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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 127 records · Page 7Linked to original sources

Acquired tracheoesophageal fistula in critically ill patients.

Acquired benign tracheoesophageal fistula (TEF) is an infrequent complication of prolonged intubation and tracheostomy. Not infrequently, it is associated with severe circumferential malacia of the trachea and a need for concomitant correction of both. Controversy exists as to whether this should be performed in a single-stage or a 2-stage procedure. Four patients with acquired TEF underwent operation in a tertiary referral medical center between 1995 and 1997. The operations were performed through either an anterior (3) or a lateral (1) neck approach. Three patients underwent closure of the fistula with tracheal resection and anastomosis in a single stage and are doing well. One patient with complete subglottic stenosis underwent closure of the TEF and was planned for tracheal reconstruction in a second stage. This patient died in the early postoperative period. The complications included aspiration of blood leading to pneumonia (2), spontaneously resolving pneumomediastinum (1), subcutaneous emphysema (2), and cardiac arrhythmia ( 1). Residual fistula, noted in 1 patient, was treated conservatively and resolved spontaneously within several weeks. We conclude that acquired TEF is amenable to repair through a cervical approach. A single-stage correction of the TEF with reconstruction of the trachea is suitable and successful in most patients. Several stages seem justified when concurrent laryngotracheal reconstruction is needed.

Critical Illness↗

Chondrosarcoma in a family with multiple hereditary exostoses.

Multiple hereditary exostoses is an autosomal dominant skeletal disorder in which there are numerous cartilage-capped excrescences in areas of actively growing bone. The condition is genetically heterogeneous, and at least three genes, ext1, ext2 and ext3 are involved. The reported risk for malignant transformation to chondrosarcoma has been from 0.6% to 2.8%. We have reviewed six generations of a family with 114 living adult members, 46 of them with multiple exostoses. Four have had operations for chondrosarcoma, giving the risk for malignant transformation as 8.3% in this family. Clinical and radiological examination revealed two additional patients with a suspicion of malignancy, but in whom the histological findings were benign. Reported elsewhere in detail, genetic linkage analysis mapped the causative gene to chromosome 11 and molecular studies revealed a guanine-to-thymine transversion in the ext2 gene. Patients with multiple hereditary exostoses carry a relatively high risk of malignant transformation. They should be informed of this possibility and regularly reviewed.

Adolescent↗

Immunosuppression with FK506 increases bone induction in demineralized isogeneic and xenogeneic bone matrix in the rat.

The aim of the present study was to investigate a systemic induction of bone formation in rats by immunosuppression with FK506 (1 mg/kg body weight intraperitoneally [ip]) in a model of osteoinduction of isogeneic and xenogeneic demineralized bone matrix (DBM) for a period of 28 days. In particular, alterations of in vitro cytokine synthesis and changes of lymphocyte subsets were studied. DBM was implanted intramuscularly in the abdominal wall of Lewis rats (seven per group). Blood was sampled on days -7, 0, 7, and 28 for determination of in vitro tumor necrosis factor a (TNF-alpha) synthesis and lymphocyte subsets by flow cytometry (CD3+, CD4+, CD8+, CD45+, ED9+, and Ia+ antibodies). Ossicles of de novo formed bone and the tibias were removed on day 28 after double tetracycline labeling for histomorphometric analysis. Immunosuppression with FK506 significantly decreased lipopolysaccharide (LPS)-stimulated in vitro cytokine synthesis after 7 days and 28 days (p < 0.05). Compared with control animals FK506 treatment significantly increased the volume of induced bone in isogeneic (2.1 +/- 0.3 mm3 vs. 10.8 +/- 0.9 mm3) and xenogeneic (O mm3 vs. 4.7 +/- 0.8 mm3) DBM. Bone histomorphometry of the tibias revealed that immunosuppression increased both bone formation and bone resorption, accompanied by a significant reduction in the relative trabecular area (Tb.Ar). FK506 caused a decrease in the counts of CD8+ T cells probably because of destruction or dislocation of these cells. This suggests that the amount of CD8+ cells and the degree of T cell activation in terms of mean fluorescence intensity (MFI) may be associated with bone metabolism. In support of this, statistical analysis revealed a significant positive correlation between parameters of bone formation as well as bone resorption and the CD4+/CD8+ ratio. There was a significant negative correlation between parameters of remodeling of the metaphysis of the tibia and induced bone volume (BV), respectively, and MFI values of CD3+/Ia+ cells. These findings suggest an important role of T lymphocytes in bone formation and bone resorption in vivo. FK506 caused a marked increase of bone formation in DBM. However, the conclusion that immunosuppression increases fracture healing warrants further investigation.

