[Early childhood intervention - access to risk families and support through actors from the health-care sector]. / Frühe Hilfe für Familien und Frühgeborene - Zugangswege und Unterstützungen aus dem Gesundheitsbereich.

Interdisciplinary cooperation and networking determine the success of activities for supporting families at risk for early childhood abuse. The integration of the healthcare sector might be important.The medical standard of perinatal care at the University hospital includes information exchange about family risk factors which may contribute to an increased risk of child abuse within the first year of life. As a result, the -pediatrician offered supporting services for the families at the time of the second examination during the official childhood health screening program (U2). A team of family-sponsorship was established and evaluated.In 281 of 1238 risk-factor questionnaires at least one stress factor was detected and 97 families had high-impact family stress. Families under the supervision of a family midwife or youth services had a significantly higher number of risk factors. The family-sponsorship program was institutionalized and positively evaluated by the families.The time of a hospital delivery is an excellent opportunity for the evaluation of familial risk factors and for the provision of supporting services. To increase the acceptance of such services by the families at risk repeated assessment of risk factors and support offers are required.

[Prophylaxis of venous thromboembolism and anticoagulation bridging. Strategies in otorhinolaryngology]. / Thromboembolieprophylaxe und überbrückende Antikoagulation. Strategien in der HNO-Heilkunde.

Various interdisciplinary guidelines recommend that in-patients at risk of venous thromboembolism should receive pharmacologic prophylaxis. Among the anticoagulants low-molecular-weight heparins (LMWH) and fondaparinux can be considered the medications of choice because of the favorable pharmacokinetic properties when compared with unfractionated heparin. Treatment with vitamin K antagonists has to be interrupted in patients undergoing major surgery or invasive procedures. Oral anticoagulation has to be temporarily replaced by short-acting anticoagulants such as LMWH in order to prevent thromboembolic complications (anticoagulation bridging). Although LMWHs have not been approved for this clinical setting their efficacy and safety has been demonstrated in several recent studies. Detailed recommendations for prophylaxis of venous thromboembolism in otorhinolaryngology are lacking although numerous surgical procedures are considered to be associated with a significant risk of thromboembolism. A strategy for pharmacologic prophylaxis of venous thromboembolism and anticoagulation bridging in otorhinolaryngology is proposed.

[Giant scalp mass]. / Monströser Tumor der Kopfhaut.

A 55-year-old man was referred to our department with bleeding from a painless tumor located at the left parietal region of the head which had been progressively growing for a period of 2 years. Physical examination showed a fist-sized pediculated mass overlying the left parietal region and the auricle. The partly livid and ulcerated surface of the tumor was interspersed with light-yellow chalky material. The mass was totally excised. Infiltration of the skull was not observed. Histopathological examination led to the diagnosis of a giant pilomatricoma. Pilomatricoma is a rare, benign skin neoplasm that originates from hair matrix cells and is most frequently located in the head and neck region.

Is phosphoadenosine phosphate phosphatase a target of lithium's therapeutic effect?

Lithium, which is approved for treating patients with bipolar disorder, is reported to inhibit 3'(2')-phosphoadenosine-5'-phosphate (PAP) phosphatase activity. In yeast, deletion of PAP phosphatase results in elevated PAP levels and in inhibition of sulfation and of growth. The effect of lithium on PAP phosphatase is remarkable for the low Ki (approximately 0.2 mM), suggesting that this system would be almost completely shut down in vivo with therapeutic levels of 1 mM lithium, thereby elevating PAP levels. To test the hypothesis that lithium inhibition of PAP phosphatase is pharmacologically relevant to bipolar disorder, we fed rats LiCl for 6 weeks, and assayed brain PAP levels after subjecting the brain to high-energy microwaving. We also measured PAP phosphatase mRNA and protein levels in frozen brain tissue of lithium-treated mice. Brain adenosine phosphates were extracted by trichloroacetic acid and assayed by HPLC with a gradient system of two phases. PAP phosphatase mRNA was measured by RT-PCR, and PAP phosphatase protein was measured by Western blotting. Brain PAP levels were below detection limit of 2 nmol/g wet weight, even following lithium treatment. Lithium treatment also did not significantly change brain PAP phosphatase mRNA or protein levels. These results question the relevance of PAP phosphatase to the therapeutic mechanism of lithium. A statistically significant 25% reduced brain ADP/ATP ratio was found following lithium treatment in line with lithium's suggested neuroprotective effects.

Measurement of the muon capture rate in hydrogen gas and determination of the proton's pseudoscalar coupling gP.

