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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 181 records · Page 10Linked to original sources
PubMed1998

Incidence of secretory otitis media following maxillectomy.

OBJECTIVE: The purpose of this investigation was to determine the incidence and characteristics of secretory otitis media after maxillectomy procedures. STUDY DESIGN: Retrospective chart analysis was performed with the cases of 49 patients who underwent maxillectomy for tumor in the Departments of Otolaryngology-Head and Neck Surgery and Oral and Maxillofacial Surgery between the years 1990 and 1996. RESULTS: In 10 patients (20%), secretory otitis media manifested itself from 1 week to 6 months after surgery; 1 patient developed a central perforation with chronic otitis media. Nearly one third of patients who underwent total maxillectomy had secretory otitis media. Six patients (8 ears) required insertion of ventilation tubes. CONCLUSIONS: Patients undergoing total and partial maxillectomies are prone to occurrences of secretory otitis media. Insertion of ventilation tubes easily resolves the problem. Preoperative and routine postoperative patient follow-up should always include otoscopy and audiometry, and tympanometry should be performed when warranted.

Adolescent↗
PubMed1998

Lectin-mediated drug targeting: preparation, binding characteristics, and antiproliferative activity of wheat germ agglutinin conjugated doxorubicin on Caco-2 cells.

PURPOSE: To investigate the usefulness of wheat germ agglutinin as a targeting carrier protein for an acid-labile chemotherapeutic prodrug directed against colon carcinoma cells in vitro. METHODS: Cis-aconityl-linked doxorubicin-wheat germ agglutinin was prepared by a two step procedure and the conjugate-binding capacity of target- and non-target cells was assayed by flow cytometry. The antiproliferative activity of the prodrug on Caco-2 and MOLT-4 cells was determined by the XTT- and BrdU-test and compared with that of the parent drug and the lectin alone. RESULTS: At pH 4.0, about 50% of the conjugated doxorubicin were released within 24 h from the water soluble prodrug exhibiting a conjugation number of 24 (mol doxorubicin/mol WGA). The prodrug-binding capacity of colon carcinoma cells exceeded that of human colonocytes and lymphoblastic MOLT-4 cells 4.5-fold. Additionally, the antiproliferative effect of the conjugate on Caco-2 cells was 39% as opposed to 5% in case of MOLT-4 cells. As the unmodified carrier protein inhibited or stimulated Caco-2 cell growth in a concentration-dependent manner, the cytostatic activity of the conjugate was determined at WGA concentrations without an effect on cell-proliferation. Considering 50% release of conjugated drug at the most, the prodrug yielded 160% of the cytostatic activity of free doxorubicin. CONCLUSIONS: WGA-prodrug targeting offers new perspectives for site-specific, cytoinvading drug delivery in colon cancer chemotherapy.

Aconitic Acid↗
PubMed1998

Mechanistic and quantitative prediction of aminopeptidase activity in stripped human skin based on the HaCaT cell sheet model.

HaCaT cell culture sheets were recently demonstrated to be a useful tool to study epidermal metabolism. Here we report on a mechanistic and quantitative correlation between the kinetics of aminopeptidase-based cleavage of L-Ala-4-methoxy-2-naphthylamide (Ala-MNA) in HaCaT sheets versus stripped human skin. Fresh human skin (breast or abdominal) was obtained from cosmetic surgery, tape-stripped, and dermatomed. HaCaT sheets were cultured on porous membranes. Diffusion and concurrent metabolism were studied under reflection and permeation conditions. Numerical simulations of simultaneous diffusion and saturable Michaelis-Menten metabolism were based on a physical model and a fixed set of independently obtained parameters (diffusion coefficient D, distance x, partition coefficient P, Michaelis constant Km, maximum metabolic rate Vmax). Under reflection conditions, cleavage of Ala-MNA in HaCaT sheets was very close to stripped skin. In contrast, in permeation studies substrate only permeated through HaCaT whereas passage through stripped skin led to full cleavage of Ala-MNA to MNA. All experimental data were in reasonable to excellent agreement with numerically generated data. Differences between HaCaT and stripped skin could be quantitatively and mechanistically explained by the thickness of the metabolically active layer, i.e., approximately 10 microm in HaCaT and approximately 40 microm in stripped skin. Full cleavage of permeating Ala-MNA in stripped skin was predicted to occur within the upper approximately 20 microm of viable epidermis. Thus epidermal aminopeptidase activity may act as an efficient metabolic barrier to fully block the permeation of aminopeptidase labile xenobiotics. Within the settings of this study the kinetics of metabolism in the viable epidermis of skin is predictable from HaCaT sheets.

