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Biomedical subjects

L Specht

Publications and source records attributed to L Specht.

At least 37 records · Page 2Linked to original sources
PubMed1992

Tumour burden as the main indicator of prognosis in Hodgkin's disease.

A method of estimating the total tumour burden in patients with Hodgkin's disease was devised, combining the number of involved regions with the tumour size in each region. Further, a method of estimating the total tumour cell burden was devised, combining the estimate of the total macroscopic tumour burden with an estimate of the concentration of tumour cells in the tumour tissue. The prognostic significance of the total tumour burden was examined in multivariate studies of 300 patients in pathological stages I and II treated in the Danish National Hodgkin Study and 506 patients in all stages treated at the Finsen Institute, Copenhagen, Denmark, during a 15-year period. The total tumour burden turned out to be the most important prognostic factor in Hodgkin's disease. Most of the hitherto known prognostic factors were shown to be correlated with the total tumour burden and to lack independent prognostic significance.

Hodgkin Disease↗
PubMed1992

Radiotherapy versus combined modality in early stages.

In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a global metaanalysis of these trials indicate that we still do not definitively know whether or not the addition of prophylactic chemotherapy up front improves survival. Arguments in favour of the addition of chemotherapy up front are: that laparotomy may be avoided, that radiation fields and doses may perhaps be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against the use of chemotherapy up front is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may be kept at a minimum. Recently, trials have been carried out testing chemotherapy alone. The results of these trials are however conflicting. In order not to jeopardize the good results achieved with the standard treatments developed over the last three decades, newer treatment approaches should be carefully tested in large randomized trials before being implemented for general clinical use.

Combined Modality Therapy↗
PubMed1992

Differential glucocorticoid effects on the fusion of Duchenne/Becker and control muscle cultures: pharmacologic detection of accelerated aging in dystrophic muscle.

We report that the glucocorticoid methylprednisolone (Mepd) enhanced myogenesis in normal primary human muscle cultures, but inhibited myogenesis of most Duchenne/Becker muscle cultures. A decline in the magnitude of myogenic stimulation of Mepd correlated with age in a random group of control patients, including some with neurologic diseases other than Duchenne/Becker dystrophy. A case of Duchenne muscular dystrophy from an exceptionally young patient yielded a muscle culture that was myogenically stimulated by Mepd. These results suggest that continuous cycles of degeneration and regeneration of dystrophic muscle in vivo may result in a change of the glucocorticoid response of the muscle progenitor cells. The glucocorticoid effects suggest caution in the long-term clinical use of these agents for muscle disease such as Duchenne muscular dystrophy.

Adolescent↗
PubMed1991

Locomotor problems in infantile facioscapulohumeral muscular dystrophy. Retrospective study of 9 patients.

A retrospective study of 9 patients with infantile facioscapulohumeral muscular dystrophy defines orthopedic deformities and progression. Patients presented in the early months of life with facial diplegia. Sensorineural hearing loss occurred in 8 out of 9 with a mean onset at 5 (2-9) years. Walking began at the normal time, but worsened progressively, which was due mainly to gluteus maximus muscle weakness. Scapular winging, extreme lumbar lordosis, and foot drop were characteristic. The majority of patients (in this and other series) lose walking ability in the second decade. Efforts to control lumbar lordosis by bracing while the patients were still walking were ineffective. Control of lumbar lordosis after the patients are wheelchair-dependent is important.

Adolescent↗
PubMed1991

Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies.

Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels.

Adolescent↗
PubMed1990

Tumor cell concentration and tumor burden in relation to histopathologic subtype and other prognostic factors in early stage Hodgkin's disease. The Danish National Hodgkin Study Group.

Prognostic factors were examined by multivariate analysis after a recent follow-up of the 300 patients with Hodgkin's disease pathologic stage (PS) I or II treated with radiotherapy +/- adjuvant combination chemotherapy in the prospective randomized trial of the Danish National Hodgkin Study. Initial biopsy material was classified according to the Rye histopathologic classification, the grading and subclassification proposed by the British National Lymphoma Investigation (BNLI), and tumor cell concentration in sections. Tumor cell concentration as a prognostic factor turned out to be better than the other classifications. However, if macroscopic tumor burden was taken into account both tumor cell concentration and the other histopathologic classification systems lost their prognostic significance. Significantly, however, a combination of macroscopic tumor burden and tumor cell concentration, yielding an estimate of the total tumor cell burden, was even better than the macroscopic tumor burden as a prognostic factor. In conclusion, a simple tumor cell concentration count seems to be the most useful form of histopathologic subtyping for prognostic purposes in early stage Hodgkin's disease.

Hodgkin Disease↗
PubMed1990

Defective dystrophin in Duchenne and Becker dystrophy myotubes in cell culture.

We examined normal and dystrophic human myotubes in cell culture for expression of dystrophin, the protein product of the Duchenne muscular dystrophy locus. Dystrophin levels in developing myotubes detected by Western blotting increased after 24 hours and reached maximum levels after 10 days in fusion medium. We did not detect dystrophin in myotubes cultured from Duchenne myoblasts (7 cases). Myotubes from a Becker muscular dystrophy patient's biopsy produced a lower molecular weight (approximately 408 kd) dystrophin, which was the same size in a whole muscle preparation from the same biopsy. This 408-kd dystrophin was the expected size for this Becker patient whose DNA was deleted for exons 45-48 of the Duchenne gene. This cell culture system will allow a detailed analysis of the effects of potential pharmacologic agents on steady-state dystrophin levels.

Adult↗
PubMed1989

[Hodgkin's disease--a histologic problem].