Alkaline Phosphatase↗

Phonon- versus electron-mediated desorption and oxidation of CO on Ru(0001)

Heating of a ruthenium surface on which carbon monoxide and atomic oxygen are coadsorbed leads exclusively to desorption of carbon monoxide. In contrast, excitation with femtosecond infrared laser pulses enables also the formation of carbon dioxide. The desorption is caused by coupling of the adsorbate to the phonon bath of the ruthenium substrate, whereas the oxidation reaction is initiated by hot substrate electrons, as evidenced by the observed subpicosecond reaction dynamics and density functional calculations. The presence of this laser-induced reaction pathway allows elucidation of the microscopic mechanism and the dynamics of the carbon monoxide oxidation reaction.

Journal Article↗

Characterization of the 17p amplicon in human sarcomas: microsatellite marker analysis.

The structure of the 17p amplicon from 9 human sarcoma specimens evaluated by comparative genomic hybridization (CGH) has been studied by analyzing 28 microsatellite markers by PCR. Eleven sarcoma specimens showing no DNA copy number increases at 17p by CGH were analyzed as control samples. Five specimens were analyzed by Southern blotting using probes that have previously shown amplification at the 17p12 region in astrocytoma and high-grade osteosarcoma samples. Microsatellite marker analyses revealed that all samples but 1 showing copy number increases at 17p by CGH displayed allelic imbalance that confirmed the CGH findings. Seven of these 9 cases displayed gain in copy number by microsatellite marker analysis. Four cases displaying gain in copy number were associated with loss of heterozygosity at other loci. Southern blot analysis showed amplification in 3 cases, all of them had shown copy number increases by CGH and microsatellite marker analysis, except one case, which was not included in the microsatellite marker analysis. Our results reveal the complexity of the 17p amplicon in sarcomas, suggesting that multiple target genes are involved in tumorigenesis.

Blotting, Southern↗

Radar and optical observations of asteroid 1998 KY26

Observations of near-Earth asteroid 1998 KY26 shortly after its discovery reveal a slightly elongated spheroid with a diameter of about 30 meters, a composition analogous to carbonaceous chondritic meteorites, and a rotation period of 10.7 minutes, which is an order of magnitude shorter than that measured for any other solar system object. The rotation is too rapid for 1998 KY26 to consist of multiple components bound together just by their mutual gravitational attraction. This monolithic object probably is a fragment derived from cratering or collisional destruction of a much larger asteroid.

Journal Article↗

The human serum deprivation response gene (SDPR) maps to 2q32-q33 and codes for a phosphatidylserine-binding protein.

The serum deprivation response gene (SDPR, alias sdr) has been previously isolated for its high mRNA expression in serum-starved cells compared to contact-inhibited NIH3T3 cells; such regulation is not observed in single-oncogene transformed NIH3T3 cells after serum starvation. More recently Sdpr has been identified as a substrate of protein kinase C (PKC): this interaction determines the compartimentalization of PKC to caveolae, a plasma membrane invagination of which Sdpr is a major component. Lack of Sdpr-PKC interaction in transformed cells has been proposed to be involved in the alteration of PKC subcellular localization and substrate specificity. Here we report the cloning of the human SDPR homologue (HGMW-approved symbol SDPR) and its mapping to 2q32-q33 in the human genome. In analogy with the murine system, SDPR mRNA expression is increased when human fibroblasts are serum starved, it becomes down-regulated during synchronous cell-cycle reentry, but it is not induced in cells arrested by contact inhibition. Analysis of SDPR expression in human tissues reveals a near ubiquitous expression, with highest levels found in heart and lung. We show that human SDPR encodes PS-p68, a previously characterized phosphatidylserine-binding protein purified from human platelets. Accordingly, recombinant Sdpr is able to specifically bind phosphatidylserine in the absence of Ca2+. SDPR is homologous to two genes in the databank, one of which, srbc, is similarly regulated during growth arrest and encodes a phosphatidylserine-binding protein that is a substrate of PKC.

