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Biomedical subjects

A Lange

Publications and source records attributed to A Lange.

At least 73 records · Page 4Linked to original sources
PubMed1999

Multiple courses of high-dose ifosfamide, carboplatin, and etoposide with peripheral-blood progenitor cells and filgrastim for small-cell lung cancer: A feasibility study by the European Group for Blood and Marrow Transplantation.

PURPOSE: To determine the feasibility and safety of multiple sequential courses of high-dose chemotherapy and peripheral-blood progenitor cells (PBPCs) administered in a multicenter setting to patients with small-cell lung cancer. PATIENTS AND METHODS: Sixty-nine patients (limited disease, n = 30; extensive disease, n = 39) treated at 15 European centers were scheduled to receive three courses of high-dose chemotherapy with ifosfamide 10 g/m(2), carboplatin 1200 mg/m(2), and etoposide 1200 mg/m(2) (ICE) divided over 4 days at 28-day intervals. PBPCs were harvested before treatment and mobilized with epirubicin 150 mg/m(2) administered via an intravenous bolus divided over 2 days and filgrastim 5 microg/kg/d administered subcutaneously. RESULTS: The performed leukaphereses (one to five per patient) yielded a median of 16.6 x 10(6)/kg (range, 1.0 to 96.6 x 10(6)/kg) CD34(+) cells, which was sufficient for three reinfusions. Fifty patients (72%) completed the treatment according to schedule. Nine patients completed two courses, and six patients completed one course of treatment. The increase in dose-intensity was 290% that of a standard ICE regimen. The median duration of myelosuppression was similar between courses, namely 4 days (range, 1 to 12 days) for leukocytes less than 0.5 x 10(9)/L and 4 days (range, 0 to 22 days) for thrombocytes less than 20 x 10(9)/L. Febrile neutropenia developed in 66% of courses, severe diarrhea in 14%, mucositis in 10%, and nausea and vomiting in 21% of courses. There were six cases of toxic death (9%), most of which occurred in the first year of accrual and thus were attributable to the learning curve. The antitumor effect of the regimen was reflected in an 86% remission rate (95% confidence interval [CI], 74% to 93%), with 51% of patients achieving a complete response (95% CI, 38% to 63%). Median overall survival was 18 months for patients with limited disease and 11 months for patients with extensive disease. CONCLUSION: This multiple sequential high-dose ICE regimen could be safely administered on a multicenter basis to patients with small-cell lung cancer. The dose-intensity could be increased to 290% that of standard ICE regimen. The benefit of this approach is currently being tested in a randomized trial that aims to double the long-term rate of survival for patients with small-cell lung cancer.

Adult↗
PubMed1999

TNF-alpha and HLA-DR genotyping as potential prognostic markers in pulmonary sarcoidosis.

We have analyzed the HLA-DRB1 alleles and -308 TNF-alpha gene polymorphism in 78 sarcoidosis patients and 50 controls. The sarcoidosis group as a whole did not show any significant correlation with the TNF-A or the HLA-DR alleles compared to the control group. However, the patient subgroups of Löfgren and non-Löfgren sarcoidosis exhibited significant allele associations. In the Löfgren patient group, the TNF-A2 and the HLA-DR3 alleles were represented significantly higher, with a highly significant relative risk resulting from the presence of the TNF-A2 or the HLA-DR3 allele or both. In the non-Löfgren patient group, the phenotype expressing HLA-DR2 and lacking TNF-A2 was significantly higher than in the Löfgren patient group. Due to these significant genetic differences in the subgroups of Löfgren and non-Löfgren sarcoidosis patients, we conclude that the genotyping of these two loci (-308 TNF-alpha promoter polymorphism and HLA-DR) may be of prognostic value for the course of disease in sarcoidosis.

Acute Disease↗
PubMed1998

Three-dimensional echocardiographic evaluation of left ventricular volume: comparison of Doppler myocardial imaging and standard gray-scale imaging with cineventriculography--an in vitro and in vivo study.

