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Biomedical subjects

K Hübner

Publications and source records attributed to K Hübner.

At least 19 recordsLinked to original sources

[Do we need an autopsy law?].

The clinical autopsy serves the purpose of identifying the underlying disease as well as the immediate cause of death. It is the major instrument of quality control in the field of medical diagnosis and treatment. In addition, autopsies are of great importance with regard to the epidemiology of diseases, to the identification of hitherto unknown disease entities and to modified clinical courses of well-known disorders. Moreover, clinical autopsies have a significant impact on the medical education of students as well as of physicians. The description of the conditions permitting autopsies in the Federal Republic of Germany is followed by a review of the rules governing autopsy practice in the european countries. It is emphasized that the clinical autopsy and its practice should be regulated by a codified law. This law, however, should ensure that the autopsy's objectives may be realized and may indeed contribute to the well-being of the population, to the expansion of scientific knowledge and to the further development of the health care system.

Autopsy

Histopathological classification of Hodgkin's lymphomas. Results from the reference pathology of the German Hodgkin Trial.

Diagnostic biopsies of 1,140 previously untreated patients with Hodgkin's lymphoma from the German Hodgkin Therapy Trial were evaluated by a panel of 4 histopathologists. Each case was classified by consensus of the four according to an extended Rye-System including the diversifying of NS.HD and the unclassifiable cases. The interobserver agreement rate was 92.1% among the panel members regarding the final classification. Primary Hodgkin diagnosis was approved in 91.7% (1045/1140 cases). The distribution of the 1,140 cases within this system was (in %) as follows: 2.7 LP.HD, 57.9 NS.HD, 17.3 MC.HD, 0.7 LD.HD, 13 HD of unclassifiable subtypes, 6.3 of not certain HD, 1.9 Non-Hodgkin Lymphoma, 1 case of non malignancy. Grading of NS.HD into 2 subgroups according to the British classification differed conspicuously by 84.5% versus 15.5% and 71.6% versus 28.4% in British results. This divergency is explained by interobserver disagreement ranking from 43% to 85%.

Biopsy

[Borderline between Hodgkin and non-Hodgkin lymphomas with unfavorable clinical course: a clinical, histological and immunohistochemical analysis of 33 cases within the German Hodgkin Lymphoma Study].

Reevaluation of diagnostic biopsies from 502 patients who entered the German Hodgkin Therapy trial was performed by a panel of four pathologists. Classification revealed 90% of unambiguous Hodgkin-lymphomas (HL), 1.6% of Non-Hodgkin-lymphomas (NHL) and 8.4% of cases difficult to evaluate, reflecting to the well-known problem of the border between these 2 groups of lymphoma. As these cases had the worst prognosis, a second attempt of reclassification, including immunohistochemical studies, was made, resulting in final classifying of 25% of these cases as NHL, 50% as HL, and 25% as further unclassifiable. The most common differential diagnostic problem was separating pleomorphic nodular sclerosing HL from large cell NHL's and HL with rather few Hodgkin- or Reed-Sternberg-cells from Lennerts lymphoma or angioimmunoblastic lymphadenopathy. Immunohistochemistry was helpful for the differential diagnostic decisions in these individual cases. A very high percentage of these problem cases had initially entered the trial as lymphocyte depleted HL, and the large majority of deaths came from the large cell NHL group.

Diagnosis, Differential

[Tumor proliferation, MDR phenotype and tumor associated t-lymphocytes in non-Hodgkin's lymphomas].

In this study we examined the P170-expression (mdr-phenotype) in 42 non-Hodgkin's Lymphomas with variant entities immunohistochemically with the mab JSB1. The mdr-phenotype was related to the tumor proliferation as measured by Ki67-expression and AgNOR numbers. Furthermore the mdr-phenotype was related to the tumor associated T-lymphocytes. The mdr-phenotype showed no relation to histological type and the proliferation of the tumor. There was a positive correlation between the mdr-phenotype and CD2-reactive lymphocytes. There was also a significant positive correlation between CD4-reactive lymphocytes and the mean number of AgNOR's. Possibly P170-expression and proliferation of the tumor cells have a lymphotactic effect on T-lymphocytes. The latter could promote tumor progression by means of paracrine mechanisms.

CD4 Antigens

[Infectious endocarditis from the morphologic viewpoint: on the pathology and clinical aspects of 97 autopsy cases].

In continuous autopsy material between 1978 and 1987 an infectious endocarditis was present in 97 cases of 8745 postmortem examinations. Hospital acquired or iatrogenic infections were at the top of the list with 60% contribution and intravasal devices, cardiovascular or abdominal surgery acting as predominant entrance spots of the infection. In community acquired disease the portal of entry could not be ascertained in most of the cases. The spectrum of causative organisms showed staphylococcus aureus in first position (37%), followed by enterococci (20%), candida (12%) and gram-negative rods (10%). Streptococcus viridans could be isolated in only one case. The majority of patients already had cardiac valve lesions before the onset of infection (48%), immune-defence tangent illnesses (47%) and/or were treated immunosuppressively (14%). In many of the patients, however, no predisposing factors could be established. Factors determining the clinical outcome were - independent of the localization - the local destruction (47%), purulent and non-purulent myocarditis (58%), fresh myocardial infarction (17%) and embolization to various organs (76%), whereby the central nervous system was affected to a high degree (43%). Only 39% of the analyzed cases were discovered at lifetime; especially mural (n = 10) and tricuspidal (n = 9) infections were overlooked. In spite of highly suspicious infection parameters, blood-cultures were drawn from only 59% of the patients; however, an antibiotic therapy had been given to 85%. Only through an early diagnosis before serious complications set in, the poor prognosis of infectious endocarditis can be improved by specific chemotherapy and well-timed surgical measures.