2-Naphthylamine↗
PubMed1998

Peripheral blood CD34+ cell count reliably predicts autograft yield.

A reliable measure to predict peripheral blood progenitor cell (PBPC) autograft CD34+ cell content is required to optimize the timing of PBPC collection. We prospectively examined the peripheral blood (PB) CD34+ cell count in 59 consecutive patients with various malignancies and analyzed the correlation between the PB CD34+ cell count and various parameters in the PBPC autograft. Two hundred and thirty-five collections were performed with a median of 4.0 collections per patient (range, 2-10). The median PB CD34+ cell count at the time of collection was 39 x 10(6)/1 (range, 0.0-285.6). The PBPC autograft parameters measured were the CD34+ cell, colony-forming unit granulocyte-macrophage (CFU-GM) and mononuclear cell (MNC) content. There was a strong linear correlation between PB CD34+ cells/l and autograft CD34+ cells/kg (r = 0.8477). The correlation with CFU-GM/kg (r = 0.5512) was weaker. There was no correlation between autograft CD34+ cells/kg and PB WBC (r= 0.0684), PB MNC (r = 0.1518) or PB platelet count (r = 0.2010). At our institution we aim to obtain a minimum of 0.5 x 10(6) CD34+ cells/kg with each day of collection. We demonstrate that such a collection can be reliably obtained if the PB CD34+ cell count exceeds 5.0 x 10(6)/l.

Blood Cell Count↗
PubMed1998

B-cell chronic lymphocytic leukaemia with CD8 expression: report of 10 cases and immunochemical analysis of the CD8 antigen.

We report 10 cases of B-cell chronic lymphocytic leukaemia (B-CLL) with expression of the T-cell antigen CD8. The majority of patients had typical B-cell CLL with stable and non-progressive stage A(O) disease except for more common expression of lambda light chain and CD25. Two patients had progressive disease and required therapy, one with atypical morphological and phenotypic features. The incidence of CD8 expression was approximately 0.5% of B-CLL patients from our institutions. Immunoprecipitation of the CD8 antigen from four of these B-CLLs showed identity to the CD8 antigen expressed on T cells with precipitation of CD8alpha bands of molecular weight approximately 34 kD. In view of the known intracellular signalling mechanism of CD8 using the tyrosine kinase p56-lck, we studied p56-lck expression by Western blot and found lack of consistent expression of the CD8 surface antigen, with most lacking p56-lck. Our report indicates that CD8 expression in B-CLL is probably underrecognized but is not a marker of disease progression. The CD8 on the B-CLL surface is immunochemically identical to the antigen on T cells, but is not accompanied by its usual signalling mechanism of p56-lck tyrosine kinase and therefore is unlikely to be a functionally active receptor.

Aged↗
PubMed1998

[Comparative findings of digital thoracic images and digital images of statistical phantoms as film copy, a radiological work station and a PC].

