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Biomedical subjects

R Warzok

Publications and source records attributed to R Warzok.

At least 19 recordsLinked to original sources
PubMed2007

Cerebral beta-amyloid angiopathy in aged squirrel monkeys.

Cerebral beta-amyloid angiopathy (CAA) is an age-related disorder of the brain vasculature that is involved in up to 20% of non-traumatic cerebral hemorrhage in humans. CAA is a risk factor for cognitive decline, and may exacerbate the dementia of Alzheimer's disease. Progress in discovering the cause and potential therapies for this disorder has been hindered by the paucity of animal models, particularly models of idiopathic CAA. The squirrel monkey (Saimiri spp) develops significant CAA in the natural course of aging. To evaluate the suitability of Saimiri as a model of human CAA, we studied the distribution and composition of Abeta subtypes in CAA and parenchymal (senile plaque) deposits in the brains of aged squirrel monkeys, as well as the relationship between vascular beta-amyloid deposition and comorbid vasculopathies that occur in aged humans. Our findings show that: 1) CAA consists ultrastructurally of classical amyloid fibrils and is the principal type of cerebral beta-amyloidosis in squirrel monkeys; 2) The two primary isoforms of Abeta (Abeta40 and Abeta42) coexist in most microvascular and parenchymal lesions of Saimiri, although Abeta40 tends to predominate in larger arterioles; 3) CAA and parenchymal plaques overlap to a considerable degree in most affected brain areas, and are distributed symmetrically in the two hemispheres; 4) Both CAA and plaques are particularly abundant in rostral regions and comparatively sparse in the occipital lobe; 5) Capillaries are especially vulnerable to CAA in squirrel monkeys; and 6) When CAA is severe, it is associated with a small, but significant, increase in other vasculopathies, including microhemorrhage, fibrinoid extravasation and focal gliosis. These findings, in the context of genetic, vascular and immunologic similarities between squirrel monkeys and humans, support the squirrel monkey as a biologically advantageous model for studying the basic biology of idiopathic, age-related CAA, and for testing emerging therapies for human beta-amyloidoses such as Alzheimer's disease.

Aging↗
PubMed2004

Towards waterjet dissection in neurosurgery: experimental in-vivo results with two different nozzle types.

Waterjet dissection is under close investigation as a new neurosurgical tool. Experimentally, a precise tissue dissection with vessel preservation has been demonstrated in the porcine cadaver brain. The safety of the device has been shown in first clinical applications. However, a detailed in-vivo analysis of the waterjet device is still awaited. In the present study, two often applied nozzle types (100 microm diameter emitting a coherent straight jet; 120 microm diameter emitting a helically rotating jet) were experimentally studied in vivo. Forty-one rabbits received a frontal waterjet corticotomy on either side with one nozzle type after microsurgical removal of the arachnoid membranes. Animals were sacrificed at 1, 3, 7 days and 6 weeks after surgery. Dissection morphology and vessel preservation were evaluated. Tissue trauma was analyzed by the extent of intra-operative haemorrhage, postsurgical oedema formation and astrocytic as well as microglial reactions. In all animals, reliable brain dissection was observed. Macroscopically, only minor bleeding occurred. Microscopically, also very precise brain dissection with both nozzle types was found. Vessels were preserved with both pressures applied (5 and 10 bar). Dissections with the 100 microm straight nozzle were more precise with respect to dissection margins. However, no significant difference in vessel preservation and extent of haemorrhage, oedema formation, astrocytic and microglial reactivity was shown. Malfunction defined as clotting of the instrument occurred only with the 100 microm nozzle. In four 100 microm straight nozzle hemispheres, even no brain dissection was seen. The results indicate that the waterjet enables very precise and reliable brain parenchyma dissection with minimal trauma and vessel preservation in vivo. If this can be proven to be of clinical relevance, the instrument will become a valuable neurosurgical tool. Based on these results, the authors selected the 120 microm Helix nozzle for further research with this device in the CNS.

Animals↗
PubMed2003

Role of variant Creutzfeldt-Jakob disease for safety of treatment with blood components: screening of lymphatic tissue is a potential tool for risk assessment.

BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are neuropathological diseases caused by prions. Prions are infectious particles (PrPSc) which can induce bovine spongiform encephalopathy and most likely also the related infectious disease, variant of Creutzfeldt-Jakob disease (vCJD). The exposure of humans to orally ingested BSE agent in contaminated meat products presumably led to the emergence of vCJD. In vCJD, prions can be detected immunohistochemically not only in neuronal tissue but also in lymphoreticular tissue. vCJD is of significance in transfusion medicine because of the hypothetical transmission of prions by blood products. METHODS: An immunohistochemistry method was used to allow screening for vCJD in human lymphoreticular tissue. RESULTS: PrPSc can be detected in the cerebrum and cerebellum of patients with sporadic Creutzfeldt-Jakob disease (sCJD) and in the lymph nodes, tonsils, and spleen of vCJD patients. This method has the major advantage of working in fixed specimens which are routinely saved in departments of pathology and therefore allows screening of large numbers of archived human lymphoreticular tissues in different regional areas and from different time points. Scrapie-positive lymphoreticular sheep tissue reacts similarly to human tissue of vCJD affected patients and is available in sufficient amounts to be used as positive control in screening programs. CONCLUSION: A method is provided which is a feasible tool for an epidemiological screening program to assess the prevalence of the assumed infectious agent of vCJD, PrPSc, in various populations.

Animals↗
PubMed2000

Treatment with nimodipine or mannitol reduces programmed cell death and infarct size following focal cerebral ischemia.

The present study was conducted to evaluate the effects of nimodipine and mannitol on infarct size and on the amount of apoptosis after transient focal cerebral ischemia. Focal cerebral ischemia was induced in male Sprague-Dawley rats (weight 300-380 g) by transient occlusion of the right middle cerebral artery (MCAO) using an intraluminal thread model. All animals underwent ischemia for 2 h, followed by 24 h of reperfusion. Group I (n=16) was untreated. Group II (n=16) received 15% mannitol (1 g/kg as bolus) and group III (n=9) received 15 microg/kg/h nimodipine intravenously beginning 15 min prior to MCAO. Twenty-four hours after reperfusion, the brain was taken and sectioned in coronal slices. The slices were stained with H&E and with the transferase dUTP nick-end labeling (TUNEL) technique. Histopathological analysis revealed a significant (P<0.05) decrease in infarct size in the striatum with both drugs: mannitol (group II) 25.4+/-5.9% and nimodipine (group III) 21.5+/-11.0% versus control (group I) 34.9+/-7.0% and in the cortex 2.7+/-2.0% (group II) and 6.3+/-2.4% (group III) versus control 14.4+/-9.0% (group I). The number of apoptotic cells was statistically lower in the therapy groups (group III 9.6, group II 25.8) versus control (group I 57.9) (Mann-Whitney-Wilcoxon U-test Z>1.96, P<0.05). This study indicates that mannitol and nimodipine provide neuroprotection by preventing both the necrotic and apoptotic components of cell death after transient focal cerebral ischemia and may be effective as neuroprotective drugs for cerebrovascular surgery.

Animals↗
PubMed2000

Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction.

BACKGROUND: P-Glycoprotein is an efflux pump in many epithelial cells with excretory function. It has been demonstrated that rifampin (INN, rifampicin) induces P-glycoprotein, particularly in the gut wall. We therefore hypothesized that rifampin affects pharmacokinetics of the P-glycoprotein substrate talinolol, a beta1-blocker without appreciable metabolic disposition but intense intestinal secretion in human beings. METHODS: Pharmacokinetics of talinolol (a single dose of 30 mg administered intravenously or 100 mg administered orally for 7 days) and duodenal expression of the MDR1 gene product P-glycoprotein as assessed by reverse transcriptase-polymerase chain reaction of the MDR1-messenger ribonucleic acid, by immunohistochemistry and Western blot analysis were analyzed before and after coadministration of rifampin (600 mg per day for 9 days) in 8 male healthy volunteers (age 22 to 26 years). RESULTS: During rifampin treatment, the areas under the curve of intravenous and oral talinolol were significantly lower (21% and 35%; P < .05). Treatment with rifampin resulted in a significantly increased expression of duodenal P-glycoprotein content 4.2-fold (2.9, 6.51) (Western blot) and messenger RNA was increased in six of the eight volunteers. P-Glycoprotein expression in biopsy specimens of gut mucosa correlated significantly with the systemic clearance of intravenous talinolol (rs = 0.74; P < .001). CONCLUSIONS: Rifampin induces P-glycoprotein-mediated excretion of talinolol predominantly in the gut wall. Moreover, clearance of talinolol from the blood into the lumen of the gastrointestinal tract may be predicted by the individual intestinal P-glycoprotein expression. Thus we describe a new type of steady-state drug interaction affecting compounds that are subject to transport rather than metabolism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Ectopic cervical thymus in a 12-year-old boy: a case report.

