PFI-ZEKE-photoelectron spectroscopy of N2O using narrow-band VUV laser radiation generated by four-wave mixing in Ar using a KBBF crystal.

A new nonlinear optical scheme relying on sum-frequency mixing in a KBe2BO3F2 crystal has been used to generate intense, broadly tunable, narrow-bandwidth, coherent vacuum-ultraviolet (VUV) radiation beyond 16 eV by resonance-enhanced four-wave mixing in Ar. The VUV radiation was used to record high-resolution pulsed-field-ionization zero-kinetic-energy photoelectron spectra of the N2O+ A+ ← N2O X photoionizing transition in the wave-number range from 132 000 cm-1 to 135 000 cm-1. The rotational structure of almost all vibrational levels of the A+ state with vibrational term values up to 2700 cm-1 could be resolved, and improved values of the first two adiabatic ionization energies of N2O, corresponding to the formation of the X+ 2Π3/2(000) J+ = 3/2 and A+ 2Σ+(000) N+ = 0 levels of N2O+ from the X 1Σ+(000) J″ = 0 ground state [103 969.30(12) cm-1 and 132 197.70(12) cm-1, respectively], were derived. The rotational intensity distributions of the bands were found to depend strongly on the value of the vibrational angular momentum of the ionic levels. The vibrational structure is discussed in terms of previously reported effective-Hamiltonian analyses.

Vacuum-ultraviolet frequency-modulation spectroscopy.

Frequency-modulation (FM) spectroscopy has been extended to the vacuum-ultraviolet (VUV) range of the electromagnetic spectrum. Coherent VUV laser radiation is produced by resonance-enhanced sum-frequency mixing (νVUV=2νUV+ν2) in Kr and Xe using two near-Fourier-transform-limited laser pulses of frequencies νUV and ν2. Sidebands generated in the output of the second laser (ν2) using an electro-optical modulator operating at the frequency νmod are directly transferred to the VUV and used to record FM spectra. Demodulation is demonstrated both at νmod and 2νmod. The main advantages of the method compared to VUV absorption spectroscopy are its background-free nature, the fact is that its implementation using table-top laser equipment is straightforward and that it can be used to record VUV absorption spectra of cold samples in skimmed supersonic beams simultaneously with laser-induced-fluorescence and photoionization spectra. To illustrate these advantages, we present VUV FM spectra of Ar, Kr, and N2 in selected regions between 105000 cm-1 and 122000 cm-1.

Target site concentrations after continuous infusion and bolus injection of cefpirome to healthy volunteers.

BACKGROUND: Recent data indicate a higher level of effectivity of beta-lactam antibiotics if serum concentrations are kept above the minimal inhibitory concentration (MIC) of the pathogen. This concept would favor continuous infusion over bolus dosing. However, it is usually not the serum concentration but the free interstitial concentration in the target tissue that determines antibiotic activity. We therefore set out to measure effective drug concentrations in the interstitial space of muscle and subcutaneous adipose tissue and to compare trough levels and times above the MIC after bolus versus continuous infusion of cefpirome. METHODS: Twelve healthy volunteers received a single dose of 2 g cefpirome as an intravenous bolus or as a continuous infusion over 8 hours in a crossover design, and the resulting free interstitial tissue concentrations were measured with use of microdialysis. RESULTS: After bolus injection, mean interstitial trough concentrations were 3.0 +/- 1.9 microg/mL and 2.1 +/-1.0 microg/mL for muscle and subcutaneous tissue, respectively; continuous infusion resulted in trough levels of 10.1 +/- 6.8 microg/mL and 10.1 +/- 4.6 microg/mL for muscle and subcutaneous tissue, respectively. This resulted in significantly longer times above the MIC with continuous infusion for Staphylococcus epidermidis and Enterobacter cloacae. Bacteria with an MIC < or =1 would be covered by either method, whereas higher doses seem to be necessary for Pseudomonas aeruginosa. CONCLUSION: Although susceptible organisms will usually be covered sufficiently with standard dosing regimens, soft tissue infections with bacteria that have MIC values of 2 to 8 may profit from continuous application. Coverage of P aeruginosa, however, would be inadequate with conventional daily doses of 4 g cefpirome regardless of the method of application.

