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Biomedical subjects

M Binder

Publications and source records attributed to M Binder.

At least 91 records · Page 5Linked to original sources
PubMed1999

A randomized, double-blind, placebo-controlled trial of botulinum A toxin for severe axillary hyperhidrosis.

Excessive axillary hyperhidrosis is a socially embarrassing condition which severely reduces quality of life and may result in psychological disturbance. Available treatment strategies do not resolve the problem in all cases. Intracutaneous injections of botulinum A toxin have been shown to be effective in patients with local sweating disorders. We performed a randomized, double-blind, within-group comparison in 13 individuals (nine women and four men) with severe axillary hyperhidrosis resistant to conventional treatment, to study the effect of intracutaneous injections of botulinum toxin on sweating. A total dose of 200 mouse units of botulinum A toxin (Dysport(R)) was injected into six different sites in one axilla, whereas the other was injected with sterile saline. Objective quantification of sweat production was performed using digitized ninhydrin-stained sheets. Three weeks after treatment, the mean difference in ninhydrin staining between botulinum-treated and placebo-treated axillae was -34.5% (P < 0.001), after 8 weeks -36.9% (P < 0.001) and after 13 weeks -28.4% (P < 0.001). Subjective rating of sweat production was evaluated on a visual analogue scale (0, no sweating, to 100, most severe sweating). Three weeks after treatment the difference between the botulinum-treated and placebo-treated axillae was -56.5% (P < 0.001), after 8 weeks -67.4% (P < 0.001) and after 13 weeks -62.5% (P < 0.001). No serious side-effects were observed.

Adult↗
PubMed1999

Oral terbinafine (Lamisil) in the short-term treatment of fungal infections of the skin: results of a post-marketing surveillance study.

Oral terbinafine (Lamisil, Novartis Pharma AG, Basel, Switzerland) is an effective therapy for fungal infections of the skin and nails. A post-marketing surveillance study was undertaken to evaluate the clinical efficacy and safety of oral terbinafine. A total of 454 patients with clinically and mycologically confirmed superficial fungal infections of the skin were enrolled from 79 dermatology clinics. Patients received oral terbinafine (250 mg day-1) for 2 weeks. Specific signs and symptoms were assessed by standard questionnaire before, immediately after, and 4 weeks after treatment. Observed improvements in patients after 2 weeks treatment were: erythema 81%, blistering 33%, exudation 50%, scaling 89%, pruritus 83%. After 4 weeks treatment, erythema was absent in 85% of patients, blistering and exudation in 99.7%, scaling in 82%, and pruritus in 94%. Overall clinical efficacy was assessed as good to excellent in 97% of patients. Adverse effects--mainly gastrointestinal and minor skin rashes--were reported in 5.3% of patients. The results of this study confirm that oral terbinafine is safe and highly effective for the short-term treatment of fungal skin infections.

Administration, Oral↗
PubMed1999

Pilot trial of infusional 5-fluorouracil, interleukin-2, and subcutaneous interferon-alpha for advanced renal cell carcinoma.

The authors developed an outpatient, three-drug combination regimen for advanced renal cell carcinoma. Treatment was administered for 5 days each week for 4 weeks, followed by 2-week rests. Each weekly treatment consisted of 5-fluorouracil 1,750 mg/m2 continuous intravenous infusion for 24 hours followed by interleukin-2 6 mIU/m2 per day continuous intravenous infusion for 4 days, and interferon-alpha2b 6 mU/m2 subcutaneously on days 1, 2, and 5. This trial was undertaken to assess tolerability to this regimen and obtain a preliminary assessment of its effectiveness. Most patients required some dose adjustments (especially of cytokines), treatment interruptions, or both. Toxicities were as would be expected from individual drug profiles with only mild to moderate hematologic toxicities. Among 16 patients with renal cell carcinoma treated, four had major (clinical partial response) responses, one of which was demonstrated to be a pathologic clinical response after surgical resection of a residual mass. Estimated median survival time of all patients was 93 weeks. Response and survival were correlated with known clinical risk factors. Responding patients were noted to be significantly older in age (X = 61.75 years) than nonresponders (X = 48.92 years). There was no correlation between age and other clinical risk factors, treatment tolerance, or survival. The authors conclude that this three-drug regimen is a practical, tolerable, and promising regimen for further study in renal cell carcinoma.

