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Biomedical subjects

M L Mlynek

Publications and source records attributed to M L Mlynek.

18 recordsLinked to original sources

Survival rates in patients with differentiated thyroid carcinoma. Influence of postoperative external radiotherapy.

Nine hundred thirty-two patients with papillary and follicular thyroid carcinomas were seen at the Departments of Medicine, Surgery, and Radiology of the University of Essen, Essen, Germany, between 1970 and 1986. In addition to standard treatment by surgery, radioactive iodine and medical thyroid stimulating hormone (TSH) suppression, 346 patients had received conventional external irradiation to the neck (mostly 40-60 Gy) before referral to our institutions, whereas 586 patients had not received radiotherapy. From the follow-up data of these patients, survival rates were calculated separately for tumor Stages T1 (n = 203), T2 (n = 552), and T3/T4 (n = 277) using life-table analysis. Distribution of risk factors (histologic type of tumor, grading of malignancy, presence of distant metastases, age and sex) was similar in all groups with the one exception, that the radiotherapy patients with Stage T3/T4 were older. There was no significant difference in the life expectancy of irradiated and not irradiated patients by Breslow and Mantel-Cox tests. In Stages T1, T2, and T3/T4, 75% of the radiotherapy patients survived for 10.6 +/- 0.32, 11.5 +/- 0.61, and 6.71 +/- 0.85 years, respectively; the figures for the nonirradiated patients were 9.4 +/- 0.17, 10.8 +/- 0.37, and 6.26 +/- 0.51 years, respectively. When survival rates were calculated separately for patients with Stage T3/T4 older and younger than 40 years, there was no obvious effect of radiotherapy in the younger group, whereas in the older patients, improvement of survival by radiation just failed to reach statistical significance (P less than 0.09). In conclusion, this retrospective analysis failed to prove that survival is prolonged in patients with differentiated carcinoma by administration of conventional external radiotherapy after surgery. A benefit to older patients with locally advanced tumors has still to be demonstrated.

Adenocarcinoma↗

[Initial symptoms of malignant thyroid tumors: the effect of age and sex in an iodine-deficient region. Experiences with 1116 patients].

Initial symptoms of thyroid cancer were collected and analysed for 1116 patients with thyroid cancer in an iodine-deficient region, retrospectively for the period 1960-80 (604 patients), prospectively for 1981-87 (512). Using the WHO classification, 56.1% of patients had papillary, 32.7% follicular, 4.8% C-cell, 3.7% anaplastic and 2.7% various other malignant tumours. In 40% of all patients the initial sign had been a solitary intrathyroid nodule. Cervical lymph node swelling as initial sign had been significantly more frequent in men (21.1%) than in women (10.3%; P less than 0.003). In patients aged under 40 years the cervical lymph node signs were three times as common as among those over 50 years. Distant metastases as initial sign of papillary carcinoma were seen only in those over 60 years. Tumour stages T3 and T4 were seen significantly more frequently in over 60-year-old (42.2%) than under 40-year-old (25.1%; P less than 0.001), independent of histological type. Composition and initial signs of this patient cohort in an iodine-deficient region differed only slightly from those in an iodine-rich region.

Age Factors↗

Electron-microscopic characterization of mixed granulated (hybridoid) leucocytes of chronic myeloid leukaemia.

In chronic granulocytic leukaemia, hybridoid leucocytes can regularly be found. Light microscopically they contain a mixture of eosinophilic, basophilic and naphthol AS-D chloroacetate esterase-positive granules. The present study was done to clarify the ultrastructural composition of these cells. It could be clearly shown that in some leukaemic granulocytes primary and secondary eosinophilic as well as basophilic granules occur side by side. There were also basophils with additional tissue mast cell granules. Since normal mast cell granules as well as granules of normal eosinophilic promyelocytes are naphthol AS-D chloroacetate esterase-positive, it would appear possible that mastocytoid as well as primary eosinophilic granules within the leukaemic basophils are responsible for the atypical, granular naphthol AS-D chloroacetate esterase-positivity of these cells. The existence in chronic myeloid leukaemia both of mixed basophilic and eosinophilic granulated leucocytes and of mixed basophilic and mastocytoid granulated leucocytes may suggest a common myeloid precursor of eosinophils, basophils and tissue mast cells. In addition, the hybridoid granulocytes may be considered an expression of a neoplasia-related lineage infidelity.

