[Hyaluronan as a key for accelerated wound healing in human 3D full thickness skin models]. / Hyaluronan als Schlüssel zur schnelleren Wundheilung in humanen 3­D-Vollhautmodellen.

BACKGROUND: Wound healing can be divided into three phases: (1) exsudation phase, (2) granulation phase, (3) regeneration phase. In particular, the epithelization phase is of great importance in order to quickly reconstitute the natural skin barrier. The aim of the present study was to determine the reepithelization kinetics of untreated and 0.5% sodium hyaluronate (NHA) treated human 3D full thickness skin models. MATERIALS AND METHODS: The test protocol consisted of topically applying 10 µl of the test substance 0.5% NHA twice a day. Evaluation of reepithelialization kinetics was carried out from days 2-6. Determination of the influence on immune response was performed based on quantification of IL-1α and IL-10. RESULTS: Application of 0.5% NHA twice a day enhanced the reepithelialization speed at all time points (p < 0.001). This observation is accompanied by a reduced expression of IL-10 paralleled by an elevated expression of IL-1α on days 2-4 (p < 0.001). DISCUSSION: The treatment of human skin models with NHA resulted in a significantly increased reepithelization velocity of wounded tissue and consequently promoted faster wound closure, compared to untreated controls. It can be assumed that the downregulation of IL-10 caused the IL1-α mediated increased immune response which finally leads to accelerated wound healing. Follow-up studies will reveal if the faster wound healing and the modulation of the immune response through the application of NHA is valid in vivo.

Long-term cognitive outcomes of extremely low-birth-weight infants: the influence of the maternal educational background.

AIM: The purpose of the present contribution is to analyse the relationships between perinatal risk factors, social parameters and neurodevelopmental outcomes in extremely low-birth-weight (ELBW) children up to the age of 10-13 years. METHODS: Of 200 live-born ELBW infants, 148 were enrolled in the high-risk infant follow-up programme. Each follow-up visit included a neurodevelopmental examination and an interview with the infant's parents. Multivariate analyses using SPSS (version 17.0, Chicago, IL, USA) were conducted, and a p-value of <0.05 indicated a statistically significant result. RESULTS: The results of the logistic regression analysis of the biological and sociodemographic risk factors illustrated that a low maternal educational background is the most important factor (OR, 21.9) associated with a decreased composite intelligence quotient (IQ) in children between 10 and 13 years old. A Grade III or Grade IV intraventricular haemorrhage (IVH) or periventricular leukomalacia (PVL) were also associated with decreased IQ at the age of 10-13 years (OR, 6.9). These results were confirmed by ANOVAs with repeated measurements. CONCLUSION: Maternal educational background is the strongest predictor of long-term neurodevelopment in ELBW children. The findings emphasize the need for special support and follow-up care services for poorly educated parents.

[CRT in atrial fibrillation--methodical and apparatus options in decision-making]. / CRT bei Vorhofflimmern. Methodische und apparative Optionen zur Entscheidungsfindung.

Heart failure and atrial fibrillation often coexist, especially with increasing degree of heart failure severity. Under this constellation, the advantage of cardiac resynchronization therapy (CRT) is still under discussion and displayed as an unresolved problem in the guidelines for cardiac stimulation and resynchronization. If ventricular desynchronization can be documented and response to CRT can be expected, the challenge is to interoperatively seek the best left ventricular electrode position and to postoperatively optimize the device in order to achieve the best therapy performance. This situation encourages the development of individualized methods and to utilize innovative apparatus features in order to consolidate individual decisions and to optimize CRT in heart failure with atrial fibrillation.

[Left ventricular electromechanical latency period is an additional indicator to upgrade from right to biventricular DDD pacing]. / Die linksventrikuläre elektromechanische Latenzzeit ist ein zusätzlicher Indikator für ein Upgrading zur biventrikulären Stimulation.