BACKGROUND: Standard gray-scale imaging (GSI), three-dimensional (3D) echocardiography has been shown to be superior to two-dimensional echocardiography in measuring left ventricular volume. However, the often relatively poor quality of transthoracic gray-scale data can limit the potential application of this technique. Doppler myocardial imaging (DMI) is a new ultrasound technique that potentially offers higher-quality 3D images with a transthoracic approach than the 3D GSI technique. This study was designed to compare the accuracy of standard GSI and DMI 3D left ventricular volume measurements in vitro and in vivo. METHODS AND RESULTS: In vitro, the minimum and maximum volume of the contracting single-chamber, tissue-mimicking phantom was calculated by using both techniques. In vivo, GSI and DMI 3D left ventricular volume measurements were performed in 16 patients. End-diastolic and end-systolic left ventricular volumes were computed for both techniques and compared with those calculated by cineventriculography. In vitro, both methods tended to underestimate the true phantom volume, but the systematic error was smaller for DMI than for GSI (-1.2% +/- 1.5% vs. -4.3% +/- 3%; p < 0.01) and was more constant in the case of DMI over the range of different sizes of true volume. In vivo, for GSI the end-diastolic volume mean difference was -12.6 ml and the limits of agreement were +/-18 ml, and for DMI the corresponding values were -4.2 and +/- 10.6 ml, respectively. The difference for end-systole was -6.5 +/- 10.6 ml and -1.5 +/- 10 ml for GSI and DMI, respectively. The magnitude of the difference in volume measurement between 3D echocardiography and cineventriculography was significantly smaller when using the Doppler technique. CONCLUSIONS: The results of this in vitro and in vivo study indicate that DMI is superior to GSI as a transthoracic acquisition technique for 3 D volume computation.

Echocardiography, Three-Dimensional↗
PubMed1998

Diagnostic value of transesophageal echocardiography in the assessment of congenitally corrected transposition of the great arteries in adult patients.

This study was designed to evaluate the relative diagnostic values of transthoracic (TTE) and transesophageal (TEE) echocardiography in the assessment of congenitally corrected transposition of the great arteries in adult patients. Twelve patients (mean age 29 years, range 21 to 39 years) with congenitally corrected transposition of the great arteries underwent both TTE and TEE examinations to assess this complex cardiac lesion. Of the 12 patients evaluated, situs solitus and inversus were present in 8 and in 4 patients, respectively. TTE correctly identified atrial situs in only 10 patients, whereas TEE, directly evaluating the morphologic features of either appendage, correctly determined situs in every patient. In all 11 patients with intact inlet ventricular septum, the spatial relationship between the septal leaflets of atrioventricular valves was correctly evaluated by both techniques. However, the chordal attachments of both valves were clearly elucidated by TEE in all patients, whereas TTE could obtain images of these in only three patients. TTE was able to evaluate the discordant connection between the right ventricle and the anterior vessel (aorta) in 10 patients, whereas the connection between the left ventricle and the posterior vessel was clearly shown only in 7 patients. Transesophageal longitudinal planes better elucidated these two discordances in all patients irrespective of the position of the heart in the chest and atrial situs. Four patients had an associated ventricular septal defect (inlet defect in one, perimembranous in two, and muscular in one); the inlet defect was unrestrictive and could be easily detected by either imaging technique, whereas the membranous was detected by TTE and by the horizontal transesophageal planes; the muscular defect was recognized only by TTE. Three patients had an associated pulmonary stenosis; Doppler transthoracic echocardiography showed a left outflow peak gradient of 100 mm Hg in two patients and of 80 mm Hg in one but failed to adequately assess the morphologic features of the stenosis, whose features were clearly visualized by transesophageal longitudinal planes in all patients. In conclusion, in our experience TEE is superior to transthoracic imaging in studying congenitally corrected transposition of the great arteries in adult patients; the horizontal plane is best suited to the evaluation of atrial situs and the atrioventricular junction, whereas the longitudinal plane is most valuable in the study of the morphologic features of the ventriculoarterial connections. These findings should be equally applicable to multiplane transesophageal studies.

Abnormalities, Multiple↗
PubMed1998

Characterisation of coronary atherosclerotic morphology by spectral analysis of radiofrequency signal: in vitro intravascular ultrasound study with histological and radiological validation.