Adolescent

Gallstone dissolution with methyl tert-butyl ether in 120 patients--efficacy and safety.

Of 612 patients with cholesterol gallbladder stones, 120 were eligible for percutaneous transhepatic litholysis with methyl tert-butyl ether (MTBE). Puncture of the gallbladder was successful in 117/120 (97.5%). In 113/117 (96.6%) the stones dissolved. With solitary stones, treatment lasted for an average of 4 hr, with multiple stones 10 hr. Mean hospitalization was 3.6 days. In 3/117 (2.6%) patients a bile leakage developed; 33% reported mild complaints. After the end of treatment 34% had some residue in the gallbladder; two of these patients developed recurrent stones. MTBE is exhaled, is distributed in fatty tissue, and is excreted renally together with its metabolite tert-butanol. Methanol was found only in traces. Gallbladder histology of six patients showed chronic cholecystitis. Since these findings were independent of treatment time and the interval between treatment end and operation, they are most consistent with stone-related changes rather than caused by MTBE.

Adult

Bone marrow findings after treatment with recombinant human interleukin-3.

In a phase I/II study, bone marrow biopsy specimens and aspirates of 20 patients with malignant tumors but normal bone marrow (n = 6), bone marrow failure resulting from chemotherapy (n = 4), myelodysplastic syndrome (n = 5), and aplastic anemia (n = 5) were evaluated before and after patients were treated with recombinant human interleukin-3 (rhIL-3). This cytokine proved to be an effective hematopoietic growth factor with only mild side effects. The rhIL-3 treatment led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells, except in most patients with aplastic anemia. In all patients, significant eosinophilia and, in some instances, bone marrow fibrosis developed. In addition to the increase in the number of circulating neutrophilic granulocytes, platelets, and reticulocytes, an increase of peripheral blood monocytes and lymphocytes was observed. The histologic and cytologic findings support the concept that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells. It appears to be a safe and efficient therapeutic modality in patients with bone marrow failure. Additional clinical studies are needed to determine which patients will profit most from rhIL-3 treatment.

Adult

[Morphology of pulmonary complications in AIDS--a study of 208 biopsy and 231 autopsy cases].

In AIDS patients infectious pulmonary complications may very frequently be demonstrated by both biopsy and autopsy. Bacterial pneumonias occur much more frequently than classic opportunistic infections, e.g. P. carinii pneumonia. Usually, several complications are present concomitantly which impairs diagnosis as well as therapy. Increased survival and modern therapeutic modalities change the spectrum of AIDS-associated pulmonary complications as well as their morphology. In the present study pulmonary complications are directly responsible for the patients' death in more than 70% of the cases.

Acquired Immunodeficiency Syndrome

[Cystic polyposis of the stomach].

An X-ray contrast medium examination revealed extensive polyposis in the gastric fundus of a 66-year-old patient with intermittent heartburn. Physical examination and laboratory tests including carcinoembryonal antigen yielded no abnormal findings. Gastroduodenoscopy showed more than 100 polyps of about 5 mm diameter in the fundus and corpus of the stomach. Gastric mucosa was histologically intact. Numerous cysts lined by non-pathological epithelia were seen in the body and neck of the gastric glands. No polyps were found in the small bowel or colon. Since cystic polyposis does not tend to become malignant, no surgery was performed. Annual endoscopic controls, however, are recommended.

Aged

[The morphology and clinical significance of pathologic changes of the adrenals and hypophysis in AIDS].

A semiquantitative morphometric technique (point counting) was applied to the pituitary and adrenals taken at necropsy from 130 AIDS patients (4 women, 126 men, mean age 39 [22-71] years) to ascertain the nature, extent and location of the pathological lesions. Abnormalities were found in 32% of the pituitaries and 76% of the adrenals. Only 17 patients had normal findings in both organs. The predominant lesions were due to opportunistic infections or infiltration by Kaposi's sarcoma or non-Hodgkin lymphoma. The commonest finding was necrotizing cytomegalovirus adrenalitis (n = 68); in one third of the cases this had caused severe destructive lesions involving over 50% of the parenchyma. The almost total destruction of the adrenals noted in some cases suggests that cytomegalovirus adrenalitis may run a progressive course; its clinical significance has hitherto been underestimated.

Acquired Immunodeficiency Syndrome

Identification of EBV-DNA in lymph nodes from patients with lymphadenopathy and lymphomas associated with AIDS.

