Biomedical subjects
Publications and source records attributed to H Budka.
This report concerns a new-born infant with the syndrome of caudal regression. His mother, an epileptic, shows borderline values in the glucose tolerance test in childbed. The pathogenesis of fetal position of discomfort in the uterus as well as etiological factors of this malformation are discussed.
The neuropathological features are presented of an autopsy series of 43 renal transplant recipients. Inflammatory CNS lesions were found in 18 cases and were attributable to secondary CNS involvement in bacterial or fungal septicaemia (8 cases) or in localized extraneural infections (5 cases). Mixed bacterial-fungal infection and bacterial-fungal-viral triple infection were seen in one case each. Isolated toxoplasmic granulomas were observed in two cases. No tissue changes typical of CNS viral infections, including cytomegaly, were found except for small glial nodules in the brain stem in 7 cases. Massive intracerebral haemorrhages were seen in 2 cases after haemodialysis; subdural haematoma occurred once. Non-specific changes including brain oedema and diffuse glial poliodystrophy were found in many cases; vascular lesions and purpura occurred only seldom. A meningocerebellar malignant lymphoma, probably of metastatic origin was found in one case. Clinico-pathological correlation was poor in 5 cases; this is considered to be due to immunosuppressive therapy, which may mask either clinical expression of severe CNS lesions or morphological expression of viral encephalitis.
Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic infiltrates in various organs including the CNS and adrenocortical atrophy with prominence of large ballooned, sometimes bizarre and occassionally striated cortical cells. CNS lesions consisted in incomplete demyelination of long tracts of brain stem and spinal cord with accentuation in the pyramical tracts; in these areas, perivascular cuffs of "epitheloid" histiocytic cells contained a strongly PAS-positive non-sudanophilic material. Electron microscopy demonstrated massive stroge of leaflet structures in perivascular histiocytes identical to the lamellar profiles previously described as specific for ALD. Some leaflets were found in close contact with compact lamellar arrays and with an electron-dense fingerprint material within astrocytes. In our case, the spastic paraplegia-AD syndrome which has been described previously in several clinical observations could be neuropathologically classified as an adult variant of ALD. Several differences to "classical" ALD occurring in young boys are stressed: the predominance of the endocrine disorder probably accounting for some of the perivascular lymphocyte infiltrates within the CNS; the absence of both clinical and pathological signs of diffuse cerebral involvement and the peculiar topistic pattern of CNS lesions and the very slow evolution of neurological signs paralleled by the absence of active sudanophilic demyelinating lesions. The possible mechanism of demyelination and the nature of the suggested metabolic defect in ALD are discussed. The ultrastructurally prominent leaflet structures may originate from myelin remnants, thus relating ALD to pathological storage of a myelin degradation product.
Light- and electron-microscope studies were performed on CSF cells from a patient with CNS leukaemia presenting with an intermittent meningitic reaction. Numerous fully matured basophilic and eosinophilic granulocytes with excess glycogen content accompained undifferentiated leukaemic blast cells in the CSF. Such a CSF cell reaction has not been previously reported. It is suggested that this isolated CSF reaction represents a special type of immediate hypersensitivity reaction triggered by an abnormal leukaemic giant cell clone, and mitigated by the accompanying eosinophilic granulocytes.
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6 autopsy cases of primary leptomeningeal sarcomatosis are presented as a distinct nosological entity with a variable clinical picture and morphology in 5 males and 1 female. The clinical course from onset of symptoms till death ran for only a few weeks in most cases. 2 infants showed brain tumor symptoms and signs. 2 patients of advanced age presented a polyradiculoneuritic syndrome and 2 young adults had spinal cord compression symptoms and a mixed clinical form. In almost all cases, clinical symptoms and signs were for most of the course confined to one part of the neuraxis. The CSF was distinctly abnormal in all cases, showing elevated protein, depressed glucose and pleocytosis of variable extent. CSF sediment was investigated in 3 cases in all of which malignant tumor cells were found so a diagnosis of malignant meningeal tumor was made during life. Electron microscopy of CSF cells in 1 case confirmed the primitive character of the tumor cells. Complete autopsies revealed absence of any neoplasm outside of the CNS. Gross meningeal involvement was visible in all cases. Histologically, 3 tumor types were distinguished: polymorphic cell sarcoma, an undifferentiated form, and fibrosarcomatosis. Clinical data are analyzed in order to distinguish the condition from other neoplasms or infectious, especially tuberculous meningeal infiltrations. CSF cytology studies are considered the most useful step in clinical diagnosis. Neuropathological features are reviewed with stress on differentiation from malignant lymphomas of the CNS, diffusely spreading medulloblastoma, meningeal melanoblastosis and gliomatosis. The origin of meningeal sarcomatosis cells is briefly discussed. The use of the term "meningeal meningiomatosis" for this condition is deprecated.
