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L Lehmann

Publications and source records attributed to L Lehmann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Etiological aspects in osteochondritis dissecans patellae.

In a retrospective study probable etiological factors of rare cases of osteochondritis dissecans of the patella were analyzed. Anamnestic data and data obtained from standardized roentgenography in the anterior-posterior, axial, and lateral views of the patella were evaluated. Anamnestic data provided no evidence of the etiology in addition to the fact that several patients mentioned a single or multiple trauma. In contrast to this, evaluation of the roentgenograms showed that most of the patients with osteochondritis patellae exhibited a flat articular surface of the patella (types I and V in Hertel's classification) and a distinct accumulation of the patellae with greater lateral than medial facet (types II and III in Wiberg's classification). Furthermore, the axial shape of the patellar groove exhibited a distinct accumulation of type III trochleae, representing a hypoplasia of the medial and hyperplasia of the lateral part of the trochlea. Evaluation of the lateromedial patellar alignment revealed in a distinct accumulation of grade II dislocation medially and laterally. Although the data were obtained from a rather small number of patients, in our opinion these results support the theory of biomechanical induction of osteochondritis dissecans patellae. Further dynamic analyses are needed to clarify biodynamic effects on the patella and the patellofemoral joint.

Adult↗
PubMed1999

A murine xenograft model for human CD30+ anaplastic large cell lymphoma. Successful growth inhibition with an anti-CD30 antibody (HeFi-1).

To develop a model for the biology and treatment of CD30+ anaplastic large cell lymphoma (ALCL), we transplanted leukemic tumor cells from a 22-month-old girl with multiple relapsed ALCL. Tumor cells were inoculated intraperitoneally into a 4-week-old SCID/bg mouse and produced a disseminated tumor within 8 weeks; this tumor was serially transplanted by subcutaneous injections to other mice. Morphology, immunohistochemistry, and molecular genetics which demonstrated the NPM-ALK fusion protein, resulting from the t(2;5)(p23;q35), confirmed the identity of the xenograft with the original tumor. The tumor produced transcripts for interleukin-1alpha, tumor necrosis factor-alpha, and interferon-gamma which could explain the patient's B-symptoms. Treatment of mice with monoclonal antibody (HeFi-1) which activates CD30 antigen administered on day 1 after tumor transplantation prevented tumor growth. Treatment with HeFi-1 after tumors had reached a 0.2 cm(3) volume caused tumor growth arrest and prevention of tumor dissemination. We conclude that transplantation of CD30+ ALCL to SCID/bg mice may provide a valuable model for the study of the biology and design of treatment modalities for CD30+ ALCL.

Animals↗
PubMed1999

Glycerol accelerates recovery of barrier function in vivo.

Two studies were performed to evaluate the influence of glycerol on the recovery of damaged stratum corneum barrier function. Measurements of transepidermal water loss and capacitance were conducted in a 3-day follow-up after tape stripping (study 1) and a 7-day follow-up after a barrier damage due to a repeated washing with sodium lauryl sulphate. In study 1 a faster barrier repair (transepidermal water loss) was monitored in glycerol-treated sites. Significant differences between glycerol open vs. untreated and glycerol occluded vs. untreated were observed at day 3. Stratum corneum hydration showed significantly higher values in the sites treated with glycerol+occlusion, compared with all other sites. In study 2 a faster barrier repair was seen in glycerol-treated sites, with significant differences against untreated and base-treated sites 7 days after the end of the treatment. Stratum corneum hydration showed highest values in the glycerol treated sites after 3 days of treatment. Glycerol creates a stimulus for barrier repair and improves the stratum corneum hydration; stratum corneum hydration is not strictly related to barrier homeostasis and can be optimized by different mechanisms and pathways. The observed effects were based on the modulation of barrier repair and were not biased by the humectant effect of glycerol. As the glycerol-induced recovery of barrier function and stratum corneum hydration were observed even 7 days after the end of treatment, glycerol can be regarded as a barrier stabilizing and moisturizing compound.