INTRODUCTION: An ROC analysis was carried out in order to determine the reliability of digital luminescence radiography review at a PC and this was compared with a radiological work station and with X-ray film on a viewing box. MATERIAL AND METHOD: 54 chest images obtained by digital luminescence radiography were selected, 31 of these contained small pulmonary nodules. In order to evaluate critical detail, five images of a phantom showing round foci were used. Five radiologists examined these, using a Siemens Magic View work station, a PC with proprietary software (ViewMed) and X-ray films on a viewing box. Image processing of the work station used the standard clinical application. ViewMed performs linear scaling of grey levels to 8 Bit. The results were examined statistically by means of a t-test. RESULTS: As far as the chest images were concerned there was no significant difference in the diagnostic value of these methods. There was, however, a highly significant loss of diagnostic information with respect to the round focus phantom when using the PC compared with the other methods. CONCLUSION: In the configuration in which it was used, the PC should not be relied on as a primary means of examination since critical details cannot always be seen. In routine use these play a subordinate role and there was no significant diagnostic loss where the chest images were concerned. We expect that by improvements in the frequency and contrast processing the PC accuracy will be considerably increased.

Humans↗
PubMed1998

The DMPK gene of severely affected myotonic dystrophy patients is hypermethylated proximal to the largely expanded CTG repeat.

Using methylation-sensitive restriction enzymes, we characterized the methylation pattern on the 5' side of the CTG repeat in the DMPK gene of normal individuals and of patients affected with myotonic dystrophy, showing expansions of the repetitive sequence. The gene segment analyzed corresponds to the genomic SacI-HindIII fragment carrying exons 11-15. There is constitutive methylation in intron 12 at restriction sites of SacII and HhaI, localized 1,159-1,232 bp upstream of the CTG repeat, whereas most, if not all, of the other sites of SacII, HhaI, and HpaII in this region are unmethylated, in normal individuals and most of the patients. In a number of young and severely affected patients, however, complete methylation of these restriction sites was found in the mutated allele. In most of these patients, the onset of the disease was congenital. Preliminary in vivo footprinting data gave evidence for protein-DNA contact in normal genes at an Sp1 consensus binding site upstream of the CTG repeat and for a significant reduction of this interaction in cells with a hypermethylated DMPK gene.

Adolescent↗
PubMed1998

Prevalence of antiphospholipid-related antibodies in unselected patients with history of venous thrombosis.

Antiphospholipid antibodies (aPL) are heterogeneous and are now accepted to be mainly phospholipid-protein-dependent antibodies. Although these antibodies are classically associated with thrombosis, their clinical relevance remains to be established. The subgroups of antibodies characterized by their proteic targets were reported to be more appropriate thrombotic markers. We analysed the prevalence of a large panel of antiphospholipid-related antibodies (aPLR), comprising antibodies directed to phospholipid-protein complexes and to different protein cofactors (beta2GPI, prothrombin, annexin V and protein S), in 122 consecutive unselected patients who had experienced at least one venous thrombotic event. The presence of lupus anticoagulants was assessed with an integrated assay using hexagonal phase phospholipids. Two types of aPL (APA and anti-beta2GPI-PL) were measured using a mixture of phospholipids containing cardiolipin and goat serum or human beta2GPI, respectively, as a source of protein cofactor. Our results show a similar prevalence, close to 15%, of lupus anticoagulants, APA and anti-beta2GPI-PL. In contrast, antibodies to beta2GPI were detected in only 8% of the patients, and very few patients had antibodies directed to other proteins. Of the 35 patients having at least one positive aPLR, 17 were classified as severe, because they had recurrent or early onset of thrombosis (< 35 years). The distribution of aPLR between severe and mild cases was not significantly different except for lupus anticoagulants. Our results clearly indicate that lupus anticoagulant is the only aPLR test to be strongly associated with the severity of thrombosis.