Adult↗
PubMed1999

Hemodynamic and catecholamine stress responses to insertion of the Combitube, laryngeal mask airway or tracheal intubation.

UNLABELLED: In a prospective, randomized, and controlled trial, we compared the stress responses after insertion of the Combitube (CT; Kendall-Sheridan Catheter Corp., Argyle, NY), the laryngeal mask airway (LMA), or endotracheal intubation (ET). Seventy-five patients scheduled for routine urological or gynecological surgery were randomly allocated to one of three groups and were ventilated via either an ET, a LMA, or a CT. All three devices could be inserted easily and rapidly, providing adequate ventilation and oxygenation. Insertion of the CT was associated with a significant increase in mean maximal systolic arterial pressure (160+/-32 mm Hg) and diastolic arterial pressure (91+/-17 mm Hg) compared with ET (140+/-24, 78+/-11 mm Hg; P < 0.05, P < 0.01, respectively) or insertion of the LMA (115+/-33,63+/-22 mm Hg, both P < 0.001). The mean maximal epinephrine and norepinephrine plasma concentrations after insertion of the CT (37.3+/-31.1 and 279+/-139 pg/mL, respectively) were significantly higher than those after ET (35.8+/-89.8 and 195+/-58 pg/mL, respectively) or insertion of a LMA (17.3+/-13.3 and 158+/-67 pg/mL, respectively). This might be attributed to the pressure of the pharyngeal cuff of the CT on the anterior pharyngeal wall. We conclude that insertion of the CT causes a pronounced stress response and that precautions should be taken when used in patients at risk of hypertensive bleeding. IMPLICATIONS: In this study, we showed that the hemodynamic and catecholamine stress responses after insertion of the Combitube (Kendall-Sheridan Catheter Corp., Argyle, NY) were significantly higher compared with laryngeal mask airway or endotracheal intubation. We conclude that the increased stress response to insertion of a Combitube may represent a serious hazard to patients with cardiovascular disease.

Adult↗
PubMed1999

PCR and blood culture for detection of Escherichia coli bacteremia in rats.

Critically ill patients often develop symptoms of sepsis and therefore require microbiological tests for bacteremia that use conventional blood culture (BC) techniques. However, since these patients frequently receive early empirical antibiotic therapy before diagnostic procedures are completed, examination by BC can return false-negative results. We therefore hypothesized that PCR could improve the rate of detection of microbial pathogens over that of BC. To test this hypothesis, male Wistar rats were challenged intravenously with 10(6) CFU of Escherichia coli. Blood was then taken at several time points for detection of E. coli by BC and by PCR with E. coli-specific primers derived from the uidA gene, encoding beta-glucuronidase. In further experiments, cefotaxime (100 or 50 mg/kg of body weight) was administered intravenously to rats 10 min after E. coli challenge. Without this chemotherapy, the E. coli detection rate decreased at 15 min and at 210 min after challenge from 100% to 62% of the animals with PCR and from 100% to 54% of the animals with BC (P, >0.05). Chemotherapy decreased the E. coli detection rate at 25 min and at 55 min after challenge from 100% to 50% with PCR and from 100% to 0% with BC (P, <0.05). Thus, at clinically relevant serum antibiotic levels, PCR affords a significantly higher detection rate than BC in this rat model. The results suggest that PCR could be a useful adjunct tool supplementing conventional BC techniques in diagnosing bacteremia.

Animals↗
PubMed1999

Cbfa2 is required for the formation of intra-aortic hematopoietic clusters.

