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Biomedical subjects

L Steinholtz

Publications and source records attributed to L Steinholtz.

12 recordsLinked to original sources

Neutrophil function in chronic bronchitis.

This study was initiated with the question: Do defects in neutrophil functions predispose patients with chronic bronchitis to their recurrent bacterial infections? Forty five patients with chronic bronchitis and recurrent bacterial infections were studied. A number of aspects of neutrophil functions reflecting migratory and phagocytic functions and oxidative metabolism were measured in vitro, once in all 45 patients and 3 times in 22 patients over a period of 6 months. A great number of abnormalities was found on the first occasion with a complete normalization for all variables except one at the end of the observation period. The number of infectious exacerbations was significantly higher (p less than 0.05) at the start of the observation period i.e. October-November, as compared to the end, i.e. April-May. The oxidative metabolism, as reflected by lucigenin-enhanced chemiluminescence, was significantly reduced (p less than 0.001) also at the period of few infections, suggesting a primary defect of the neutrophil. Smoking was shown to adversely affect luminol-enhanced chemiluminescence and the chemokinetic activity of the patients' cells. We conclude that most variables were altered in a way which was anticipated from the study of individuals with acute bacterial infections. The probable primary defect in oxidative metabolism of the neutrophils in addition to the acquired defects as a consequence of smoking may add to the predisposition of some individuals to their recurrent bacterial infections.

Adult↗

Neuron-specific enolase as a follow-up marker in small cell bronchial carcinoma. A prospective study in an unselected series.

The value of measurement of serum neuron-specific enolase (NSE) as a follow-up marker was investigated in 88 patients with small cell bronchial carcinoma. Of these, 42 had extensive disease and 46 had limited disease. The mean NSE levels before treatment, at response, and at recurrence in extensive disease were 107, 10, and 52 ng/ml, respectively, and the corresponding levels in limited disease were 35, 10, and 19 ng/ml, respectively. All differences were statistically clearly significant. However, the sensitivity of NSE in serum at response was 66% and at recurrence, 38%. The predictive value of an NSE decrease at response was 88%, and at recurrence, 72%. It is concluded that NSE changes during follow-up support the evaluation of the outcome but cannot be used as a monitoring agent in an individual patient.

Adult↗

Local failure in patients treated with radiotherapy and multidrug chemotherapy for small cell lung cancer.

Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumour. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than +/- 5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases.

Adult↗

Increased expression of N-myc in human small cell lung cancer biopsies predicts lack of response to chemotherapy and poor prognosis.

Amplified and increased expression of the myc family of protooncogenes (c- and N-myc) has been described to be associated with rapid proliferation in a number of cell lines, including small cell lung cancer (SCLC). In SCLC, c-myc was demonstrated to be amplified in a subset of SCLC cell lines denoted as variant type, which show a more aggressive way of growth in vitro. The N-myc oncogene, which has extensive homology in the second exon with c-myc, has been shown to be implicated in the oncogenesis of several primary tumors, including SCLC. The authors describe, using in situ hybridization, that increased expression of the N-myc oncogenes in primary biopsies from 15 untreated patients with SCLC are strongly associated with poor response to chemotherapy, rapid tumor growth, and short survival.

Adult↗

Serum deoxythymidine kinase in small cell carcinoma of the lung. Relation to clinical features, prognosis, and other biochemical markers.

Thymidine kinase (s-TK), lactate dehydrogenase (LDH), and carcinoembryonic antigen (CEA) were determined in pretreatment serum from 125 patients with small cell carcinoma of the lung. The distribution of marker levels into three ranges, when including all patients were as follows: s-TK less than 5 units 49%, 5-less than 10 units 25%, greater than or equal to 10 units 26%; LDH less than 6.7 mukat 31%, 6.7-less than 13.4 mukat 48%, greater than or equal to 13.4 mukat 21%; CEA less than 7.5 micrograms/l 51%, 7.5-less than 15 micrograms/l 25%, greater than or equal to 15 micrograms/l 24%. The percentages of patients with limited and with extensive disease within each range were s-TK less than 5 82/18, 5-less than 10 29/71, greater than or equal to 10 9/91; LDH less than 6.7 76/24, 6.7-less than 13.4 51/49, greater than or equal to 13.4 21/79; CEA less than 7.5 70/30, 7.5-less than 15 39/61, greater than or equal to 15 23/77. Analyses in relation to metastases present showed that patients with skeletal and bone marrow metastases had significantly higher s-TK and LDH than those without, while this was not the case for CEA. A strong correlation between s-TK and LDH level, a weaker correlation between CEA and s-TK, and no correlation between CEA and LDH level, was found. Both the level of s-TK and LDH correlated to the patients' performance, as defined by the Karnofsky index. These correlations were mainly confined to the patients with extensive disease. Analyses of the prognostic capacity of variables showed that s-TK, stage, and Karnofsky index could divide the patients into groups with highly significant difference in survival time, while LDH and CEA were of less value. Longitudinal studies showed that the serum markers mirrored the disease activity, with the exception that highly increased s-TK was found during remission induction for some patients. It was concluded that the expression of pathologic levels for the serum markers were dependent on different biological parameters. Of the serum markers, only s-TK was judged useful for estimation of disease spread and prognosis of the individual patient.

Actuarial Analysis↗

Corynebacterium parvum in malignant pleural effusion. A randomized prospective study.