Amino Acid Sequence↗

Comparison of COBE Spectra software version 4.7 PBSC and version 6.0 auto PBSC program.

Until recently, the collection of peripheral blood progenitor cells (PBPC) has been semi-automated by using the COBE Spectra, with the operator manually maintaining the position of the white cells being collected. The COBE Spectra Version 6.0 apheresis device offers the user an automated program for the collection of PBPC. In this study, we compared the new software Version 6.0 to that of Version 4.7. Patients (n = 46) undergoing PBPC collection were allocated to cell processing with either Version 4.7 (n = 24) or Version 6.0 (n = 22). The CD34+ cell count, mononuclear cell (MNC) count, white cell count (WCC), hemoglobin (Hb), and platelet content in the autograft product by using the two versions were compared. We divided the analysis into three subsets according to peripheral blood (PB) CD34 content: <10x10(6)/L, 10-50x10(6)/L and >50x10(6)/L. Analysis of the three subsets showed no statistical difference between results obtained when the starting PB CD34+ cell count was 10-50x10(6)/L (P=0.08) or >50x10(6)/L (P=0.4065). At lower starting PB CD34+ cell counts of <10x10(6)/L, Version 4.7 was superior (P=0.0167). However, autograft platelet contamination of the autograft was significantly higher using Version 4.7 (P=<0.0001).

Antigens, CD34↗

Comparison of cerebral blood volume measured by near infrared spectroscopy and contrast enhanced magnetic resonance imaging.

Cerebral blood volume (CBV) can be quantified by both near infrared spectroscopy (NIRS) and magnetic resonance imaging (MRI). The aim is to compare CBV results obtained by NIRS and MRI in adult patients. 10 adult patients, 6 females and 4 males, age median 24 (range 21 to 76) years, were included in this study. All needed a MRI investigation with contrast medium for clinical reasons. The NIRS instrument, the Cerebral RedOx Monitor 2020 from Critikon, quantifies cerebral haemoglobin concentration using a sensor with two receiving channels at different distances. Geometrical detector arrangements of this type enable a ratio measurement to be achieved, which reduces the contribution of the skull and skin, thus allowing quantification. Cerebral haemoglobin concentration can be converted in CBV, as the haemoglobin concentration in the blood is known. CBV can be quantified by MRI using an indicator dilution method. The method requires an injection of a paramagnetic contrast agent. The input function can be measured at the throat and thus perfusion images can be quantified. CBV was measured by NIRS just before the patient entered the magnet and after he had left it. The sensor for the NIRS measurement was applied to the patients front three times for 1 minute to each side, avoiding the sinuses. CBV was determined by contrast enhanced MRI between the NIRS measurements. The mean CBV (NIRS) was 8.6 (SD 1.3) ml/100 g and CBV (MRI) was 7.1 (SD 2.5). The correlation between CBV (NIRS) and CBV (MRI) was Pearson's correlation coefficient -0.297 (p = 0.204) respectively Spearman's rho (nonparametric) -0.266 (p = 0.257). The CBV values obtained by NIRS and MRI, even though they are in the same range, do not correlate.

Adult↗

Successful salvage treatment for relapse after autologous stem cell transplantation in a patient with Hodgkin's disease--a case report.

