A randomized, double-blind, parallel-group, dose-response study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients.

BACKGROUND: Severely immunocompromised individuals are highly susceptible to Candida infection of the esophagus. This randomized, double-blind study assessed the dose-response relationship of the new echinocandin antifungal, micafungin, compared with that of standard fluconazole treatment. METHODS: A total of 245 patients (age, > or =18 years) with a prior diagnosis of acquired immunodeficiency syndrome/human immunodeficiency virus (HIV) infection and esophageal candidiasis, confirmed by endoscopy and culture, were randomized to receive micafungin (50, 100, or 150 mg per day) or fluconazole (200 mg per day). Both agents were administered once per day by a 1-h intravenous infusion for 14-21 days. The primary efficacy end point was endoscopic cure rate, defined as endoscopy grade of 0 at the end of therapy. RESULTS: The endoscopic cure rate (grade 0) was dose-dependent with 50, 100, and 150 mg of micafungin per day at 68.8%, 77.4%, and 89.8%, respectively. Symptoms improved or resolved rapidly (3-7 days of treatment in the majority of patients). The endoscopic cure rate for 100 and 150 mg of micafungin per day (83.5%) was comparable to that for 200 mg of fluconazole per day (86.7%; 95% confidence interval for the difference in endoscopic cure rate, -14.0% to 7.7%). The overall safety and tolerability was acceptable, with no important differences between micafungin (all doses) and fluconazole. CONCLUSIONS: The dose-response findings demonstrate a greater efficacy with micafungin at 100 and 150 mg per day than at 50 mg per day. This study also indicates that the efficacy of micafungin (at dosages of 100 and 150 mg per day) was comparable to that of fluconazole, suggesting that micafungin represents a valuable new treatment option for esophageal candidiasis in HIV-positive patients.

Metabolic disturbances in male workers with rotating three-shift work. Results of the WOLF study.

OBJECTIVES: The aim of the present study was to investigate the relationship between important metabolic risk factors for coronary heart disease (CHD) and type 2 diabetes in shift workers and day workers. METHODS: Cross-sectional data from a sub-population in the WOLF study consisting of 665 day workers and 659 three-shift workers in two plants were analysed. RESULTS: A higher proportion of shift workers than day workers had high triglyceride levels (> or =1.7 mmol/l), low levels of HDL-cholesterol (<0.9 mmol/l) and abdominal obesity (waist/hip ratio>0.9). The risk of low HDL-cholesterol was doubled in shift workers, (odds ratio (OR): 2.02, 95% confidence interval (95% CI): 1.24-3.28) after being adjusted for age, socio-economic factors, physical activity, current smoking, social support and job strain. High levels of triglycerides were also significantly associated with shift work (OR: 1.40, 95% CI: 1.08-1.83). The OR for abdominal obesity was 1.19, (95% CI: 0.92-1.56). The prevalence of hyperglycaemia (serum glucose > or =7.0 mmol/l) was similar in day and shift workers. No significant interaction was seen between shift work and abdominal obesity with regard to the associations with triglycerides and HDL-cholesterol. CONCLUSIONS: We found a significant association between shift work and lipid disturbances (i.e. low HDL-cholesterol and high triglyceride levels). We did not find any association with hyperglycaemia.

Beam injection flame furnace atomic absorption spectrometry: a new flame method.

A new flame method of atomic absorption spectrometry is described. The liquid sample to be analyzed is transported as a high-speed liquid jet into a heated tube which is positioned in an air/acetylene flame. The jet is generated by means of an HPLC pump which feeds a smooth jet nozzle having a diameter of 50 microns or smaller. After traveling a distance of 10 cm, the liquid jet enters a small sample introduction hole, impacts onto the opposite inner wall of the tube furnace, and immediately vaporizes (jet impact vaporization, JIV). Both the complete introduction of the entire sample and the extended residence time inside the absorption volume result in an improvement in power of detection from 6- to 202-fold for 17 elements (Ag, As, Au, Bi, Cd, Cu, Hg, In, K, Pb, Pd, Rb, Sb, Se, Te, Tl, Zn). A standard deviation of 1.7-4.0% (n = 12, 50 microL) was achieved. Sample volumes between 10 microL and 1 mL have been investigated. For 50 microL sample volumes, the sampling frequency is 4/min. The new method can also be considered a simple, effective interface between HPLC and flame AAS.

Determination of Cd and Pb at microg/L levels by HHPN-beam injection flame furnace-AAS.