Administration, Topical↗
PubMed1998

Genetic heterogeneity in a prostatic carcinoma and associated prostatic intraepithelial neoplasia as demonstrated by combined use of laser-microdissection, degenerate oligonucleotide primed PCR and comparative genomic hybridization.

We combined laser-assisted microdissection from H&E-stained paraffin sections, degenerated oligonucleotide-primed polymerase chain reaction (DOP-PCR), and comparative genomic hybridization (CGH) to analyse chromosomal imbalances in small tumour areas consisting of 50-100 cells. This approach was used to investigate intratumour genetic heterogeneity in a case of metastatic prostatic adenocarcinoma and chromosomal changes in areas of prostatic intraepithelial neoplasia (PIN) adjacent to the invasive tumour. In four microdissected invasive tumour areas with different histological patterns (acinar, cribriform, papillary and solid) marked intratumour heterogeneity was found by CGH. Recurrent chromosomal imbalances detected in at least two microdissected tumour areas were gains on 1p32-->p36, 2p22, 3q21, 7, 8q21-->q24, 11q12-->q13, 16p12-->p13, 17, 19 and loss on 16q23. Additional chromosomal changes were found in only one of the microdissected areas (gains on 16q21-->q23, 20q22 and losses on 8p21-->p23, 12p11-->q12, 12q21-->q26, 13q21-->q34, 16q12, and 18q22). In PIN, gains on chromosomes 8q21-->q24 and 17 were found in both samples investigated (low and high grade PIN), while gains on chromosomes 7, 11q, 12q, 16p, and 20q and losses on 2p, 8p21-->p23, 12q were found only in one PIN area. Controls to ensure reliable CGH results consisted in CGH analyses of (i) approximately 80 microdissected normal epithelial cells, which showed no aberrations after DOP-PCR and (ii) larger cell numbers (approximately 10(5) or 10(7) cells) of the primary tumour investigated without DOP-PCR and partially displaying the chromosomal imbalances (gain on 16p12-->p13, losses on 2p25, 8p21-->p23, 12p11-->p12, 12q21-->q26, 18q22) found in the small microdissected areas. Microsatellite and FISH analyses further confirmed our CGH results from microdissected cells. The combined approach of laser-assisted microdissection, DOP-PCR and CGH is suitable to identify early genetic changes in PIN and chromosomal imbalances associated with the particular histological patterns of invasive prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Effect of methimazole, with or without L-thyroxine, on remission rates in Graves' disease.

Medical treatment of Graves' disease involves antithyroid drugs with or without the addition of exogenous T4. There have been conflicting reports as to whether the addition of T4 improves remission rates or delays relapse. To evaluate this issue in a North American population, 199 patients were treated with methimazole until they were euthyroid. They were then randomized to either methimazole alone in a dose sufficient to normalize TSH (group 1), or to 30 mg methimazole daily plus sufficient T4 to maintain TSH in the upper normal range (group 2), or to 30 mg methimazole daily plus sufficient T4 to suppress TSH below 0.6 mIU/L (group 3). After 18 months, methimazole was stopped, and T4 was continued in groups 2 and 3. Because not all patients in groups 2 and 3 achieved their target TSH concentration, they were reassigned to group A (TSH > or = 1.0) or group B (TSH < 1.0), based on the mean TSH achieved during methimazole treatment. One hundred forty-nine patients have been followed for at least 6 months after stopping methimazole (mean 27 months). Fifty-eight percent of patients have relapsed. There were no significant differences in relapse rates after stopping methimazole. Among those patients who did relapse, however, there was a significant difference in the months to relapse after stopping methimazole between groups B and 1 (group 1: 3.3 +/- 0.7, group A: 5.6 +/- 0.8, group B: 7.4 +/- 1.7; P = 0.01 for the comparison between groups B and 1). We conclude that the addition of T4 to methimazole does not improve long-term remission rates in Graves' disease.

