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To determine the therapeutic effect of sulfur amino acid supplementation in HIV infection we randomized 40 patients with antiretroviral therapy (ART; study 1) and 29 patients without ART (study 2) to treatment for 7 months with N-acetyl-cysteine or placebo at an individually adjusted dose according to a defined scheme. The main outcome measures were the change in immunological parameters including natural killer (NK) cell and T cell functions and the viral load. Both studies showed consistently that N-acetyl-cysteine causes a marked increase in immunological functions and plasma albumin concentrations. The effect of N-acetyl-cysteine on the viral load, in contrast, was not consistent and may warrant further studies. Our findings suggest that the impairment of immunological functions in HIV+ patients results at least partly from cysteine deficiency. Because immune reconstitution is a widely accepted aim of HIV treatment, N-acetyl-cysteine treatment may be recommended for patients with and without ART. Our previous report on the massive loss of sulfur in HIV-infected subjects and the present demonstration of the immunoreconstituting effect of cysteine supplementation indicate that the HIV-induced cysteine depletion is a novel mechanism by which a virus destroys the immune defense of the host and escapes immune elimination. [ABSTRACT FROM AUTHOR]

An increasing number of farmers use cover crop mixtures instead of monoculture cover crops to improve soil and crop quality. However, only little information is available about the weed suppression ability of cover crop mixtures. Therefore, two field experiments were conducted in Baden-Württemberg between 2010 and 2012, to compare growth and weed suppression of monoculture cover crops and cover crop mixtures. In the first experiment, heterogeneous results between yellow mustard and the cover crop mixture occurred. For further research, a field experiment was conducted in 2012 to compare monocultures of yellow mustard and hemp with three cover crop mixtures. The evaluated mixtures were: “MELO”: for soil melioration; “BETA”: includes only plant species with no close relation to main cash crops in Central Europe and “GPS”: for usage as energy substrate in spring. Yellow mustard, MELO, BETA and GPS covered 90% of the soil in less than 42 days and were able to reduce photosynthetically active radiation (PAR) on soil surface by more than 96% after 52 days. Hemp covered 90% of the soil after 47 days and reduced PAR by 91% after 52 days. Eight weeks after planting, only BETA showed similar growth to yellow mustard which produced the highest dry matter. The GPS mixture had comparatively poor growth, while MELO produced similar dry matter to hemp. Yellow mustard, MELO and BETA reduced weed growth by 96% compared with a no cover crop control, while hemp and GPS reduced weeds by 85% and 79%. In spring, weed dry matter was reduced by more than 94% in plots with yellow mustard and all mixtures, while in hemp plots weeds were only reduced by 71%. The results suggest that the tested cover crop mixtures offer similar weed suppression ability until spring as the monoculture of the competitive yellow mustard.

Lopsided oat (Avena strigosa) has been cultivated for many years, especially in Brazil, as a summer annual cover crop. Experiments were conducted in Stuttgart-Hohenheim in 2010 to estimate the capability of lopsided oat, yellow mustard (Sinapis alba), phacelia (Phacelia tanacetifolia) and a cover crop mixture to suppress weeds and volunteer wheat. A pot experiment was conducted to analyze the emergence and growth of the different cover crop species. Twelve weeks after planting, lopsided oat produced 20.7 dt/ha of shoot- and 5.5 dt/ha of root dry matter. A field experiment was established in the summer after harvest of winter wheat. The soil was cultivated with a disc harrow and the cover crops were sown one day later. At four week intervals, the plant density and dry matter of cover crops, weeds and volunteer wheat were determined. Twelve weeks after planting, lopsided oat produced 17.8 dt/ha shoot- and 6.2 dt/ha root dry matter. In the lopsided oat plots, shoot dry matter of weeds and volunteer wheat were reduced by 98 % compared with control plots without cover crops. This was the highest weed reduction of all cover crops studied. The root dry matter of weeds and volunteer wheat was reduced by 55 % to 97 % in all cover crops, compared to the control plots. Lopsided oat reduced the plant density of weeds and volunteer wheat. While there were 54.5 plants/m² in the control plots, only 5.5 plants/m² were counted in the lopsided oat plots. The results showed that lopsided oat has a high potential for suppression of weeds and volunteer wheat in autumn. It also enlarges the number of cultivated cover crops in Central Europe.