In DDD pacing, the left-ventricular electromechanical latency period defines the duration between premature ventricular stimulation and the prematurely ending left-atrial contribution to left-ventricular filling. It has to be considered in diastolic AV delay optimization. Individual duration of this parameter seemed to reflect the ventricular function. Therefore, we compared the left-ventricular electromechanical latency period due to right ventricular stimulus with the documented ejection fraction of two groups, 33 congestive heart failure patients carrying biventricular systems and 13 right ventricular paced bradycardia patients. A mean latency period of 168+/-26 ms was found in the heart failure patients (ejection fraction: 25+/-5%) which was significantly longer (p=0.0039) compared to the bradycardia patients (ejection fraction: 51+/-12%) with a mean latency of 119+/-13 ms. Thus, an increasing latency period during right ventricular DDD pacing therapy indicates decreasing ejection fraction. A cut-off interval of 135 ms allowed the discrimination of 93% of our patients as having an individual ejection fraction of either up to 35% or above. Thus, the left ventricular electromechanical latency period can be used as an additional parameter indicating the necessity to upgrade from right to biventricular DDD pacing.

[Feasibility and safety of long-term AAI(R) pacing in isolated sinus node syndrome]. / Realisierbarkeit und Sicherheit einer alleinigen AAI(R)-Schrittmacherbehandlung beim isolierten symptomatischen Sinusknotensyndrom.

Recent investigations prove that AAI(R) pacing is the "ideal" stimulation mode in isolated sick sinus syndrome. Nevertheless, in Germany this bradycardia is treated by AAI(R) pacemakers in less than 4% of cases compared to 25% in other countries. In our institution treatment of patients with isolated sick sinus syndrome is uniform and corresponds to the actual guidelines since the early 1990s; therefore the aim of our study was to analyze feasibility and safety of AAI(R) pacing in a retrospective study. Between 1998 and 2000, 52 of 165 patients (31.5%) with isolated sick sinus syndrome were treated by an AAI(R) pacemaker. The median follow-up duration was 51.5 months (minimal: 36 months). 6 patients died, in all cases unrelated to the stimulation mode. Three patients required reoperations, however, in only one case due to second degree AV block with the need for upgrading to DDD stimulation. Thus, the yearly incidence of this specific complication in the AAI(R) cohort is 0.64%.In conclusion, permanent atrial stimulation in isolated sick sinus syndrome is feasible in a quarter of all cases. It is safe if performed corresponding to actual guidelines. Additionally, single lead AAI(R) pacing is a cost-effective therapy and the only stimulation mode which, today, reliably prevents unnecessary right ventricular stimulation. If, on the other hand, algorithms providing automatic mode switching from AAI to DDD and vice versa are implemented reliably into all dual chamber pacemakers, single chamber atrial pacing will no longer be a subject for discussion.

Results of a systematic adverse drug reaction (ADR)-screening concerning bradycardia caused by drug interactions in departments of internal medicine in Rostock.

OBJECTIVES: The concomitant intake of drugs, which is frequently needed, may be associated with drug interactions. We report results on the screening of ADRs responsible for hospital admissions involving bradycardia. This investigation was part of a BfArM pilot project with the objective of monitoring and reporting ADRs. METHOD: Beginning in 1997, a trained medical staff member of the Pharmacovigilance Center, Rostock, prospectively screened all hospital admissions to the Departments of Internal Medicine of the 2 hospitals in Rostock (40,000 hospital admissions). ADRs leading to hospital admission were registered, evaluated and reported. RESULTS: A total of 1,441 ADRs were recorded by the Pharmacovigilance Center Rostock in the period up to December 2000. 12% (n = 173) of all ADRs involve the cardiovascular system; 83 patients (5.7% of all ADRs) suffered from bradycardia. Bradycardia was the most frequent cardiovascular ADR observed. Of these patients, 88% were receiving 3 - 10 different drugs. Drugs suspected of causing bradycardia were: digitalis (n = 62), beta-blockers (n = 47), calcium channel blockers with negative chronotropic effect (n = 45), and antiarrhythmic drugs (n = 3). 54 patients had received more than I of these drugs concomitantly as outpatients, increasing the risk of drug interactions: 18 patients received digitalis + calcium channel blocker; 14 patients digitalis + beta-blocker; 7 patients beta-blocker + calcium channel blocker; 12 cases digitalis + beta-blocker + calcium channel blocker. CONCLUSION: The results show that special attention should be given to patients who receive more than 1 drug when there is a high risk of bradycardia. Drug combinations which may cause drug interactions should be avoided, especially when other equivalent therapeutic options are available.

Management of negative symptoms among patients with schizophrenia attending multiple-family groups.