We report a patient who relapsed 12 months after undergoing high-dose chemotherapy followed by autologous stem cell transplantation for refractory Hodgkin's disease, nodular sclerosis. The patient received sequential single-dose chemotherapy consisting of 140 mg/m2 epirubicin, 1.4 mg/m2 vincristine, and 50 mg/m2 prednisole on day 1, followed by 4000 mg/m2 cyclophosphamide on day 15 and 2000 mg/m2 etoposide on day 30. This regimen was given twice, predominantly on an outpatient basis without major toxicity. The patient reached a complete remission and has remained free of disease after an observation period of 48 months. Single-dose sequential treatment should be considered for refractory Hodgkin's disease, even for relapse after high-dose chemotherapy, as escalated single doses of cytostatic agents may overcome drug resistance.

Adolescent↗

Gastric tonometry accurately predicts mortality in experimental peritonitis in both laparoscopic and conventional surgery.

OBJECTIVES: Tonometry is widely used in the diagnosis of sepsis and splanchnic ischemia. This study was devised to analyze the predictive value of gastric tonometry for outcome of experimental viscus perforation-induced peritonitis. The impact of conventional and laparoscopic intervention on tonometric measurements was the main scope. METHODS: This randomized controlled intervention trial was performed in a University experimental laboratory, using 24 female Duroc pigs. Pigs were subjected to gastric perforation followed by a 12 h interval of peritonitis, and then to either laparoscopic or conventional surgical repair of the defect with peritoneal lavage. Gastric tonometry and cardiocirculatory monitoring were performed. RESULTS: Septic shock associated with peritonitis and subsequent lethal outcome was accurately predicted with gastric tonometry. Changes of gastric mucosal pH correlated significantly with decreases of MAP (r2=0.880; P<0.001) and SVR (r2=0.678; P<0.001), increase of QT (r2=0.486; P=0.013), and mortality (r=0.752; P<0.001). Mortality was significantly higher in laparoscopically treated animals compared to those subjected to the open procedure (78% vs 22%; P<0.045). CONCLUSIONS: Gastric tonometry accurately predicted mortality in experimental peritonitis. The decline of gastric mucosal pH in the laparoscopic group was more than double that of to conventionally treated animals. This finding not only reflected the increase of systemic CO2 due to higher absorption during CO2-pneumoperitoneum, but probably also indicated a more severe form of splanchnic ischemia during laparoscopic surgery. Even though tonometry can be used to accurately predict mortality and separate the high risk group, extreme caution should be applied under conditions associated with severe peritonitis.

Animals↗

DNA copy number losses in human neoplasms.

This review summarizes reports of recurrent DNA sequence copy number losses in human neoplasms detected by comparative genomic hybridization. Recurrent losses that affect each of the chromosome arms in 73 tumor types are tabulated from 169 reports. The tables are available online at http://www.amjpathol.org and http://www. helsinki.fi/ approximately lglvwww/CMG.html. The genes relevant to the lost regions are discussed for each of the chromosomes. The review is supplemented also by a list of known and putative tumor suppressor genes and DNA repair genes (see Table 1, online). Losses are found in all chromosome arms, but they seem to be relatively rare at 1q, 2p, 3q, 5p, 6p, 7p, 7q, 8q, 12p, and 20q. Losses and their minimal common overlapping areas that were present in a great proportion of the 73 tumor entities reported in Table 2 (see online) are (in descending order of frequency): 9p23-p24 (48%), 13q21 (47%), 6q16 (44%), 6q26-q27 (44%), 8p23 (37%), 18q22-q23 (37%), 17p12-p13 (34%), 1p36.1 (34%), 11q23 (33%), 1p22 (32%), 4q32-qter (31%), 14q22-q23 (25%), 10q23 (25%), 10q25-qter (25%),15q21 (23%), 16q22 (23%), 5q21 (23%), 3p12-p14 (22%), 22q12 (22%), Xp21 (21%), Xq21 (21%), and 10p12 (20%). The frequency of losses at chromosomes 7 and 20 was less than 10% in all tumors. The chromosomal regions in which the most frequent losses are found implicate locations of essential tumor suppressor genes and DNA repair genes that may be involved in the pathogenesis of several tumor types.

