Exposure of monomolecular lithographic patterns to ambient: an X-ray photoemission spectromicroscopy study.

Patterned self-assembled monolayers (SAMs) of alkanethiolates (AT) on Au and Ag substrates were imaged and characterized by scanning photoelectron microscopy (SPEM). The patterns were prepared in situ by direct writing with the zone-plate-focused X-ray beam provided by the SPEM station. Whereas both AT/Au and AT/Ag behaved alike upon the irradiation, which resulted in similar contrasts in the fabricated patterns and similar microspot spectra from the irradiated areas, the intensity relationship between the patterned and nonpatterned areas changed by different pathways for the Au and Ag substrates after the exposure of the patterns to ambient. The SPEM data imply that weakly bound molecular fragments are desorbed from the irradiated areas upon air exposure in the case of Ag, whereas adsorption of airborne molecules from ambient occurs for the Au substrate. The origin of the observed differences is presumably related to the specific branching patterns of irradiation-induced modification of AT/Au and AT/Ag.

New developments in the management of cytomegalovirus infection and disease after renal transplantation.

The clinical management of cytomegalovirus infection and disease in renal transplant recipients has recently been significantly improved with the availability of data on prophylaxis with oral ganciclovir and valacyclovir. In addition, significant progress in early diagnosis and the quantitation of viral load has been achieved. The influence of novel immunosuppressants on the clinical course of cytomegalovirus infection has been clarified to some extent by recent clinical data. The identification of risk factors for cytomegalovirus disease beyond seroconstellation and immunosuppression is an ongoing process that might lead to a more targeted use of antiviral agents, given the risk of ganciclovir resistance. The understanding of the effects of cytomegalovirus on long-term graft outcome still needs to be deepened in order to design cytomegalovirus-specific interventions to improve graft survival.

Rapidly progressive glomerulonephritis and carcinoma of the hypopharynx.

We report on a 50-year-old man with rapidly progressive glomerulonephritis and carcinoma of the hypopharynx. Because cancer treatment was followed by remission of proteinuria and complete restoration of renal function, a causal relationship between tumor and glomerular injury seems possible.

Long-term oral ganciclovir prophylaxis for prevention of cytomegalovirus infection and disease in cytomegalovirus high-risk renal transplant recipients.

BACKGROUND: Although specific therapy is available with ganciclovir, cytomegalovirus (CMV) disease remains a major problem after renal transplantation especially in CMV seronegative recipients of organs of seropositive donors (D+R-). METHODS: In an open-labeled prospective controlled trial we evaluated the effect of long-term oral ganciclovir prophylaxis (3 g/day for 3 months posttransplantation) in a cohort of 31 CMV-high risk (D+R-) renal transplant recipients (GC) compared with a cohort of 28 high-risk patients with targeted CMV prophylaxis (CO) receiving i.v. ganciclovir during antirejection therapy. Primary end-points were CMV infection, diagnosed by pp65 antigenemia assay or serologic method, and CMV disease. Additionally severity of CMV disease quantified by a scoring system was evaluated. RESULTS: CMV prophylaxis significantly reduced the incidence of CMV infection (CO: 75%, GC: 45%; P<.05) and CMV disease (CO: 60%, GC: 29%; P<.05) without relevant side effects and without any clinical suspicion of ganciclovir resistance. Severity of CMV disease as quantified by a scoring system was reduced from 8.3+/-6.7 points in controls to 3.3+/-2.6 points in ganciclovir-treated patients (P<.05). Mortality did not differ significantly between the two groups (CO: n=3, GC: n=1; NS). However, there was one lethal CMV disease and a second death possibly attributable to CMV disease in the control group, whereas in ganciclovir-treated patients there was no CMV-associated fatal outcome. CONCLUSION: Long-term oral ganciclovir prophylaxis is effective and safe in CMV high-risk renal transplant recipients.

The Soft X-ray Scanning Photoemission Microscopy Project at SRRC.