OBJECTIVE: To determine whether spectral analysis of unprocessed radiofrequency (RF) signal offers advantages over standard videodensitometric analysis in identifying the morphology of coronary atherosclerotic plaques. METHODS: 97 regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at 250 MHz. Two different sizes of ROI were identified from scan converted images, and relative amplitudes of different frequency components were analysed from raw data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth (17-42 MHz). RF images were constructed and compared with comparative histology derived from microscopy and radiological techniques in three dimensions. RESULTS: Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral slope was steeper in heavy calcium (-0.45 (0.1)) than in dense fibrotic tissue (-0.31 (0.1)), and maximum power was higher for heavy calcium (-7.7 (2.0)) than for dense fibrotic tissue (-10.2 (3.9)). Maximum power was significantly higher in heavy calcium (-7.7 (2.0) dB) and dense fibrotic tissue (-10.2 (3.9) dB) than in microcalcification (-13.9 (3.8) dB). Y-axis intercept was higher in microcalcification (-5.8 (1.1) dB) than in moderately fibrotic tissue (-11.9 (2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power: moderate -20.2 (1.1) dB, dense -14.7 (3.7) dB; and y-axis intercept: moderate -11.9 (2.0) dB, dense -5.5 (5.4) dB. Different densities of fibrosis, loose, moderate, and dense, were discriminated with both y-axis intercept, spectral slope, and mean power. Lipid could be differentiated from other types of plaque tissue on the basis of spectral slope, lipid -0.17 (0.08). Also y-axis intercept from lipid (-17.6 (3.9)) differed significantly from moderately fibrotic tissue, dense fibrotic tissue, microcalcification, and heavy calcium. No significant differences in any of the measured parameters were seen between the results obtained from small and large ROIs. CONCLUSION: Frequency based spectral analysis of unprocessed ultrasound signal may lead to accurate identification of atherosclerotic plaque morphology.

Calcinosis↗
PubMed1998

Application of microsatellite markers for monitoring of reconstitution pattern in patients after bone marrow transplantation/peripheral blood progenitor cell transplantation.

We present data on application of microsatellite markers for detection of complete vs. mixed chimerism in individuals after bone marrow transplantation (BMT) and peripheral blood progenitor cell transplantation (PBPCT). Genotypes of the peripheral blood or bone marrow cells of three donor/recipient pairs were studied at several microsatellite loci. In two cases we identified complete chimerism in recipients' peripheral blood and bone marrow after transplantation. These two patients were alive with no symptoms of disease relapse and/or transplant rejection long time after BMT or PBPCT. In the third patient we observed mixed chimerism with the prevalence of donor's genotype while she was alive and well and the prevalence of recipient's genotype when she relapsed and required interferonotherapy. Results of our molecular studies correlated with the patients' clinical outcome. We show that molecular detection of mixed chimerism may be used for prediction of relapse in patients after BMT or PBPCT.

Adolescent↗
PubMed1998

Localization of a putative progesterone membrane binding protein in porcine hepatocytes.

A putative membrane bound steroid receptor was localized using a peptide specific antibody. Surprisingly, the distribution of immunocytochemical staining in porcine hepatocytes cells provides evidence for the localization to endomembranes (endoplasmic reticulum, Golgi apparatus). Immunofluorescence experiments with HEK cells, which were transfected with a pcDNA3.1 vector containing the coding sequence of the putative progesterone binding protein shows staining within the cells supporting these results. Additionally, 3H-progesterone binding and glucose-6-phosphatase activity as marker enzyme for endoplasmic reticulum were closely correlated in subcellular fractions of porcine liver cells.

Animals↗
PubMed1998

[XY gonadal dysgenesis (Swyer syndrome) with gonadoblastoma].