Cbfa2 (AML1) encodes the DNA-binding subunit of a transcription factor in the small family of core-binding factors (CBFs). Cbfa2 is required for the differentiation of all definitive hematopoietic cells, but not for primitive erythropoiesis. Here we show that Cbfa2 is expressed in definitive hematopoietic progenitor cells, and in endothelial cells in sites from which these hematopoietic cells are thought to emerge. Endothelial cells expressing Cbfa2 are in the yolk sac, the vitelline and umbilical arteries, and in the ventral aspect of the dorsal aorta in the aorta/genital ridge/mesonephros (AGM) region. Endothelial cells lining the dorsal aspect of the aorta, and elsewhere in the embryo, do not express Cbfa2. Cbfa2 appears to be required for maintenance of Cbfa2 expression in the endothelium, and for the formation of intra-aortic hematopoietic clusters from the endothelium.

Animals↗
PubMed1999

Realization of a CPR using HL7 queries from communication server to information server.

A communication server is often used in Germany to interface legacy systems. It handles the translation, duplication, and transmission of messages to all systems that might need this information. Based on the principles of "for every data there is only one master" and "information on demand" we have built an information server that reduces the messages required and simplifies the handling of messages, the update of data already sent compared to a communication server. It also allows to implement a security policy as required by the German data privacy legislature.

Computer Communication Networks↗
PubMed1998

Mcl-1 in transgenic mice promotes survival in a spectrum of hematopoietic cell types and immortalization in the myeloid lineage.

Mcl-1 is a member of the Bcl-2 family that is expressed in early monocyte differentiation and that can promote viability on transfection into immature myeloid cells. However, the effects of Mcl-1 are generally short lived compared with those of Bcl-2 and are not obvious in some transfectants. To further explore the effects of this gene, mice were produced that expressed Mcl-1 as a transgene in hematolymphoid tissues. The Mcl-1 transgene was found to cause moderate viability enhancement in a wide range of hematopoietic cell types, including lymphoid (B and T) as well as myeloid cells at both immature and mature stages of differentiation. However, enhanced hematopoietic capacity in transgenic bone marrow and spleen was not reflected in any change in pool sizes in the peripheral blood. In addition, among transgenic cells, mature T cells remained long lived compared with B cells and macrophages could live longer than either of these. Interestingly, when hematopoietic cells were maintained in tissue culture in the presence of interleukin-3, Mcl-1 enhanced the probability of outgrowth of continuously proliferating myeloid cell lines. Thus, Mcl-1 transgenic cells remained subject to normal in vivo homeostatic mechanisms controlling viable cell number, but these constraints could be overridden under specific conditions in vitro. Within the organism, Bcl-2 family members may act at "viability gates" along the differentiation continuum, functioning as part of a system for controlled hematopoietic cell amplification. Enforced expression of even a moderate viability-promoting member of this family such as Mcl-1, within a conducive intra- and extracellular environment in isolation from normal homeostatic constraints, can substantially increase the probability of cell immortalization.

Animals↗
PubMed1998

The nitura study--effect of nitroglycerin or urapidil on hemodynamic, metabolic and respiratory parameters in hypertensive patients with pulmonary edema.

