Comparison of round and knife-edge-like cathodes on gas-puff implosions.

Preionization is believed to play an important role on the implosion of gas-puff Z pinches. Some experiments have used an external preionization source, e.g., UV light or electron beam. In contrast, other experiments rely completely on over voltage breakdown by the own generator's voltage pulse. However, this approach lacks shot-to-shot reproducibility since self-breakdown is mainly a stochastic process. In this work, we performed a systematic study on self-breakdown using two different cathode geometries: (i) a smooth, round cathode to provide a homogeneous electric field, (ii) a sharp, knife-edge-like geometry to enhance the electric field locally and eventually electron emission. The experiments were carried out on the Llampudken current generator, which provides a current pulse of ∼400kA amplitude and 200 ns rise time (10%-90%). We implemented gated XUV imaging, filtered diodes and time-integrated x-ray imaging to obtain information about the implosion as well as the stagnation phase for the two cathode geometries. We found that erosion of the knife-edge cathode might be a serious problem, and we had to replace it every 15 shots. On the other hand, the round cathode lasted for the whole series of experiments. We also measured a more reproducible and larger peak current for the knife cathode. From the photo-conductive detectors we observed that even if the round cathode might present shots with higher x-ray yield compared to the knife cathode, dispersion is almost twice as large. Moreover, after a statistic analysis, it is demonstrated that the dispersion in the yield is due solely to differences imposed by the cathodes and not to variations in the driver, as no correlation was found between them. We found that in order to fit the experimental data with the snowplow model, only ∼60% of the total mass is compressed in the knife cathode while ∼20% for the round one, highlighting the importance of the cathode and preionization. Therefore, we conclude that the use of the knife cathode increases the reproducibility of the experiment in comparison with the round cathode.

Prediction of creatinine clearance from serum creatinine in patients with rheumatoid arthritis: comparison of six formulae and one nomogram.

The estimation of glomerular filtration rate is important for the medical treatment of patients with rheumatoid arthritis (RA). However, the determination of endogenous creatinine clearance (Clcr) from a 24-h urine collection is an unreliable and time-consuming procedure. We therefore tested the accuracy of six equations and one nomogram for the prediction of Clcr from serum creatinine (Scr) in 38 patients with RA and 20 controls. A positive correlation was found for all methods in the controls (r = 0.83-0.94) and RA patients (r = 0.51-0.69). The methods did not overestimate Clcr in RA. In the RA group the simple formula published by Cockcroft [Clcr = ((140 - age) x body weight)/(72 x Scr), x 0.85 for females] showed the best correlation with the measured Clcr. In RA the Cockroft formula can reliably be used to predict Clcr from Scr.

Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis.

Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.

Hyperlipidemia under treatment with proteinase inhibitors.

To define the extent and time course of HIV-proteinase inhibitor (PI) effects on serum lipid levels 148 patients on triple combination therapy including PIs and 91 patients on therapy with two nucleosides as a control group were evaluated. In the PI group there was a significant increase in total cholesterol after 3, 6 and 12 months compared to the baseline level (198, 204 and 203 vs. 176 mg/dl). The increase in triglycerides was 25.5% from the baseline at month 3. Indinavir had a significantly higher impact on cholesterol levels than saquinavir. No changes in lipids were seen in the control group. It was concluded that hyperlipidemia is associated with PI use, becomes evident within 3 months of treatment and seems to be substance specific.

Endothelin-1 is elevated in the cerebrospinal fluid of HIV-infected patients with encephalopathy.

