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Biomedical subjects

R Kleinert

Publications and source records attributed to R Kleinert.

At least 55 records · Page 3Linked to original sources

Mucopolysaccharidosis I and intracranial tumor in a patient with high-pressure hydrocephalus.

In a 19-month-old patient with mucopolysaccharidosis I (Pfaundler-Hurler, MPS I/H) high-pressure hydrocephalus required the implantation of a ventriculo-peritoneal shunt. Despite a reduction in both ventricular volume and intracranial pressure, clinical symptoms suggesting compression of the brain stem persisted. Brain MRI revealed a tumor within the posterior cranial fossa. Cytologic examination of the cerebrospinal fluid was suggestive of a poorly differentiated ependymoma. High-pressure hydrocephalus is a common complication in MPS I/H. As changes in mucopolysaccharide metabolism may be associated with an increased risk of developing neoplasms, the possibility of an intracranial tumor should be considered in patients with MPS I/H and high-pressure hydrocephalus.

Brain Neoplasms↗

Paraneoplastic polymyositis associated with a renal carcinoma.

A 56-year-old patient was admitted to hospital because of difficulties in swallowing and in opening his mouth. The serological transaminases were increased. Over the next 6 weeks a bioptically proven polymyositis (more proximally located) caused a respiratory insufficiency which had to be treated by artificial respiration. A tetraplegia connected with a large increase of creatine-kinase was also seen. The general investigations were focused on malign processes with a particular search for bronchial carcinoma. At first a kidney cyst detected by ultrasound but was classified as harmless by several investigators. Finally, a computer tomogram of the abdomen demonstrated a cystic degenerated renal carcinoma, which had been cytologically tested also. The clinical course showed a typical aspect of a paraneoplastic syndrome: after extended nephrectomy a distinct regression of the musculary symptoms developed, but with the development of metastases the symptoms increased again. The interdependence of polymyositis and primary renal carcinoma would appear to be proven.

Carcinoma, Renal Cell↗

Bilateral medial medullary infarction: magnetic resonance imaging and correlative histopathologic findings.

Bilateral medial medullary infarction is a rare event which clinically presents with flaccid tetraplegia sparing the face, bilateral disturbance of deep sensation, hypoglossal nerve palsy and respiratory failure. We here report a patient with such symptoms in whom magnetic resonance imaging enabled the detection of signal abnormalities in the lower brainstem as soon as 9 h after onset. Results of a control study 3 weeks later correlated well with the extent of infarction that was seen at autopsy. Early lesion detection in the lower medulla by magnetic resonance imaging and the unfavorable prognosis of patients with ischemic damage at that location may provide the rationale for aggressive therapeutic strategies in such a condition.

Cerebral Infarction↗

Pathologic correlates of incidental MRI white matter signal hyperintensities.

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

Aged↗

[Proliferation markers, enzyme markers and oncogene expression profile of intraocular melanoma].

In this study 9 uveal melanomas, 1 iris melanoma and 1 conjunctival melanoma were evaluated for their proliferation activity with antibodies to KI67 protein. In addition, the distribution of glutathion-S transferase (alkaline and acid isoforms) and lysosomal cathepsin D protease was demonstrated immunohistochemically. The expression of the oncoproteins c-neu (internal and external domaine) and ras (mutated and non-mutated isoform) were also analyzed with specific monoclonal antibodies. In the case of the metastasing melanoma significant Ki67 protein expression and marked expression of the oncoproteins ras p21 and pan ras were obvious. All other melanomas showed less proliferation and enzymatic activity with a moderate expression pattern for oncoproteins. Regarding the results of the proliferation and enzymatic markers, the tumors were heterogeneous; single cells or clusters may play a role in the prognosis of the tumor if there is an intense immunohistochemical reaction. The influence of histomorphological criteria, e.g., cell subtype, seems to be minor compared to immunohistochemical criteria.

Biomarkers, Tumor↗

Primitive neuroectodermal tumor (PNET) extending into the cerebellopontine angle: case report.

The most common primary tumors of the cerebellopontine angle are growths of the 8th cranial nerve. The occurrence of other tumors in this area is very rare and may cause neuroradiological misinterpretation. We report the findings in a 37-year-old male patient suffering from a primitive neuroectodermal tumor (PNET) extending from the latero-basilar cerebellar hemisphere into the cerebellopontine angle (CPA) and causing cerebellar dysfunction as well as symptoms of typical cerebellopontine angle lesions. Differential diagnosis of tumors found in this area is given as well as a histological description of the tumor along with immunohistochemical findings and aspects of possible prognostic relevance.