Annexin A5↗
PubMed1998

Wavelet versus JPEG (Joint Photographic Expert Group) and fractal compression. Impact on the detection of low-contrast details in computed radiographs.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate different lossy image compression algorithms in direct comparison. METHODS: Computed radiographs were reviewed after compression with Wavelet, Fractal, and Joint Photographic Expert Group (JPEG) algorithms. For receiver operating characteristic (ROC) analysis, 54 thoracic computed radiographs (31 showing pulmonary nodules) were compressed with a ratio of 1:60. Five images of a test-phantom were coded at 1:13. All images were reviewed on a PC. Uncompressed images were reviewed at a PC and at a radiologic workstation (with image processing). RESULTS: For thorax images, decrease of diagnostic accuracy was significant with Wavelets. Fractal performed worse than Wavelets. No ROC curve was observed for JPEG due to poor image quality. No diagnostic loss was noted comparing PC and Workstation review. For low-contrast details of the phantom, results of Wavelet compression were equal to uncompressed images. Fewer true positives and increased true negatives were noted with Wavelets though. Wavelets were superior to JPEG, and JPEG images were superior to Fractal. Workstation review was superior to PC review. CONCLUSIONS: Only Wavelets provided accurate review of low-contrast details at a compression of 1:13. Frequency filtering of Wavelets affects contrast even at a low compression ratio. JPEG performed better than Fractal at low and worse at high compression ratio.

Algorithms↗
PubMed1998

Increased risk of salivary gland tumors after low-dose irradiation.

OBJECTIVE: To assess the risk of neoplastic development among persons exposed to scalp irradiation. STUDY DESIGN: Historical cohort study initially; prospective follow-up subsequently. METHOD: Two control groups--population and siblings--matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. RESULTS: A 4.5-fold incidence of cancer (P < .01) and a 2.6-fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. CONCLUSIONS: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.

Adolescent↗
PubMed1998

Early indicators of prognosis in upper gastrointestinal hemorrhage.

OBJECTIVE: Endoscopy allows accurate risk stratification of patients presenting with gastrointestinal bleeding; frequently, however, it is not immediately available. Initial management and triage of patients thus depends on nonendoscopic information. We sought to risk stratify patients with upper gastrointestinal bleeding using variables available on initial presentation (ie., before endoscopy). METHODS: A retrospective observational study was performed using data from 335 admissions with an initial diagnosis of upper gastrointestinal hemorrhage. All patients underwent endoscopy and were evaluated for an adverse outcome during their hospitalization. An adverse outcome was defined as death, the need for any operation, recurrent hematemesis, recurrent melena after initial clearing, or a hematocrit falling despite transfusion. RESULTS: Univariate analysis identified 17 distinct variables associated (p < 0.05) with an adverse outcome. A stepwise logistic regression identified five variables as independent predictors (p < 0.05) of an adverse outcome: an initial hematocrit <30%, initial systolic blood pressure < 100 mm Hg, red blood in the nasogastric lavage, history of cirrhosis or ascites on exam, and a history of vomiting red blood. We derived a decision rule based on patients having 0-5 of these independent predictors. This decision rule allowed identification of a large patient population with a <10% chance of an adverse outcome. CONCLUSION: Risk stratification is possible from information available at the time of initial presentation. If confirmed in other populations, these predictors can be used to identify patients who require a less intensive level of care.

Female↗
PubMed1998

Low-dose versus standard-dose lenograstim prophylaxis after chemotherapy: a randomized, crossover comparison.

PURPOSE: Granulocyte colony-stimulating factor (G-CSF) administered prophylactically after chemotherapy reduces the duration and severity of neutropenia. This randomized crossover study was designed to assess whether a lower dose of G-CSF is as effective as a standard dose of 5 microg/kg daily. PATIENTS AND METHODS: Patients who received standard-dose chemotherapy regimens expected to cause neutropenia received G-CSF (lenograstim) that started the day after chemotherapy for 14 days or until the absolute neutrophil count (ANC) recovered to greater than 10 x 10(9)/L. The lenograstim dose was randomly allocated to be 2 or 5 microg/kg daily in the first cycle of chemotherapy and crossed over to the alternate dose for the second cycle. The study was designed to accrue 40 assessable patients to provide a power of 80% to detect a difference in duration of neutropenia of 1 day. Fifty-two patients were randomized to treatment and 43 patients completed two cycles of identical chemotherapy. RESULTS: There was little neutropenia irrespective of the dose used. Twenty-three patients (53%) had no grade III or IV neutropenia and 30 patients (70%) had no grade IV neutropenia. Crossover trial methodology was used to assess the difference in outcome caused by the lower dose compared with the standard dose (estimated treatment effect). There was no significant difference in the measures of neutropenia, hospitalization, or other clinical outcomes. The 95% confidence interval (one-sided) for the additional duration of neutropenia caused by the lower dose of lenograstim was 0.43 days or less for grade III or IV neutropenia and 0.34 days or less for grade IV neutropenia. CONCLUSION: Lenograstim 2 microg/kg provides similar protection to 5 microg/kg against neutropenia that complicates standard-dose chemotherapy. The use of a lower dose has important implications for the cost-effectiveness of prophylactic G-CSF therapy.