Multiple-dose pharmacokinetics of cefpirome in long-term hemodialysis with high-flux membranes.

Cefpirome is a cephalosporin eliminated primarily by kidneys that requires dosage reduction in patients with renal failure. The pharmacokinetic parameters were studied in 10 patients with end-stage renal disease who were receiving hemodialysis. Repeated intravenous administration of 2 gm cefpirome three times a week resulted in trough levels of 12.2 +/- 5.4 micrograms/ml and peak serum concentrations of 99.6 +/- 82.1 micrograms/ml. After 3 1/2 hours of hemodialysis with polysulfone high-flux membranes, 62.3% +/- 23.3% of cefpirome was removed. The interdialytic half-life was 9.35 +/- 0.99 hours, and the intradialytic half-life was 2.02 +/- 0.7 hours.

Relationship of CD15 immunoreactivity and prognosis in sporadic medullary thyroid carcinoma.

Immunoreactivity with monoclonal antibody CD15 (Leu-M1) was investigated in the primary tumours, the metastases and local recurrences of 47 cases of sporadic medullary carcinoma of the thyroid (MTC). Of these tumours, 36.5% showed a varying degree of CD15 immunostaining; in 7 carcinomas the CD15 immunoreactivity was found to be significant (greater than 15% tumour cells positively stained). Staining of the amyloid stroma was observed in 3 tumours. Significantly higher epithelial CD15 positivity was seen more frequently in the group with larger tumours (greater than 4 cm) and was found exclusively in the presence of lymph node metastases. No substantial difference in the percentage of immunostained cells was seen between primary tumours and metastatic or recurrent lesions, except for two cases that revealed a significant increase in the number of CD15-immunostained cells in metastatic and recurrent lesions. Five of 7 patients with recurrences showing significant CD15 immunostaining died of cancer, while in the absence of significant CD15 staining all patients with recurrences were still alive at the conclusion of the study. The prognostic value of CD15 immunoreactivity, found by univariate analysis, becomes weaker after adjustment for the size and stage of tumour. Particularly in patients with tumour recurrences CD15 immunostaining may be of clinical relevance for the selection of patients in whom a more radical surgical approach would be justified.

Increased serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease.

AIM: To measure serum laminin and angiogenin concentrations in patients with peripheral arterial occlusive disease (PAOD) Fontaine stages IIb, III, and IV. METHODS: The study population comprised 38 patients (20 men and 18 women) with stage IV PAOD, 11 patients (six men and five women) with stage III PAOD, 18 patients (10 men and eight women) with stage IIb PAOD, and 23 patients (10 men and 13 women) with deep vein thrombosis. Fifteen normal subjects (matched for risk factors) and 10 patients (five men and five women) without PAOD served as controls. Serum samples were obtained at admission and serum laminin and angiogenin concentrations were measured using an enzyme linked immunosorbent assay. RESULTS: Patients with stage IV PAOD had higher serum laminin (mean +/- SEM; 826 +/- 97 ng/ml) and angiogenin concentrations (467 +/- 26 pg/ml) than normal subjects (laminin: 379 +/- 21 ng/ml; angiogenin: 358 +/- 16 pg/ml) and patients without PAOD (laminin: 277 +/- 34 ng/ml; angiogenin: 406 +/- 25 pg/ml). A significant correlation was found between angiogenin and laminin and between serum laminin and fibrinogen concentrations in patients with stage IV disease. CONCLUSIONS: Raised laminin and angiogenin concentrations may be indicators of endothelial damage caused by reduced vascular perfusion or compensatory revascularisation, or both.