OBJECTIVE: Outcomes for negative symptoms over a one-year period were examined in two groups of patients, one receiving psychoeducational multiple-family group treatment and one receiving standard care. METHODS: A total of 63 outpatients, ages 18 to 45 years, with DSM-IV diagnoses of schizophrenic disorders were randomly assigned to standard care or multiple-family group psychoeducation treatment at a large mental health center in Spokane, Washington. Treatment assignment was stratified by whether patients were taking typical or atypical antipsychotic medications. Negative symptom status was monitored monthly for one year by raters blind to group assignment and measured as a composite of five symptoms using the Modified Scale for the Assessment of Negative Symptoms. RESULTS: When the analysis controlled for baseline negative symptoms, participants in the multiple-family group experienced significantly reduced negative symptoms compared with those receiving standard care. Taking atypical antipsychotic medication or having a diagnosis of substance abuse was not associated with the severity of negative symptoms. An additional analysis of the five individual negative symptoms indicated small but consistent group differences on all dimensions except inattention. Negative symptoms were significantly correlated with relapse to acute illness but not with outpatient or inpatient service use. CONCLUSIONS: The study demonstrated that a psychoeducational multiple-family group intervention was more effective than standard care in managing negative symptoms over a 12-month period. The results are particularly relevant because negative symptoms are associated with relapse, poor social and occupational functioning, cognitive impairment, and lower subjective quality of life.

Neurovegetative symptoms in multiple sclerosis: relationship to depressed mood, fatigue, and physical disability.

Some authors have suggested that when evaluating depression in multiple sclerosis (MS) patients, neurovegetative symptoms should be discounted and/or not considered, given the ostensibly high overlap between symptoms of MS (e.g., sleep disturbance, fatigue) and neurovegetative symptoms of depression. A further assertion is that inclusion of items assessing neurovegetative symptoms may artificially inflate overall depression scores and that mood scales may provide more accurate indices of depression in MS patients. The current study investigated the possibility that some neurovegetative symptoms may be specifically related to MS patients' depressed mood and are not simply indicators of physical disability and/or fatigue. Seventy-six clinically definite MS patients in the northwestern United States were administered two depression inventories and measures of physical disability and fatigue as part of a larger study. Results revealed that one neurovegetative symptom--disinterest in sex--was uniquely associated with depressed mood, and other neurovegetative symptoms were associated with both depression and fatigue but not physical disability. The present findings suggest that certain neurovegetative symptoms are differentially associated with depression, fatigue, and physical disability in MS. Routinely discounting all neurovegetative symptoms when assessing depression in MS patients may thus be unwarranted.

The ecological validity of clinical tests of memory and attention in multiple sclerosis.

Ecological validity--the degree to which clinical tests of cognitive functioning predict functional impairment--has recently become an area of interest in neuropsychology. The current study used a sample of 31 cognitively and functionally impaired multiple sclerosis (MS) patients to determine if tests commonly used to assess memory and attentional functioning in MS are ecologically valid. Two methods of improving the ecological validity of cognitive testing were employed. Stepwise multiple regression analyses suggested that tests of memory and attention more analogous to everyday tasks are better predictors of functional impairment in MS than both standard clinical tests of memory and attention, and memory questionnaires completed by the patient or a significant other. Nonetheless, both standard clinical tests and more ecologically valid tests significantly predicted functional impairment. Importantly, they were not significantly correlated with one another, suggesting that the inclusion of both types of tests in evaluating MS patients is warranted.

Depression in multiple sclerosis: relationship to working memory capacity.

Recent research has shown that depression in multiple sclerosis (MS) is associated with deficits on cognitively demanding tasks. One explanation for this relationship is that depressed MS patients may have reduced working memory capacity. The present study was designed to test this hypothesis. Depressed MS patients were compared with nondepressed MS patients and nondepressed healthy controls on a task of working memory capacity (reading span) and a short-term memory task not taxing working memory capacity (word span). In support of the capacity-reduction model, compared with the nondepressed groups, depressed MS patients performed significantly worse on reading span (p<.001) but not on word span. Additionally, reading span was significantly correlated with capacity-demanding tasks shown to be impaired in depressed MS patients in previous reports. Results suggest that depressed MS patients are characterized by limited working memory capacity and that the central executive component of the working memory system may be most affected.

Depressed mood in multiple sclerosis: relationship to capacity-demanding memory and attentional functioning.