Flame-heated tubes are widespread in flame-AAS, mainly for the determination of hydride-forming elements. Instead of the introduction of gaseous compounds liquids can also be introduced continuously in such an absorption cell. With the aid of an HPLC pump the liquid is forced through a very fine nozzle, generating an aerosol beam less than 0.5 mm in diameter. This beam travels a distance of 10cm as a "free-flying aerosol jet" into the sample introduction hole of a metal tube furnace placed in the flame. Both introduction of the entire sample and the long residence time lead to a considerable improvement in power of detection. The detection limit for 100 microL samples amounts to 7 microg/L (Pb) and to 0.2 microg/L (Cd), which means an increase in power of detection of between one and two orders of magnitude compared to conventional flame-AAS. The relative standard deviation (100 microL sample volume, N = 10) was found to be 1.3% (signal area) for 600 microg/L Pb and to be 1.5% (signal-area) for 15 microg/L Cd. RSD values from measurements in peak-height amounted to 2.2% (Pb) and to 1.7% (Cd).

A novel high-temperature (360 degrees C)/high-pressure (30 MPa) flow system for online sample digestion applied to ICP spectrometry.

A flow injection sample digestion system has been developed comprising an indirectly electrically heated Pt/Ir capillary. Such a capillary allows reaction temperatures of up to 360 degrees C and pressures of up to 30 MPa (300 bar) and withstands concentrated acids. This temperature is 130 degrees C to 160 degrees C higher compared to the operating temperatures of microwave heated flow systems. A combination of an ultrasonic nebulizer and membrane desolvator serves as an interface between the flow digestion system and an ICP/AES spectrometer. The membrane desolvator removes interfering gaseous digestion products so effectively before the sample stream enters the plasma that the measured residual carbon concentration falls in the region of the detection limit of ICP/OES measurements. Sewage sludge samples were digested using nitric acid and the elemental traces online determined. The detection limits related to the original dry substances amount to the lower microg/g range.

[Treatment satisfaction in cardiologic rehabilitation and attitude to various forms of rehabilitation]. / Behandlungszufriedenheit in der kardiologischen Rehabilitation und Einstellungen zu verschiedenen Rehabilitationsformen.

A great majority (85% to 92%, N = 196) of the cardiological patients in inpatient rehabilitation, who were investigated in this study, expressed clear satisfaction with inpatient care and in particular with medical treatment as well as with the commitment and skills of doctors and other caregivers. The usefulness of treatments and measures was mainly confirmed, especially with respect to remedial gymnastics, physiotherapy and rehabilitation sports. But unspecific offers of inpatient rehabilitation are obviously also evaluated positively, e.g. "distancing from everyday stress" and "cultural events" outside the clinics. Relaxation training and psychosocial counseling were used only by one third approximately, but most of the users gave "useful" or "very useful" evaluation ratings. 77% would again choose inpatient rehabilitation if they were confronted with this decision. 15% would prefer partial-hospitalization, only 4% ambulatory rehabilitation. 36% say that "near-home rehabilitation" basically is more favourable, but 33% prefer the opposite and say that rehabilitation far away from home has greater advantages. Only 8% consider ambulatory rehabilitation a possible replacement of inpatient rehabilitation, 66% say it is complementary to the inpatient mode.

Metal Speciation in the ppt Range by HPLC and Diode Laser Atomic Absorption Spectrometry in a Flame.

A simple, compact, and powerful instrument for metal speciation in the ppt range is described. The instrument includes a HPLC module for separation and a diode laser for element-selective detection by wavelength modulation absorption spectrometry in an analytical flame. The high detection power for metal species is due to a two-beam arrangement with logarithmic amplification of the normalized signal, which compensates the laser residual amplitude modulation noise, the offset, and its fluctuation. The analytical figures of merit are demonstrated by measurements of very low concentrations of Cr(VI) in tap water.

Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study.