A child with acute infantile lymphoblastic leukaemia in remission after cytostatic therapy contracted apparently uncomplicated measles. 8 weeks later, an acute neurological syndrome developed, which led to death within 2 weeks. At autopsy, a peculiar type of inclusion body "encephalitis" almost without signs of inflammatory infiltration was found. Electron microscopic examination showed changes of paramyxovirus infection, which were attributable to slow measles virus disease of the CNS. There was evidence of disturbed nucleocapside synthesis, which is considered to be one of the basic defects in the development of slow-virus processes and their altered viral maturation. Possible pathogenetic factors are discussed in the light of our case.
Clinico-pathological report on a boy with cytostatically treated leukemia, dying with cerebral symptoms after passing clinical measles 10 weeks before death. At autopsy, numerous nuclear inclusion bodies in glial and nerve cells were found. By electron microscopy, nuclear inclusions appeared as loosely arranged smooth tubules, corresponding to paramyxovirus nucleocapsids. Frequently, cytoplasmic changes appeared too, consisting of incomplete tubular structures and an abundant dense "fuzzy" material. No regular tubuli of the coated granular type were present, as in common measles virus infection, nor any mature viral structures or differentiation of the surface membrane. The lack of maturation in cytoplasm together with a predominance of nuclear changes suggested a slow type of measles virus infection, while the particular cytoplasmic changes suggested a defect in synthesis of granular nucleocapsids, possibly a basic factor for the slow type of the viral infection. Possible pathogenetic factors are discussed.
Partial resection of a cystic cerebellar astrocytoma with well-differentiated histomorphology in a 13 year old girl was followed by a course of X-ray therapy. After a period of 27 years symptoms recurred. The patient died 2 days after a second operation, and autopsy showed a large partly cystic cerebellar astrocytoma with distinct morphological evidence of malignancy in some areas. The role of the X-ray therapy in the formation of peculiar bizarre giant cells in our case is discussed. Radio-induction of malignant tumour evolution after long latency has to be considered, but the possibility seems remote. However, the value of radiotherapy for cystic cerebellar astrocytomas needs some reconsideration. More caution in the long term prognosis of cystic cerebellar astrocytomas of childhood might be appropriate.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Dysembryoplastic neuroectodermal tumor (DNT) is a rare brain neoplasm. Although the tumor pathology is relatively well charactererized, its full clinicopathological spectrum is still discussed, and ultrastructural data on it are very limited. Here, the authors describe detailed ultrastructural pathology of 7 cases of DNT. Each tumor consisted of 3 major elements: neoplastic cells (oligodendroglial-like cells, OLC), elongated processes forming neuropil-like structure, and expanded "mucoid" extracellular space, the latter giving an impression of cellular elements floating within it. Neoplastic cells had round, oval, or elongated nuclei, no discernible nucleoli, and a relatively narrow rim of cytoplasm. Some nuclei were irregular and invaginated, and pseudoinclusions (invaginations of cytoplasm penetrated into toroid-like nuclear formations) were observed. Part of the cytoplasm sequestrated within pseudoinclusions often appeared degenerated with large blebs and electron-lucent vesicles, and some of these contained, in turn, semicircular profiles of unknown significance. Chromatin was clustered below the nuclear membrane. The cytoplasm contained a few mitochondria, round rather than elongated, a few stacks of rough endoplasmic reticulum, and scanty microtubules and clear vesicles. The second element consisted of innumerable cellular processes. Some of these were elongated and formed stacks connected by symmetric or asymetric adhesive plaque junctions. Others had shorter "neck" containing microtubules extending into bulbous extensions. Dense-cored vesicles were occasionally observed, both in the cytoplasm of neoplastic cells and within processes. In one cell, cross-sectioned annulate lamellae were found. In the cytoplasm of a few cells, unusual inclusions reminiscent of ribosome-lamellae resembled "laboratory tubes" with cone-like endings. At higher power, walls of the "tubes" resolved into layered structures composed of several laminae; between these, ribosome-like structures were visible. The authors conclude that OLC exhibit clear-cut characteristics of neuronal cells and not true oligodendocytes.
We report a detailed ultrastructural study based on a large series of samples from a recent case of Gerstmann-Sträussler-Scheinker disease from the original Austrian family. Numerous PrP-immunopositive plaques dominated light microscopic neuropathology. Ultrastructurally, several types of plaques were observed: unicentric "kuru," multicentric, and neuritic. Dystrophic neurites accompanied amyloid plaques to differing degrees. Plaques were enveloped by astrocytic processes and invaded by microglial cells. A prominent astrocytic reaction accompanied abundant spongiform change. Unusual crystalloids were observed in mitochondria while another type of crystalloid was seen within lysosomes. We conclude that Gerstmann-Sträussler-Scheinker disease is distinct also at the ultrastructural level.
