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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 145 records · Page 8Linked to original sources

Detection of micrometastasis by cytokeratin 20 RT-PCR is limited due to stable background transcription in granulocytes.

The reverse transcription polymerase chain reaction (RT-PCR) amplification of cytokeratin 20 (CK20) mRNA is considered a promising candidate method for the detection of circulating tumour cells in bone marrow and peripheral blood of cancer patients. In this study we have investigated the diagnostic specificity of the CK20 mRNA detection in samples from healthy donors (HD; n = 33), intensive care units patients (ICU; n = 20) and bone marrow obtained from patients suffering from chronic inflammatory diseases (CID; n = 14). RNAs purified from stabilized lysates showed positive results in 24% of the HD group (8/33), 35% of the ICU group (8/20) and in 40% of the CID group (5/14). The use of Ficoll gradients to separate nucleated cells completely restored the specificity of this CK20 RT-PCR assay. The CK20-expressing cells are positively identified to belong to the granulocyte fraction of leucocytes, which appear to express the gene on a background level. Our results demonstrate for the first time that CK20 mRNA expression is not limited to epithelium. Its occurrence in normal granulocytes has to be considered in tests designed to detect circulating cancer cells or micrometastases.

Biomarkers, Tumor↗

Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis.

Previous molecular cytogenetic studies by comparative genomic hybridization (CGH) on primary tumours of human malignant mesothelioma have revealed that loss of genetic material at chromosome 14q is one of the most frequently occurring aberrations. Here we further verify the frequency and pattern of deletions at 14q in mesothelioma. A high-resolution deletion mapping analysis of 23 microsatellite markers was performed on 18 primary mesothelioma tumours. Eight of these had previously been analysed by CGH. Loss of heterozygosity or allelic imbalance with at least one marker was detected in ten of 18 tumours (56%). Partial deletions of varying lengths were more common than loss of all informative markers, which occurred in only one tumour. The highest number of tumours with deletions at a specific marker was detected at 14q11.1-q12 with markers D14S283 (five tumours), D14S972 (seven tumours) and D14S64 (five tumours) and at 14q23-q24 with markers D14S258 (five tumours), D14S77 (five tumours) and D14S284 (six tumours). We conclude from these data that genomic deletions at 14q are more common than previously reported in mesothelioma. Furthermore, confirmation of previous CGH results was obtained in all tumours but one. This tumour showed deletions by allelotyping, but did not show any DNA copy number change at 14q by CGH. Although the number of tumours allelotyped was small and the deletion pattern was complex, 14q11.1-q12 and 14q23-q24 were found to be the most involved regions in deletions. These regions provide a good basis for further molecular analyses and may highlight chromosomal locations of tumour suppressor genes that could be important in the tumorigenesis of malignant mesothelioma.

Adult↗

Ifosfamide in combination with paclitaxel or doxorubicin: regimens which effectively mobilize peripheral blood progenitor cells while demonstrating anti-tumor activity in patients with metastatic breast cancer.

For patients with metastatic breast cancer (MBC) who undergo high-dose therapy with autologous peripheral blood progenitor cell (PBPC) transplantation, an important prerequisite is a mobilization regimen that efficiently mobilizes PBPCs while producing an effective anti-tumor effect. We prospectively evaluated ifosfamide-based chemotherapy for mobilization efficiency, toxicity and disease response in 37 patients. Patients received two cycles of the ifosfamide-based regimen; ifosfamide (5 g/m2 with conventional-dose cycle and 6 g/m2 with mobilization cycle) with either 50 mg/m2 doxorubicin (if limited prior anthracycline and/or progression more than 12 months after an anthracycline-based regimen) or 175 mg/m2 paclitaxel. For the mobilization cycle, all patients received additional G-CSF (10 microg/kg SC, daily) commencing 24 h after completion of chemotherapy. The target yield was >6x10(6) CD34+ cells/kg, sufficient to support the subsequent three cycles of high-dose therapy. The mobilization therapy was well tolerated and the peak days for peripheral blood (PB) CD34+ cells were days 10-13 with no significant differences in the PB CD34+ cells mobilization kinetics between the ifosfamide-doxorubicin vs. ifosfamide-paclitaxel regimens. The median PBPC CD34+ cell content ranged from 2.9 to 4.0x10(6)/kg per day during days 9-14. After a median of 3 (range 1-5) collection days, the median total CD34+ cell, CFU-GM and MNC for all 44 individual sets of collections was 9.2x10(6)/kg (range 0.16-54.9), 37x10(4)/kg (range 5.7-247) and 7.3x10(8)/kg (range 2.1-26.1), respectively. The PBPC target yield was achieved in 35 of the 37 patients. The overall response rate for the 31 evaluable patients was 68% with 10% having progressive disease. Thirty-three patients have subsequently received high-dose therapy consisting of three planned cycles of high-dose ifosfamide, thiotepa and paclitaxel with each cycle supported with PBPCs. Rapid neutrophil and platelet recovery has been observed. Ifosfamide with G-CSF in combination with doxorubicin or paclitaxel achieves effective mobilization of PBPC and anti-tumor activity with minimal toxicity.