The rate of nuclear muon capture by the proton has been measured using a new technique based on a time projection chamber operating in ultraclean, deuterium-depleted hydrogen gas, which is key to avoiding uncertainties from muonic molecule formation. The capture rate from the hyperfine singlet ground state of the microp atom was obtained from the difference between the micro(-) disappearance rate in hydrogen and the world average for the micro(+) decay rate, yielding Lambda(S)=725.0+/-17.4 s(-1), from which the induced pseudoscalar coupling of the nucleon, g(P)(q(2)=-0.88m(2)(micro))=7.3+/-1.1, is extracted.

Evolutionary algorithms for finding optimal gene sets in microarray prediction.

MOTIVATION: Microarray data has been shown recently to be efficacious in distinguishing closely related cell types that often appear in different forms of cancer, but is not yet practical clinically. However, the data might be used to construct a minimal set of marker genes that could then be used clinically by making antibody assays to diagnose a specific type of cancer. Here a replication algorithm is used for this purpose. It evolves an ensemble of predictors, all using different combinations of genes to generate a set of optimal predictors. RESULTS: We apply this method to the leukemia data of the Whitehead/MIT group that attempts to differentially diagnose two kinds of leukemia, and also to data of Khan et al. to distinguish four different kinds of childhood cancers. In the latter case we were able to reduce the number of genes needed from 96 to less than 15, while at the same time being able to classify all of their test data perfectly. We also apply this method to two other cases, Diffuse large B-cell lymphoma data (Shipp et al., 2002), and data of Ramaswamy et al. on multiclass diagnosis of 14 common tumor types. AVAILABILITY: http://stravinsky.ucsc.edu/josh/gesses/.

[Congenital hypopituitarism and giant cell hepatitis in a three month old girl]. / Konnataler Panhypopituitarismus und Riesenzellhepatitis bei einem 3 Monate alten Säugling.

CASE REPORT: A three month old girl, with recurrent hypoglycemia and neonatal cholestasis, is reported. A metabolic disease could be excluded. The liver biopsy revealed giant cell hepatitis and intrahepatic bile duct hypoplasia. ACTH, Cortisol and hGH measured during hypoglycemia were low. Magnetic tomography (MR) of the brain showed an "empty sella". After beginning a replacement therapy with hydrocortisone, growth hormone and thyroxine there was no further episode of hypoglycemia. Transaminases and bilirubin levels normalized. The girl is in good condition, growth and development are normal. DISCUSSION: Hypoglycemia is often the first sign in childrens with neonatal hypopituitarism. The association of liver disease and hypopituitarism has been documented in a few reports. The pathophysiological mechanism leading to the liver dysfunction is not well understood. The prognosis of neonatal hypopituitarism as well as the concomitant liver disease is good under sufficient replacement therapy.

Assay of the concentration and 13C-isotopic enrichment of malonyl-coenzyme A by gas chromatography-mass spectrometry.

We developed gas chromatography-mass spectrometry assays for the concentration and mass isotopomer distribution of malonyl-CoA in tissues. The assay involves perchloric acid extraction of the tissue, spiking the extract with [U-13C3]malonyl-CoA or dimethylmalonyl-CoA internal standard, isolation of short-chain acyl-CoA fraction on an oligonucleotide purification cartridge, alkaline hydrolysis to malonate, trimethylsilyl derivatization, and analysis of the mass isotopomer distribution of malonate. The assay was applied to labeling of malonyl-CoA from various [13C]substrates in perfused rat livers and hearts. In livers perfused with [1,2-13C2]acetate, malonyl-CoA is doubly labeled from [1,2-13C2]acetate and singly labeled from 13CO2. In livers perfused with either NaH13CO3 or [3-13C]lactate + [3-13C]pyruvate, the half-lives of singly labeled malonyl-CoA were less than 20 s and 6.95 min, respectively. In rat heart, the half-life of malonyl-CoA, traced with NaH13CO3, was about 1.25 min. Thus, our assay allows us to measure the turnover of tissue malonyl-CoA, the contribution of various [13C]substrates to its production in lipogenic and nonlipogenic organs, and the cycling between acetyl-CoA and malonyl-CoA in nonlipogenic organs.

Should we screen for lead poisoning after 36 months of age? Experience in the inner city.

INTRODUCTION: Current lead screening guidelines recommend monitoring lead levels in children under 3 years of age. There are, however, a number of children between the ages of 3 and 6 years who have elevated blood lead levels. Whether these lead elevations are new or chronic has not been examined. OBJECTIVE: To determine the proportion of children with lead levels greater than or equal to 10 microg/dL after their third birthday when all prior testing had been normal. METHODS: Retrospective study based on 39000 venous lead tests obtained between 1993 and 1998. From this group, 2046 children were located who had blood lead levels of less than 10 microg/dL before 36 months and who had a follow-up lead level after 36 months. All lead assays were done by the City of New York laboratories, which had an intrasample variability of 13%. RESULTS: Sixty-six (3.2%) of the 2046 children showed an elevation in blood lead for the first time after their third birthday. The abnormal values ranged from 10 to 25 microg/dL. The majority (72%) of the screen-positive children, however, had lead levels of 10 to 12 microg/dL, and 63.3% of screen-positive children with repeat tests had lead levels that reverted to below 10 microg/dL. CONCLUSIONS: The data indicate that some new cases of lead level elevations did occur after 3 years of age in this 'high-risk' community; however, the current study provides evidence that universal screening for lead poisoning beyond 3 years of age is not warranted in this community as it is not likely to pick up clinically important exposure.