Because it is theorized that depression results in reduced available attentional capacity that, in turn, can explain the impaired performance on capacity-demanding tasks in depressed individuals, the authors predicted that multiple sclerosis (MS) patients with depressed mood would have difficulty with these types of tasks. Twenty depressed mood MS participants were compared with 41 nondepressed mood MS participants and 8 nondepressed mood controls on 5 attentional capacity-demanding clinical memory and attentional tasks and 3 tasks with minimal capacity demands. Depressed mood MS patients performed significantly worse than both nondepressed mood groups on the 3 speeded capacity-demanding attentional measures but not on any of the tasks requiring few capacity demands, supporting the authors' predictions. The possibility that the impaired performance of depressed mood MS patients on speeded attentional tasks was mediated by reduced verbal working memory capacity, impaired deployment of executive strategies that access working memory capacity, or psychomotor slowing is explored.

Glove powder affects skin roughness, one parameter of skin irritation.

Most patients with immediate-type-hypersensitivity to natural rubber latex (NRL) give a history of hand eczema. Susceptibility to allergens is increased by irritant hand eczema due to damage to the skin barrier. Therefore, especially for employees in medical or paramedical professions, reduction in skin irritation is of importance. The present study reports the effect of glove powder on skin roughness, one feature of skin irritancy. Skin replicas, performed before and after wearing different types of gloves, were evaluated by laser profilometry. Significant alteration of skin roughness was evident and determined by different factors. Use of unpowdered Biogel gloves on prepowdered hands results in an increase in skin roughness, in contrast to the use of Biogel gloves on hands without any pre-application. On the other hand, powdered Manex neoderm gloves show no influence on the skin structure, whereas powdered Peha taft gloves also increase the roughness of the skin. Other potential candidates causing skin morphology alteration could be the glove pH, rubber chemicals with irritant potential and other characteristics of gloves, which are already under investigation.

What range of programmable AV delays is necessary in antibradycardia DDD stimulation?

DDD pacemakers differ considerably in device specific extents of AV delay (AVD) programmability. To demonstrate the requirements of a mean DDD pacemaker patient population optimal AVDs in 200 DDD pacemaker patients (age 8 to 91 years) were estimated by left atrial electrography. The results should help to define an AVD programmability standard. Left atrial electrograms were recorded via a bipolar filtered esophageal lead. The method aims on adjusting the left atrial electrogram to 70 ms prior to the ventricular spike, both during VDD and DDD operation of the pacemaker. In atrial sensed stimulation the optimal AVD varied from 40 to 205 ms (100.5 +/- 24.5 ms) and in atrial paced stimulation from 85 to 245 ms (169.1 +/- 24.5 ms). The difference of the mean values is statistically significant (p < 0.001). The difference between both values in the individual patient, the individual AVD correction time, varied from 0 to 170 ms (68.7 +/- 26.6 ms). Thus, from our findings requirements on AV delay programmability standard can be derived: AVDs (1) should have a range from 40 to 250 ms, (2) should be independently programmable during atrial sensed and atrial paced operation, and (3) should provide as nominal settings 100 ms for atrial sensed and 170 ms for atrial paced stimulation.

The impact of motivationally neutral cues on psychopathic individuals: assessing the generality of the response modulation hypothesis.

Psychopathic individuals' lack of responsiveness to punishment cues and poor self-regulation have been attributed to fearlessness (D. T. Lykken, 1957, 1982, 1995). Alternatively, deficient response modulation (RM) may hinder the psychopathic individual's processing of peripheral information and self-regulation when they are engaged in goal-directed behavior (C. M. Patterson & J. P. Newman, 1993). Although more specific than the fearlessness hypothesis in some respects, the RM hypothesis makes the more general prediction that psychopathic individuals will have difficulty processing motivationally neutral as well as fear-related stimuli. The authors assessed this prediction by using psychopathic and nonpsychopathic male inmates subdivided by level of anxiety/negative affectivity (NA). As predicted by the RM hypothesis, peripheral presentation of motivationally neutral cues produced significantly less interference in low-NA psychopathic individuals than in low-NA controls.

Skin smoothing effects of Dead Sea minerals: comparative profilometric evaluation of skin surface.

The skin smoothing effects of three different liquid gels were compared on 20 mature women. Treatment applications were performed twice a day over a period of 4 weeks, and the skin roughness parameter (Rz) of all test participants was determined at the beginning and at the end of the study using a computer-aided laser profilometry, in accordance with DIN 4768 ff. At the end of the application period, the liquid gel with 1% of a Dead Sea mineral solution had an average skin roughness parameter reduction of 40.7%. The liquid gel without mineral additives showed an average reduction in skin roughness of 27.8%. The control gel without anti-wrinkle agents or the additives showed an average reduction of only 10.4%.

