Biomedical subjects
Publications and source records attributed to P Schenk.
We describe a 66-year-old woman with right-sided heart failure and cardiogenic shock resulting from severe pulmonary embolism. Her hemodynamic status improved dramatically with the use of inhaled nitric oxide. A proposed mechanism of action and a review of the literature are presented.
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The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 +/- 18.6 ml/min and 2.46 +/- 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 +/- 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 +/- 2.7 microgram/ml, and trough levels after 6 h of CVVH were 6.6 +/- 1.5 microgram/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 +/- 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.
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.
BACKGROUND AND OBJECTIVE: The specifics of the ablation mechanism of the holmium:YAG laser remain largely unexplored. Following laser exposure to the oral mucosa of rats, the ultrastructural damage profile obtaining to varying degrees in blood vessels, erythrocytes, nerves, and muscle cells was examined. An attempt was made to relate the cytoplasmatic alterations to the tissue ablation modes of midinfrared lasers described in the literature. STUDY DESIGN/MATERIALS AND METHODS: The biological effects of a new pulsed holmium:YAG laser (lambda = 2,120 nm) on the oral mucosa of rats were examined by light and transmission electron microscopy. Laser incisions reaching into the muscle layer were made on different sites of the tongue of white rats. Laser energy (400 mJ, 2.5 microseconds pulse, 2 Hz) was delivered to the target via 400 microns nylon fibers. RESULTS: The fine-structural morphology of the sublingual mucosa after laser surgery of the epithelial surface revealed no carbonization layer but a 150-micron-wide zone of lacunar structures extending to the lamina propria. In the muscle cells there is partial decomposition of the cell contents resulting in the development of electron optically empty spaces within the cortical cytoplasm underneath the intact plasma membrane of the muscle cell. The organelles within the cell remain ultrastructurally intact. CONCLUSION: These features support the assumption of an additional nonthermal holmium:YAG laser-tissue interaction.
Cefdinir is an extended-spectrum oral cephalosporin that is active against pathogens commonly seen in acute community-acquired bacterial sinusitis (ACABS), including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Two randomized, investigator-blind, multicenter trials (one in the United States and one in Europe) compared two dosage regimens of cefdinir (600 mg once a day for 10 days and 300 mg twice a day for 10 days) to amoxicillin-clavulanate (A-C) (500 mg three times a day for 10 days) for adult and adolescent patients with ACABS. Twelve hundred twenty-nine patients entered the U.S. study, 698 with antral puncture; 569 patients entered the European study, all with antral puncture. Clinical response (cure or improvement) was determined 7 to 14 days and 3 to 5 weeks posttherapy. Microbiologic eradication rates were determined 10 to 30 days posttherapy in a subset of patients who underwent pre- and posttherapy sinus aspirate culture. Rates of adverse events and treatment discontinuations due to adverse events were examined. Cefdinir, given once or twice daily, was as effective clinically (approximately 90% cure rate) as amoxicillin-clavulanate given three times daily in the treatment of ACABS. Microbiologic eradication rates were also similar in the three groups. The major side effect was mild diarrhea, occurring in approximately 20% of each group. Cefdinir caused fewer adverse events requiring treatment discontinuation.
The case is described of a 58 year old man with systemic Whipple's disease with pericardial and pleural effusions and severe pulmonary hypertension. After three months of antibiotic treatment there was a complete resolution, not only of the symptoms known to be associated with Whipple's disease (diarrhoea, arthralgia, pericardial and pleural effusions), but also of pulmonary hypertension.