Since the Rye classification of Hodgkin's disease, many lesions which resemble Hodgkin's disease microscopically have been described. The histological features of Hodgkin's disease, including the BNLI subclassification of nodular sclerosis, and the lesions which resemble Hodgkin's disease microscopically such as reactive lymph node hyperplasias, some non-Hodgkin's B- and T-cell lymphomas are reviewed. Recent reclassifications of lymphomas originally diagnosed as Hodgkin's disease have indicated that the disease was overdiagnosed, before the description of these lesions and before the development of monoclonal antibodies.

Hodgkin Disease↗
PubMed1989

Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease.

Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in antibody response was compared to the findings in 12 healthy volunteers with the aim of establishing the optimal time for vaccination. Serum antibodies against 6 of the pneumococcal polysaccharide antigens (types 1, 4, 7F, 14, 18C and 23F) contained in the vaccine were determined by an ELISA. Antibody response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response.

Adolescent↗
PubMed1989

Hodgkin's disease and age.

506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic nodal tumour burden, intraabdominal nodal tumour burden, and number of involved extranodal sites), pretreatment ESR, lymphocytopenia, and treatment modality were examined in multivariate analyses. The only factors of independent prognostic significance for disease-free survival proved to be treatment modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate treatment for relapse. The present study indicates that Hodgkin's disease in older patients is not prognostically very different from Hodgkin's disease in younger patients.

Adolescent↗
PubMed1988

Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy.

A deficiency of the protein dystrophin has recently been shown to be the probable cause of Duchenne's muscular dystrophy. We sought to determine the relation between the clinical phenotype and the status of dystrophin in muscle-biopsy specimens from 103 patients with various neuromuscular disorders. We found very low levels (less than 3 percent of normal levels) or no dystrophin in the severe Duchenne phenotype (35 of 38 patients), low concentrations of dystrophin in the intermediate (outlier) phenotype (4 of 7), and dystrophin of abnormal molecular weight in the mild Becker phenotype (12 of 18). Normal levels of dystrophin of normal molecular weight were found in nearly all the patients (38 of 40) with 20 other neuromuscular disorders we studied. These data show the clinical consequences of both quantitative alterations (in Duchenne's and intermediate dystrophy) in a single protein. The biochemical assay for dystrophin should prove helpful in delineating myopathies that overlap clinically with Duchenne's and Becker's dystrophies, and it shows promise as an accurate diagnostic tool.

Adolescent↗
PubMed1988

Tumor burden as the most important prognostic factor in early stage Hodgkin's disease. Relations to other prognostic factors and implications for choice of treatment.

Two hundred ninety patients with Hodgkin's disease pathologic stage (PS) I or II were treated in the prospective randomized trial of the Danish National Hodgkin Study (see Appendix) with radiotherapy +/- adjuvant combination chemotherapy. The initial tumor burden of each patient was assessed, combining tumor size of each involved region and number of regions involved. Multivariate analyses of prognostic factors including treatment, tumor burden, histologic subtype, pathologic stage, number of involved regions, mediastinal size, systemic symptoms, erythrocyte sedimentation rate (ESR), sex, and age were carried out. With regard to disease-free survival tumor burden was by far the most important prognostic factor for patients treated with adjuvant chemotherapy as well as for patients treated with radiotherapy alone. With regard to survival from Hodgkin's disease only tumor burden and age were independently significant. A combination of tumor burden, histologic subtype, and sex singled out patients with a high relapse rate both after radiotherapy only, and after radiotherapy plus chemotherapy. This combination also singled out patients destined to die from Hodgkin's disease more accurately than other prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Prognostic factors in Hodgkin's disease stage IV.

104 patients with previously untreated Hodgkin's disease stage IV were examined and treated at the Finsen Institute between 1969 and 1983. 99 patients were treated with combination chemotherapy (MOPP or equivalent regiments) with or without additional irradiation of some involved areas. Prognostic factors including age, sex, peripheral plus intrathoracic nodal tumour burden, intraabdominal nodal tumour burden, B-symptoms, histologic subtype, number of involved nodal regions, mediastinal involvement, number of involved extranodal sites, type of extranodal involvement, ESR, and haematologic and other blood values, together with exploratory laparotomy and treatment were examined in multivariate analyses. With regard to disease-free survival, the only factors of independent prognostic significance were sex and lymphocytopenia. With regard to overall survival the factors of independent significance were age, sex, bone marrow involvement, and an elevated serum creatinine. If only deaths of Hodgkin's disease were considered in overall survival, both lymphocytopenia and bone marrow involvement had independent prognostic significance. These two factors thus emerged as the most important prognostic factors in disseminated Hodgkin's disease, and both would appear to be related to the patient's total tumour burden.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Hodgkin's disease stages I and II with infradiaphragmatic presentation: a rare and prognostically unfavourable combination.

Out of 323 patients with Hodgkin's disease CS I or II treated during the period 1969 to 1983 at Denmark's Finsen Institute, 35 presented with infradiaphragmatic disease. Patients with infradiaphragmatic presentation were older than patients with supradiaphragmatic presentation and were more often in stage II as opposed to stage I. NS histology was less prevalent among infradiaphragmatic than among supradiaphragmatic patients. Disease-free survival and overall survival was poorer in infradiaphragmatic patients. When other factors of prognostic importance were taken into account in a multivariate analysis, infradiaphragmatic presentation turned out to be an adverse prognostic factor with regard to disease-free survival, whereas it was not of significant independent prognostic value with regard to overall survival. Staging laparotomy in 11/35 infradiaphragmatic patients revealed 1 stage-IV case. The 34 remaining early stage patients were treated by irradiation plus combination chemotherapy (21 patients), irradiation only (9 patients), or combination chemotherapy only (4 patients). They were followed until death or from 4 to 171 months after initiation of therapy. With regard to disease-free survival, combined modality treatment (as opposed to radiotherapy only) was found to be of prognostic significance.

Adult↗