Basophils↗

Lineage infidelity in chronic myeloid leukemia. Demonstration and significance of hybridoid leukocytes.

Blood smears from 13 cases of chronic myeloid leukemia (CML) were examined for bigranulated (basophil/eosinophil) cells. The cells were stained with May-Grünwald-Giemsa, toluidine blue, Biebrich scarlet, Adams' reaction, and were reacted for KCN-resistant peroxidase in two cases. A sequential stain (toluidine blue/Biebrich scarlet/Adams' reaction) was applied to 50 cells in each case. Hybridoid cells occurred in all cases with varying frequency. Double granulation was not only found in immature, non-segmented cells but often in mature segmented cells. The chimeric cells were difficult to detect with May-Grünwald-Giemsa. Biebrich scarlet and Adams' reaction being superior in this respect to Biebrich scarlet. Some granules that were positive by Adams' reaction did not stain with Biebrich scarlet. This is in sharp contrast to the normal and is, therefore, interpreted as a granule atypicality. Since under normal circumstances, eosinophilic and basophilic granules can be viewed as mutually exclusive markers of the respective granulocytic lineages, the simultaneous occurrence in CML cells of both markers demonstrates lineage infidelity. Until now lineage infidelity has been reported only in immature cells. However, our results show that lineage infidelity also occurs in mature segmented cells. This indicates that the progenitors of these chimeric granulocytes follow false genetic programs producing cells with profound irreversible neoplastic aberrations.

Basophils↗

[Toxoplasmosis after bone marrow transplantation].

An opportunistic infection with Toxoplasma gondii is a rare complication in the immunocompromised host following bone marrow transplantation. In addition to the variability in the clinical picture, difficulty in interpretation of the antibody titers is one of the main obstacles limiting early diagnosis of manifest toxoplasmosis. This report deals with 3 patients out of 86 bone marrow transplant recipients who had manifest toxoplasmosis mainly affecting the central nervous system and cardiac muscle. The clinical picture was that of acute disseminated encephalitis and myocarditis, while the nature of the disease was only disclosed at autopsy.

Adult↗

Mucin in carcinomas of the thyroid.

One hundred forty-two cases of thyroid carcinomas were studied to assess the frequency with which mucinous deposits occur within the neoplastic cells. In contrast to the literature, which contains only a few scattered reports on this topic, the production of mucin by carcinomas of the thyroid was relatively frequently observed in our material. Almost one half of the cases displayed mucinous substances, which occurred in about 50% of the papillary and the medullary carcinomas, 35% of the follicular types, and about 21% of the anaplastic varieties. The amount of mucinous substances varied considerably: 28 cases were weakly positive, 30 cases were moderately positive, and 6 cases were strongly positive. These findings are discussed with respect to diagnostic and differential diagnostic problems, especially with respect to the interpretation of mucinous deposits that occur in metastatic carcinomata.

Adenocarcinoma↗

Relapsing acute non-lymphatic leukemia with changing phenotypes.