The Synchrotron Radiation Research Center (SRRC) and the Institute of Atomic and Molecular Sciences (IAMS) have initiated a project to construct a scanning photoelectron spectromicroscopy end station at SRRC (SRRC-SPEM). High-brightness soft X-rays will be provided by the U5 undulator beamline. Zone-plate-based soft X-ray optics will be used to focus the beam to form the microprobe. A hemispherical sector analyser with multichannel detection capability will collect the photoelectrons. A total of up to 32 images can be acquired concurrently. The apparatus is also equipped with a sample distribution system for in situ sample preparation and characterization in conjunction with other surface spectroscopic techniques.

Impact of high-dose oral acyclovir prophylaxis on cytomegalovirus (CMV) disease in CMV high-risk renal transplant recipients.

Recent studies showed contradictory results concerning the efficacy of oral acyclovir in the prevention or amelioration of cytomegalovirus (CMV) disease after renal transplantation (TX). This study evaluated the incidence and severity of CMV disease within the first year after TX in high-risk renal transplant recipients (CMV-seropositive donor, seronegative recipient) treated prophylactically with oral acyclovir (800 to 3200 mg/day) over a period of 12 wk (ACY, N = 22), compared with high-risk patients randomly assigned as controls (CO, N = 10). Follow-up for CMV infection included serological determination of CMV-specific immunoglobulin G and immunoglobulin M antibodies, antigen detection in peripheral blood leukocytes (PP 65), shell vial culture (blood), and virus isolation/early antigen detection (urine). Severity of CMV disease was quantified by a scoring system for CMV-related symptoms. Nine patients (40.1%) in the acyclovir group and four patients (40%) in the control group developed CMV disease. Neither severity (ACY, 11.4 versus CO; 12.5 points score), nor duration of disease (ACY, 21 days; CO, 22 days), nor transplant function at the end of the observation period differed significantly. The onst of CMV disease was not delayed significantly in acyclovir-treated patients compared with controls (ACY, 47 +/- 34 days versus CO, 27 +/- 14 days after TX, not significant). Our results show no beneficial effect of oral acyclovir prophylaxis in CMV high-risk renal transplant recipients.

Effect of danazol-induced chronic hyperglucagonaemia on glucose tolerance and turnover.

It has been shown that danazol (14-ethinyltestosterone) induces hyperglucagonaemia. To investigate the effect of chronic glucagon excess on carbohydrate metabolism, we studied six patients before and after treatment with danazol for immunothrombopenia. Glucose tolerance and insulin, C-peptide and glucagon secretion during an oral glucose tolerance test (oGTT) as well as peripheral and hepatic insulin sensitivity were determined by means of euglycaemic clamp technique (40 mU m-2 min-1) before and after 3 months of danazol therapy. Overall glucose turnover (Rd) was assessed radioisotopically. (1) Plasma glucagon levels rose significantly from 88 +/- 16 pg mL-1 before to 683 +/- 148 pg mL-1 after therapy (P < 0.01). (2) Glucose levels during an oGTT were not significantly different before and after therapy. Glucose-stimulated insulin secretion at 60 and 120 min and the area under the curve (AUC) for insulin during the oGTT, were significantly increased after danazol treatment compared with pre-treatment values (P < 0.05), whereas glucagon secretion showed a similar decrease at both time points of investigation (NS). (3) Rd during steady state showed a significant decrease during the entire period of euglycaemic clamp following therapy (after 240 min, 3.8 +/- 0.6 vs. 5.3 +/- 0.7 mg kg-1 min-1, P < 0.05). The decline in glucagon during the clamp was similar during steady state before and after therapy. (4) Basal hepatic glucose output did not differ significantly before and after therapy (1.74 +/- 0.41 vs. 1.45 +/- 0.22 mg kg-1, NS), whereas hepatic glucose output during the clamp was significantly less suppressed after danazol therapy. The authors conclude that chronic glucagon excess leads to a decrease in peripheral and hepatic insulin action which is accompanied by an increase in insulin secretion.

Influence of various irrigation fluids on articular cartilage.