Adult↗
PubMed1997

p53 mutations in childhood thyroid tumours from Belarus and in thyroid tumours without radiation history.

Mutations in the p53 tumour-suppressor gene (exons 5-8) were investigated in 31 Belarussian childhood thyroid tumours (24 cases of papillary thyroid carcinoma, 3 benign tumours and 2 cases each of thyroiditis and goiter); 33 thyroid tumours from juveniles and adults without radiation exposures (25 carcinomas of various histological types, including 11 papillary carcinomas and 8 adenomas) and 6 tumours from adults (4 papillary carcinomas, 1 adenoma, 1 goiter) served as controls. The mutational spectrum of p53 differed greatly between the childhood thyroid carcinomas from Belarus and the control groups. In the control groups of 29 malignant thyroid tumours, 7 different mutations were detected on exons 5-8, none of which occurred among the 15 papillary carcinomas in this group. Five mutations were found in tissue samples of the 24 childhood papillary carcinomas, and they were all the same p53 point mutation (CGA --> CGG) on codon 213 of exon 6. To determine whether this mutation is simply a polymorphism or whether it is specific to the tumour cells, laser-assisted microdissection was applied to collect various areas of tumorous and non-tumorous cells (10-20 cells per sample) from each paraffin-embedded tissue section of 8 of the papillary thyroid carcinomas. Using PCR-SSCP and sequence analysis on these cells, the very same p53 mutation on codon 213 was detected in various microdissected tumour samples of 2 cases, but it was not found in any microdissected non-tumorous sample. The exclusive occurrence of this p53 mutation in selective microdissected samples of tumour cells, even as homozygous mutation in 1 case, reflects a distinct tumour heterogeneity within papillary childhood thyroid carcinomas.

Adolescent↗
PubMed1997

Cytogenetic and molecular genetic characterization of a chromosome 2 rearrangement in a case of human papillary thyroid carcinoma with radiation history.

Karyotype analysis of a primary culture from a case of papillary thyroid cancer (PTC) showed an abnormal short arm of one homologue of chromosome 2 as sole abnormality in 4 of 16 metaphases. Based on G-banding analysis, two different aberration types on chromosome 2 could be assumed representing either a del(2)(p22-23) or a pericentric inversion. Further comparative genomic hybridization (CGH) analysis as well as fluorescence in situ hybridization (FISH) analysis were performed to confirm the assumed alterations. While CGH analysis showed no loss of chromosome 2 material, FISH with yeast artificial chromosome (YAC) probes homologous to the region 2p22-23 demonstrated two pericentric inversions of chromosome 2 involving different breakpoints on 2p in 6.8% and 4.2% of the metaphases, respectively. Polymerase chain reaction (PCR) analysis with degenerated oligonucleotide primers that bind within the conserved catalytic domain of tyrosine kinase (tk) genes resulted in amplification products with DNA of YAC 851D11 suggesting the presence of such genes at or near the translocation breakpoint.

Adult↗
PubMed1997

Comparative FISH analysis of numerical chromosome 7 abnormalities in 5-micron and 15-micron paraffin-embedded tissue sections from prostatic carcinoma.