Adjuvants, Immunologic↗
PubMed1998

Prognostic markers of disease activity in Hodgkin's disease.

The erythrocyte sedimentation rate (ESR), liver alkaline phosphatase (ALP), serum copper (Cu) and urinary nucleoside excretion (UNs) have been proposed as independent prognostic markers in Hodgkin's Disease (HD). However, their prognostic value has not satisfactorily been directly compared to recognised clinical prognostic factors. One hundred and sixty-eight patients with HD had the above markers performed prior to initial treatment. At a median follow-up of 10.9 yrs, the predicted 10 year relapse free survival (RFS) and overall survival (OS) for the entire cohort is 64% and 66%, respectively. In general, patients with elevated markers were significantly less likely to achieve CR, remain in CR and survive. However, multivariate analysis revealed this was due to the association of elevated markers with stage and constitutional symptoms. Following therapy, elevated markers were also correlated with evidence of clinically detectable disease. We conclude that although UNs, Cu, ALP and ESR reflect disease activity, they do not provide independent information beyond that of clinical assessment.

Adult↗
PubMed1998

[Pro-inflammatory cytokines IL-1 beta and TNF-alpha reduce growth hormone receptor mRNA concentration in cultivated rat hepatocytes after stimulation with growth hormone].

Critical illness is associated with catabolism caused by the alteration of several hormonal systems. Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. Since proinflammatory cytokines mediate many of the acute responses in critical illness, we evaluated the effects of IL-1 beta and TNF-alpha on growth hormone receptor-(GHR-)mRNA in cultured rat hepatocytes. Diminished GHR-mRNA concentrations in response to cytokine stimulation indicate that low IGF-I levels in the beginning of severe illness, may at least be partially a cause of GHR synthesis suppression by proinflammatory cytokines.

Animals↗
PubMed1998

[Prognostic value of gastric tonometry in peritonitis due to intestinal perforation and laparoscopic versus conventional management in the swine model].

After a 12 hour period of experimental peritonitis induced by gastric perforation mortality was significantly higher in the laparoscopically treated group of pigs when compared to the open procedure. In both groups the treatment was simple oversowing of the defect plus peritoneal lavage. Septic shock associated with peritonitis and subsequent "multi organ failure syndrome" could accurately be predicted with gastric tonometry. In both groups the decline of pHi in septic animals that died was higher than expected.

Animals↗
PubMed1998

DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies.

This review summarizes reports of recurrent DNA sequence copy number amplifications in human neoplasms detected by comparative genomic hybridization. Some of the chromosomal areas with recurrent DNA copy number amplifications (amplicons) of 1p22-p31, 1p32-p36, 1q, 2p13-p16, 2p23-p25, 2q31-q33, 3q, 5p, 6p12-pter, 7p12-p13, 7q11.2, 7q21-q22, 8p11-p12, 8q, 11q13-q14, 12p, 12q13-q21, 13q14, 13q22-qter, 14q13-q21, 15q24-qter, 17p11.2-p12, 17q12-q21, 17q22-qter, 18q, 19p13.2-pter, 19cen-q13.3, 20p11.2-p12, 20q, Xp11.2-p21, and Xp11-q13 and genes therein are presented in more detail. The paper with more than 150 references and two tables can be accessed from our web site http://www.helsinki.fi/lglvwww/CMG.html. The data will be updated biannually until the year 2001.

Chromosome Aberrations↗