When bovine articular cartilage was incubated in Ringer's solution, considerable amounts of proteoglycan were washed out of the cartilage. Thus, 4% of the proteoglycan was lost into the medium during an incubation of 4 hours. Subsequently, it was found that ionic aqueous media like saline or Ringer's solution extracted much more proteoglycan than ion-free media like distilled water or a variety of carbohydrate containing solutions. In separate experiments, it could be shown that solutions of 20% sorbitol and 2% mannitol exhibited particularly low proteoglycan extracting properties. It was found that the extraction of proteoglycan was dependent on the ion concentration in the aqueous media. The extraction of proteoglycan by sodium chloride was negligible at NaCl concentrations of 0.1% and lower. Proteoglycan loss from cartilage was only induced at 0.9% NaCl. Using intact rat femoral heads it could be shown that the elution of proteoglycan from cartilage occurred as well when the cartilage was intact. Here, the elution occurred at a slower rate but the differences between ionic and ion-free solutions were greater. By electronmicroscopic examination of bovine cartilage incubated in different media, it was observed that Ringer's solution induced a more uneven and rougher appearance of the cartilage surface than did 10% mannitol solution, indicating that probably a denudation of collagen fibers occurs on the loss of proteoglycan from the cartilage. Because the observed proteoglycan washout occurred within rather short periods of contact of the cartilage with the medium, it is concluded that this may be of relevance for the clinical situation during arthroscopic procedures. The use of preferably isotonic carbohydrate solutions like 5% mannitol is suggested to prevent unnecessary loss of proteoglycan from hyaline cartilage.

Effect of repeated Aprosulate and Enoxaparin administration on tissue factor pathway inhibitor antigen levels.

Tissue factor pathway inhibitor (TFPI) is a naturally occurring, Kunitz-type serine protease inhibitor whose anticoagulant activity is due to an inhibition of the extrinsic coagulation pathway. Heparin injection has previously been shown to increase the plasma levels of TFPI. In this study, plasma samples were obtained from a multiple dose phase I tolerance study with a synthetic analogue of heparin, namely Aprosulate (PALLAS). Volunteers were randomized into four treatment groups: (A) 35 mg Aprosulate b.i.d. s.c.; (B) 70 mg Aprosulate b.i.d. s.c.; (C) 70 mg Aprosulate o.d. + placebo o.d. s.c.; (D) 40 mg of a low molecular weight heparin, Enoxaparin o.d. + placebo o.d. s.c. All treatments were for 7 days, with blood samples taken periodically over this time period. TFPI antigen levels were determined using Imubind TFPI ELISA kits (American Diagnostica, Greenwich, CT). TFPI antigen levels were observed to rapidly increase to levels two- to three-fold over baseline in all groups. Aprosulate caused a slightly larger increase in TFPI antigen levels than Enoxaparin, though this may be related to the doses chosen for this study. These data indicate that plasma concentrations of TFPI are increased following Aprosulate administration. TFPI may be important in mediating the antithrombotic activity of Aprosulate.

Effects of different irrigation liquids and times on articular cartilage: an experimental, biomechanical study.

To characterize the suitability of different solutions [6% Dextran, 5% sorbitol (I); 5% fructose (II); 5% mannitol (III); Ringer's solution (IV)] for arthroscopy, bovine knee articular cartilage specimens (n = 52) were immersed for 0, 2, 4, or 20 h before indentation creep testing, known as a sensitive probe for tissue degeneration. Immersion in liquid I for up to 20 h produced significant softening of articular cartilage [p < 0.05, Friedman two-way analysis of variance (ANOVA)]. Liquids II-III produced no statistically significant changes in the deformational characteristics of articular cartilage. After 2 h of immersion in liquid IV deformation increased and remained elevated over the observation period (p < 0.05, Friedman two-way ANOVA). Based on these results, the first and most remarkable softening of cartilage took place with Ringer's solution as compared with nonionic solutions. Therefore, the nonionic solutions, such as 5% fructose or mannitol, may have potential for use as an irrigation liquid during arthroscopic procedures.

Recombinant human erythropoietin in renal transplant recipients with renal anemia.

Thirty-seven kidney graft recipients with chronically declining transplant function accompanied by renal anemia were treated with recombinant human erythropoietin for 3 months. In all these patients anemia improved and mean hemoglobin levels increased from 7.67 +/- 1.26 g/dl to 9.83 +/- 1.94 g/dl (p < 0.01). Mean creatinine increased from 4.23 +/- 1.82 to 4.62 +/- 2.42 (p < 0.05) but the progression of transplant failure was not influenced when compared with pretreatment values obtained at least 6 months before study entry. Mean blood pressure levels were not altered but 12 patients required additional antihypertensive medication.