Adult↗

Clinical manifestations of late onset cerebral storage disease: a case of metachromatic leukodystrophy.

Clinical symptoms, MRI of the brain and neuro pathological findings of a case with adult metochromatic leukodystrophy are presented. Clinically it is important to consider a possible late-onset manifestation of an inborn cerebral storage disease, when uncertain psychopathological symptoms are difficult to assign to well-known diseases. These cerebral storage diseases may appear as "juvenile behaviour disturbance" or "schizophrenia". The clinical suspicion may further be confirmed by simultaneous or subsequent neurological or ophthalmological symptoms. The definitive diagnosis is possible by biochemical or histopathological methods. MRI of brain and neuro pathological findings correspond well with regard to white matter lesions.

Adult↗

Interstitial 1.06 Nd:YAG laser thermotherapy for brain tumors under real-time monitoring of MRI: experimental study and phase I clinical trial.

This paper presents the experimental and clinical results of interstitial 1.06 Nd:YAG laser thermotherapy (ILTT) for brain tumors under real-time monitoring by magnetic resonance imaging. The authors chose a laser heat source for interstitial thermotherapy of brain tumors for several important reasons: (1) Laser heat delivery is less complicated and more controlled; (2) laser effects on tissue can be tested, monitored, and controlled by MRI. A 1.064 nm Nd:YAG laser and a specially designed laser optic fiber (ILTT) were used in C.W. mode this study. The laser was used at 4 W at a C.W. mode pulse and total exposure duration was 10 minutes (total energy was 2400 joules). Temperature distribution was determined with a microprocessor-based thermometer and by the levels of the signal intensity under MRI. The relationship between the temperature and MRI signal intensity allowed exploration of the possibility of using MRI as a noninvasive temperature monitoring method. Two patients with glioblastoma and one patient with a brain metastasis were treated with this modality. The results and indications are presented and discussed.

Brain Neoplasms↗

Lansoprazole versus famotidine: efficacy and tolerance in the acute management of duodenal ulceration.

Lansoprazole (AG 1749/CG 4801) is an inhibitor of gastric acid secretion by blocking H+,K(+)-ATPase. In this 2:1 randomized, double-blind, multicentre trial lansoprazole 30 mg am was compared to 40 mg famotidine nocte in 264 out-patients suffering from uncomplicated duodenal ulcer. After 2 weeks of treatment ulcer healing was confirmed endoscopically in a significantly higher proportion (P = 0.027) of patients treated with lansoprazole (94/174 = 54.0%) compared to patients receiving famotidine (35/90 = 38.9%). Cumulative healing rates after 4 weeks were 91.4% for the lansoprazole group and 83.3% for the famotidine group (P = 0.065). Pain relief and decrease of concomitant antacid consumption during treatment were comparable in both groups. Both compounds were well tolerated. Rates of recurrent duodenal ulcer in the 6 months after trial treatment were 45/158 (28.5%) after lansoprazole, and 18/69 (26.1%) after famotidine.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Malignant biliary obstruction: histologic findings after treatment with self-expandable stents.

Histologic analysis was performed of bile duct tissue from 15 patients who underwent treatment for malignant obstructive jaundice with a self-expandable stent. Stents were in place from 5 days to 21 months. Malignancies included adenocarcinoma of the pancreas or gallbladder or cholangiocellular, hepatocellular, or gastric carcinoma. Stents were blocked by sludge in two cases and tumor overgrowth in two others. Microscopic evaluation showed that stent placement caused complete denudation of the mucosa and mild submucosal inflammation with edema. In all but one patient, the stent was incorporated into the bile duct wall and was covered by a fibrogranulomatous tissue layer after 2 months. In some cases, an epithelium-like cell formation covered the inner surface of the stent. Tumor ingrowth was observed in two patients with poorly differentiated tumors. In stents placed for longer than 2 months, mild to moderate fibrosis and foreign body reaction were observed. Hyperplastic biliary epithelium was not found within the stent or at the stent ends.

Adult↗

[Acoustic evoked brainstem potentials--patterns of stimulus artefacts in irreversible coma].