Correlation of functional independence measure (FIM) and SPECT Iofetamine (I-123) as a predictor of functional return in stroke.

Function following stroke is often measured using the Functional Independence Measure (FIM). Independence occurs when the patient achieves certain levels of functions. SPECT imaging assesses the regional cerebral blood flow (rCBF). Is it possible to correlate the FIM scores with SPECT imaging and predict functional return? We evaluated total of 69 stroke patients with SPECT imaging using Iofetamine (I-123). Patients were scanned within 14-21 days post-stroke. CT scans were evaluated and correlated with the SPECT images. This information was compared with the admission and discharge FIM scores. The rCBF reperfusion changes and region of stroke were evaluated and correlated with discharge functional status. The right parietal areas demonstrated a strong correlation with SPECT and FIM changes as predictors of return of functional living status (p-value = 0.0438). The right parietal area demonstrated an improvement in ambulation (p-value = 0.0578); the right brain correlated with overall improvement in FIM scores and change in SPECT imaging (p-value = 0.0833); the left brain did not exhibit significant values. Our conclusion was that there were trends seen with the predictive value of stroke recovery using SPECT imaging. The current sample number was not large enough to provide an adequate study, especially for the left brain; a larger study is needed. This information could be useful to help determine patient placement for rehabilitation.

[Selection of the optimal pacemaker - Are age and secondary disease related health conditions significant?]. / Indikationsgerechte Wahl des Schrittmachers - Welche Bedeutung haben durch Alter und Zweitleiden bedingte Zustände?

UNLABELLED: In pacemaker statistics a dichotomy exists between the theoretically possible and the actually implanted number of physiological pacemakers. Hence, the aim of the study was to investigate the influences of age and non rhythm related health conditions on the selection of the pacemaker system.In 468 pacemaker patients the arguments for mode selection at first implantation were listed prospectively during a period of 3 years and 9 months. Mode selection followed electrocardiographic (recommendations of the German working Group on Cardiac Pacing), clinical (incidence of only intermittent bradycardias, stage of the underlying cardiac or of a second noncardiac disease) and sociomedical (non rhythm related general heath condition) aspects. Regarding the ECG findings physiological pacing was possible in 329 cases. Nevertheless, 57 of them (17.3%) received a VVI(R) system. Analysis of the reasoning leading to this dicision demonstrated that age-related problems and non-rhythm-caused health conditions became superior instead of rhythmologic aspects in 1.0% of all patients (pts) under 70, in 2.7% of all pts between 70 and 79, and in 10.8% of all pts 80 or more years of age. CONCLUSIONS: Beyond the age of 80 years, in about 11% of the pts who need a pacemaker, non-rhythm-related clinical and sociomedical aspects gain priority over the electrophysiologic defect. Thus, complete coincidence of the theoretically possible and the actually implanted number of physiological pacemakers in this age group cannot be attained. Regarding all factors influencing the selection of the pacemaker system 45 to 55% are more realistic.

Exercise induced sympathetic influences do not change interatrial conduction times in VDD and DDD pacing.

Using telemetry, right atrial electrogram (RA), and marker channel of atrial sense events (MA) in combination with the left atrial electrogram (LA), recorded by a filtered bipolar esophageal lead, interatrial conduction during submaximal exercise and at rest was examined in 46 DDD pacemaker patients. The RA-LA and MA-LA conduction times measured in the presence of atrial sensing (VDD) as well as the conduction time SA-LA from atrial stimulus (SA) to LA, determined during atrial pacing (DDD) were found to be individual constants independent of exercise induced sympathetic influences. Thus, having determined an optimal mechanical interval (LA-LV)mech/opt from left atrium to ventricle by other methods, the optimal AV delay for DDD as well as for VDD operation can be calculated by the sum of the appropriate interatrial conduction time (SA-LA, respectively MA-LA) and the (LA-LV)mech/opt interval. Due to the constant SA-LA and MA-LA, the difference between these two values (AV delay correction interval) is a constant as well, which remains unchanged during exercise. Therefore, in selecting the rate responsive AV delay, only hemodynamic and not electrophysiological measurements need to be considered.