Chromosomes, Human↗

Cyclical fluctuations in blood pressure, heart rate and cerebral blood volume in preterm infants.

Many recently published papers describe cyclical changes of cerebral circulatory variables, mainly in cerebral blood flow velocity (CBFV) performed with Doppler sonography. In this paper we focus on another important variable of cerebral circulation: on cerebral blood volume (CBV) measured by near infrared spectrophotometry (NIRS). In a retrospective analysis of NIRS measurements in 20 preterm infants (median 27 3/7 weeks of gestation), the dominating frequencies and prevalence of cyclical changes of CBV and its possible correlation with peripheral circulatory variables (mean arterial pressure and heart rate) was examined. In 19 out of the 20 infants cyclical changes of CBV were found within a frequency range of 2-4.7 cycles/min which is comparable to the results of the Doppler studies describing fluctuations in CBFV. A dominating frequency of heart rate (HR), was found only in 12 out of 20 infants, and it was with 2.1-3.8 cycles/min in a similar range compared to CBV. In mean arterial blood pressure (MABP), however we detected cycles with longer periods every 1-2.5 min in 14 out of 20 infants. There was a significant coherence between MABP/CBV and HR/CBV. The area under the coherence curve, however, was significantly larger between MABP and CBV as compared to HR and CBV (P = 0.0007, Wilcoxon signed-rank test).

Blood Pressure↗

Prophylactic antibiotic therapy is associated with an increased prevalence of Aspergillus colonization in adult cystic fibrosis patients.

Aspergillus colonization is a common phenomenon in adult cystic fibrosis (CF) patients. The clinical significance of Aspergillus for the pathogenesis of CF lung disease remains unclear and factors predisposing to such colonization are still completely unknown. We investigated the prevalence of Aspergillus colonization in 104 adult CF patients who attended our outpatient clinic in 1997. With respect to demographic and clinical data, and antibiotic therapy received, we further examined which factors were associated with Aspergillus colonization in these patients. Repeated investigations of CF sputum samples revealed Aspergillus species in 43/104 (41.3%; 95% confidence interval 30.2-52.5%) of the patients. We found no significant relationship between Aspergillus colonization and age (P > 0.4), gender (P = 0.4), colonization with pseudomonas species (P > 0.6), lower lung function values (P > 0.9), or worse chest radiography (P > 0.1). Surprisingly, the prevalence of Aspergillus colonization was higher in CF patients receiving prophylactic antibiotic therapy (oral antibiotics: P = 0.05; inhalative antibiotics: P = 0.035; both antibiotics: P = 0.048). Prophylactic antibiotics are widely used to eradicate or decrease chronic bronchopulmonary infection in CF. Our results indicate that long-term antibiotic therapy may predispose CF patients to Aspergillus colonization.

Adult↗

Three-dimensional computer vision for tooth restoration.

If a person with carious lesions needs or requests crowns or inlays, these dental fillings have to be manufactured for each tooth and each person individually. We survey computer vision techniques which can be used to automate this process. We introduce three particular applications which are concerned with the reconstruction of surface information. The first one aims at building up a database of normalized depth images of posterior teeth and at extracting characteristic features from these images. In the second application, a given occlusal surface of a posterior tooth with a prepared cavity is digitally reconstructed using an intact model tooth from a given database. The calculated surface data can then be used for automatic milling of a dental prosthesis, e.g. from a preshaped ceramic block. In the third application a hand-made provisoric wax inlay or crown can be digitally scanned by a laser sensor and copied three dimensionally into a different material such as ceramic. The results are converted to a format required by the computer-integrated manufacturing (CIM) system for automatic milling.

Adolescent↗

Repetitive high-dose therapy with ifosfamide, thiotepa and paclitaxel with peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study.