Adult↗

Three different autoimmune bullous diseases in one family: is there a common genetic base?

We report an unusual familial occurrence of autoimmune bullous diseases. Three members of a family suffered from three different autoimmune bullous diseases: pemphigus vulgaris (PV), linear IgA disease (LAD) and cicatricial pemphigoid (CP). The HLA type was determined in five family members: all were positive for HLA-DQ5/DR6, which is reported to be associated with susceptibility to PV. The CP patient was DQ7(3) positive, which is in concordance with enhanced susceptibility to ocular CP and CP. The LAD patient was B8 and DR3 negative but positive for HLA-A1. Our study supports the hypothesis that there is a genetically transmitted susceptibility to autoimmune bullous diseases but that additional factors seem necessary actually to develop a particular disease.

Adult↗

Epley's manoeuvre for benign paroxysmal positional vertigo: a prospective study.

The treatment of benign paroxysmal positional vertigo (BPPV) by the Epley, canalith repositioning, manoeuvre was popularized following clinical reports which demonstrated a significant success rate. Benign paroxysmal positional vertigo is considered a self-limiting disease, yet only few authors have analysed the effect of this manoeuvre in randomized, controlled terms. A prospective 3-year, controlled study of patients with BPPV of long duration (mean = 6 months) verified its benefit: the recovery course differed significantly between a group of 31 patients treated with the manoeuvre and a control group of 10 untreated patients. Symptoms subsided within 72 h in 35% and within a week in 74% of patients after one session of treatment. Only two treated patients (6.5%) did not recover versus a 50% failure rate among untreated patients (P = 0.0005). The rate of recovery was not affected by the duration of symptoms before initiation of treatment, or by the patient's age and gender.

Female↗

The influence of a clear layer on near-infrared spectrophotometry measurements using a liquid neonatal head phantom.

It is difficult to test near-infrared spectrophotometry instruments in vivo. Therefore we constructed a liquid phantom which mimics the neonatal head. It consists of a spherical 3.5 mm thick layer of silicone rubber simulating skin and bone and a 0.5 mm thick clear layer of polypropylene imitating cerebrospinal fluid. It acts as container for a liquid solution with Intralipid, 60 micromol l(-1) haemoglobin and yeast. The solution was oxygenated using oxygen and then deoxygenated by the yeast. From the instrumental (Critikon 2020) algorithm, we found that with increasing scattering (0.5%, 1%, 1.5% and 2% Intralipid concentration) the reading was increasingly offset from the expected value of 0 micromol l(-1) by 55.7, 68.6, 76.5 and 80.4 micromol l(-1) (oxyhaemoglobin) and 16.0, 24.4, 29.6 and 31.7 micromol l(-1) (deoxyhaemoglobin). This reduced the range of the oxygen saturation reading from the expected 100% to 31.5, 21.1, 14.3 and 11.5%. Haemoglobin concentration changes were increasingly underestimated by a factor of two to four. For a second algorithm based on the diffusion approximation the offsets were smaller: oxyhaemoglobin 11.4, 17.8, 22.5 and 25.1 micromol l(-1) and deoxyhaemoglobin 1.3, 3.4, 5.2 and 6.0 micromol l(-1). The range of the oxygen saturation reading was higher: 41.3, 29.2, 23.4 and 16.6%. Concentration changes were underestimated by a factor of six to ten. This study demonstrates the need to develop algorithms which take into consideration anatomical structures.

Algorithms↗

Reduction of blood loss and transfusion requirement by aprotinin in posterior lumbar spine fusion.