[Peripheral lymphadenopathy in childhood--recommendations for diagnostic evaluation]. / Periphere Lymphknotenschwellungen im Kindesalter--Empfehlungen für eine rationelle Diagnostik.

BACKGROUND: Enlargement of peripheral lymph nodes most commonly caused by a local inflammatory process is frequently seen in childhood. The aim of the present study was to analyze the most common causes of peripheral lymphadenopathy and to develop a simple algorithm for the primary diagnostic evaluation of peripheral lymph node enlargement in this age group. PATIENTS: Between April and September 1999 87 unselected children (median age: 5 1/2 years) with peripheral lymphadenopathy were referred to the Department of Pediatrics, University of Graz, for further investigation. RESULTS: EBV infection was diagnosed in 20 (23.0%) children. 19 (21.8%) patients had acute bacterial lymphadenitis. In 21 (24.1%) patients lymph node enlargement was classified as "post/parainfectious (viral)". Four patients each had toxoplasmosis and cat scratch disease. In 11 (12.6%) patients neither physical nor laboratory examinations revealed pathologic results. Among the remaining 8 children sarcoidosis and Hodgkin disease was diagnosed in one patient each. Small, soft, mobile, nontender, cervical, axillary or inguinal lymph nodes do not require further investigations. In case of enlarged, tender lymph nodes with overlying skin erythema and fever diagnostic evaluation should include complete blood count, erythrocyte sedimentation rate and/or c-reactive protein level, supplemented by appropriate antibody testing (EBV, CMV, Toxoplasma gondii, Bartonella henselae). Firm, enlarged, painless lymph nodes which are matted together and fixed to the skin or underlying tissues necessitate a more detailed diagnostic evaluation in order to exclude malignant or granulomatous diseases. CONCLUSIONS: Our study demonstrated that primary diagnostic evaluation of childhood peripheral lymphadenopathy is mainly based on clinical grounds. In most cases a small number of additionally performed laboratory tests allow to correctly identify the cause of the peripheral lymph node enlargement.

Vinorelbine-gemcitabine in advanced non-small-cell lung cancer (NSCLC): an AASLC phase II trial. Austrian Association for the Study of Lung Cancer.

PURPOSE: The purpose of the present phase 11 trial was to determine the efficacy and toxicity of vinorelbine-gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From December 1997 to February 1999, 78 chemotherapy-naive patients (median age 60 years, Karnofsky performance status of 100, 90, 80 and 70 present in 5%, 41%, 36% and 18% of the patients, respectively) with stage IIIB (17%) or IV (83%) NSCLC (65% adenocarcinomas, 22% squamous-cell carcinomas, 10% large-cell carcinomas, 3% mixed-cell carcinomas) received 25 mg/m2 vinorelbine and 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a four-week cycle. RESULTS: In an intent-to-treat analysis, partial responses were seen in 19% of the patients. The median duration of response was 4.4 months. The median survival time was seven months and the one-year survival rate was 32%. Myelosuppression was the main side effect with WHO grade 3/4 neutropenia and thrombocytopenia in 35% and 11% of the patients, respectively. Other side effects were usually mild to moderate. CONCLUSIONS: Vinorelbine-gemcitabine is active, well tolerated and easy to administer on an outpatient basis in advanced NSCLC. Thus a randomized comparison of this combination with platinum-based protocols is warranted in patients with advanced NSCLC.

Interferon-alpha and ribavirin in treating children and young adults with chronic hepatitis C after malignancy.

