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Biomedical subjects

M Winkelmann

Publications and source records attributed to M Winkelmann.

At least 37 records · Page 2Linked to original sources
PubMed1987

Significance of polyploidy in megakaryocytes and other cells in health and tumor disease.

Polyploidy--the doubling of chromosome sets of cells caused by a stop of mitosis at different levels of the mitotic cycle--is a phenomenon widely observed in plants, protozoa, metazoa, and animals. In man obligate polyploid tissues are found in liver parenchyma, heart muscle cells, and bone marrow megakaryocytes. Polyploidy occurs mostly in stable and highly differentiated cells and tissues. Besides age, stimulation of proliferation and increased metabolic function lead to polyploidization in these organs. Aneuploidy, however, is exclusively found in tumor cells. Megakaryocyte differentiation and polyploidy are controlled by thrombopoietin-like activities, of which the loci of production are still unknown. Megakaryocytes are unique among polyploid mammal cells. On the precursor level they maintain their proliferative activity independently of the mammal's age. Once having entered the incomplete mitotic cycle they stop cytokinesis and develop into highly polyploid cells. Polyploidization of megakaryocytes is the basic requirement for establishing highly effective hemostasis in mammals, which exhibit blood circulation based on high blood pressures. Every polyploidization results in increased production of membrane materials with which the platelet becomes endowed. By shedding cytoplasmic fragments approximately 3000 platelets are set free from a 32c megakaryocyte, compared with only 16 nucleated thrombocytes by mitotic division. There is further evidence that the heterogeneity of platelets mostly depends on the different polyploidy classes of the megakaryocytes from which they are derived. Changes in the polyploidy pattern of megakaryocytes could therefore have consequences for hemostatic disorders in several human diseases, particularly in malignancy.

Humans↗
PubMed1987

Acute myelofibrosis in megakaryoblastic leukemia with translocation between chromosomes 8 and 14.

In a 45-year-old woman with severe normochromic anemia (Hb 2.8 g%) an extensive myelofibrosis and infiltration of the bone marrow with small blasts was observed histologically. Cytochemical examination of the blasts showed a negative peroxidase and a strongly positive alpha-NE reaction. PAS reaction was slightly granular positive in the cytoplasmic protuberances of the blasts and in the platelets. Marker analysis yielded no evidence of lymphatic origin of the blasts. In flow-cytometric studies of 230,000 cells a homogeneous 2c blast population could be identified. Cytogenetic analysis revealed an abnormal pseudo-diploid karyotype characterized by 2 acrocentric marker chromosomes caused by a translocation of chromosomes 8 and 14, as usually seen in Burkitt type lymphoma. Finally the reaction product of platelet-specific peroxidase could be demonstrated in the perinuclear cisternae of the endoplasmic reticulum by electron microscopy. Highly elevated beta-thromboglobulin and platelet factor 4 plasma levels were also measured. Following an ineffective treatment with daunoblastine and ARA-C, the patient died of pseudomonas aeruginosa septicemia after having received high-dose ARA-C treatment.

Biopsy, Needle↗
PubMed1987

Correlation of abdominal CT imaging with autopsy findings in patients with malignant tumors.

The value of abdominal computed tomography (CT) in diagnosing localized involvement of liver, pancreas, adrenals, and lymph nodes was evaluated in 117 patients with suspected or known malignant tumors by correlation with autopsy findings. Sensitivity, specificity, and accuracy of CT for localized liver disease was calculated to be 80% (84%), 96% (97%), and 90% (92%); for pancreatic tumors: 81% (86%), 98% (100%), and 95% (97%); for adrenal tumors: 65% (92%), 100% (100%), and 92% (98%); and for lymph node enlargement 75 (88%), 97% (98%), and 87% (94%), respectively. Results of routine evaluation could be improved, especially in the adrenal region, when scans were reevaluated by highly experienced examiners (results given in parenthesis). Computed tomography is a highly valuable diagnostic tool in the primary diagnosis and in the follow-up of tumor patients. The high costs are offset by a reduction in invasive procedures and a shortened hospital stay.

Abdominal Neoplasms↗
PubMed1986

Severe hemolysis caused by antibodies against the mushroom Paxillus involutus and its therapy by plasma exchange.

It has been shown that fatal "poisoning" with the mushroom species Paxillus involutus is caused by antibodies against the fungus in sensitized patients. Because circulating immune complexes play an important role, therapeutic procedures which can eliminate those complexes could stop immune hemolysis. A 37-year-old patient became severely ill after repeated ingestion of sufficiently cooked Paxillus involutus. As a result of hemolysis with reversible shock symptoms, acute renal failure developed. Plasma exchange with 3,000 ml albumin 5% was carried out daily during the first 3 days after admission. Each plasma exchange lowered free hemoglobin and immune complex levels by 60%-75%. Acute renal failure was successfully treated with hemodialysis. Specific IgG-antibodies against membrane particles of Paxillus involutus were detected by hemagglutination tests in the serum of the patient. The sequence of reactions resulting from the testing procedures strongly suggests the formation of immune complexes. These complexes are likely to bind to erythrocytes acting as innocent bystanders. Activation of the complement system finally results in hemolysis and shock. In addition to adequate shock treatment elimination of these immune complexes by plasma separation seems to be the therapy of choice.

Adult↗
PubMed1986

Is lower ploidy of megakaryocytes another reason for uremic thrombocytopathy?