Interphase fluorescence in situ hybridization (FISH) was performed on 15-micron-thick paraffin sections from prostatic carcinomas using a chromosome 7-specific alpha-satellite DNA probe. A confocal laser scanning microscope (CLSM) was used for optical sectioning of the thick sections and reconstruction of 3D images. The number of FISH signals was determined by a gallery of optical sections evaluating only complete nuclei. To investiate the influence of section thickness and truncation and nuclei on scoring results, we compared the FISH data from 15-micron sections with signal counts obtained from 5-micron sections. The latter were evaluated by conventional fluorescence microscopy in the same tumor regions previously defined and marked on the slides. After statistical analysis of spot frequencies in tumor and non-tumorous cells (chi 2 test), we transferred the signal frequencies into a cytogenetic classification (-7, +7, polysomy 7). Based on this classification, most cases showed more than one chromosome 7 aberration type. Trisomy 7 (+7) became apparent in 15-micron thick sections in all 19 tumors, polysomy 7 (> 3 spots) in 18/19 cases, and monosomy 7 (-7) in 13/19 cases. In 5-micron sections, however, trisomy 7 and polysomy 7 were found in only 7/19 and 13/19 cases, respectively, and monosomy 7 in 7/19 cases. When comparing the classification results of tumor cells of the same tumor regions originating either from 5-micron or 15-micron sections, the following discrepancies were noted: in 15-micron sections exclusively, in 12/19 tumors, trisomy 7 was found; in 6/19 cases, polysomy 7; in 8/19 cases, monosomy 7. The high proportion of cases with tumor nuclei expressing only one hybridization signal of chromosome 7 in 15-micron sections could be confirmed as monosomy 7 in five selected cases by double-hybridization using centromere-specific probes for chromosomes 7 and 12. These results demonstrate that numerical chromosome 7 aberrations are more frequently observed in thick (15-micron) paraffin-embedded tissue sections by evaluating only complete nuclei. The use of routine sections (5-micron) for interphase cytogenetic analyses is compromised by a remarkable underestimation of the real chromosome copy numbers.

Adenocarcinoma↗
PubMed1997

[Whole body spiral CT in primary diagnosis of patients with multiple trauma in emergency situations].

PURPOSE: The aim of this study was to evaluate the role of a fast whole body helical CT scanner for primary diagnosis in trauma patients. METHODS: 27 severely injured patients (9 women, 18 men; mean age 43 years) were first examined with a helical CT scanner allowing for digital radiograms up to a length of 1024 mm and continuous helical scans of up to 70 seconds (slice thickness 3 to 10 mm, pitch factor up to 2). The primary CT diagnosis was verified either by x-ray after the CT examination or during the subsequent days, by abdominal ultrasound, by additional CT scans in the following days, and by clinical follow-up. RESULTS: CT showed all clinically relevant injuries of the head, spine, chest, abdomen and pelvis. The diagnosis and classification of vertebral fractures was performed immediately. 4% of the fractures of the extremities and the ribs were not seen primarily. 6% of the injuries were outside the CT scan field. CONCLUSION: Helical CT is a reliable and fast method to obtain vital information and to improve management planning in severely injured patients. It reduces the number of conventional x-ray examinations. In certain cases, additional x-rays of extremity fractures may be required.

Abdominal Injuries↗
PubMed1997

Numerical aberrations of chromosome 7 detected in 15 microns paraffin-embedded tissue sections of primary cutaneous melanomas by fluorescence in situ hybridization and confocal laser scanning microscopy.

Fluorescence in situ hybridization (FISH) to sections of formalin-fixed paraffin-embedded archival tissues allows the detection of gene or chromosome copy number changes in interphase cell nuclei within the histological context and thus may be of particular interest in tumor pathology. In this report, we describe the application of FISH to thick (15 microns) paraffin sections of 7 primary cutaneous malignant melanomas. A chromosome 7-specific centromeric DNA probe was used to detect numerical aberrations of chromosome 7. By optical sectioning using confocal laser scanning microscopy (CLSM) only complete, uncut interphase cell nuclei were scored. The mean percentage (+/- SEM) of melanoma cell nuclei with three hybridization spots was (20.7 +/- 2.8)%; (6.8 +/- 1.0)% of nuclei showed one spot and (5.0 +/- 1.2)% four or more spots. The frequency distribution of spot numbers among melanoma cell nuclei and normal keratinocyte nuclei was significantly different (chi(2) = 176.8, df = 5, p < 0.001). Trisomy 7 was detected in all 7 cases analyzed, mostly associated with monosomy 7 or polysomy 7. The approach used in our study and the data obtained could be useful for further studies designed to investigate a possible involvement of chromosome 7 in melanocytic tumor progression.

Adult↗
PubMed1996

Chromosome translocations in thyroid tissues from Belarussian children exposed to radioiodine from the Chernobyl accident, measured by FISH-painting.