In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [=5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets. The New Era (NE) study recruited patients with primary HIV infection (PHI) or chronically HIV-infected patients with conventional ART (CHI) and applied an intensified 5-drug regimen containing maraviroc and raltegravir for several years. We compared the frequencies of the immune suppressive cells, namely, the myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), and regulatory T cells (Tregs), of the treatment intensification patients to the control groups, especially to the patients with conventional 3-drug ART, and analyzed the Gag/Nef-specific CD8 T cell responses. There were no differences between PHI and CHI in the NE population ( p  > 0.11) for any of the studied cell types. Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic myeloid-derived suppressor cell (M-MDSC), and the Breg frequencies were comparable to those of patients with a 3-drug ART. However, the Treg levels were significantly lower in the NE patients than those in 3ART-treated individuals and other control groups ( p  ≤ 0.0033). The Gag/Nef-specific CD8 T cell response was broader ( p  = 0.0134) with a higher magnitude ( p  = 0.026) in the NE population than that in the patients with conventional ART. However, we did not find a correlation between the frequency of the immune suppressive cells and the interferon-gamma + CD8 T cell response. In the treatment intensification subjects, the frequencies of the immune suppressive cells were comparable or lower than those of the conventional ART-treated subjects, with surprisingly broad HIV-specific CD8 T cell responses, suggesting a preservation of immune function with the applied treatment regimen. Interestingly, these effects were seen in both treatment intensification subpopulations and were not attributed to the start of treatment in primary infection.

Objective: To investigate if early treatment of primary HIV-1 infection (PHI) reduces viral set point and/or increases CD4 lymphocytes., Methods: Analysis of two prospective multi-centre PHI cohorts. HIV-1 RNA and CD4 lymphocytes in patients with transient treatment were compared to those in untreated patients. Time to CD4 lymphocyte decrease below 350/ microl after treatment stop or seroconversion was calculated using Kaplan-Meier and Cox-PH-regression analyses., Results: 156 cases of PHI were included, of which 100 had received transient HAART (median treatment time 9.5 months) and 56 remained untreated. Median viral load (563000 cop/ml vs 240000 cop/ml; p<0.001) and median CD4 lymphocyte (449/ microl vs. 613/ microl; p<0.01) differed significantly between treated and untreated patients. Median viral load was 38056 copies/ml in treated patients (12 months after treatment stop) and 52880 copies/ml in untreated patients (12 months after seroconversion; ns). Median CD4 lymphocyte change was +60/ microl vs. -86/ microl (p = 0.01). Median time until CD4 lymphocytes decreased to <350/ microl (including all patients with CD4 lymphocytes <500/ microl during seroconversion) was 20.7 months in treated patients after treatment stop and 8.3 months in untreated patents after seroconversion (p<0.01). Cox-PH analyses adjusting for baseline VL, CD4 lymphocytes, stage of early infection and symptoms confirmed these differences., Conclusions: Treatment during PHI did not lower viral set point. However, patients treated during seroconversion had an increase in CD4 lymphocytes, whereas untreated patients experienced a decrease in CD4 lymphocytes. Time until reaching CD4 lymphocytes <350/ microl was significantly shorter in untreated than in treated patients including patients with CD4 lymphocytes <500/ microl during seroconversion.

Aim: For several years Nonnucleoside reverse transciptase inhibitors (NNRTIs) in antiretroviral therapy have been associated with hepatic side effects. Particularly the hepatotoxic potential of Nevirapine is well analysed today. We performed a prospective, multicenter study to compare the hepatotoxicity of Efavirenz (EFV) with that of Nevirapine (NVP) and to investigate further risk factors., Material and Methods: The study included HIV-1-infected patients from five clinics and private medical practices in southwestern Germany who initiated an antiretroviral therapy with NVP or EFV between July 1998 and December 2001. Among 296 patients in total, 151 received EFV and 145 received NVP. Laboratory tests during the course of treatment included liver enzymes, HIV-RNA and CD4 cell-count. Additionally, signs of clinical hepatitis were recorded. Hepatotoxicity was graded in the manner of Sulkowsky et al. (2000), who used a scale modified from that of the AIDS Clinical Trials Group., Results: Hepatitis C virus and hepatitis B virus were detected in 10.1% and 4.1% of patients, respectively. The overall rate of severe hepatotoxicity (grade 3 to 4 elevations in aspartate aminotransferase and/or alanine aminotransferase) was 2 of 151 (1.3%) in patients prescribed EFV and 3 of 145 (2.1%) in patients prescribed NVP. Mild-to-moderate hepatotoxicity (grade 2 elevation) was observed in 6.0% (EFV) and 3.4% (NVP) of patients. Incidence of mild-to-moderate and severe hepatotoxicity did not differ significantly between the study groups. 3 of 14 patients (2.1%) with grade 2 elevation of liver enzymes (LEE) and 4 of 5 patients (80%) with grade 3 to 4 LEE were symptomatic. Only risk factor for the development of mild-to-moderate hepatotoxicity was hepatitis C coinfection., Conclusion: Increases of liver enzymes during therapy with NVP or EFV are not unusual, but are mostly mild-to-moderate and asymptomatic. LEE occurs just as frequent in patients prescribed EFV as in patients prescribed NVP.