Effect of endothelin-1 in man--impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin.

The effect of endothelin-1 on basal and stimulated serum (plasma) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH), prolactin (PRL), growth hormone (GH), and corticotropin was investigated in healthy male volunteers (n = 5). Intravenous (IV) administration of endothelin-1 (5 ng/kg/min for 15 minutes, followed by 2.5 ng/kg/min for 105 minutes) induced an increase in basal plasma concentrations of corticotropin. Serum concentrations of PRL, TSH, LH, FSH, and GH remained unchanged. The increase in serum concentrations of these pituitary hormones induced by IV administration of LH-releasing hormone ([LH-RH] 100 micrograms), thyrotropin RH ([TRH] 400 micrograms), GH-RH (100 micrograms), and corticotropin-releasing factor ([CRF] 100 micrograms) was suppressed in regard to PRL (P < .01) and GH (P < .01) and enhanced in regard to corticotropin (P < .01). Stimulated serum concentrations of LH and FSH also tended to be higher following administration of endothelin-1 (P < .05), whereas the increase in serum concentrations of TSH remained unchanged. Thus, when administered in pharmacological doses, endothelin-1 influences pituitary hormone secretion in man.

Serum levels of erythropoietin in acute Plasmodium falciparum malaria.

The pathophysiologic backgrounds of anemia in malaria are complex and multifactorial. The purpose of the present study was to measure serum concentrations of erythropoietin (EPO) and to evaluate the adequacy of EPO production in patients suffering from acute Plasmodium falciparum malaria. Fifteen patients with complicated malaria were included in the study. Serum samples were taken on the day of admission, and days 7, 14, 21 and 28. Serum EPO concentrations were measured using an enzyme-linked immunosorbent assay. The median serum EPO concentration was 15.6 mU/ml on the day of admission (range 0.5-567) mU/ml, 10.6 mU/ml (1.2-863) on day 7, 11.8 mU/ml (0.5-72.8) on day 14, 10 mU/ml (0.5-74.6) on day 21, and 8.3 mU/ml (2.2-61.6) on day 28. Inadequate EPO production was found in 46.6% of the patients on the day of admission, which increased to 67% and 68% on days 7 and 14, and reached a maximum of 80% on day 21. Almost 54% of patients had inadequate EPO production on day 28. Our data indicate inadequate EPO production in patients suffering from acute P. falciparum malaria, which might contribute to the prolonged anemia observed in these patients.

Serum procalcitonin levels in severe Plasmodium falciparum malaria.

Levels of procalcitonin (ProCT) have been found to be elevated in individuals with severe bacterial infections such as sepsis and peritonitis, and this correlates well with the severity of the disease. Recently, increased levels have been described in melioidosis and Plasmodium falciparum malaria. In this study ProCT levels were measured in 27 Thai patients with complicated malaria before and during/after treatment with artesunate and mefloquine. Initial parasite counts averaged 290,680/microl (range = 533-1,147,040). On admission, ProCT levels were elevated in all but one patient (median = 40 ng/ml, range = 0.04-662, normal values < 0.5 ng/ml). With treatment, levels decreased to 1.3 ng/ml (range = 0.01-6.5). Nitrite/nitrate levels in patients were higher than in controls throughout the study. The ProCT levels correlated with initial parasite density (P < 0.05), which is a marker of disease severity, and with nitrite/nitrate levels (P < 0.05). Based on the changes of ProCT levels over the course of the disease a possible role in the acute-phase reaction seems likely.

Serum protein concentrations in Plasmodium falciparum malaria.

