efficacy of the cognitive treatment program seems to be satisfactory. With its group format and short treatment duration, the cognitive program is attractive from a cost-effective standpoint.     

Identification of gram-negative aerobic fermentors in a clinical bacteriological laboratory

A basic set of six biochemical tests (indol, urease, hydrogensulphide production, acetoin, ornithine decarboxylase andΒ-galactosidase) were selected from an original set of fourteen tests and found to give more than 97% accurate reactions within 18 h of incubation for the identification of bacteria belonging toEnterobacteriaceae. This set permits identification on the genus and/or species level forEscherichia, Shigella, Salmonella, Edwardsiella, Citrobacter andProteus. For theKlebsiella-Enterobacter-Serratia group, where a species diagonsis was considered desirable, eight additional tests (esculin, raffinose, sorbitol, malonate, citrate, lysine decarboxylase, deoxyribonuclease and motility) permitting identification within 18 to 72 h were added. The use of this two-step test set for the identification of almost 6000 strains isolated from clinical specimens during an eight month period is reported.