Derivatives of bis-aldonic acid amides and their anticoagulant and antithrombotic properties.

Aprosulate sodium was the first representative of a new class of synthetic polyanions showing antithrombotic efficacy in different animal models. In several clinical trails (Phase I) in human volunteers aprosulate demonstrated anticoagulant properties, too. Searching for other active substances of similar structure, a series of bis-aldonic acid amides were synthesized. These compounds exhibited interesting antithrombotic and anticoagulant activities. The pharmacodynamic activities of the compounds LW 10121, LW 10125, LW 10114, 10244, and LW 10168 are summarized in this article. These substances prolonged the APTT to 150% of the blank values at concentrations of 1.5 to 13.5 micrograms/mL. The thrombin time and anti-Xa test were only slightly influenced by concentrations up to 100 micrograms/mL. All compounds were investigated in a jugular vein hemostasis model in rats to examine their antithrombotic potential. They all had an antithrombotic activity lower than aprosulate, except compound LW 10121, which seemed to be a little more active. The subcutaneous injection of 10 mg/kg LW 10121 resulted in a longer duration of action than aprosulate and heparin. On the basis of the chemical structure and the profile of action, it is assumed that the new compounds may possess the same mode of action as aprosulate, but the mechanism of action may be different from heparin and low molecular weight heparins.

Emergency intubation with the Combitube in a grossly obese patient with bull neck.

A grossly obese patient with bull neck required immediate intubation. Endotracheal intubation failed because visualization of the vocal cords was not possible. As an alternative, the Combitube was inserted without difficulty and the patients lungs were ventilated via the Combitube until tracheotomy was performed on the following day. The patient survived and was discharged alive from the hospital 5 weeks later. The Combitube has gained worldwide interest and is now included in the Guidelines of the American Heart Association and the American Society of Anesthesiologists.

Emergency intubation with the Combitube: comparison with the endotracheal airway.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of the Combitude as used by ICU nurses under medical supervision compared with endotracheal airway established by ICU physicians during CPR. DESIGN: Prospective study of ICU patients over a seven-month period. SETTING: Medical ICU. PARTICIPANTS: Thirty-seven patients suffering from cardiac arrest. INTERVENTIONS: Emergency intubation with either the Combitube by nurses or the endotracheal airway by physicians and subsequent mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Evaluation of blood gases after 20 minutes of mechanical ventilation. Intubation time was shorter for the Combitube (P < .001). Blood gases for each device showed comparable results; PaO2 was slightly higher during ventilation with the Combitube (P < .001). CONCLUSION: The Combitube as used by ICU nurses was as effective as establishment of the endotracheal airway by intensivists during CPR. The Combitube may be used whenever endotracheal intubation cannot be performed immediately.

Secondary hyperparathyroidism and acute tubular necrosis following renal transplantation.

In the present study we investigated the relationship between secondary hyperparathyroidism in renal graft recipients and post-transplantation acute tubular necrosis (ATN). Patients were divided into two groups according to graft function: group A consisted of 28 patients who had an uneventful postoperative period and did not require haemodialysis. Group B comprised 26 patients with primary non-function of the graft due to biopsy-proven ATN who required continued haemodialysis for the first postoperative week or longer (mean 14.2 +/- 8.7 days). Both groups had comparable donor characteristics, HLA-matching and ischaemia times. All patients were given cyclosporin and low-dose prednisolone for immunosuppression. Pretransplant levels of intact PTH were significantly greater in group B than in group A (203.5 +/- 193.1 pg/ml versus 81.7 +/- 45.2 pg/ml, P < 0.01). Group B patients had more transplant biopsies (50 versus 7) and a longer hospitalization time (33.4 +/- 10.9 days versus 21.9 +/- 11.9 days, P < 0.01), although serum creatinine on the day of discharge was higher in group B (1.77 +/- 0.51 mg/dl versus 1.5 +/- 0.45 mg/dl, P < 0.05). We conclude that patients with secondary hyperparathyroidism as assessed by measuring circulating levels of intact PTH have an increased incidence of ATN.