In a cross-sectional, non-randomized, prospective study in an outpatient clinic a possible relationship between the cerebrospinal fluid (CSF) concentrations of the potent vasoconstrictor peptide endothelin-1 (ET-1) and prevalence and degree of HIV-encephalopathy was studied. Forty-eight CSF samples from HIV-infected patients undergoing lumbar punction for diagnostic reasons were investigated for ET-1 concentrations. In 37 patients ET-1 was also measured in plasma. Patients were investigated clinically and staged with respect to HIV encephalopathy. Patients with arterial hypertension, diabetes or acute opportunistic infections were excluded from the study. In the remaining, 18 of the CSF samples were from patients with normal neurological findings (grade 0-0.5), whereas 30 were from patients with HIV encephalopathy (grade 1-3). The mean CSF ET-1 concentration was significantly elevated (P = 0.001) in patients with HIV encephalopathy (1.97 +/- 2.33 pmol/l) as compared to those patients without encephalopathy (0.57 +/- 0.67 pmol/l). Moreover, there was a significant correlation between ET-1 CSF concentrations and the degree of HIV encephalopathy (r = 0.49, P < 0.001). In addition, there was a significant correlation between ET-1 levels in the CSF and the IgG serum to CSF ratio. However, we found no correlation between HIV encephalopathy and neither CSF total protein, IgG, albumin or the serum to CSF ratio of IgG or albumin. In conclusion, we could demonstrate a close relationship between CSF ET-1 concentrations and the degree of HIV encephalopathy. Thus, by virtue of its long-lasting and potent vasoconstrictor activity ET-1 might contribute to the pathogenesis of HIV encephalopathy.

HIV-1-infected long-term slow progressors heterozygous for delta32-CCR5 show significantly lower plasma viral load than wild-type slow progressors.

OBJECTIVE: Patients heterozygous for delta32-CCR5 may have a delayed progression of HIV-1 disease. The aim of the present study was to investigate the influence of CCR5/delta32-CCR5 genotype in long-term slow progressors using plasma viral load as a marker of disease progression. DESIGN: We analyzed 70 long-term slow progressors (diagnosis > 8 years previously; CD4 count > 500/microl; asymptomatic, never received antiretroviral therapy) for CCR5 genotype, plasma viral load, and lymphocyte subsets. Distribution of CCR5 genotypes was compared with a cohort of 61 multiply exposed noninfected individuals and a group of 336 control subjects. All study participants were white. METHODS: CCR5 genotype was determined by polymerase chain reaction (PCR) amplification. Plasma viral load was quantified by branch DNA hybridization, lymphocyte subsets were determined by fluorescence-activated cell sorter (FACS) analysis. The Mann-Whitney-Wilcoxon test was used for statistical analyses. RESULTS: The frequency of the CCR5/delta32-CCR5 heterozygote genotype was higher in long-term slow progressors (37.1%) and multiply exposed noninfected individuals (26.2%), compared with the control group (15.8%). In addition, plasma viral load was found to be significantly lower in CCR5/delta32-CCR5 heterozygous long-term slow progressors (median < log10 2.70; 53.8% < log10 2.70; 0% > log10 4.0) relative to that seen in CCR5/CCR5 long-term slow progressors (median log10 3.64; 22.7% < log10 2.70; 22.7% > log10 4.0). CONCLUSIONS: These findings strengthen the hypothesis of a favorable influence of CCR5/delta32-CCR5 genotype on progression of HIV-1 infection. Therefore, evaluation of CCR5 genotype might influence antiretroviral therapy strategies in early stages of HIV-1 infection.

Liposomal doxorubicin in pulmonary Kaposi's sarcoma: improved survival as compared to patients without liposomal doxorubicin.

OBJECTIVE: Pulmonary Kaposi's sarcoma (KS) in HIV-infected patients is characterised by a poor prognosis with a mean survival time of 2 to 6 months. Our goal was to evaluate survival in patients with pulmonary KS treated with Stealth liposomal doxorubicin (SL-DOX) and to compare it with patients without SL-DOX therapy. PATIENTS AND THERAPY: 29 AIDS patients with confirmed pulmonary Kaposi's sarcoma were studied. Group 1 (n = 20): Patients treated with SL-DOX. Group 2 (n = 9): 4 patients who received bleomycin and vinblastine or vincristine and 5 patients without chemotherapy. RESULTS: Survival analysis by Kaplan-Meier plot showed a significant benefit for patients with SL-DOX treatment. Mean survival times were 11.8 +/- 1.78 months (group 1: range 1-28) versus 4.4 +/- 1.68 months (group 2; range 1-17). Average CD4 levels did not differ significantly at diagnosis of pulmonary Kaposi's sarcoma. Clinical response included improvement of general health, particularly cough and dyspnea, of arterial pO2 and radiographic KS pattern in the lung. CONCLUSION: Our analysis suggests a clear survival and quality of life benefit for patients with pulmonary Kaposi's sarcoma on liposomal doxorubicin.

Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV-infected patients: progression from localized to systematic disease, German Aids Study Group (GASG/IDKF).

Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.