OBJECTIVE: Chronic hepatitis C is a major long-term problem for children who survive cancer. Interferon (IFN)-alpha has been shown to be effective in treating patients with chronic hepatitis C; however, the rate of sustained response is low. Combining IFN-alpha and ribavirin (RBV) has been shown to significantly improve the response in adult patients with chronic hepatitis C. The aim of this pilot study was to evaluate the efficacy and safety of a combined virostatic treatment with IFN-alpha and RBV in a small cohort of children and adolescents with chronic hepatitis C and previous malignancy. METHODS: Twelve patients with a history of a hematooncologic disease (median follow-up: 13.5 years; range: 7-14.7 years) and chronic hepatitis C were treated with recombinant IFN-alpha-2a (6 megaunits/m(2) body surface area, 3 times a week, subcutaneously) combined with RBV (15 mg/kg body weight/day, orally) for 12 months. They were tested monthly for blood counts and liver function, and for serum virus concentrations (hepatitis C virus RNA by polymerase chain reaction) every 3 months. RESULTS: At the end of the treatment, hepatitis C virus RNA could not be detected in the serum of 8 of the 12 patients; 2 of these patients relapsed soon after therapy withdrawal, whereas 6 patients maintained in sustained virologic and biochemical remission (follow-up: 12 months). Treatment-induced toxicity was moderate and reversible with influenza-like symptoms and a decrease in blood counts in all 12 patients, alopecia in 5 of the 12, hemolysis in 4 of the 12, and weight loss of >10% in 2 of the 12. CONCLUSIONS: As demonstrated in adults with chronic hepatitis C, treatment with IFN-alpha and RBV also seems to be an effective and safe therapeutic option for children and adolescents with chronic hepatitis C after malignancy.

Orthopedic rehabilitation using the "Rutgers ankle" interface.

A novel ankle rehabilitation device is being developed for home use, allowing remote monitoring by therapists. The system will allow patients to perform a variety of exercises while interacting with a virtual environment (VE). These game-like VEs created with WorldToolKit run on a host PC that controls the movement and output forces of the device via an RS232 connection. Patients will develop strength, flexibility, coordination, and balance as they interact with the VEs. The device will also perform diagnostic functions, measuring the ankle's range of motion, force exertion capabilities and coordination. The host PC transparently records patient progress for remote evaluation by therapists via our existing telerehabilitation system. The "Rutgers Ankle" Orthopedic Rehabilitation Interface uses double-acting pneumatic cylinders, linear potentiometers, and a 6 degree-of-freedom (DOF) force sensor. The controller contains a Pentium single-board computer and pneumatic control valves. Based on the Stewart platform, the device can move and supply forces and torques in 6 DOFs. A proof-of-concept trial conducted at the University of Medicine and Dentistry of New Jersey (UMDNJ) provided therapist and patient feedback. The system measured the range of motion and maximum force output of a group of four patients (male and female). Future medical trials are required to establish clinical efficacy in rehabilitation.

Folate sufficient subjects do not accumulate additional folates during supplementation.

In a double-blinded placebo-controlled trial of folic acid supplementation in 82 alcoholic subjects, it was found that whole blood folate levels, determined by a mass spectrometric method, do not increase in subjects whose baseline folate levels are above the third quartile (folate sufficiency). Since a state of folate sufficiency can now be identified, a recommended daily allowance (RDA) for folate can be determined using objective means.

Glutathione oxidation in real time by thermospray liquid chromatography-mass spectrometry.

The oxidation and reduction of glutathione and oxidized glutathione were studied in real time by liquid chromatography-mass spectrometry during exposure to hydrogen peroxide and mercaptoethanol. By mass spectrometry mixed disulfides and both reversible and irreversible oxidations of sulfur to higher states (sulfinic and sulfonic acids) were directly observed during exposure to hydrogen peroxide. The irreversible oxidation of glutathione to glutathione sulfonic acid could be detected after 30 min exposure of glutathione to 40 mM H2O2 at 20 degrees C. A peak consistent with glutathione-sulfinic acid was transiently present, suggesting this compound behaved as an oxygen consuming antioxidant. Liquid chromatography-mass spectrometry appears to be an excellent method to study oxidation and reductions of sulfur containing peptides and amino acids.

Efficacy of supplementary intracameral lidocaine in routine phacoemulsification under topical anesthesia.

OBJECTIVE: To determine whether the routine use of supplementary intracameral lidocaine has any benefit over topical anesthesia alone when performing phacoemulsification surgery. DESIGN: A prospective single-center, randomized, double-masked, clinical trial. PARTICIPANTS: A total of 204 patients undergoing phacoemulsification surgery with lens implantation under planned topical anesthesia. METHODS: Patients were randomly allocated to receive either topical anesthesia plus 0.5 ml intracameral balanced salt solution or topical anesthesia plus 0.5 ml preservative-free 1% intracameral lidocaine. MAIN OUTCOME MEASURES: On the day after surgery, patients were asked to document the discomfort they had experienced using a visual analog scale. Intraoperative discomfort, postoperative discomfort, and discomfort caused by the microscope light were assessed. RESULTS: Multiple linear regression analysis did not show any significant relationship between the use of intracameral lidocaine and either intraoperative (P = 0.34) or postoperative (P = 0.45) pain scores. There was a small reduction in the discomfort caused by the operating microscope when intracameral lidocaine was used (P = 0.04). CONCLUSIONS: In this study, the routine use of intracameral lidocaine as a supplement to topical anesthesia was shown not to have a clinically useful role.