Objective: To evaluate the long-term effects of antiretroviral treatment (ART) interruptions on metabolic, immunological, virological and clinical outcomes in chronically HIV-1 infected patients., Methods: Multi-centric, prospective, controlled 24-month cohort study in HIV-1 infected patients interrupting ART once or several times and for at least two weeks. Patients were compared to a frequency-matched control group continuing on ART., Results: A total of 399 HIV-1 infected patients were included, among them 133 patients with treatment interruption (TI) and 266 control patients. Baseline characteristics were well matched. Median baseline CD4 cell count was 379/microl in TI-patients and 410/microl in control patients (p = ns). Median duration of the first TI was 1.1 months, and 37 % of patients had two or further TI's. Whereas CD4 cell count in control patients had increased significantly by a median of 67/microl at month 24 (p<0.0001), median CD4 cell count at month 24 in the TI-patients did not differ significantly from baseline. However, two-year AIDS-free survival was not significantly different between TI- and control patients. Liver enzymes and blood lipids improved significantly during TI., Conclusion: TI was associated with a significant immunological disadvantage at 24-month follow-up compared to continued ART. In this relatively immunocompetent cohort, however, TI's did not lead to an increased risk of disease progression within two years of follow-up.

Purpose: To show Didanosin in a new formulation as a once-a-day capsula as a well-tolerated and effective HIV-therapy when used in a protease sparing regimen including genotypic resistance pattern in blood, semen and cerebrospinal fluid before and during treatment., Method: Two groups of 58 patients, each containing 9 patients who had not been previously treated with any antiretroviral medication, and 49 patients heavily pretreated for 3,7 (DDI group) and 2,8 (non-DDI group) years, have been followed up for at least half a year. A group of 24 patients taking a special combination of Didanosin plus Efavirenz and Stavudine have been analysed with genotypic resistance testing concerning viral load response and resistance pattern under therapy., Results: Suppression of plasma HIV-1 RNA to <50 copies/mL and <500 copies/mL in the DDI group was achieved in 74% and 84% of the pretreated patients, respectively, and in 100% of the naive patients after 24 weeks. In the non-DDI group suppression was achieved in 59% and 69% of the pretreated patients, respectively, and in also 100% of the naive patients. The viral load reduction in the DDI containing regimen at week 24 was 1.7 log subset 10 for the pretreated and 3,4 log subset 10 for the naive patients. In the non-DDI group, the reduction was 1.5 for the pretreated and 4,0 for the naive patients. CD4 cell counts increased from 440 to 517 cells/microL at week 24 for the pretreated, and from 171 to 289 for the naive patients in the DDI containing regimen. In the other group, cells increased from 396 to 406 for the pretreated and from 155 to 321 for the naive patients. In each group, 12 patients discontinued treatment; 4 patients in the DDI group and 7 patients in the non-DDI group because of adverse events. There were no AIDS-defining events in the antiretroviral-treated patients in both groups. 16 patients of the special combination group (DDI, D4T and EFV) were evaluated for more than 24 weeks. Suppression of HIV-1 RNA to <50 copies /mL were found in 75% of the naive and 43% of the pretreated patients. No relevant mutations were found during treatment., Conclusion: The new formulation of Didanosin as a once-a-day capsula in a protease sparing regimen was well-tolerated, effective in reducing viral load and in preventing AIDS-defining events. The combination of DDI, D4T and EFV proved to be a potent therapy without developing relevant mutations.