OBJECTIVE: To assess the effects of nitroglycerin or urapidil on hemodynamic, respiratory and metabolic parameters in hypertensive patients with pulmonary edema. DESIGN: Open, randomized and prospective clinical study. SETTING: Out-of-hospital setting and Emergency Department in a 2000-bed hospital. PATIENTS: Hundred twelve patients with evidence of hypertensive crises with pulmonary edema (systolic blood pressure (SBP) > 200 mmHg and/or diastolic blood pressure (DBP) > 100 mm Hg and rales over both lungs) at the time when the emergency physician arrived. INTERVENTIONS: The out-of-hospital treatment consisted of oxygen via face mask, 80 mg furosemide i.v., 10 mg morphium s.c., and either nitroglycerin sublingually (initial dose: 0.8 mg; repetitive administration of 0.8 mg every 10 min to a cumulative dose of 3.2 mg) or urapidil (initial dose: 12.5 mg i.v.; repetitive administration every 15 min to a cumulative dose of 50 mg). If SBP was more than 180 mm Hg and/or DBP more than 90 mm Hg on admission, antihypertensive treatment was continued with nitroglycerin (0.3-3 mg/h) or urapidil (5-50 mg/h). MEASUREMENTS AND RESULTS: Blood pressure (BP) was measured every 5 min with the use of an automatic oscillometric device. Serum lactate, PO2, pH value, and base excess (BE) were evaluated on admission and 6 h later. Blood pressure, serum lactate and BE on admission were significantly lower (SBP: 155 +/- 30 vs 179 +/- 33 mm Hg; p = 0.0002; DBP: 82 +/- 17 vs 93 +/- 19 mmHg; p = 0.001; lactate: 2.2 +/- 1.6 vs 3.9 +/- 2.7; p = 0.0001; BE: -1.9 +/- 3.9 vs -4.4 +/- 1.7; p = 0.0005) and PO2 and pH values were significantly higher in the urapidil group compared to the nitroglycerin group (PO2: 75 +/- 25 vs 66 +/- 17; p = 0.036; pH: 7.33 +/- 0.08 vs 7.29 +/- 0.09; p = 0.042). After 6 h no differences between the two groups were observed. CONCLUSION: The more pronounced BP reduction in the urapidil group was associated with an improved respiratory and metabolic situation in hypertensive patients with pulmonary edema. Therefore, urapidil is a valuable alternative to nitroglycerin in patients with pulmonary edema and systemic hypertension.

Aged↗
PubMed1998

Fate and role of peroxisomes during the life cycle of the yeast Saccharomyces cerevisiae: inheritance of peroxisomes during meiosis.

Sporulation in the yeast Saccharormyces cerevisiae is a meiotic developmental process that occurs in MATa/MATalpha heterozygotes in response to nutrient deprivation. Here, the fate and role of peroxisomes during sporulation and germination has been examined by a combination of immunoelectron microscopy and the use of pex mutants defective in peroxisomal functions. Using a green fluorescent protein probe targeted to peroxisomes we show that peroxisomes are inherited through meiosis and that they do not increase in number either during sporulation or spore germination. In addition, there is no requirement for peroxisome degradation prior to spore packaging. Unlike the situation in filamentous fungi, peroxisomes do not proliferate during the yeast life cycle. Functional peroxisomes are dispensable for efficient meiotic development on acetate medium since homozygous delta pex6 diploids sporulated well and produced mature spores that were resistant to diethyl ether. Like haploids, diploid cells can proliferate their peroxisomes in response to oleate as sole carbon source in liquid medium, but under these conditions they do not sporulate. On solid oleate medium, homozygous pex5, delta pex6, and pex7 cells were unable to sporulate efficiently, whereas the wild type was. The results presented here are discussed in terms of the transmission of organelles to progeny cells.

Culture Media↗
PubMed1998

Treatment of metastatic malignant melanoma with dacarbazine plus fotemustine.

Despite the poor prognosis of metastatic malignant melanoma, polychemotherapy with dacarbazine and fotemustine has shown promising results in several studies. We report on the clinical efficacy of a new sequential administration regimen with dacarbazine at a dose of 200 mg/m2 followed 24 h later by fotemustine 100 mg/m2 every 4 weeks in 63 patients with metastatic melanoma. A complete response was noted in 3 patients (5%), a partial response in 4 patients (6%), stable disease in 33 patients (5%) and progressive disease in 23 patients (37%). The duration of the 3 complete responses was 5, 14+ and 60+ months, for the 4 partial responses, 3, 4, 6 and 13 months. The median duration for stable disease was 4 months. The best response rates were obtained for lung and lymph node metastases. Toxicity was mild and mainly limited to haematological without pulmonary side-effects. Although there was a relatively low objective response rate, this chemotherapy regimen as a palliative treatment, is potentially valuable for patients with progressive stage IV melanoma.