Brainstem auditory evoked potentials (BAEP) were performed in a total of 20 subjects (mean age 33.2 +/- 15.1 years; severe head injury in most cases) with the diagnosis of coma dépassé. The control group consisted of 33 healthy volunteers (mean age 26.9 +/- 5.3 years). The presence, latency and amplitude of the single BAEP-components and the variations of the stimulus artifact were evaluated. The mean amplitudes of the stimulus artifact of the brain dead subjects were calculated (means +/- SD) to be 0.26 +/- 0.12 microV (control group: 0.11 +/- 0.03 microV). Pathological alterations of the mechanics of the inner ear as well as extracerebral changes in conductivity or stimulus related depolarization processes in extracerebral parts of the auditory system were taken into consideration to be possible reasons for this significant (p less than 0.001; t-test) difference.

Adolescent↗

Immunohistochemical characterization of primitive neuroectodermal tumors and their possible relationship to the stepwise ontogenetic development of the central nervous system. 1. Ontogenetic studies.

Aim of the present study was to establish different immunohistochemical staining patterns for a subsequent comparison with those of primitive neuroectodermal (PNET) subsets, i.e. PNET-NOS (not otherwise specified) or PNET with focal neuronal, astrocytic or ependymal differentiation, to relate neoplastic to embryonal development. Tissue of the developing central nervous system, with special emphasis on the stepwise development of the rhombencephalon, the cerebellar and the retinal anlage, from 20 different human embryos and fetuses ranging from 3 to 30 weeks of gestational age (GA) was examined. Six neuronal markers, synaptophysin, chromogranin A, neuron-specific enolase (NSE), neurofilament protein (NFP; 160 kDa, 200 kDa, 70 and 200 kDa) and six other markers, glial fibrillary acidic protein (GFAP), S-100 protein, vimentin, myoglobin, desmin, cytokeratin, were assessed immunohistochemically. GFAP and S-100 protein appeared at the 6th week of GA in primitive glial cells of the cerebellar anlage, brain stem, rhombencephalon, and developing spinal cord, together with--as first neuronal marker--chromogranin A, then NFP (70 and 200 kDa, and 160 kDa) from the 8th week onward. NSE started in the 11th week and synaptophysin not earlier than the 16th week of GA. Interestingly, the differentiation of the retinal anlage started rather late with NSE positivity beginning from the 16th week and positive reactions to synaptophysin and NFPs only from the 25th and chromogranin A from the 28th week of GA onward.

Central Nervous System↗

Immunohistochemical characterization of primitive neuroectodermal tumors and their possible relationship to the stepwise ontogenetic development of the central nervous system. 2. Tumor studies.

Thirty-five selected intracranial tumors qualifying as primitive neuroectodermal tumors (PNETs) were investigated; these included medulloblastomas, cerebral neuroblastomas, pinealoblastomas, retinoblastomas, polar spongioblastomas, ependymoblastomas. For control purposes 11 tumors, including glioblastomas (small cell, spongioblastic variants), one anaplastic astrocytoma (astroblastic component), anaplastic oligo-astrocytomas, gangliogliomas, one primary melanoblastoma, and one pineal germinoma, were also studied. Six neuronal markers, i.e., synaptophysin, chromogranin A, neuron-specific enolase (NSE), neurofilament protein (NFP) (160 kDa, 200 kDa, 70 and 200 kDa), and six other markers (glial fibrillary acidic protein, S-100 protein, vimentin, myoglobin, desmin, cytokeratin) were investigated immunohistochemically. A certain recapitulation of the ontogenetic development of neuronal differentiation in PNETs is given by the fact that chromogranin A immunoreactivity can regularly be seen already in poorly differentiated neurons and synaptophysin in well-differentiated ones. Immunostaining for NFPs showed different results depending on the subunit investigated. NSE reaction gave different results even within the single tumor groups. This study is, to the best of our knowledge, the first attempt to evaluate and compare, by combined morphological and immunohistochemical methods, PNETs without and with different stages of cellular differentiation with the stepwise differentiation of the human embryonic neuroectoderm.

Adolescent↗

MRI in tuberculous meningoencephalitis: report of four cases and review of the neuroimaging literature.

The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response.

Adolescent↗

Acute effect of neodymium yttrium aluminium garment laser on the cerebral cortical structure, blood-brain barrier, and pial vessel behaviour in the cat.