Fourteen examples of non-Hodgkin's lymphoma (NHL) and four of Hodgkin's disease in patients with AIDS as well as lymph nodes exhibiting changes related to the lymphadenopathy syndrome (LAS) from 11 HIV-positive individuals were studied for the presence of Epstein-Barr virus (EBV) genome both by in situ DNA hybridization and blotting techniques. Both methods were performed using formalin-fixed paraffin-embedded material. All the NHLs were of high malignancy and all but one were of the B-cell type. Of the four examples of Hodgkin's disease, two were lymphocytic predominant, one of mixed cellularity and one of the nodular sclerosing variety. The lymph nodes of patients with LAS were mostly stage I with marked follicular hyperplasia. In 7 of the 14 NHLs the presence of EBV-DNA was clearly demonstrated by dot-blotting and by in situ hybridization. All lymph nodes from the patients with LAS and AIDS-related Hodgkin's disease were negative for EBV by dot-blot and in situ hybridization assays. We conclude that EBV plays a role in the development of AIDS-related lymphomas, but the fact that half these lymphomas are EBV-negative suggests that other mechanisms such as polyclonal stimulation of B-cells by HIV products may also be important.

AIDS-Related Complex

Mouse monoclonal antibody directed against hepatitis B virus X protein synthesized in Escherichia coli: detection of reactive antigen in liver cell carcinoma and chronic hepatitis.

A mouse monoclonal antibody directed against the protein product of the hepatitis B virus X open reading frame was prepared. This antibody was used to screen liver tissue sections from patients with chronic hepatitis (CH) and patients with liver cell carcinoma (LCC). Reactive antigen was detected by immunohistochemistry in about 30% auf the samples from CH patients and in about 80% of the samples from LCC patients regardless of whether tumor or surrounding nontumor tissue was analyzed. A predominant localization of the antigen in the cytoplasm was observed. In liver sections of CH patients the presence of HBx or HBx-related protein appeared to correlate with the presence of the classical viral antigens HBs- and/or HBcAg. A similar correlation was not found in liver or tumor tissue samples from LCC patients. The occurrence of X-monoclonal-antibody-reactive protein (Xarp) at a low frequency in liver tissue from patients without hepatitis B virus related disease suggests that Xarp in some cases may not be identical with the putative viral X antigen.

Animals

[Effects on bone marrow during stimulation of hematopoietic stem cells with recombinant human interleukin-3].

Bone marrow aspirates and biopsies of 20 patients with malignant tumors (n = 6), bone marrow failure due to chemotherapy (n = 4), myelodysplastic syndromes (n = 5) and aplastic anemia (n = 5) were analysed before and after treatment with recombinant human interleukin-3. rhIL-3 led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells. In all patients marked eosinophilia and, in some, fibrosis was observed. These results show that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells and may contribute to the treatment of bone marrow failure.

Anemia, Aplastic

[In vitro and in vivo effects of recombinant human interleukin-3 on hematopoietic progenitor cells].

As part of a phase I/II clinical trial with recombinant human Interleukin-3 (rhIL-3), bone marrow and peripheral blood cells from patients treated with rhIL-3 were assessed in vitro for effects on the cycling status and frequencies of erythroid, myelomonocytic and multilineage progenitor cells. Treatment with rhIL-3 induced a pronounced increase in S-phase rate of BFU-E, CFU-GEMM and day 14 CFU-GM. Circulating CFU-GEMM and day 14 CFU-GM were increased on day 7 of therapy whereas circulating BFU-E were reduced in the majority of patients. After i.v. bolus injection of IL-3 an acute effect on the peripheral blood count with neutrophilia and, after an initial nadir, monocytosis was observed. IL-6 serum-levels increased in 5 out of 14 patients after IL-3 administration with concomitant side effects in 2 patients in whom IL-6 levels increased above 75 pg/ml. In the majority of the patients a stimulation of peripheral leukocytes and platelets was observed during the 15 day treatment course. In conclusion rhIL-3 induces a multilineage response in vivo by stimulating proliferation of hemopoietic progenitor cells with a resulting elevation in peripheral blood counts.

Bone Marrow

[Comparison of HIV-associated dyshemopoiesis in myelodysplastic HIV-negative patients].

Bone marrow biopsies of 23 HIV-1 infected patients and 29 patients with myelodysplastic disorders were examined histologically by immuno- and enzyme-histochemical techniques and morphometrical methods. The nucleolar organizer regions (AgNOR) were demonstrated and visually counted. Hypercellularity in marrows of AIDS patients is substantially caused by an increase of erythropoiesis and CD68+ macrophages/reticular cells. However, hypercellularity in preleukemia results from hyperplasia of all hematological cell lines and CD68+ bone marrow macrophages/reticular cells. AgNOR count is positively correlated with granulo- and erythropoiesis in preleukemia. In AIDS there is such a positive correlation between AgNOR count and granulopoiesis whereas an inverse relationship appears in erythropoiesis. The results suggest that HIV-associated bone marrow alterations differ from merely reactive changes and are related to myelodysplastic disorders.

Acquired Immunodeficiency Syndrome