Adult↗
PubMed1998

Estimation of the volume-weighted mean nuclear volume discriminates keratoacanthoma from squamous cell carcinoma.

Keratoacanthoma (KA) is a fairly common neoplasm that in the past has been considered by many to be benign. Keratoacanthoma is usually differentiated from squamous cell carcinoma (SCC) by histopathologic criteria. However, the cytologic features of KA and SCC are often similar. Hence, KA may be confused with SCC at the histopathologic level. Volume-weighted mean nuclear volume (Vv) is determined by a technique that permits an unbiased and efficient estimation of nuclear volumes in tissues without any assumptions regarding nuclear shape. In this study, the volume-weighted mean nuclear volume was determined in 18 KAs and 19 SCCs to investigate whether this stereologic approach may be of use in the differentiation of these two tumors. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on Feulgen-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. The mean Vv of KA was 704.5 microm3 (SD +/-170.5), whereas SCC exhibited a significantly lower Vv of 533.9 microm3 (SD+/-164.9) (p = 0.006). The sensitivity and specificity of Vv for the discrimination between KA and SCC was 0.80 and 0.78, respectively. We found that KAs show a significantly larger Vv than SCCs and thus, the estimation of the volume-weighted mean nuclear volume may be regarded as a helpful tool for the differential diagnosis of KA and SCC.

Aged↗
PubMed1998

Diagnostic informativeness of compressed digital epiluminescence microscopy images of pigmented skin lesions compared with photographs.

Epiluminescence microscopy (ELM) is a useful method for improved diagnostic accuracy in early cutaneous melanoma. Conventional photographs of ELM images are commonly used for clinical research and documentation. Electronic images have advantages compared with photographs and are essential for medical informatics, computerized learning and telemedicine. Compression of electronic images allows a reduction in volume of data, but significant image deterioration may occur at high compression rates. We sought to study the diagnostic informativeness of compressed digital ELM images compared with conventional photographs. Fifty photographs of pigmented skin lesions, including 23 melanomas, were presented to eight dermatologists as photographic slides and as digital images with 30:1 Joint Photographic Experts Group (JPEG) compression. The diagnostic performance of the media and the readers was described in terms of sensitivity, specificity and areas under receiver operating characteristic curves (AUC). Agreement between the readings of the two types of media regarding the presence or absence of ELM criteria was assessed using kappa (kappa) statistics. The mean AUC was 0.81 (95% confidence interval [CI] = 0.73-0.90) for slides and 0.81 (95% CI = 0.72-0.90; P = 0.89) for digital images. Agreement between the readings of the two types of media regarding the presence or absence of ELM criteria ranged from kappa = 0.55 (95% CI = 0.22-0.88) for grey-blue area to kappa = 0.89 (95% CI = 0.74-1.00) for radial streaming. In conclusion, digital ELM images with 30:1 JPEG compression appear to be as informative as photographic slides when used to differentiate between melanoma and non-melanoma.

Area Under Curve↗
PubMed1998

Epiluminescence microscopy-based classification of pigmented skin lesions using computerized image analysis and an artificial neural network.