In patients with uncomplicated Plasmodium falciparum infection cytokine-mediated serum protein levels of C-reactive protein (CRP), coeruloplasmin (COE), beta 2-microglobulin (B2M), alpha 1-acid glycoprotein (AAG), alpha 1-antitrypsin (AAT), haptoglobin (HPT), prealbumin (PRE), retinol binding protein (RBP), albumin (ALB) and transferrin (TRF) were measured in an endemic area of the Amazonian rain forest. Semi-immune (SI) and nonimmune (NI) patients were investigated. In both patient groups the serum concentrations of CRP, COE and B2M were elevated on admission. In addition AAG and AAT concentrations were increased in NI patients compared to control subjects. Significantly lower serum concentrations of HPT, PRE, RBP, ALB and TRF were seen in both patient groups during the acute phase of the disease, and were more pronounced in NI patients. After a 28-day follow-up, AAT and B2M were normal in SI patients but HPT, AAT and B2M were still significantly altered in NI patients.

Pharmacokinetics of teicoplanin during continuous hemofiltration with a new and a 24-h used highly permeable membrane: rationale for therapeutic drug monitoring-guided dosage.

OBJECTIVE: Continuous venovenous hemofiltration (CVVH) is widely used in the management of critically ill patients, but only few administration guidelines for antimicrobial drugs are available. It is unclear whether the use of a filter for more than 24 hours might lead to less efficient extraction. This study describes the pharmacokinetics of teicoplanin during CVVH using a highly permeable membrane. METHODS: Pharmacokinetics of teicoplanin during continuous hemofiltration with a new (group 1) and a 24-h used (group 2), highly permeable polyamide membrane were assessed in 3 patients. RESULTS: The teicoplanin serum concentrations (44.0 +/- 18.5 mg/l vs 109.5 +/- 34.5 mg/l) and half-life of teicoplanin (4.6 +/- 1.1 h vs 5.2 +/- 0.7 h) differed significantly between the 2 groups indicating a smaller elimination of the drug on the second day. Substantial binding of teicoplanin to filter membranes could explain this observation. CONCLUSION: The results suggest that daily adjustment of the dosage is necessary to achieve sufficient teicoplanin concentrations and a fixed dosage recommendation is not suitable for this drug.

[Autoantibodies in lepromatous leprosy]. / Autoantikörper bei lepromatöser Lepra.

84 Turkish patients with lepromatous and borderline lepromatous leprosy were investigated with regard to the presence of antibodies to a variety of tissue constituents and immunoglobulins. Thirty Turkish-born volunteers and two groups of patients with systemic lupus erythematosus and primary biliary cirrhosis respectively served as controls. No increased incidence of autoantibodies to smooth muscle cells, nuclei, mitochondria, striated muscle, thyroid microsomes and thyroglobulin was detected. A high incidence of rheumatoid factor and circulating immune complexes was found.

Renal tolerability of four different once-daily dose regimen of netilmicin in critical care patients.

A prospective, randomized trial was conducted in a medical intensive care unit to assess safety and tolerability of four different dose regimens of intravenous netilmicin given once daily in the treatment of febrile episodes in critically ill patients. Eighty patients with febrile episodes during their stay in the intensive care unit were included in the study. The patients were randomized into four groups: Group 1 received a single daily dose of netilmicin based upon weight, age and renal function according to a dosage nomogram [13] (mean dose 298 +/- 29 mg, median 300 mg, range 250-350 mg), group 2 received 150% of this standard dose (mean 418 +/- 45 mg, median 400 mg, range 350-500 mg), group 3 200% (mean 525 +/- 41 mg, median 500 mg, range 400-550 mg) and group 4 250% (mean 710 +/- 39 mg, median 650 mg, range 600-750 mg). Duration of treatment was six days. Positive cultures were obtained in 29 patients. Serum creatinine and creatinine clearance, as well as netilmicin trough levels and levels of alpha 1-microglobulin showed no significant difference between the groups before, during, and after therapy. Our results indicate that with once daily dosing even high doses of netilmicin are well tolerated in patients with a creatinine clearance of > 70 ml/min before therapy. Necessary precautions include monitoring of drug trough levels (< 1 mg/L) and maintenance of adequate volume status.