Objective: To prospectively document the incidence of game injury rates in youth ice hockey tournaments to compare with season-long game injury rates and to analyze the injuries occurring at tournaments by mechanism, type, body location, severity, player position, and period of play., Design: A prospective injury report form completed for injured players by the tournament athletic trainer., Setting: Four boys' tournaments and one girls' tournament during the 1993-94 season., Participants: 807 boys and girls, ages 9-19., Measurements/main Results: 60 injuries occurred in boys and 4 occurred in girls. There were 26 boys with significant injuries and no girls with significant injuries. The significant game injury rates per 1000 player hours were 50.9 for boys combined, 57.9 for boys' Peewee A, 42.7 for boys' Bantam A, 64.8 for boys' varsity high school, 44.8 for boys' Junior Gold, and 0 for girls' Peewee A and B. Cerebral concussion comprised 15% of boys' injuries., Conclusions: The significant injury rate for boys' tournament game play was 4-6 times higher than the season game injury rates in two previous season-long studies. In boys' games, 65% of "all" injuries and 77% of "significant" injuries were related to collisions. The girls' rules of play do not allow body checking, and there were no significant injuries in girls' games. The boys had high rates of cerebral concussion injury at all age levels. Minimizing the frequency and intensity of collisions in the boys' game may decrease the injury rates, especially in the tournament setting.

Clinical services must monitor hospital-acquired morbidity, but what rates are expected specifically for neurology inpatients is not evident from published studies. We studied prospectively 1317 consecutive admissions to a neurology service in a university-affiliated city hospital from 1987 to 1990 and recorded all nosocomial infections, nosocomial pneumonia, and decubitus ulcers of stage III or IV. Over the 3-year period, 6.8% of patients had > or = 1 nosocomial infection (and almost half of these had a nosocomial bloodstream infection); 3.1% had > or = 1 case of nosocomial pneumonia; 1.2% developed severe decubitus ulcers, and 8.4% had one or more of the three complications. The incidence of nosocomial infection exceeds that expected from multihospital studies. How much of the excess is peculiar to neurology patients and how much can be attributed to factors in our community and at our hospital cannot be determined from this study. Furthermore, our statistics are not meant as norms, but as initial estimates for quality assurance.

This paper considers the financial burden of parents caring for severely disabled children. A model to predict parents' out-of-pocket expenses and caregiving time demands is described. Discriminant analysis correctly classified high and low group membership for out-of-pocket expenses and caregiving time at 72 percent and 77 percent, respectively. Expected rates were 50 percent. Time spent caregiving was the best predictor for out-of-pocket expenses, and out-of-pocket expenses was the best predictor of caregiving time. A need-based approach for the distribution of resources that recognizes and adjusts for caregiving time and out-of-pocket costs is recommended.

Home care programs for severely disabled, usually technology-dependent, children got a boost in 1981 when the Federal Government gave States permission to use Medicaid to fund home care under the Medicaid model home- and community-based waiver (2176). The model waiver program was unique because it eliminated the bias toward hospitalization by waiving parental income and assets when determining eligibility for children cared for at home and by allowing Medicaid to cover needed home care services. In 1985 Minnesota received Federal approval for the model waiver, and the results are detailed in this report. Although the waiver could provide funding for up to 50 children, after 2 years only 24 children had received approval. Stringent and complex eligibility criteria acted as barriers to accessing the model waiver. In addition, the interaction between the waiver and the State's health care system contributed to inconsistencies in eligibility. This interaction demonstrates the difficulty of administering publicly funded programs in the current health care environment. Recommendations are made for adjusting criteria for eligibility in the waiver program. Unresolved problems facing technology-dependent children on home care programs are discussed.

Seizures, epilepsy, and alcohol are complexly interrelated. Although it is commonly perceived that patients with epilepsy experience problems with seizure control if they use alcohol, this is not confirmed by the few experimental studies that have tested the hypothesis. The last 30 years have emphasized the role of withdrawal from alcohol as a mechanism of seizure production. However, this is but one of many potential mechanisms by which seizures and epilepsy may be related to alcohol use and abuse. The rare but clear situations in which alcohol can act as a convulsant drug need further study, and mechanisms by which the long-term neurotoxic effects of alcohol lead to chronic epilepsy also need further elucidation.