[Methylphenidate of retard forms in children and adolescents with ADHD - an overview]. / Methylphenidat-Retard-Präparate bei Kindern und Jugendlichen mit ADHs - eine Ubersicht.

As yet, stimulants remain the preferred means of treating attention-deficit/hyperactivity disorder (ADHD) pharmacologically. They are indicated when measures based on behavioural therapy or psychoeducation alone are not sufficient. How-ever, the period of effectiveness of immediate release stimulants is often not satisfactory. A variety of retarded forms of methylphenidate have now been developed and approved for the German market. This paper presents an overview of clinical studies on effectiveness, period of effectiveness and the profile of side effects of different forms stimulants available in Germany. In clinical practice, the new retard products represent effective alternatives. There is an advantage in administering this drug in a once-daily single dose. At the same time, the side effects that are caused by an extended period of effectiveness have to be studied in detail. A more precise adaptation to the daily obligations and needs of children and adolescents is needed. Possibly, a combination with unretareded MPH might lead to a better effect/side-effect profile.

Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients.

OBJECTIVE: To evaluate the prophylactic use of enteral fluconazole to prevent invasive candidal infections in critically ill surgical patients. SUMMARY BACKGROUND DATA: Invasive fungal infections are increasingly common in the critically ill, especially in surgical patients. Although fungal prophylaxis has been proven effective in certain high-risk patients such as bone marrow transplant patients, few studies have focused on surgical patients and prevention of fungal infection. METHODS: The authors conducted a prospective, randomized, placebo-controlled trial in a single-center, tertiary care surgical intensive care unit (ICU). A total of 260 critically ill surgical patients with a length of ICU stay of at least 3 days were randomly assigned to receive either enteral fluconazole 400 mg or placebo per day during their stay in the surgical ICU at Johns Hopkins Hospital. RESULTS: The primary end point was the time to occurrence of fungal infection during the surgical ICU stay, with planned secondary analysis of patients "on-therapy" and alternate definitions of fungal infections. In a time-to-event analysis, the risk of candidal infection in patients receiving fluconazole was significantly less than the risk in patients receiving placebo. After adjusting for potentially confounding effects of the Acute Physiology and Chronic Health Evaluation (APACHE) III score, days to first dose, and fungal colonization at enrollment, the risk of fungal infection was reduced by 55% in the fluconazole group. No difference in death rate was observed between patients receiving fluconazole and those receiving placebo. CONCLUSIONS: Enteral fluconazole safely and effectively decreased the incidence of fungal infections in high-risk, critically ill surgical patients.

Surveillance strategies and impact of vancomycin-resistant enterococcal colonization and infection in critically ill patients.

OBJECTIVE: To determine the optimal site and frequency for vancomycin-resistant enterococci (VRE) surveillance to minimize the number of days of VRE colonization before identification and subsequent isolation. SUMMARY BACKGROUND DATA: The increasing prevalence of VRE and the limited therapeutic options for its treatment demand early identification of colonization to prevent transmission. METHODS: The authors conducted a 3-month prospective observational study in medical and surgical intensive care unit (ICU) patients with a stay of 3 days or more. Oropharyngeal and rectal swabs, tracheal and gastric aspirates, and urine specimens were cultured for VRE on admission to the ICU and twice weekly until discharge. RESULTS: Of 117 evaluable patients, 23 (20%) were colonized by VRE. Twelve patients (10%) had VRE infection. Of nine patients who developed infections after ICU admission, eight were colonized before infection. The rectum was the first site of colonization in 92% of patients, and positive rectal cultures preceded 89% of infections acquired in the ICU. This was supported by strain delineations using pulsed-field gel electrophoresis. Twice-weekly rectal surveillance alone identified 93% of the maximal estimated VRE-related patient-days; weekly or admission-only surveillance was less effective. As a test for future VRE infection, rectal surveillance culture twice weekly had a negative predictive value of 99%, a positive predictive value of 44%, and a relative risk for infection of 34. CONCLUSIONS: Twice-weekly rectal VRE surveillance of critically ill patients is an effective strategy for early identification of colonized patients at increased risk for VRE transmission, infection, and death.

Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit.