UNLABELLED: Aprotinin reduces blood loss in many orthopedic procedures. In posterior lumbar spine fusion, blood loss results primarily from large vein bleeding and also occurs after the wound is closed. Seventy-two patients undergoing posterior lumbar spine fusion were randomly assigned to large-dose aprotinin therapy or placebo. All patients donated three units of packed red blood cells (RBCs) preoperatively. Postoperative blood loss was harvested from the surgical wound in patients undergoing two- and/or three-level fusion for reinfusion. The target hematocrit for RBC transfusion was 26% if tolerated. Total (intraoperative and 24 h postoperative) blood loss, transfusion requirements, and percentage of transfused patients per treatment group were significantly smaller in the aprotinin group than in the placebo group (1935 +/- 873 vs 2809 +/- 973 mL per patient [P = 0.007]; 42 vs 95 packed RBCs per group [P = 0.001]; 40% vs 81% per group [P = 0.02]). Hematological assessments showed an identically significant (a) intraoperative increase in both thrombin-antithrombin III complexes (TAT) and in activated factor XII (XIIa) and (b) decrease in activated factor VII (VIIa), indicating a similar significant effect on coagulation in patients of both groups (P = 0.9 for intergroup comparisons of postoperative VIIa, XIIa, and TAT). Intraoperative activation of fibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P < 0.0001 for intergroup comparison of postoperative D-dimer levels). No adverse drug effects (circulatory disturbances, deep venous thrombosis, alteration of serum creatinine) were detected. Although administered intraoperatively, aprotinin treatment dramatically reduced intraoperative and 24-h postoperative blood loss and autologous transfusion requirements but did not change homologous transfusion in posterior lumbar spine fusion. IMPLICATIONS: In our study, aprotinin therapy significantly decreased autologous, but not homologous, transfusion requirements in posterior lumbar spine fusion.

Adult↗

Delayed metastases in skin cancer of the head and neck: the case of the "known primary".

Regional metastases from head and neck cutaneous tumors are uncommon, and most present within 2 years from initial diagnosis. Occasionally such metastases may manifest at a later date, increasing the possibility of being derived from a second noncutaneous primary cancer of the head and neck region. The authors studied the course of disease in patients treated for cutaneous neoplasms manifesting with delayed regional metastases. They evaluated patients treated for cutaneous neoplasms with regional metastases presenting more than 3 years from initial treatment. There were 10 cases of squamous cell carcinoma, one case of basal cell carcinoma, and one case of basosquamous carcinoma. Mean duration from initial diagnosis to presenting neck metastases was 4 years 2 months. Mean overall follow-up is 2 years 5 months, and 3 years for patients alive without disease. Four patients died of unrelated causes and 3 patients died of their disease. Five patients are alive and free of disease. A diligent search for a second primary must always be carried out when neck metastases appear. Yet, delayed regional metastases appearing more than 3 years after resection of skin neoplasms is not uncommon and are usually associated with the primary skin cancer. Prolonged follow-up is essential, even in T1 patients. Patients with regional recurrence should be treated aggressively.

Aged↗

Radiation exposure in spiral computed tomography. Dose distribution and dose reduction.

RATIONALE AND OBJECTIVES: The authors investigate the dose distribution of spiral and conventional computed tomography (CT) with film densitometry and to present a new method of evaluating the possibility of dose savings with spiral CT. METHODS: Films were exposed in a cuboid polymethyl-methacrylate phantom in conventional and spiral scan technique. Axial density profiles were obtained by digitizing the films using a fluorescent light scanner. The ratio of the number of rotations in spiral CT to the number of slices in conventional CT was calculated. RESULTS: In spiral CT with a pitch of 2, the densities in all points were lower than those in corresponding points in spiral CT with a pitch of 1 and in conventional CT with slice distance equal to slice thickness. A pitch of 1.5 in spiral CT led to a dose reduction of 14% to 30% compared with conventional CT. CONCLUSIONS: Increasing the pitch in spiral CT leads to a reduction of both integral dose and absorbed doses within the examined body region. The reduction of the integral dose can be significant, especially in cases where slice overlapping is diagnostically advantageous.

Humans↗

Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors.