Carcinomas metastatic to the brain usually grow very well circumscribed, with sharp delineation. Radiosurgery takes advantage of this fact by using the gamma knife for definitive treatment of small metastases. We report a systematic study of the growth pattern of cerebral metastases, focusing on tumor delineation. In 26 cases of 66 metastatic anaplastic small cell carcinomas and in one case of adenocarcinoma, we observed poorly defined borders and a highly diffuse pattern of invasion. Infiltrating carcinoma cells changed to an elongated shape adapting to preexisting tissue structures. This pseudogliomatous growth pattern of some brain metastases--apparently most likely in neuroendocrine carcinomas--is of potential importance for therapeutic strategies in the treatment of brain metastases, especially when considering treatment with radiosurgery and gamma knife.
Seventy-six pituitary adenomas of akromegalic patients were investigated to find out the prognostic relevance of the intracytoplasmic distribution of cytokeratins (CK), immunohistochemically defined hormone production profile, proliferative activity and clinical presentation. CK distribution, growth fraction (MIB1 index) and hormone production profile were analyzed by means of immunohistochemistry. Apoptotic activity was investigated by the TUNEL method. Two different CK distribution patterns were seen: a dot-like pattern in 29 cases (type 1 adenomas), and a perinuclear fibrillary pattern in 47 cases (type 2 adenomas). Type 2 adenomas showed more prominent coexpression of prolactin (p < 0.0001), luteotrophic hormone (p < 0.002), follicle-stimulating hormone (p < 0.005), thyroid-stimulating hormone (p < 0.0001), and alpha-subunit (p < 0.005), as compared to type 1 adenomas. The mean MIB1 index was significantly higher in type 1 vs. type 2 tumors (4.23%, range: 1.93% - 9.83% vs. 2.07%, range: 0.67% - 4.87%, p < 0.0001). Apoptotic activity was too low in both examined groups to be used for balancing of tumor cell turnover. Clinical analysis of patients with type 1 adenomas revealed female predominance, younger age, larger tumor size, and more frequently aggressive growth with higher incidence of suprasellar extension (p < 0.0001) and cavernous sinus infiltration (p < 0.0001), as well as larger proportions of re-operations and incomplete resections (34.5% vs. 8.51%). Additionally, the interval until re-operation was shorter in type 1 adenomas (mean: 16 months, range: 9 - 21 months vs. mean: 57 months, range: 18- 158 months). We conclude that classification of adenomas of akromegalic patients based on intracytoplasmic CK distribution, combined with examination of proliferative activity, and immunohistochemically defined hormone production profile, provides important prognostic information for the management of akromegalic patients.
Myofibrillar or desmin-related myopathies encompass neuromuscular disorders with abnormal deposits of desmin and myofibrillar alterations. We report 3 unrelated patients presenting with proximal and distal myopathy, and, as a unique congenital syndrome, diffusely distributed myopathy, osteoporosis and myopia. Muscle biopsies shared cytoplasmic inclusions, rimmed vacuoles, and ragged-red-like fibers. Sarcoplasmic inclusions, either plaque-like or amorphous, strongly immunoreacted on dystrophin and variably for desmin, alphaB crystallin and ubiquitin. Cyclin-dependent kinases CDK1, CDK2 and CDK5 were overexpressed in affected fibers. Ultrastructurally, focal myofibrillar disruption was accompanied by tubulo-filamentous inclusions in one case and abundant glycogen and enlarged mitochondria displaying respiratory chain dysfunction at biochemistry in another case. Molecular analysis of the alphaB crystallin gene coding sequence and exons 4, 5 and 6 of the desmin gene did not reveal any mutation. The morphologic denominator of hyaline structures and areas of myofibrillar destruction occurs in heterogeneous conditions and may overlap with features of inclusion body myopathy and mitochondrial myopathy.
A primitive tumor of the pineal region in a 9-year-old girl led to death after 5 months of increased intracranial pressure with occlusive hydrocephalus. Histological investigation including immunocytochemistry revealed a broad spectrum of neuroectodermal differentiation with neuroblastic, neuronal, ependymal and retinoblastomatous features. Melanotic epithelial formations were similar to those of the so-called retinal anlage tumor and of the developing pineal gland. Striated muscle fibers indicated additional ectomesenchymal differentiation reminiscent of the close topographical relationship between neural crest and neural tube on the prosencephalic level of the pineal anlage. This developmental situation seems to be neoplastically reflected by the differentiation features of this tumor.