BACKGROUND: Development and progression of human malignancies involve multiple genetic changes. New techniques to distinguish neoplastic from benign diseases unequivocally with small amounts of cells as gained by bronchoscopy are needed to come closer to the goal of an early diagnosis in lung cancer. STUDY OBJECTIVE: The aim of this study was to determine whether interphase fluorescence in situ hybridization (FISH) can be used to visualize chromosomal aberrations in bronchoscopically gained cells from lung cancer patients and could eventually become a complementary technique to conventional cytology. METHODS: We examined 20 cancerous specimens (10 primary tumors, 10 malignant effusions) of 18 lung cancer patients by FISH with DNA probes specific for chromosomes 3, 8, 11, 12, 17, and 18. From five additional patients, endobronchial brushings and/or forceps biopsy specimens were subjected to interphase FISH analysis. RESULTS: In all primary tumors and malignant effusions, highly aneuploid cells were detectable by FISH. Chromosomal aberrations always consisted of gains of chromosomal signal numbers, and all chromosomes were found to be aneuploid to a similar extent. Using chromosomal aneuploidy as a marker of malignancy, material obtained by bronchoscopy was then examined for the presence of malignant cells. In all specimens, evidence for malignancy was obtained by FISH, including three specimens in which cells appeared to be normal or reactively changed by cytologic criteria. CONCLUSION: We conclude that interphase FISH is useful in detecting aneuploidy associated with malignancy in bronchoscopically gained cells that do not clearly meet the criteria of malignancy by conventional cytologic study.
Elongation, coiling and/or kinking of the interal carotid artery occur in 10-25% of the population. While coiling of the internal carotid artery is ascribed to embryological causes, elongation and kinking are due to atherosclerosis or fibromuscular dysplasia. Seventy-seven patients with carotid kinking were examined using different diagnostic imaging methods. Of these, 64 underwent surgery because of cerebrovascular symptoms that ranged from local disturbances, vertigo, diplopia and cerebrovascular insufficiency producing ischemic attacks or infarction. The treatment of choice was surgical correction of the carotid kinking in symptomatic cases and, if indicated, endarterectomy of atherosclerotic lesions of the internal carotid artery to prevent ischemic stroke. Because of the anatomical position of the interal carotid artery kink there is a potential risk of complications in head and neck surgery. For this reason, the presence of carotid kinking should be excluded preoperatively by means of non-invasive diagnostic imaging, such as afforded by ultrasonic testing. The merits of the different diagnostic imaging methods to diagnose internal carotid artery disease were compared and discussed.
Studies have been performed with human liver microsome preparations in vitro, to investigate the reaction mechanisms involved in the conversion of acitretin to the corresponding ethyl ester, etretinate. The results indicate that: Three fresh samples of human liver, which had been stored in liquid nitrogen for up to 8 months, all produced traces of etretinate (5.8 +/- 0.8 ng/ml) in the presence of ethanol but not when the acitretin was added in acetone, or when the sample was denatured by preheating. Studies with pooled human liver microsomes, to identify the cellular location of the enzymes and the co-factors involved in this esterification, indicate a primary requirement for both ethanol and CoA + ATP with a secondary potentiation in the presence of an NADPH regenerating system. A possible explanation for these finding is that the microsomal ligase enzymes form an intermediate ester between CoA and acitretin, which is then trans-esterified by the ethanol. The low formation with CoA + ATP may indicate that second stage of this process occurs spontaneously, with the NADPH potentiation suggesting that it could also be mediated enzymically.
A new oral prodrug cephalosporin, cefcanel daloxate, was compared with cefaclor, another oral cephalosporin, in the treatment of acute purulent maxillary sinusitis. Three hundred fifty-four patients with purulent sinus secretion were recruited and randomized at thirteen European ENT clinics for the double blind study. The patients were treated with either cefcanel 300 mg tablets twice daily or cefaclor 250 mg capsules three times daily for ten days. Apart from the sinus puncture and secretion aspiration, the existence of sinus pain and purulent nasal secretion were inclusion criteria. Between days 12 and 15, reaspiration of the sinus was performed and signs and symptoms noted. The latter were checked again at the final visit between days 25 and 30. Samples of blood and urine were obtained for safety evaluation at inclusion, during and after treatment. The bacteriological culture of the purulent sinus secretion in 58.4% of patients revealed Haemophilus influenzae (37.9%) as the most prevalent pathogen followed by Streptococcus pneumonia (19.7%), while Streptococcus pyogenes, Branhamella catarrhalis, and Staphylococcus aureus amounted each to 6-7% only. The overall clinical outcome was defined as cure/improvement in 83.3% of the patients in the cefcanel group and 89.3% in the cefaclor group, respectively. No statistically significant differences with regard to efficacy were found between the two treatment groups. Adverse events, mostly related to gastrointestinal reactions, were reported by 36 patients (15.7%) in the cefcanel group and by 16 (13.4%) in the cefaclor group. Both cefcanel 300 mg twice daily and cefaclor 250 mg three times daily were highly effective with only minimal adverse events in the treatment of acute purulent maxillary sinusitis.