Early detection of pathophysiological factors associated with permanent brain damage is a major issue in neonatal medicine. The aim of our study was to evaluate the significance of the CO2 reactivity of cerebral blood flow (CBF) in neonates with perinatal risk factors. Fourteen ventilated neonates with perinatal risk factors (pathological cardiotocogramm, low cord pH, postpartal encephalopathy) were enrolled into this prospective study. The study was performed 18-123 h after birth. CBF was measured using the noninvasive intravenous 133Xe method. Two measurements were taken with a minimal PaCO2-difference of 5 mm Hg. From the two CBF values the CO2 reactivity was calculated. Outcome was evaluated 1 year after birth. The CBF values at a lower PaCO2 ranged from 6.6 to 115. 2 ml/100 g brain issue/min (median = 18.2) and at a higher PaCO2 level from 7.1 to 125.7 ml/100 g brain tissue/min (median = 18.75). The calculated CO2 reactivity ranged from -9.6 to 6.6% (median 1.1%) change in CBF/mm Hg change in PaCO2. CO2 reactivity correlated with lowest pH (r2 = 0.35, p = 0.02). Two infants died, one of neonatal sepsis, the other of heart failure. Neurological outcome at the age of 1 year was normal in 11 patients, 1 had severe cerebral palsy. From the 12 surviving patients the patient with severe neurological deficit showed the highest CBF values (125.7 ml/100 g/min). Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors. CO2 reactivity in these newborns correlates with the lowest pH and may reflect the severity of perinatal asphyxia.

Blood Flow Velocity↗

CO2 reactivity of the cerebral hemoglobin concentration in healthy term newborns measured by near infrared spectrophotometry.

CO2 reactivity of cerebral hemoglobin concentration was studied in 16 healthy term neonates on days 1 and 4 after birth using the near infrared spectrophotometry (NIRS) technique. The aim was to establish data on the physiological range of CO2 reactivity in healthy newborns and to investigate the influence of postnatal age on it. The CO2 reactivity measured by NIRS is expressed as the change of the total cerebral hemoglobin concentration (tHbR) per change of CO2 tension in micromol/l/kPa. We evaluated CO2 reactivity during increases and decreases of transcutaneous CO2 partial pressure and found in our methodological setting the data of the increases more reliable. In all infants but 1 we found a tHbR on day 1 with a mean value of 8.19 micromol/l/kPa (-1.39 to 18.87), in all infants on day 4 with a mean value of 9.54 micromol/l/kPa (2.76-25. 88). There is a trend to higher values between day 1 and day 4 (difference = 2.25 micromol/l/kPa; p = 0.08). The noninvasive NIRS technique enabled us to test the cerebrovascular CO2 reactivity of the tHbR for the first time in healthy term newborns. Data on its physiologic range and variability are presented and compared to findings from ventilated infants and other age groups. As the CO2 reactivity might be an indicator for infants at risk of cerebral damage, it is necessary to have data on the physiological range of this parameter.

Brain↗

An analysis of the suitability of home health visits for telemedicine.

To determine what percentage of traditional home health nursing visits could be done by telemedicine, we carried out a retrospective review of nursing charts (clinical records). Data of two types were recorded. The objective data, which were abstracted from the records, included demographic information, patient assessments, teaching activities and interventions. The subjective data were the opinions of four observers as to whether the visit could have been done using currently available telemedicine technology. Records were sampled randomly for patients who had received home nursing care from three home health agencies in rural and urban areas during the winter and summer of 1996. A 54-item coding instrument was applied to 906 different charted home nursing visits. For 412 (46%) of these, the on-site nursing could reasonably have been replaced by telenursing. Significant factors determining the possible use of telenursing included primary diagnosis, number of interventions and patient age. Among the 10 most common primary diagnoses, the most amenable to telenursing care were chronic airway obstruction and joint disorders; the least amenable were coagulation disorders and anaemia. Telenursing visits could substitute for a substantial fraction of on-site home nursing visits. This has important implications in terms of reducing the cost of home nursing care.

Feasibility Studies↗

Relationships between physical dose quantities and patient dose in CT.

Patient dose in CT is usually expressed in terms of organ dose and effective dose. The latter is used as a measure of the stochastic risk. Determination of these doses by measurements or calculations can be time-consuming. We investigated the efficacy of physical dose quantities to describe the organ dose and effective dose. For various CT examinations of the head, neck and trunk, organ doses and effective doses were determined using conversion factors. Dose free-in-air on the axis of rotation (Dair) and weighted computed tomography dose index (CTDIw) were compared with the absorbed doses of organs which are located totally within the body region examined. Dose-length product (DLP) was compared with the effective dose. The ratio of the organ dose to CTDIw was 1.37 (0.87-1.79) mSv mGy-1. DLP showed a significant correlation with the effective dose (p < 0.005). The average ratio of effective dose to DLP was 0.28 x 10(-2) mSv (mGy cm)-1 for CT of the head, 0.62 x 10(-2) mSv (mGy cm)-1 for CT of the neck and 1.90 x 10(-2) mSv (mGy cm)-1 for CT of the trunk. CTDIw and DLP can be used for estimating the organ dose and effective dose associated with CT examinations of the head, neck and trunk.

Female↗