BACKGROUND: This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: The planned treatment was three cycles of high-dose ifosfamide, thiotepa and conventional-dose paclitaxel delivered every 28 days with progressive dose-escalation in successive cohorts. Each cycle was supported by peripheral blood progenitor cells (PBPC) and filgrastim. RESULTS: Twenty-three patients were entered into this trial. Of the planned 69 treatment cycles, 59 were delivered and fifteen patients completed all three cycles. The dose-limiting toxicities were renal tubular acidosis, encephalopathy, mucositis and enterocolitis. There was one treatment-related hemorrhagic death. CONCLUSIONS: The recommended doses for phase II or III studies are ifosfamide (10 g/m2), thiotepa (350 mg/m2) and paclitaxel (175 mg/m2).

Adult↗

Phase I and subsequent phase II study of filgrastim (r-met-HuG-CSF) and dose intensified cyclophosphamide plus epirubicin in patients with non-Hodgkin's lymphoma and advanced solid tumors.

BACKGROUND: To define a maximum tolerated dose (MTD) for the combination of epirubicin and cyclophosphamide with filgrastim (r-met-HuG-CSF) in patients with advanced solid tumors and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-five patients with advanced solid tumors were enrolled in stages I and II. Twenty-one patients were treated in stage I in sequential cohorts of at least three patients at increasing dosage levels of cyclophosphamide and epirubicin, for up to six cycles every 21 days. At the completion of stage I, a MTD for epirubicin was established. Fourteen patients were treated in stage II, in cohorts of three or more. The epirubicin dose remained constant at the MTD dosage from stage I. Cyclophosphamide was further dose-escalated to establish its MTD. Twenty-one patients with previously untreated non-Hodgkin's lymphoma were treated in stage III with the MTD established in the prior stages. RESULTS: The MTD in stage I was epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with cumulative neutropenia as the dose-limiting toxicity (DLT). Cumulative thrombocytopenia prevented further dose-escalation of cyclophosphamide in stage II. The stage III regimen consisted of six, 21-day cycles of epirubicin 150 mg/m2, cyclophosphamide 1500 mg/m2, vincristine 2 mg, and prednisolone 100 mg for five days with filgrastim support. Nineteen of twenty-one patients (90%) completed six cycles of treatment, eight (38%) without dose reduction. Common toxicity criteria (CTC) grade 4 neutropenia (neutrophil nadir < 0.5 x 10(9)/l) was documented in 85 of 118 cycles (72%). Neutropenic fever was documented in 17 of 21 patients (81%) on at least one occasion. Severe thrombocytopenia (< 25 x 10(9)/l) was seen in fourteen of 118 cycles (12%) and increased with cycle number. There was no significant non-hematological toxicity. CONCLUSION: Significant dose-escalation of epirubicin and cyclophosphamide was possible with filgrastim support. The MTD achieved was approximately double that of standard-dose therapy. This study forms the basis of an ongoing randomized study evaluating dose-intensification in intermediate grade NHL.

Adult↗

Prothrombin 20210G/A mutation in two patients with mesenteric ischemia.

Primary cases of splanchnic vein thrombosis are now less common since a systematic screening for hypercoagulability is performed. In 1996, a sequence variation in the 3'-untranslated region of the prothrombin gene (F.II 20210G/A mutation) has been linked to a threefold increased risk for venous thrombosis. The role of this thrombophilic disorder is not documented in patients with thrombosis of the splanchnic veins. This report presents two patients with a mesenteric ischemia associated with a heterozygous state for the F.II 20210G/A mutation. The first patient developed an ischemic colitis and the second one an ischemic necrosis of the terminal ileum related to a thrombosis of the superior mesenteric vein. In both cases, another thrombotic risk factor was associated: either a general prothrombic state (primary antiphospholipid syndrome) or a focal factor (abnormal hemodynamic conditions related to a liver cirrhosis). It has recently been proposed that several conditions need to be combined for deep vein thrombosis to develop. Screening for the combination of multiple underlying prothrombotic conditions thus appears justified in patients with splanchnic thrombosis. The role of the F.II 20210G/A mutation as a predisposing factor for thrombosis of the digestive vessels should be considered and needs further investigation.

Adult↗