cDNA complementary to the 3'-terminal half of RNA 1 of wheat spindle streak mosaic virus (WSSMV) from Southern France has been cloned and sequenced. One large open reading frame (ORF) of 4410 nucleotides and a nontranslated region (NTR) of 213 nucleotides at the 3'-end excluding the poly(A)-tail were found. Because of the amino acid sequence homology to the polyprotein of barley yellow mosaic virus (BaYMV) RNA 1, the encoded polyprotein of the sequenced region of WSSMV is supposed to comprise the C-terminal part of the putative cytoplasmic inclusion (CI) protein, the nuclear inclusion a (NIa) proteinase, the (NIb) RNA-polymerase and the capsid protein. The first 19 N-terminal amino acids of the capsid protein were determined by direct sequencing of proteins of purified WSSMV particles and confirmed this hypothesis. The deduced capsid protein has 294 amino acids and shows 74% identity with the BaYMV capsid protein sequence. This high sequence homology with BaYMV, in addition to the significant identities with barley mild mosaic virus (BaMMV, 35%) and its marginal homology to capsid protein sequences of aphid and mite-borne potyviruses (22-24%), supports the classification of WSSMV as a distinct member of the genus Baymovirus, family Potyviridae.
To evaluate the effect of lung transplantation on right ventricular (RV) and left ventricular (LV) volumes and function, magnetic resonance imaging (MRI) was performed in 11 patients before and 6 to 24 months after single (n = 7) or double (n = 4) lung transplantation as well as in 15 healthy control subjects. Prior to transplantation, RV end-diastolic (RVEDVI, ml/m2) and end-systolic (RVESVI, ml/m2) volume indices were significantly increased in patients compared with those in control subjects. RV ejection fraction (RVEF, %), although within the lower normal range, was significantly reduced. In contrast, LV volume indices (ml/m2) were significantly smaller in patients than in control subjects, whereas LV ejection fraction (LVEF, %) was not different from that in normal subjects. After lung transplantation, MRI revealed a significant reduction in RVEDVI from 73 +/- 29 to 54 +/- 14 (p = 0.03) and RVESVI from 38 +/- 23 to 20 +/- 6 (p = 0.01) with a concomitant significant increase in RVEF from 48 +/- 14 to 63 +/- 6 (p = 0.01). Consecutively, the LV expanded to normal (LVEDVI from 49 +/- 12 to 65 +/- 14, p = 0.01; LVESVI from 23 +/- 9 to 28 +/- 7, p = 0.05), whereas LVEF remained unchanged (55 +/- 9 versus 56 +/- 8).