HYPOTHESIS: Catheter-related bloodstream infection (CRBSI) in critically ill surgical patients with prolonged intensive care unit (ICU) stays is associated with a significant increase in health care resource use. DESIGN: Prospective cohort study. SETTING: Surgical ICU at a large tertiary care center. PATIENTS: Critically ill surgical patients (N = 260) with projected surgical ICU length of stay greater than 3 days. INTERVENTIONS: Central venous catheters were cultured for clinical suspicion of infection. MAIN OUTCOME MEASURES: Increases in total hospital cost, ICU cost, hospital days, and ICU days attributable to CRBSI were estimated using multiple linear regression after adjusting for demographic factors and severity of illness (APACHE III [Apache Physiology and Chronic Health Evaluation III] score). RESULTS: The incidence of CRBSI per 1000 catheter-days was 3.6 episodes (95% confidence interval [CI], 2.1-5.8 episodes). Microbiologic isolates were Gram-positive bacteria in 75%, Gram-negative bacteria in 20%, and yeast in 5%. After adjusting for demographic factors and severity of disease, CRBSI was associated with an increase of $56 167 (95% CI, $11 523-$165 735; P =.001) (in 1998 dollars) in total hospital cost, an increase of $71 443 (95% CI, $11 960-$195 628; P<.001) in ICU cost, a 22-day increase in hospital length of stay, and a 20-day increase in ICU length of stay. CONCLUSIONS: For critically ill surgical patients, CRBSI is associated with a profound increase in resource use. Prevention, early diagnosis, and intervention for CRBSI might result in cost savings in this high-risk population.

The diagnostic value of fungal surveillance cultures in critically ill patients.

BACKGROUND: Heavy fungal colonization is a known risk factor for fungal infection, yet the value of fungal surveillance cultures is uncertain. METHODS: To evaluate the utility of fungal surveillance cultures in predicting fungal infections, we evaluated surveillance fungal cultures over a three month period in a prospective, cohort study conducted at a university medical center with a large tertiary referral population. We enrolled 172 patients in the Oncology Center and the medical and surgical intensive care units at Johns Hopkins Hospital. RESULTS: Surveillance cultures from five sites were obtained twice weekly and evaluated for prediction of subsequent fungal infection. Infections were prospectively defined and evaluated by a panel of clinicians. Test characteristics were assessed. Of 159 eligible patients, 14 (9%) developed invasive fungal infections. Having two or more surveillance sites positive in a single day had an odds ratio of 8.2 (1.1-358.0) (p = 0.03), a negative predictive value of 0.98, sensitivity of 0.92, and a likelihood ratio of 1.6 for a fungal infection. In a multiple logistic regression model and Kaplan-Meier analysis, fungal burden was strongly and independently associated with infection (p < 0.05). CONCLUSIONS: Surveillance cultures are helpful in determining fungal colonization but do not have a high positive predictive value for fungal infection in a broad population of intensive care unit patients. However, fungal infection is more likely in heavily colonized patients, and surveillance cultures show that fungal infection is extremely unlikely in patients without fungal colonization.

Subunit composition and quantitative importance of hetero-oligomeric receptors: GABAA receptors containing alpha6 subunits.

In cerebellum, GABAA receptors containing alpha6 subunits are expressed exclusively in granule cells. The number of alpha6 receptor subtypes formed in these cells and their subunit composition presently are not known. Immunoaffinity chromatography on alpha6 subunit-specific antibodies indicated that 45% of GABAA receptors in cerebellar extracts contained alpha6 subunits. Western blot analysis demonstrated that alpha1, beta1, beta2, beta3, gamma2, and delta subunits co-purified with alpha6 subunits, suggesting the existence of multiple alpha6 receptor subtypes. These subtypes were identified using a new method based on the one-by-one immunochromatographic elimination of receptors containing the co-purifying subunits in parallel or subsequent experiments. By quantification and Western blot analysis of alpha6 receptors remaining in the extract, the proportion of alpha6 receptors containing the eliminated subunit could be calculated and the subunit composition of the remaining receptors could be determined. Results obtained indicated that alpha6 receptors in cerebellum are composed predominantly of alpha6betaxgamma2 (32%), alpha1alpha6betaxgamma2 (37%), alpha6betaxdelta (14%), or alpha1alpha6betaxdelta (15%) subunits. Other experiments indicated that 10%, 51%, or 21% of alpha6 receptors contained homogeneous beta1, beta2, or beta3 subunits, respectively, whereas two different beta subunits were present in 18% of all alpha6 receptors. The method presented can be used to resolve the total number, subunit composition, and abundancy of GABAA receptor subtypes in the brain and can also be applied to the investigation of other hetero-oligomeric receptors.

