Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.

OBJECTIVE: There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics' vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. APPROACH: We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. MAIN RESULTS: We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed 're-excitation', arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. SIGNIFICANCE: Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle force recordings may be unreliable as quantitative measures of neural activity for in vivo studies or as biomarkers in closed-loop clinical devices.

Severe phenotype in a girl with partial tetrasomy 7, karyotype 46,XX,trp(7)(q35q36).

On prenatal ultrasonography, polyhydramnion, internal hydrocephalus, hypoplasia of the corpus callosum, and dysmorphic features were detected in a fetus of a 22-year-old mother. Subsequent karyotyping of amniocytes revealed supernumerary material in distal 7q. The baby was delivered after 38+4 weeks of gestation, and postnatal array CGH analysis showed a triplication of 7q35-->q36, resulting in partial tetrasomy. The triplication was not distinguishable from a duplication by conventional and molecular cytogenetic methods, but was clearly identified by array CGH analysis. The phenotype was rather severe with limited cardiac contractility and subsequent respiratory problems, as well as progressive neurologic deterioration and several dysmorphic features. Triplications in general are rare, and this case is the first report of a microscopically visible triplication in 7q. Duplication patients of the same chromosomal segment also showed a severe phenotype, however, in our opinion there are no common features suggesting a clinically recognizable distal 7q duplication/triplication syndrome.

[Qualifying a broad range of professionals to master the demographic challenge: the Master's course of Gerontology at the University of Applied Sciences in Cottbus]. / Gerüstet für den demografischen Wandel : Gerontologische Qualifikation für viele Berufsfelder durch den Masterstudiengang Gerontologie an der Fachhochschule Lausitz.

Our new five-semester MA course in gerontology has been designed as a programme of continuing education for professionals from various fields being confronted with hitherto unknown challenges by "the greying of societies". While many services are directed to meet the needs of older clients, the elderly also represent a huge potential of various resources indispensable to society. Coming from various fields of study and different positions (mainly management or self-employed), our students engage in an interdisciplinary discourse from the beginning which helps them acquire knowledge and competencies to later deal with the complex tasks requiring interdisciplinary problem solving skills and establish "best practice" models. Universities are expected to engage in continuing education, thus being the places of choice for postgraduate studies in gerontology, which also offer research opportunities. Universities of Applied Sciences, intended to foster regional development, integrate students into applied research projects thereby transferring knowledge and skills to reach out to the community. During the first four semesters, each student enrolled in the MA Gerontology course plans, implements and evaluates a project of his/her own. This ensures the integration of gerontological knowledge and research methods and helps to extend and improve practical skills. We support students by regular coaching and supervision.

[Susceptibility to strategy of the drug component of the IPHCC+RxGroups classification system in a risk-adjusted morbidity compensation scheme--a conceptional and data-supported analysis]. / Zur Strategieanfälligkeit der Arzneimittelkomponente des IPHCC+RxGroups-Klassifikationssystems in einem morbiditätsorientierten Risikostrukturausgleich--Eine konzeptionelle und datengestützte Analyse.

BACKGROUND: A report commissioned by the German Ministry of Health recommends to the existing scheme for calculating risk-adjusted transfers to sickness funds supplement with the IPHCC+RxGroups method. The method is based on inpatient diagnoses and prescribed drugs as health status measures deduced from prior use. OBJECTIVE: The present study investigates the sickness fund's expected net return from gaming based on the drug component of the risk adjuster. METHODS: The study explores three possible strategies using the RxGroups method. For the stimulations, insurees are assigned to additional indications or to higher valued RxGroups within the same indication. Then, costs and financial benefits attributable to the altered drug use are estimated and compared with the status quo. The study uses 2000 and 2001 sample data of more than 370,000 insurees of Germany's company-based sickness funds system (BKK). RESULTS: While upgrading increases overall costs, it can be beneficial for the individual sickness funds. Their net return crucially depends on the number of sickness funds gaming the system: the more participating in the game, the smaller is the average net return. Moreover, not participating often is even worse, which in turn points to a prisoner's dilemma. CONCLUSIONS: When extending the risk adjustment scheme in social health insurance, the German legislator should take into account the perverse incentives of risk adjusters such as the described prescription drug model.

Premixed insulin aspart 30 vs. premixed human insulin 30/70 twice daily: a randomized trial in Type 1 and Type 2 diabetic patients.

AIM: To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes. METHODS: People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level. RESULTS: BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments. CONCLUSION: Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.