This is a case report of 46 xy gonadal dysgenesis (Swyer-syndrome) with bilateral androgen producing gonadoblastoma in streak gonads in a 15-year-old patient. The presenting features were: hypergonadotrophic hypogonadism, male pseudohermaphroditism and virilisation. A hypoplastic uterus with normal looking Fallopian tubes and bilateral adnexal tumors were detected through laparoscopy. A laparotomy was performed and the streak gonads with bilateral gonadoblastoma were removed. This led to a normalisation of serum testosterone and serum beta-HCG levels and an amelioration of signs of virilisation. Uterus and fallopian tubes were conserved during the operation. A second look laparoscopy 6 months later showed no evidence of recurrent tumor. No mutation were found in the sex-determining gene (SRY) on DNA-screening using SSCP assay.

Adolescent↗
PubMed1998

Confirmatory typing results of the National Polish Bone Marrow Donors Registry.

Preliminary analysis of HLA class I typing of 618 individuals (patients and healthy members of 153 families) referred to the National Polish Bone Marrow Donors Registry (NPBMDR) for a donor search revealed that the number of undetected locus A and B antigens was more frequent than it was reported in a large scale population study in Poland (0.28 vs 0.076, p=0.000). This was associated with a lack of typing of family members for 51 out of 153 patients. 171 individuals primary typed (140 by serology and 31 by DNA typing) in 6 different Polish institutions were retyped in our laboratory with the use of PCR-SSO or PCR-SSP techniques. The results were discrepant in 50 cases (29%) including 19 patients and 31 family members. In 46% one DR specificity was missing, false typing of one or two specificities was evident in 46% and 14% of erroneous typing, respectively. The highest rate of errors was found in DRw52 group of specificities with the most difficult DR13 (32% of all false typing and 67% of errors within DRw52 group).

Bone Marrow↗
PubMed1997

20-Hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C.

20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 metabolite of arachidonic acid, is a potent vasoconstrictor, and has been implicated in the myogenic activation of renal and cerebral arteries. We examined the role of protein kinase C (PKC) in the signal transduction pathway by which 20-HETE induces vasoconstriction and inhibition of whole-cell K+ current in cat cerebral vascular smooth muscle. 20-HETE induced a concentration-dependent constriction in isolated pressurized cat middle cerebral arteries (-29 +/- 8% at 1 microM). However, in the presence of an N-myristoylated PKC pseudosubstrate inhibitor peptide (MyrPsiPKC-I(19-27)), 20-HETE induced a concentration-dependent vasodilation (26 +/- 4% at 1 microM). In whole-cell voltage clamp studies, application of 20-HETE inhibited whole-cell K+ current recorded in cat cerebral vascular smooth muscle cells, an effect that was attenuated by MyrPsiPKC-I(19-27). Further evidence for the role of PKC activation in response to 20-HETE is the finding that 20-HETE increased the phosphorylation of myristoylated, alanine-rich PKC substrate in cultured cat cerebral vascular smooth muscle cells in a concentration- and PKC-dependent manner. These data provide evidence that PKC is an integral part of the signal transduction pathway by which 20-HETE elicits vasoconstriction of cerebral arteries and inhibition of whole-cell K+ current in cat cerebral vascular smooth muscle.

Animals↗
PubMed1997

[Acute chloroquine poisoning].

HISTORY: After a quarrel with her husband a 50-year-old woman swallowed, together with some alcohol, 15 tablets of a chloroquine preparation (3.75 g chloroquine phosphate) with suicidal intent. She had no known psychiatric history. CLINICAL FINDINGS: An emergency physician called by the husband two hours after the tablet ingestion found her to be deeply comatose. After preventive nasotracheal intubation she had a grand mal seizure. On advice from a Poison Emergency Centre which was contacted while in the patient's apartment diazepam, 60 mg as a bolus, was injected intravenously, and controlled respiration was started. COURSE: After admission in hospital, gastrolavage was performed and diazepam therapy was continued with 40 mg per hour, gradually reduced until discontinued after 45 hours. The patient was transferred to an ordinary ward from the intensive care unit on the fifth day, without cardiac or neurological sequelae. CONCLUSION: The most important measures after a diagnosis of chloroquine poisoning are immediate intubation so that diazepam (1 mg/kg) can be administered intravenously as specific antidote without danger of severe respiratory failure.

Anticonvulsants↗