[Carotenoid intake in the German National Food Consumption Survey]. / Die Carotinoidzufuhr in der Nationalen Verzehrsstudie.

In nutritional epidemiological studies high consumption of fruits and vegetables was shown to be an important preventive measure to reduce the risk of cancer, coronary heart disease, and cataracts. These effects cannot be explained completely and in a sufficient way by the intake of beta-carotene and vitamin C. Other carotenoids differing in their antioxidative and biological properties are also provided with fruits and vegetables in significant amounts. Because data for other carotenoids than beta-carotene are not considered in computerized German food database and food composition tables, representative carotenoid intake calculations for the German population are missing. Therefore a carotenoid database, containing alpha- and beta-carotene, lycopene, lutein/zeaxanthin, and cryptoxanthin values for different fruits, vegetables, and other carotenoid-containing foods, was developed. With this database the carotenoid intake of the German population--stratified by sex and age--was evaluated on the basis of the German National Food Consumption Survey (NVS). The mean total carotenoid intake amounts to 5.33 mg/day. The average intake lutein was 1.91 mg/day, beta-carotene intake amounts to 1.81 mg/day, lycopene intake was 1.28 mg/day, alpha-carotene intake was 0.29 mg/day, and cryptoxanthin intake was 0.05 mg/day. Tomatoes and tomato products provide most of the lycopene. Green salads and vegetables are the most important contributors of lutein in Germany. Zeaxanthin is mainly consumed with maize but also with spinach and other vegetables like cabbage; alpha- and beta-carotene are mainly consumed with carrots. Peppers, oranges, and orange-juice are the most important cryptoxanthin sources.

The risks and benefits of childhood bacille Calmette-Guérin immunization among adults with AIDS. International MAC study groups.

OBJECTIVE: To define the risks of disseminated bacille Calmette-Guérin (BCG) or disseminated Mycobacterium tuberculosis in adults with AIDS who were immunized with BCG in childhood. DESIGN: HIV-infected patients with CD4 < 200 x 10(6)/l were enrolled from five study sites (New Hampshire, Boston, Finland, Trinidad and Kenya). Prior BCG immunization was determined and blood cultures for mycobacteria were obtained at study entry and at 6 months. Acid-fast bacilli were identified as Mycobacterium tuberculosis complex (MTBC) using DNA probes. MTBC isolates were then typed by both IS6110 restriction fragment length polymorphism and polymerase chain reaction/restriction enzyme analysis. SETTING: Most patients in New Hampshire and Finland were outpatients; most patients in Trinidad were inpatients with terminal illness; and most patients in Kenya were outpatients, although 44 were inpatients with terminal illness. PARTICIPANTS: A total of 566 patients were enrolled, including 155 with childhood BCG immunization; 318 patients had a single study visit and culture, and 248 patients had two study visits and cultures. MAIN OUTCOME MEASURES: Isolation and identification of mycobacteria from blood cultures. RESULTS: Blood cultures were positive for MTBC in 21 patients; none were positive for M. bovis BCG, and 21 were M. tuberculosis-positive. In Trinidad, seven (87%) out of eight isolates of M. tuberculosis were indistinguishable by IS6110 typing; BCG immunization was associated with a decreased risk of bacteremic infection with M. tuberculosis (P = 0.05). CONCLUSIONS: The risk of disseminated BCG among adult AIDS patients with childhood BCG immunization is very low. Childhood BCG immunization is associated with protection against bacteremia with M. tuberculosis among adults with advanced AIDS in Trinidad.

Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression.

Cerebellar granule cells express six GABAA receptor subunits abundantly (alpha1, alpha6, beta2, beta3, gamma2, and delta) and assemble various pentameric receptor subtypes with unknown subunit compositions; however, the rules guiding receptor subunit assembly are unclear. Here, removal of intact alpha6 protein from cerebellar granule cells allowed perturbations in other subunit levels to be studied. Exon 8 of the mouse alpha6 subunit gene was disrupted by homologous recombination. In alpha6 -/- granule cells, the delta subunit was selectively degraded as seen by immunoprecipitation, immunocytochemistry, and immunoblot analysis with delta subunit-specific antibodies. The delta subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a post-translational loss of the delta subunit. These results provide genetic evidence for a specific association between the alpha6 and delta subunits. Because in alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot rescue the delta subunit, certain potential subunit combinations may not be found in wild-type cells.