In a randomized trial, pleurodesis was attempted with Corynebacterium parvum in one group and bleomycin in another. Patients with malignant pleural effusion which required repeated drainage were treated with instillation of one of these agents after complete drainage of the pleural effusion. There were 32 patients who could be evaluated. Sixty-five per cent of the patients treated with C. parvum had no recurrence after one treatment and another 29% after two treatments. In the bleomycin group, two patients needed only one treatment while the remainder - 13 out of 15 patients - needed further drainage treatments even after two instillations of the drug. The difference was highly significant (p less than 0.001).

Adjuvants, Immunologic↗

Immunocytochemical demonstration of neuron-specific enolase (NSE) in human lung cancers.

An anti-serum against human neuron-specific enolase (NSE), raised in sheep, has been characterized and used for immunocytochemical localization of NSE in paraffin sections of normal tissues and lung cancers. Of the small cell carcinomas (SCC), 69 out of 99 (70%) cases stained with the anti-serum. Maltreated biopsies showed a lower frequency of positive staining (19/39), indicating the importance of well-preserved biopsies. There was no clear difference in the staining between the oat cell and intermediate cell type of SCC. A majority (14 out of 21) of the non-SCC:s (large cell, adenocarcinoma and squamous cell carcinoma) were also stained by the anti-serum. Generally, this staining was weak and it could be blocked by preabsorption of the anti-serum by purified NSE. It is concluded that NSE expression, in conjunction with traditional histology, serves as a useful but not exclusive marker for SCC.

Adenocarcinoma↗

Neurone specific enolase: a useful diagnostic serum marker for small cell carcinoma of the lung.

Among lung cancers small cell carcinoma is the most sensitive to chemotherapy and radiation. This has emphasised the importance of an accurate diagnosis of this cell type, and the present study examined the use of serum neurone specific enolase (NSE) as a diagnostic marker for small cell carcinoma. NSE was measured in pretreatment sera from 103 patients with small cell carcinoma and in sera from relevant controls, including patients with other lung cancers, non-malignant lung diseases, and healthy adults. Serum NSE concentration was raised (greater than 25 ng/ml) in 72% of patients with small cell carcinoma. Ninety one per cent of patients with extensive disease and 50% of patients with limited disease were serum NSE positive. Patients with extensive disease in general had higher serum NSE concentrations than patients with limited disease. No definite difference in serum NSE positivity could be shown between oat cell and intermediate cell subtypes. Out of 51 patients with other lung cancers, four (8%) had a raised serum concentration, whereas all patients with non-malignant diseases and healthy individuals had normal serum NSE concentrations. Serum NSE determination seems to be a valuable tool for the diagnosis of small cell carcinoma.

Adult↗

Neuron-specific enolase as a marker for neuroblastoma and small-cell carcinoma of the lung.

The use of neuron-specific enolase (NSE, E.C. 4.2.1.11) as a clinical marker for neuroblastoma and small-cell carcinoma of lung (SCCL) is presented. Both tumors have a high content of NSE as demonstrated enzymatically or by immunocytochemistry. Other retroperitoneal tumors in children and other lung tumors had insignificant NSE concentrations. NSE can thus be used in the differential diagnosis of neuroblastoma and SCCL. 73% of patients with SCCL had elevated serum NSE levels. The corresponding figure for patients with other types of lung cancer was 3%. There was a good correlation between serum NSE levels and the clinical course of patients with SCCL.

Adult↗

Freeze fracturing of the human stria vascularis.

The stria vascularis is an important functional element in the mammalian cochlea. This special tissue is considered to be the source of the endocochlear potential and thus the driving force for the production of a receptor response to the auditory stimulus. In order to maintain its function, the stria vascularis needs to be separated from the endolymphatic space by a tight seal. This seal is comprised of tight junctions in the marginal cell layer. The junctional arrangement in the stria vascularis is described, utilizing the freeze-fracturing technique which allows the visualization of large expansions of plasma membrane. The marginal cells are generally separated by tight junctions of the moderately tight to tight type. In places, however, even so-called leaky junctions with only a few sealing strands are present. Whereas the intermediate cell layer seems to lack tight junctions, the basal cells are connected by extensive tight junctions more or less covering the entire cell. These junctions seem to form an extremely tight barrier against the spiral ligament. Gap junctions are also present in the tissue. Intermediate cells as well as the basal cells are coupled by gap junctions. In the basal cell layer, gap junctional elements may also be found inside the large tight junctions comprising so-called mixed junctions.

Adult↗

Neuron-specific enolase in small-cell carcinoma of the lung: the value of combined immunocytochemistry and serum determination.

The value of neuron-specific enolase (NSE) as a marker for small-cell carcinoma of the lung has been the subject of several reports. Taken together, about 70 per cent of patients with small-cell carcinoma had a raised serum concentration of NSE, and in a majority of patients NSE could be detected immunocytochemically in tumor biopsy speciments. This study examined the diagnostic value of combined immunocytochemical detection and serum determination of NSE in 96 unselected patients with small-cell carcinoma. Seventy-one patients had raised serum concentrations and in 69 a positive immunoreaction for NSE was demonstrated in the biopsy cells. However, for 87 (91%) of the patients, both or either of the NSE assays were positive. The combined use of immunocytochemistry and serum determinations thus gave better information on tumor NSE expression than either method alone. When patients with small or mechanically maltreated biopsy specimens were excluded, the accuracy of the combined assays was even higher (47/49, 96%). We therefore conclude that NSE, although not a specific marker for small-cell carcinoma of the lung, is useful as a complement to conventional diagnostic procedures and, when assayed both in biopsy material and in patient sera, tumor NSE expression can be demonstrated with a high precision.

Biomarkers, Tumor↗