One hundred twenty-six patients with cirrhosis, hyperammonemia (>50 micromol/L), and chronic (persistent) hepatic encephalopathy (HE), which developed spontaneously without the existence of known precipitating factors, were enrolled in a randomized, double-blind, placebo-controlled clinical trial of intravenously administered L-ornithine-L-aspartate (OA). Patients with subclinical (grade 0, West-Haven criteria) hepatic encephalopathy (SHE), characterized by a prolonged number connection test A (NCT-A) time, and manifest HE (grades I and II, West-Haven criteria) were included in the investigation. The trial was planned as a confirmatory clinical trial OA administered in a dose of 20 g/d, as well as placebo, were dissolved in 250 mL of 5% fructose and infused intravenously for a period of 4 hours during 7 consecutive days with a superimposed protein load at the end of the daily treatment period. Primary variables were postprandial venous ammonia and NCT-A performance time measured following OA or placebo infusions to evaluate the net effect of the treatment on the prevention of the protein-induced hyperammonemia, and on parameters such as NCT-A influenced by hyperammonemia. Mental state gradation, portal systemic encephalopathy index (PSEI), and fasting ammonia levels were estimated as additional efficacy parameters. The data presented are based on the total study sample (intent-to-treat analysis), which included 63 patients in the placebo group and 63 patients in the OA group. Of the 126 patients, 114 met all the criteria for inclusion and completed the trial and treatment as outlined in the protocol (treated-per-protocol analysis). During baseline, the placebo and treatment groups were homogeneous with regard to mental states, NCT-A performance time, fasting venous blood ammonia levels, and Child-Pugh criteria. Although a slight improvement occurred in the placebo group, NCT-A performance times (P < .001) and postprandial venous ammonia concentrations in the OA-treated group showed improvements in comparison with placebo. In addition, venous fasting blood ammonia concentration (P < .01), mental state gradation (P < .001), and PSEI (P < .01), which includes the mental state gradation, NCT-A time, and postprandial venous ammonia in this trial, improved to a much higher degree in the OA group than in the placebo group. In subgroups retrospectively classified according to their initial mental state gradation, OA showed differential but uniformly significant efficacies in patients with manifest HE with respect to ammonia-lowering, improvement in NCT times, and mental state gradation. In patients with initial SHE, OA revealed differences between the medications in the psychometric test used. Adverse events consisting of mild gastrointestinal disturbances were observed in 3 of the OA-treated patients (5%). OA infusion appears to be a safe, effective treatment of chronic (persistent) manifest HE in cirrhotic patients. Additional investigations are required to assess the efficacy of OA in patients with SHE, as well as in patients with more severe grades of HE.

High-performance flow atomic spectrometry: New nebulization techniques, on-line speciation and on-line sample pretreatment.

An interface-free combination of HPLC separation techniques and methods for element determination by atomic spectrometry can be achieved by hydraulic high-pressure nebulization (HHPN). With high-temperature HHPN (300 ( degrees )C) super heated liquids can be nebulized providing aerosol yields of up to 90% in flame AAS. This new nebulization method combines the advantages of HHPN and thermospray techniques (very small aerosol droplets, high aerosol yield, nebulization of saturated salt solutions).

Flame AAS/flame AES for trace determination in fresh and used lubricating oils with sample introduction by hydraulic high-pressure nebulization.

In hydraulic high-pressure nebulization (HHPN) an aerosol is produced by means of an HPLC-pump and a special nebulization nozzle, applying a pressure of about 200 bar. This spray technique has been employed for sample introduction of mineral oil samples in flame atomic absorption/flame emission spectrometry. The determination of the trace elements Al, Cr, Cu, Fe, K, Na, Ni, Pb, Si and V has been investigated. Viscosity hardly acts upon the sensitivity of the determination, thereby avoiding a time consuming dilution of oil samples. By means of two interconnecting sampling valves a calibration method based on the standard addition technique can be performed which is both simple and easy to carry out. In samples of used oils, results for Cu and Pb equalled those of XRF-analysis. Regarding Fe traces, data obtained from AAS and XRF measurement correlate. In comparison with sample uptake by pneumatic nebulization, which is restricted to diluted oil samples, detection limits decrease by a factor of 2 to 4, indicating the dilution required in pneumatic nebulization.

The acoustic properties of normal and imbedded bovine bone as measured by acoustic microscopy.

The acoustic impedance of bovine femoral cortical bone was measured with a scanning acoustic microscope used in the reflection mode. The bone was measured in the unimbedded state and after plastic imbedding. The acoustic impedance of the unimbedded specimens was also measured with a standard transmission ultrasonic technique. For the unimbedded bovine specimens there was a good correlation between the bulk transmission impedance and the reflection surface impedance (r2 = 0.976) and the values were 9.32 and 9.29 MRayls, respectively. Plastic imbedding produced a consistent and statistically significant increase in the acoustic impedance of the bone (9.71 MRayls). This experiment verified the use of acoustic microscopy as a quantitative materials analysis technique and it demonstrated the potential for material property analysis of imbedded bone.