Chromosome painting of chromosomes 1, 4 and 12 was performed on metaphase preparations of cultured thyroid cells to analyse the frequency of radiation-induced stable chromosome translocations in papillary thyroid carcinomas from 40 Belarussian children exposed to radioiodine from the Chernobyl accident, and from 31 reference case. As expected, we found the highest translocation frequencies in secondary thyroid tumours after radiotherapy, but there were also high frequencies in tumour tissues as well as in non-tumourous tissues from childhood papillary carcinoma samples from Belarus. Among the Belarussian tumours the cases from the Gomel region exhibited the highest frequency of translocations and five cases lie within the range of frequencies observed in secondary thyroid tumours after radiotherapy. The findings support the assumption that radiation was the principal cause of the tumours in Belarus, but they indicate also that only a minority of the Belarus cases, which have developed papillary carcinomas, were exposed to very high doses of radioiodine.

Adolescent↗
PubMed1996

Effect of methimazole with or without exogenous L-thyroxine on serum concentrations of thyrotropin (TSH) receptor antibodies in patients with Graves' disease.

Medical treatment of Graves' disease involves use of antithyroid drugs with or without the addition of exogenous L-T4. There have been conflicting reports as to whether the addition of T4 reduces TSH receptor antibodies and improves remission rates more than antithyroid drugs alone. To further examine the effect of drug therapy on serum concentrations of TSH receptor antibodies. 70 patients with Graves' disease were treated with methimazole (Tapazole) alone until they were euthyroid. Then they were randomized to receive either: 1) methimazole alone in a dose sufficient to normalize TSH (0.3-5.4 mIU/L; Group 1); 2) 30 mg methimazole daily plus sufficient T4 (Synthroid) to maintain TSH in the high-normal range (2.0-5.4 mIU/L; Group 2); or 3) 30 mg methimazole daily plus sufficient T4 to suppress TSH to below 0.6 mIU/L (Group 3). The duration of treatment in all groups was 18 months. At baseline and after 6 and 18 months, TSH receptor antibodies were measured both by the ability of patients' sera to stimulate cAMP production by FRTL-5 cells (thyroid-stimulating Ig) and by the ability of patients' sera to inhibit binding of radiolabeled TSH to solubilized porcine thyroid membranes (TSH-binding, inhibiting Ig). Thyroid-stimulating Ig(TSI) and TSH-binding, inhibiting Ig(TBII) concentrations were similar among the three groups at baseline. Mean baseline TSI (expressed as the percent of normal control) for all patients combined was 306 +/- 21%. Mean baseline TBII (expressed as percent inhibition of TSH binding) was 38 +/- 2%. TSI was elevated in 85% and TBII was elevated in 75% of patients at baseline. After 18 months, TSI was elevated in 64% of patients, and TBII was elevated in 28%. Serum TSI decreased by 36 +/- 5% during the study, and there was no significant difference in the degree of reduction among the three groups (P = 0.99). Serum TBII decreased by 59 +/- 3%, and there also was no significant difference among the groups (P = 0.83). At baseline, serum TBII correlated with free T4 (r = 0.33, P < 0.01), total T3 (r = 0.55, P < 0.01), and thyroid size (r = 0.35, P < 0.01). There was no correlation between TSI and any of the baseline parameters or between TSI and TBII at any timepoint. In conclusion, we found that the addition of T4 to methimazole does not result in a greater decrease in TSH receptor antibody concentrations than treatment with methimazole alone. From these results, we would predict no difference in remission rates among these patients, but confirmation of this prediction will need to await long-term follow-up of these subjects.

Adolescent↗
PubMed1995

Electrical resistances of interstitial and microvascular space as determinants of the extracellular electrical field and velocity of propagation in ventricular myocardium.