Formation of hydride-Meisenheimer complexes of picric acid (2,4, 6-trinitrophenol) and 2,4-dinitrophenol during mineralization of picric acid by Nocardioides sp. strain CB 22-2.

There are only a few examples of microbial conversion of picric acid (2,4,6-trinitrophenol). None of the organisms that have been described previously is able to use this compound as a sole source of carbon, nitrogen, and energy at high rates. In this study we isolated and characterized a strain, strain CB 22-2, that was able to use picric acid as a sole source of carbon and energy at concentrations up to 40 mM and at rates of 1.6 mmol. h(-1). g (dry weight) of cells(-1) in continuous cultures and 920 micromol. h(-1). g (dry weight) of cells(-1) in flasks. In addition, this strain was able to use picric acid as a sole source of nitrogen at comparable rates in a nitrogen-free medium. Biochemical characterization and 16S ribosomal DNA analysis revealed that strain CB 22-2 is a Nocardioides sp. strain. High-pressure liquid chromatography and UV-visible light data, the low residual chemical oxygen demand, and the stoichiometric release of 2.9 +/- 0.1 mol of nitrite per mol of picric acid provided strong evidence that complete mineralization of picric acid occurred. During transformation, the metabolites detected in the culture supernatant were the [H-]-Meisenheimer complexes of picric acid and 2,4-dinitrophenol (H--DNP), as well as 2,4-dinitrophenol. Experiments performed with crude extracts revealed that H--DNP formation indeed is a physiologically relevant step in picric acid metabolism.

Chromosomal aberrations in couples undergoing intracytoplasmic sperm injection: influence on implantation and ongoing pregnancy rates.

OBJECTIVE: To determine the incidence of chromosomal aberrations in couples undergoing intracytoplasmic sperm injection (ICSI) and their influence on subsequent implantation and ongoing pregnancy rates. DESIGN: Prospective study. SETTING: Fertility center. PATIENT(S): Candidates for ICSI. INTERVENTION(S): Chromosomes were trypsin-banded in 2,280 patients. In all cases, 10 metaphases were karyotyped. Sex chromosome analysis was performed in 10 additional metaphases. When apparent chromosomal aberrations were detected, 100 metaphases were analyzed. MAIN OUTCOME MEASURE(S): Implantation and ongoing pregnancy rates in couples with a chromosomal disorder. RESULTS: A chromosomal abnormality was demonstrated in 7.2% of all couples. Among the male partners, 4.48% had aberrations. Autosomal aberrations were present in 2.96%, and numerical or structural sex chromosome abnormalities were found in 1.52%. Among the female partners, numerical or structural abnormalities were documented in 9.79%. Only 2.32% of the female partners had autosomal structural abnormalities. Numerical or structural anomalies involving sex chromosomes were found in 7.47%. Implantation rates of 9.4% and 16.3% per embryo were observed in female partners with sex chromosome mosaicism and autosomal aberrations, respectively. In male partners, the respective rates were 3.8% and 23.1%. CONCLUSION(S): The incidence of chromosomal disorders in couples seeking ICSI treatment is considerable, especially minor mosaicism (<10%) of sex chromosomes in the female partners. Preliminary data indicate a low implantation rate in couples with minor mosaicism of sex chromosomes.

Bile acid-independent bile flow is differently regulated by glucagon and secretin in humans after orthotopic liver transplantation.

The present study characterizes recovery of bile secretion after orthotopic liver transplantation (OLT) in humans with special regard to hormonal regulation of bile acid-independent bile flow by glucagon and secretin. Sixty-seven patients with an uncomplicated postoperative course were studied during the first 3 weeks after OLT to determine normalization of bile flow. A group of 7 and 10 patients, respectively, underwent a biliary stimulation test by either glucagon at days 7, 14, and 21 after OLT or by secretin at days 2, 10, and 21 after OLT. Secretin tests were similarly performed in patients with acute severe rejection during the first 10 days after OLT, while glucagon tests were performed in patients with acute allograft rejection occurring 2 weeks after OLT. Furthermore, hormone effects were studied in nontransplanted patients after cholecystectomy with indwelling biliary T tube. After OLT, bile secretory function recovered and stabilized within 14 days after surgery by reconstitution of both bile acid-dependent and -independent bile flow. Two weeks after OLT, bile secretion was comparable with nontransplanted patients after cholecystectomy. Glucagon and secretin stimulated bile acid-independent bile flow in transplanted and nontransplanted patients significantly, yet secretin choleresis, unlike glucagon choleresis, had already occurred during the first days after OLT and was unaffected by acute allograft rejection. These results allow the speculation that, in humans, glucagon and secretin exert their choleretic activity by different mechanisms and/or at different anatomical sites in the liver. Assuming that secretin acts at the bile duct cells, its secretory capacity was not altered by the transplantation procedure and during moderate or severe rejection episodes, as opposed to glucagon choleresis, which most likely originates in the hepatocytes and requires an entirely reconstituted canalicular transport system after OLT.