Epiluminescence microscopy (ELM) is a non-invasive technique for in vivo examination which can provide additional criteria for the clinical diagnosis of pigmented skin lesions (PSLs). In the present study we attempt to determine whether PSLs can be automatically diagnosed by an integrated computerized system. This system should recognize the PSL, automatically extract features and use these features in training an artificial neural network, which should--if sufficiently trained--be capable of recognizing and classifying a new PSL without human aid. One hundred and twenty images of randomly selected histologically proven PSLs (33 common naevi, 48 dysplastic naevi and 39 malignant melanomas) were used in this study. The images were digitally obtained and the morphological features of the PSLs were extracted electronically without human assistance. The numerical data were then divided into learning and testing cases and linked to an artificial neural network for training and for further classification of lesions that the system had not been trained on. Our results show that the computerized system was able to automatically identify 95% of the PSLs presented. The sensitivity and specificity of the computerized system were 90% and 74% respectively. In contrast, when differentiating between individual types of lesions, the system performed at true positive rates of only 38% for malignant melanoma, 62% for dysplastic naevi and 33% for common naevi. Our data indicate that (1) ELM images of PSLs provide an excellent source for digital image analysis; (2) the vast majority of PSLs can be correctly identified by a relatively simple (and thus not "intelligent") application of digital image analysis; (3) automatic feature extraction based mainly on ABCD rules provides reliable data on the distinction between benign and malignant PSLs; and (4) there is evidence that artificial neural networks can be trained to adequately discriminate between benign and malignant PSLs.

Dysplastic Nevus Syndrome↗
PubMed1998

Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.

PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS: Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.

Adjuvants, Immunologic↗
PubMed1997

Molecular and biochemical characterization of phosphoglucomutases from Entamoeba histolytica and Entamoeba dispar.

Entamoeba histolytica and Entamoeba dispar have only recently been defined as two separate species. E. histolytica, the pathogenic species, is the microorganism causing invasive intestinal amoebiasis and/or liver abscess, while the morphologically similar E. dispar is nonpathogenic and noninvasive. The gold standard for the distinction of the two species has been the isoenzyme electrophoresis of phosphoglucomutases (EC 5.4.2.2) and hexokinases (EC 2.7.1.1), but there had also been a controversy about the possibility of a conversion of isoenzyme patterns. In this study, we cloned the phosphoglucomutase (PGM) cDNAs from the pathogenic and the nonpathogenic species. The deduced amino acid sequences were only 2.4% different. The cDNAs were expressed in Escherichia coli under the control of a T7 RNA polymerase promoter. The recombinant polypeptides displayed strong phosphoglucomutase activity, each of the recombinant enzymes comigrated with its natural counterpart from E. histolytica and E. dispar in the starch gel electrophoresis. Our results give a biochemical interpretation of the PGM isoenzyme pattern and support the clear distinction between the two species.

Amino Acid Sequence↗
PubMed1997

The Saccharomyces cerevisiae peroxisomal 2,4-dienoyl-CoA reductase is encoded by the oleate-inducible gene SPS19.

beta-Oxidation is compartmentalized in mammals into both mitochondria and peroxisomes. Fatty acids with double bonds at even-numbered positions require for their degradation the auxiliary enzyme 2,4-dienoyl-CoA reductase, and at least three isoforms, two mitochondrial and one peroxisomal, exist in the rat. The Saccharomyces cerevisiae Sps19p is 34% similar to the human and rat mitochondrial reductases, and an SPS19 deleted strain was unable to utilize petroselineate (cis-C18:1(6)) as the sole carbon source, but remained viable on oleate (cis-C18:1(9)). Sps19p was purified to homogeneity from oleate-induced cells and the homodimeric enzyme (native molecular weight 69,000) converted 2,4-hexadienoyl-CoA into 3-hexenoyl-CoA in an NADPH-dependent manner and therefore contained 2,4-dienoyl-CoA reductase activity. Antibodies raised against Sps19p decorated the peroxisomal matrix of oleate-induced cells. SPS19 shares with the sporulation-specific SPS18 a common promoter region that contains an oleate response element. This element unidirectionally regulates transcription of the reductase and is sufficient for oleate induction of a promoterless CYC1-lacZ reporter gene. SPS19 is dispensable for growth and sporulation on solid acetate and oleate media, but is essential for these processes to occur on petroselineate.

Amino Acid Sequence↗