Though it has been generally accepted that uremic serum contains substances which impair platelet function and inhibit erythropoiesis, the mechanism of uremic thrombocytopathy and bleeding tendency is still not clearly understood. By measuring the nuclear DNA content of the megakaryocytes of 20 patients with end-stage renal failure, we demonstrated that ploidy levels correlate with parameters of uremia. High creatinine and BUN levels as well as low hemoglobin or creatinine clearance values correlate with low average ploidy of megakaryocytes. In explaining this phenomenon, uremic inhibition of DNA replication seems to be more important than dialysis or the type of renal disease. As megakaryocytes of higher ploidy are thought to produce more reactive platelets than megakaryocytes of lower DNA content, this could be another reason for uremic thrombocytopathy and bleeding tendency.

Adult↗
PubMed1986

[Infectious endocarditis in hypertrophic obstructive cardiomyopathy].

Clinical and pathological findings in a 37-year-old female patient with HOCM and infective endocarditis of the aortal and mitral valves were reported. The patient died of septic shock. Infective endocarditis with acute insufficiency of the aortal and/or mitral valves is a severe complication in patients with HOCM, because the left ventricle with a disturbed compliance is unable to compensate the acute volume overload. The standard use of nitrates for congestive lung failure and catecholamines for septic shock is problematic. As with other valvular heart diseases, preventive treatment for infective endocarditis is also recommended for patients with HOCM. In the case of acute endocarditis combined with HOCM early surgical intervention must be discussed.

Adult↗
PubMed1985

Differential diagnosis of acute allograft rejection and CMV-infection in renal transplantation by urinary cytology.

Acute allograft rejection and CMV-infection are the most common complications after renal transplantation. Quick differential diagnosis between these two complications is still difficult but necessary, since both complications demand a different therapy. More than 2500 urinary samples from 33 transplanted patients were prospectively examined and part of them evaluated quantitatively. Urinary samples of patients with acute renal failure, long-term haemodialysis or immunosuppressive therapy served as controls. The following cytomorphological criteria proved to be useful: Tubular epithelial cells, casts, oxalate crystals (sand-glass shaped), dirty background, increasing erythrocyturia, mixed cell clusters, lymphocytes and mitoses. Rejection is going on when the number of renal tubular cells is increased and two or more further criteria are positive. 25 acute allograft rejections without acute renal failure were diagnosed clinically. All 25 rejections were also diagnosed by urinary cytology. Nevertheless, it is not possible to differentiate between acute allograft rejection and acute renal failure of other origin. CMV-infection was serologically detected in 7 patients. In 6 of them viral infected cells were found in the urine shortly after the onset of unspecific clinical symptoms. Besides the typical "owl-eye" cells milkglass nuclei, sometimes with eosinophilic condensation, were seen while criteria for transplant rejection were never observed at the same time. Cytologic examination of voided urine is a simple diagnostic help for the differentiation between allograft rejection and CMV-infection after renal transplantation.

Acute Disease↗
PubMed1984

Ploidy pattern of megakaryocytes in patients with metastatic tumors with and without paraneoplastic thrombosis and in controls.

In order to measure megakaryocyte DNA content in a greater number of well-defined patients, the use of bone marrow aspirates obtained postmortem is a basic requirement. We could show that the distinction between the ploidy classes in DNA histograms is possible until 18 h postmortem. Thus, bone marrow aspirates obtained up to 12 h after death can be expected to give reliable results. Megakaryocytes of the following patient groups were studied: 15 patients with metastatic tumors and paraneoplastic thrombosis, 15 patients with metastatic tumors without paraneoplastic thrombosis and 10 controls. A higher ploidy of the megakaryocytes was found in all 30 patients with metastatic tumors, independently of whether these patients suffer from thrombosis or not. Higher megakaryocyte ploidy, however, is correlated with a larger cytoplasmic mass of megakaryocytes, which leads to an increased platelet production. Besides an overcompensation for increased platelet consumption, a mitogenic or thrombopoietin-like factor produced by the tumor itself must be considered.

Adult↗
PubMed1982

[Portal vein aneurysm and liver fibrosis in myelofibrosis].

In a 54-year-old woman with oesophageal varices there were the unusual morphological findings of portal-vein aneurysm and irregular hepatic fibrosis. The patient had been treated for 8 years for polycythaemia vera with transition into myelofibrosis. Histologically the hepatic tissue showed occlusion of intrahepatic portal-vein branches by organised thrombi, as well as angiomatous vessels in the sclerosed portal areas. the increased pressure as well as medial atrophy with portal-vein sclerosis were the cause of the portal-vein aneurysm. Portal hypertension may have been the result of intrahepatic vascular obstruction and of the increased flow through the enlarged spleen. It is suggested that interaction of several factors, related to the basic disease of myelofibrosis led to these complex anomalies of the liver and portal vascular system.

Aneurysm↗
PubMed1982

[Fatal immunohaemolytic anaemia after eating the mushroom Paxillus involutus (author's transl)].

A 49-year-old previously healthy man fell gravely ill after repeatedly eating the mushroom Paxillus involutus. Haemolysis and circulatory shock caused acute renal failure, acute respiratory failure and disseminated intravascular coagulation. The patient died three-and-a-half days after the mushroom meal in protracted shock. In addition to the signs of haemolysis, post-mortem examination revealed signs of intravascular coagulopathy in lungs, kidneys, adrenals, myocardium, liver and spleen. There were also extensive fat emboli to both lungs. An IgG antibody against paxillus involutus extract was demonstrated in the patient's serum. The immunological reaction pattern suggests primarily the formation of an immune complex, which secondarily attaches itself to the erythrocyte surface and causes intravascular haemolysis by activation of the complement chain. In the first instance the diagnosis is made from anamnestic data. In addition to adequate treatment of circulatory shock, immediate plasma separation could provide a chance of effective treatment.

Acute Disease↗