["Retirement at age 58"--improvement or deterioration of living status?]. / "Rente mit 58 Jahren"--Verbesserung oder Verschlechterung der Lebenslage?

The BRD social security system contains numerous regulations concerning the smoothness of regulating social security benefits between unemployment benefit to pension benefit. Raising the retirement age for unemployed will lead to long-term unemployment or to a decreasing pension payment in the case of early retirement. In both cases the material income situation will deteriorate. Using the regulation for people who are or will be unemployed at the age 58, it can be shown that benefits were already clearly reduced before the new regulation of 14.2. 1996 come into effect-especially for those with unemployment assistance. The political objective of reducing the extent of early retirement will be paid by the unemployed themselves.

Vitamin B12 absorption after ileorectal anastomosis for Crohn's disease: effect of ileal resection and time span after surgery.

OBJECTIVE: To examine the impact of ileorectal anastomosis on vitamin B12 absorption, as measured by the Schilling test, in patients with Crohn's disease. PATIENTS: Eighty-two patients with Crohn's disease who had undergone ileorectal anastomosis. METHODS: Of the 82 patients with Crohn's disease and ileorectal anastomosis, 75 had their absorption of vitamin B12 tested using the Schilling test at least once while their first ileorectal anastomosis was functioning, corresponding to 605 years of observation. RESULTS: An ileal resection of more than 60 cm invariably resulted in decreased vitamin B12 absorption. In patients who had less than 60 cm of their ileum resected 53% had test results, indicating that vitamin B12 was malabsorbed. The extent of malabsorption did not correlate with the length of ileal loss in this subgroup of patients (r = -0.26; P = 0.053). Even resections of 10 cm or less were associated with malabsorption in 38% of patients. This suggests that factors other than the remaining ileal length are important for vitamin B12 absorption in Crohn's disease patients with ileorectal anastomosis. An improvement in vitamin B12 absorption over the years was not observed in the 35 patients in whom the test was repeated, and intraindividual Schilling test results fluctuated between pathological and normal values in several patients. CONCLUSIONS: Most Crohn's disease patients with ileorectal anastomosis have vitamin B12 malabsorption. Individuals with more than 60 cm of ileal loss are particularly affected and testing for malabsorption appears superfluous in this group. Approximately 50% of the patients with resections of 60 cm or less malabsorbed vitamin B12, but it was not possible to predict which patients should receive vitamin B12 substitutes based on the length of the remaining ileum alone. However, it may also be difficult to make a rational therapeutic decision based on the results of the Schilling test, because the test shifted between normal and pathological values over time in many of the patients studied.

Ornithine transcarbamylase (OTC) deficiency in a female patient with a de nova deletion of the paternal X chromosome.

A girl with ornithine transcarbamylase (OTC) deficiency was investigated for molecular and cytogenetic abnormalities that might explain this phenotype. Analysis with polymorphic DNA markers indicated that the patient did not inherit paternal alleles of the OTC locus, but that she did inherit the proximal locus DXS7 and the long arm of chromosome X. High-resolution cytogenetic analysis of the patient indicated a deletion of Xp11.4-p21, whereas both parents had normal karyotypes. Since the mother might be heterozygous according to biochemical tests, a second mutation within the maternal OTC gene cannot be excluded.

[Labor market status and early retirement of elderly employees since 1980]. / Arbeitsmarktsituation und Frühverrentung älterer Arbeitnehmer seit 1980.

The labour market situation for older employees has become increasingly difficult in the first half of the 1980s. The length of time spent unemployed has increased and the trend towards early retirement has intensified. New legal action aims at lowering the costs of this development for the social security system. The increased participation of the partners of collective bargaining in the problem solving process aims at a more even distribution of costs incurred, as well as at a reduction of unemployment. Action taken and agreements reached tend to restrict themselves to a limited span of time, to the foreseeable future. They influence the situation of the unemployed and prematurely retired older workers in positive as well as in negative ways.