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Noninvasive assessment of pulmonary artery hypertension would be of great value in patients with chronic obstructive pulmonary disease (COPD). Although continuous wave Doppler echocardiographic measurement of right atrial to right ventricular pressure gradient is the most useful method of noninvasive assessment of pulmonary artery hypertension, this technique is often limited in patients with COPD. In order to evaluate the usefulness of pulsed Doppler echocardiography, for the estimation of pulmonary artery pressure in COPD patients in whom continuous wave Doppler ultrasound has failed, we compared right ventricular systolic time intervals: pre-ejection period (PEP, ms), acceleration time (AT, ms), right ventricular ejection time (RVET, ms), and AT/RVET and PEP/RVET ratios, as measured by pulmonary artery pulsed Doppler traces, in 30 COPD patients, with the time intervals of 15 age- and sex-matched healthy volunteers, using the subcostal approach. In addition, right ventricular systolic time intervals of the COPD patients were correlated with invasive catheterization data (systolic and mean pulmonary artery pressure (PAPs and PAPm). AT and AT/RVET were significantly shorter in COPD patients (AT 92 +/- 4.3 ms; AT/RVET 0.38 +/- 0.03) as compared with healthy volunteers (AT 132 +/- 4.5 ms; p < 0.001; AT/RVET 0.46 +/- 0.02; p < 0.005), whereas RVET, PEP and PEP/RVET were not significantly different in both groups. A significant correlation was demonstrated between AT and PAPs (r = -0.76; p < 0.001) and PAPm (r = -0.82; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
The RAD3 gene of Saccharomyces cerevisiae encodes an ATP-dependent 5'-3' DNA helicase, which is involved in excision repair of ultraviolet radiation damage. By hybridisation of a Schizosaccharomyces pombe genomic library with a RAD3 gene probe we have isolated the S. pombe homologue of RAD3. We have also cloned the rad15 gene of S. pombe by complementation of radiation-sensitive phenotype of the rad15 mutant. Comparison of the restriction map and DNA sequence, shows that the S. pombe rad15 gene is identical to the gene homologous to S. cerevisiae RAD3, identified by hybridisation. The S. pombe rad15.P mutant is highly sensitive to UV radiation, but only slightly sensitive to ionising radiation, as expected for a mutant defective in excision repair. DNA sequence analysis of the rad15 gene indicates an open reading frame of 772 amino acids, and this is consistent with a transcript size of 2.6 kb as detected by Northern analysis. The predicted rad15 protein has 65% identity to RAD3 and 55% identity to the human homologue ERCC2. This homology is particularly striking in the regions identified as being conserved in a group of DNA helicases. Gene deletion experiments indicate that, like the S. cerevisiae RAD3 gene, the S. pombe rad15 gene is essential for viability, suggesting that the protein product has a role in cell proliferation and not solely in DNA repair.
The in-vivo bone ablation characteristics of a pulsed solid-state erbium:YAG laser were compared to those of a pulsed solid-state holmium:YAG laser. Partial osteotomies in the maxillary, the mandibulary, and the nasal bones of white rats were performed. The tissue response was examined by light microscopy. Thermal gradients following the laser application were also measured. Over all energy levels tested the erbium:YAG laser produced ablation of bone with minimal thermal damage to the adjacent tissue. The results of this study are promising for future application of the infrared holmium- and erbium:YAG lasers in otorhinolaryngology.
The in-vivo tissue ablation characteristics of a pulsed infrared laser (Holmium:YAG, lambda = 1980) and a pulsed excimer laser (XeCl, lambda = 308 nm) were studied. The holmium laser energy was coupled into nylon fibres. The excimer laser energy was coupled into quartz fibers. Laser incisions were made on white rats at different sites of the tongue. Power settings of 400 mJ per 2.5 microseconds pulse at 5 pulses per second for the holmium:YAG laser and 250 mJ per 1 microsecond pulse at 20 pulses per second for the excimer laser were used. Thermal gradients following laser application were measured. Excellent control of depth of tissue ablation was noted for both types of lasers. The tissue response was examined by light microscopy. Histological studies revealed tissue defects with clean contours. The coagulative necrosis zone for the 400 mJ holmium:YAG injuries measured from 370 microns to 640 microns, compared with 40 microns to 160 microns with the 250 mJ UV-excimer injuries. Wound healing was studied over a six-week period. Histologically, wound closure was completed after four weeks showing re-epithelialization without scar formation for both types of laser. The in-vivo tissue ablation characteristics and the operation reliability of the two lasers were compared.