Experimental brain lesions were created by Nd:YAG laser (wave length 1.06 microns) irradiation on the cerebral cortex of anaesthesized adult cats with 20 Watts impacts of 0.5, 1.0, 2.5, and 5.0 seconds exposure time through cranial windows. Histological changes, disruption of the blood-brain barrier (Evans blue extravasation) and pial vessel reaction (large vessels more than 100 microns and vessels smaller than 100 microns) were studied under constant PaCO2, blood pH, and mean arterial pressure. Histological changes of the lesions consisted of a zone of dense coagulation, a pale zone of homogeneous coagulation and an oedematous zone. Evans blue extravasation was uniformly seen extending from the histologically changed area into the surrounding tissue in all experiments. Pial arteries in the area with morphological changes showed pronounced dilatation (100.0 +/- 7.2%) and one third of these arteries were closed by thrombi. Pial arteries in the area of Evans blue extravasation but outside of histological changes also dilated (large arteries 60 +/- 4.1%, small arteries 77 +/- 5.9%). Pial arteries outside of the Evans blue extravasation were affected transiently and only in a very small zone: Within a distance of 200 microns from the Evans blue extravasation, large arteries initially dilated by 41 +/- 8.3%; small arteries dilated within 400 microns (42 +/- 3.7%). Within 4 minutes after irradiation arterial dilatation was again significantly reduced (p less than 0.01). It is concluded that no important vascular changes occur beyond the zones of histologically altered brain tissue.

Animals↗

Hydroxyethyl-starch in transient experimental focal cerebral ischemia.

In a model of focal cerebral ischaemia in the cat (transorbital occlusion of the middle cerebral artery for 60 minutes, thereafter 6 hours reperfusion by clip removal), hydroxyethyl-starch (HAES) (ELOHES; Leopold Pharma GmbH, Graz, Austria) was administered intravenously before and during the ischaemic episode as a 6% or as a 10% solution in a randomised manner (6 animals each group). The size of the developing cerebral infarct was not significantly different when comparing the 6% and the 10% group with the controls (SALINE). Collateral circulation to the infarct border (pial arteries on the suprasylvian gyrus) was also not significantly different between the two groups, except for the first hour of reperfusion, where vessels of the 6% group were wider than vessels of the 10% group. At the infarct border (ectosylvian gyrus) small resistance vessels were significantly more dilated in the 6% than in the 10% group both during the occlusion period and during the reperfusion episode after removal of the clip. Pial arteries dilated less in both HAES-groups than in the controls. It can be assumed, that HAES-incuded decrease of plasma viscosity led to an elevation of blood flow velocity and blood flow quantity (CBF). But the latter might be counteracted by autoregulation of CBF, i.e. vasoconstriction. Thus, a possible positive effect of HAES might in part be counteracted by autoregulation, which explains that no significant therapeutic effect could be achieved.

Animals↗

Dose-related healing of duodenal ulcer with the proton pump inhibitor lansoprazole.

Lansoprazole (AG 1749) is a novel substituted benzimidazole which inhibits gastric acid secretion by blocking H+,K(+)-ATPase. This randomized, double-blind multicentre trial studied the dose-response relationship of lansoprazole on ulcer healing and compared it with ranitidine in 314 out-patients with endoscopically assessed, symptomatic duodenal ulcer. Cumulative healing rates with Lansoprazole 7.5, 15, and 30 mg o.m. were 48, 59, and 74% at 2 weeks and 75, 84, and 95% at 4 weeks, respectively (intention-to-treat); the difference of the healing rates between 7.5 and 30 mg groups was significant (P less than 0.001). Corresponding healing rates for 300 mg ranitidine nocte were 51 and 89%. Pain relief was similar in all treatment groups. Lansoprazole was well tolerated. During a follow-up of 6 months relapse rates after lansoprazole 7.5, 15, and 30 mg were 21, 29, and 22%, respectively; the relapse rate after ranitidine 300 mg was 20%. In conclusion, lansoprazole provides faster healing of duodenal ulcer than ranitidine and a similar relapse pattern. For further trials in peptic ulcer disease a daily dose of lansoprazole 30 mg o.m. is recommended.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Chronic Lyme disease with an expansive granulomatous lesion in the cerebellopontine angle.

Expansive granulomatous lesions in the posterior cranial fossa are rare and have not been reported in conjunction with Lyme disease. We report a patient with verified Borrelia burgdorferi infection who developed a tumor in the cerebellopontine angle. Rapid growth of the tumor led to signs of cerebral compression and to hydrocephalus. Surgical intervention was required despite florid meningitis. The histological examination showed inflammatory, nonspecific granulation tissue. The origin of this tissue is almost certainly causally related to the B. burgdorferi infection. Signs of inflammation resolved rapidly after subtotal resection. The clinical, radiological, and biochemical course is documented. This is the first report of an expansive cerebral lesion in the chronic phase of Lyme disease.

Antibodies, Bacterial↗