Single-dose pharmacokinetics of teicoplanin during hemodialysis therapy using high-flux polysulfone membranes.

Teicoplanin is a new glycopeptide antibiotic with potent activity against Gram-positive bacteria. It has been considered to be non-dialyzable due to its high molecular weight (1875-1891 d) and high protein binding (89%). Therefore, a reduced dose was recommended for patients on hemodialysis therapy, with the loading dose being followed by a considerably lower maintenance dose and/or extension of the interval between doses. The present study was performed to evaluate the pharmacokinetics of teicoplanin during hemodialysis therapy using high flux membranes. The pharmacokinetic parameters of teicoplanin were studied in 15 patients with chronic renal failure on hemodialysis. A high flux polysulfone membrane (ultrafiltration coefficient of 40 ml/h/mmHg) was used. Teicoplanin was administered at a dosage of 10 mg.kg-1 body weight in 100 ml isotonic saline solution during the first 10 minutes of hemodialysis therapy. Pharmacokinetic analysis was performed using a three compartment analysis. After a single dose of teicoplanin plasma peak levels were 26.4 +/- 12.0 micrograms/mL (mean +/- SD) after 30 minutes. Teicoplanin concentrations rapidly declined to a nadir of 6.1 +/- 2.5 micrograms/mL at the end of the 3.5-hour session dialysis. Extracorporeal clearance was 39.7 +/- 24.5 mL/min. Removal of 19.3 +/- 7.7% of the drug was estimated if infused during hemodialysis. T 1/2 alpha were 0.37 +/- 0.25 hrs, t 1/2 beta 20.1 +/- 7.1 hrs, and t 1/2 gamma 549.7 +/- 210.5 hrs. We conclude that teicoplanin levels are reduced to a subtherapeutic range during one single high-flux dialysis session if the drug is administered during hemodialysis. Thus, in contrast to previous suggestions relevant amounts of teicoplanin are removed during hemodialysis and thus teicoplanin cannot be viewed as non-dialyzable drug. We recommend obligatory drug monitoring to achieve therapeutic plasma concentrations.

Serum nitrate concentrations in patients with peripheral arterial occlusive disease.

BACKGROUND: Nitric oxide (NO), an endogenous product of L-arginine oxidation, seems to account for the vasodilatatory effect of the endothelium-derived relaxing factor. It was the aim of the present study to measure serum nitrate concentrations, the degradation product of nitric oxide in patients with peripheral arterial occlusive disease (PAOD). PATIENTS AND METHODS: 20 patients with PAOD in Fontaine stage IIb, 10 patients in stage III and IV respectively were included in the study. Serum samples for determination of nitrate were taken at admission after fasting overnight. Nitrate concentrations were determined using a recently developed high performance liquid chromatography which allows direct measurement of nitrate. The control group comprised 14 age and risk factor matched volunteers. RESULTS: We found significantly increased nitrate concentrations in patients with PAOD compared to the control group [stage IIb: 6.65 +/- 1.58 mumol/l; stage III: 6.94 +/- 1.85 mumol/l, stage IV: 7.05 +/- 1.16 mumol/l; control: 4.41 +/- 1.24 mumol/l], however no significance was calculated within the different PAOD groups. There was no association of either diabetes mellitus, hypertension and smoking behaviour with increased nitrate levels. CONCLUSION: These data might indicate that NO might be involved in adaptive vasodilatation already in the early phase of the disease. The source of nitrate in PAOD patients, however, remains unclear.

Long-term results of a three-week intensive cardiac out-patient rehabilitation program in motivated patients with low social status.