BACKGROUND: In myocardial ventricular tissue, extracellular electrical resistance (ro) is an important determinant of propagation velocity (theta) and the magnitude of the extracellular bipolar electrogram (delta Vo). The extracellular space is composed of two compartments, the vascular space and the interstitial space. To assess the electrical equivalent of this compartmentation in the ventricular myocardium and its effect on ro, theta, and delta Vo, electrical cable analysis was performed in an arterially perfused rabbit papillary muscle. METHODS AND RESULTS: Vascular resistivity was changed from 75 to 86 to 143 and to 221 omega/cm by variation of hematocrit in the perfusate from 0% to 10% to 40% and to 60%. As a means to vary the volume of the interstitial space and with this as its resistivity, colloid osmotic pressure (COP) in the perfusate was changed from 9 to 36 and to 94 mm Hg by altering the dextran concentration in the perfusate from 10 to 40 to 80 g/L. Decreasing COP had a marked effect on ro (56% decrease), delta Vo (decrease from 61 to 42 mV), theta (increase from 48 to 59 cm/s), and the diameter of the muscle fiber (increase of 12%). If COP was increased from 36 to 94 mm Hg, ro (by 35%) and delta Vo (from 62 to 75 mV) increased; theta and diameter showed no significant changes. In contrast, alterations of intravascular electrical resistivity in a range from 75 to 221 omega/cm did not induce any significant changes in ro, delta Vo, theta, and diameter of the preparations. CONCLUSIONS: We conclude from our data that (1) the microvascular tree in ventricular myocardium is electrically insulated to a large degree from the interstitial space and that (2) electrical current flow in the extracellular space during excitation is confined to the narrow, anisotropic interstitial space.

Animals↗
PubMed1995

Suicidal behavior among patients in the VA health care system.

A total of 167 Department of Veterans Affairs medical centers responded to a survey that sought information on suicidal behavior during a one-year period among patients in inpatient or outpatient treatment. Of 248 completed suicides during the period, about 60 percent occurred among patients in outpatient mental health treatment. The incidence of anxiety disorder diagnoses (17.7 percent), particularly posttraumatic stress disorder, among patients who completed suicide was much higher than that reported for persons who completed suicide in the general population. Many patients with psychiatric diagnoses who completed suicide had comorbid substance abuse diagnoses.

Adult↗
PubMed1994

Numerical abnormalities of chromosome 7 in human prostate cancer detected by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections with centromere-specific DNA probes.

Fluorescence in situ hybridization (FISH) using chromosome-specific alpha-satellite DNA probes for chromosomes 7, 8, and 12 was performed on paraffin-embedded tissue sections and touch imprint preparations of 53 cases of human prostate cancer. Subsequent haematoxylin and eosin (H & E) staining of the hybridized tissue sections allowed unambiguous assignment of hybridization signals either to tumour or to non-tumorous parenchyma. Fifty-three cases of human prostate cancer were evaluated for numerical aberrations of chromosome 7. Scoring 200 cells of tumour and non-tumorous parenchyma in each case revealed abnormalities exclusively in tumour parenchyma in 41 cases (77 per cent). Ten of 41 cases (24 per cent) showed trisomy 7, and 15 cases (37 per cent) monosomy 7 or trisomy 7 in combination with monosomy 7, respectively. Sixteen cases (39 per cent) exhibited polysomy 7 in cells of the tumour parenchyma. In the tumour tissue in one case, different polyploid clones (triploid, tetraploid) and polysomy 7 could be identified by double hybridization with chromosome-specific DNA probes for chromosome 7, plus 8 or 12. The indicated numerical aberrations of chromosome 7 were correlated with 78 per cent of advanced pathological stages or poorly differentiated tumours (pT3/4 or G3) of prostate carcinomas. A statistical analysis of the data revealed significant relationships of particular numerical abnormalities of chromosome 7 to different pathological categories (pT, G, pN) of tumour classification. For the T-classification, the frequency of cells carrying polysomy 7 and polysomy 7/+7 increases significantly from pT1 to pT3/4 (P = 0.022).(ABSTRACT TRUNCATED AT 250 WORDS)

Centromere↗