Morphological and cytochemical findings in a case of acute myeloid leukemia (AML) with 3 relapses are described. The disease began as a subtype M4 with atypical eosinophils according to the French-American-British (FAB)-classification. At the time of the first relapse, the phenotype had converted into an M2-subtype, while the second relapse presented the picture of an M1-type of acute myeloid leukemia with non-granulated peroxidase-positive blasts. When the third relapse occurred, the diagnosis was again an M4-type of acute myeloid leukemia. The observed changes of the phenotype can be interpreted as an expression of tumor cell heterogeneity, even though the observed emergence of new leukemic clones would be attributed entirely or in part to effects of the applied cytostatic drugs, because tumor cell heterogeneity concerns also the response to therapy, which may result in a growth advantage for certain leukemic subpopulations. In so far, AML behaves like all other human malignant neoplasias. In addition, morphological changes in leukemias such as are reported here, have been observed long before the introduction of cytostatic drugs. Also, the validity of the FAB-classification is discussed in the light of the presented observation. It is concluded that the FAB-classification is not a classification in a strict sense, but merely a crude and simplistic list of subtypes of acute myeloproliferative diseases that is difficult to reproduce and that disregards major aspects of this group of diseases, for instance tumor cell heterogeneity.

Adult↗

[Recognition and significance of hybrid granulocytes in chronic myeloid leukemia].

The demonstration and frequency of mixed granulated, hybrid leukocytes in chronic myeloid leukemia are reported. The cells exhibit basophilic granules, and, in addition, variable quantities of eosinophilic and/or azurophilic (chloroesterase-positive) granules. The existence of further subtypes of granules in these cells, such as neutrophilic or tissue mast cell granules, cannot be excluded thus far. All cases under investigation showed such cells, though in varying frequency. Quality and quantities of the granule population in these cells differed considerably. This is interpreted as an expression of tumor cell heterogeneity, which represents a general criterion of malignant neoplasias. The cells under discussion may be termed hybrid or chimeric, since they are characterized by the co-expression in the same cells of markers (granules) normally subject to lineage specificity. Therefore, the cells represent the phenomenon of "lineage infidelity". Thus far, "lineage infidelity" has been found only with blast cell leukemias, but applies also to chronic myeloid leukemias, as our results show. The occurrence of "lineage infidelity" in segmented end stage cells expresses grave irreversible genetic disturbances of the differentiation program in the progenitors of the hybrid leukocytes.

Basophils↗

Comparative investigations on the specificity of Adams' reaction and the Biebrich scarlet stain for the demonstration of eosinophilic granules.

Since there is some doubt on the specificity of Adams' reaction for eosinophilic granules, the validity of this method has been compared with the Biebrich scarlet stain by means of a subsequent application of both procedures. It was found that the two methods yielded exactly the same results with the same grade of specificity.

Bone Marrow Cells↗

The cytochemical demonstration of cyanide resistant peroxidase does not identify eosinophils selectively.

Potassium cyanide (KCN) resistant peroxidase is generally accepted by hematologists as a selective stain for the eosinophilic cell line. However, it has been demonstrated biochemically that not only the peroxidases of neutrophils but also those of eosinophils can be inhibited by KCN. Therefore, bone marrow smears of hematologically normal patients were subjected to the peroxidase reaction in the presence of varying concentrations of KCN. It was found that with increasing concentrations of KCN not only neutrophils but also eosinophils were inhibited. Moreover, there were always neutrophilic promyelocytes that were still positive when a considerable number of the eosinophils was already inhibited. Therefore, it can be concluded from our results as well as from biochemical data that there is no concentration of KCN which demonstrates the total of the eosinophilic cell line selectively. The implications of these findings are discussed.

Eosinophils↗

Long-term results of prosthetic ureteral replacement in minipigs.

In a 3-year study, silicone rubber prostheses were implanted in 6 minipigs as ureteric replacement. A Dacron velour cuff was applied for the proximal anastomosis and a disc of the same material implanted into the bladder wall to anchor the prosthesis distally. The silicone tube incorporated a metal spiral to prevent kinking. On autopsy all anastomoses were firm and resistant to tearing except in 1 animal where the proximal end of the prosthesis had loosened without further complications. Incrustation or leakage never occurred. On histology dense ingrowth of collagen fibres into the meshes of Dacron velour was evident. Malignant cells could never be demonstrated. The findings are compared with a previous 12-month study. The growth of polypoid structures occluding the prosthesis was found to be a new problem with long-term alloplastic ureteric replacement. The best results were achieved with unilateral prostheses after contralateral nephrectomy.

Animals↗