UNLABELLED: The short-term benefits of cardiac rehabilitation (CR) are well established. In contrast, well-documented long-term results are rare. The objective of this longitudinal multi-centre observational study was to examine the effects of intensive out-patient CR in a larger patient cohort, especially for patients with low social status. We present the final results 24 months after CR. METHODS: The study group of 327 patients (288 men, 39 women, aged 56.0+/-10.8 years, coronary artery disease in 295, other cardiac diseases in 32) participated in a 3- week CR programme followed by clinical re-evaluations 6 (III), 12 (IV) an 24 (V) months later. RESULTS: The improvement in mean maximal performance of 100.5+/-31.4 to 123.1+/-36.2 W (p<0.01) achieved during CR was further improved to 128.7+/-40.9 W (p < 0,01) after 24 months. Of the patients, 61.2% reported regular physical activity during the 24 months of the study. The lipid management achieved by CR was maintained over 24 month. At I 65%, at II 84.4% and at V 82.4% of the patients with coronary artery disease (CAD) were undergoing lipid lowering therapy. BMI increased from 26.8+/-3.0 to 27.6+/-3.6 kg/m2 (p < 0.01) during follow-up. Of the patients, 23.2% were active smokers at V. Cardiovascular diagnosis remained unaltered in 74.3% of patients. The obtained results are interesting with respect to the social status of the patients since 68% were general laborers. The results confirm the long-term effectiveness of an intensive 3-week out-patient CR programme. Most of the benefits achieved by CR appear to be sustainable in this population for at least 2 years.

Indication of a cosmological variation of the proton-electron mass ratio based on laboratory measurement and reanalysis of H2 spectra.

Based on highly accurate laboratory measurements of Lyman bands of H2 and an updated representation of the structure of the ground X 1sigma(g)+ and excited B 1sigma(u)+ and C 1pi(u) states, a new set of sensitivity coefficients K(i) is derived for all lines in the H2 spectrum, representing the dependence of their transition wavelengths on a possible variation of the proton-electron mass ratio mu = m(p)/m(e). Included are local perturbation effects between B and C levels and adiabatic corrections. The new wavelengths and K(i) factors are used to compare with a recent set of highly accurate H2 spectral lines observed in the Q 0347-383 and Q 0405-443 quasars, yielding a fractional change in the mass ratio of deltamu/mu = (2.4 +/- 0.6) x 10(-5) for a weighted fit and deltamu/mu = (2.0 +/- 0.6) x 10(-5) for an unweighted fit. This result indicates, at a 3.5sigma confidence level, that mu could have decreased in the past 12 Gyr.

Production of narrowband tunable extreme-ultraviolet radiation by noncollinear resonance-enhanced four-wave mixing.

Fourier-transform-limited extreme-ultraviolet (XUV) radiation (bandwidth approximately < 300 MHz) tunable around 91 nm is produced by use of two-photon resonance-enhanced four-wave mixing on the Kr resonance at 94 093 cm(-1). Noncollinear phase matching ensures the generation of an XUV sum frequency 2 omega1 + omega2 that can be filtered from auxiliary laser beams and harmonics by an adjustable slit. Application of the generated XUV light is demonstrated in spectroscopic investigations of highly excited states in H2 and N2.

Disseminated intravascular coagulation (DIC) and rhabdomyolysis in fulminant varicella infection--case report and review of the literature.

Primary infection with varicella-zoster virus usually is a mild, self-limiting childhood illness. However, certain rare but potentially life-threatening complications can be associated with the disease. Adults and immunosuppressed patients are at increased risk for these events. We report a case of a patient on chronic immunosuppressants with fulminant varicella infection complicated by rhabdomyolysis and disseminated intravascular coagulation. Mechanisms of muscle damage in viral diseases might be direct invasion of skeletal muscle and/or induction of harmful cytokines. Aggressive fluid therapy, alkalinization of urine and supportive measures correcting electrolyte imbalances, hypothermia and hypoxemia should result in preservation or complete restoration of renal function. Disseminated intravascular coagulation occurs in conjunction with various diseases and may range from mild laboratory abnormalities to fulminant lethal thrombosis and bleeding. Apart from elimination of the causative process therapeutic strategies are still highly disputed.