The case of a 12-year-old boy with ectopic cervical thymus is reported. This is a rare differential diagnosis in cervical tumors in childhood. The clinical symptoms might present as complications; in rare cases malignant transformations have been reported. The diagnosis ectopic cervical thymus can be achieved only histologically. Due to possible malignant transformation, it is mandatory to excise this thymus tumor totally.

Child↗
PubMed1999

Severe clinical expression in X-linked Emery-Dreifuss muscular dystrophy.

X-linked Emery-Dreifuss muscular dystrophy (EDMD) is a relatively rare benign neuromuscular disorder which can vary remarkably in onset, course and severity. In the present study, a TCTAC deletion spanning the nucleotides 631-635 of the emerin gene caused an unusually severe disease phenotype including loss of ambulation and severe muscle wasting in two affected brothers. The same mutation has been reported previously in an unrelated family showing a significantly milder phenotype. The interfamilial heterogeneity in distribution and in severity of the features in the two families point to environmental or genetic modification as the cause of clinical variability in Emery-Dreifuss muscular dystrophy.

Adolescent↗
PubMed1998

[Primary high malignancy B-cell lymphoma of the lacrimal sac].

Case report on a 44-year-old woman in good health with the symptoms of epiphora, a plump elastic, not distressing swelling under the medial canthal tendon of 1 cm size on the right side. In ultrasonography and intraoperatively a tumour of moderate reflectivity with infiltration of the lacrimal sac was found. The histological evaluation, including immunohistochemical studies of the removed lesion, revealed a malignant B-cell lymphoma.

Adult↗
PubMed1998

Waterjet dissection of the brain: experimental and first clinical results. Technical note.

Control of bleeding during dissection is a problem that is still not completely resolved in neurosurgical procedures. To overcome this problem in some settings, the authors, in close collaboration with their institution, developed a new device for blunt dissection of brain tumors that is based on a waterjet technique. This report describes their first experimental and clinical experience with this new method. Numerous cutting experiments were performed in porcine cadaver brains. The best results were obtained using pressures from 4 to 6 bars with a 100-microm tip, which produced very small, precise cuts. Histological evaluation showed no disruption or vacuolization of the surrounding tissue. The authors have used the new device in nine patients (seven with gliomas and two undergoing temporal lobe resections for epilepsy), and no complications have been observed. The waterjet device allowed dissection of the brain tissue while even small exposed vessels were spared injury. The instrument was found to be easy to use. Future investigations will concentrate on adapting this new method to endoscopic surgery and evaluating fluids with low surface tension to avoid foaming and bubbling during open surgery.

Animals↗
PubMed1996

Classification, oscillatory and alternating oscillatory firing of alpha 1 (FF) and alpha 2-motoneurons (FR) in patients with spinal cord lesion.

Single-nerve fibre action potentials (APs) were recorded extracellularly from sacral nerve roots of people with spinal cord lesion (patients with paraplegia). Single-fibre APs of certain fibres were identified by the conduction velocity and the AP waveform, and simultaneous impulse patterns were extracted from the summed impulse traffic and analysed with respect to spacio-temporal relationships. The velocity values of components of compound APs, induced by electrical nerve root stimulation or electrical intravesical stimulation, were similar to the group conduction velocity values obtained from single-nerve fibre APs of natural impulse traffic. When changing the root temperature in one case from 32 degrees C to 35.5 degrees C, the group conduction velocities changed in the following way: secondary muscle spindle afferents (SP2): 40 m/s (32 degrees C) to 50 m/s (35.5 degrees C); bladder stretch afferents (S1): 31.3 to 40 m/s; bladder tension afferents (ST): 25 to 33.8 m/s; mucosal afferents (M): 12.5 to 13.8 m/s; alpha 1:-; alpha 2-motoneurons: 40 to 50 m/s; alpha 3: 33 to 40 m/s. The group conduction velocities showed different temperature dependence apart from SP2 fibres and alpha 2-motoneurons, which were therefore used for calibration. The distance between two Pacinian corpuscle (PC) receptors in a sacral dermatome of one paraplegic patient was calculated to be approximately 20 mm. A similar distance between PC receptors was found in a brain-dead individual. Receptor densities seem therefore to remain unchanged following spinal cord lesion. Motoneurons fired irregularly repeatedly with impulse trains. In paraplegics the oscillation periods and the interspike intervals of the impulse trains varied much more than observed for brain-dead and normal individuals. Motoneurons could therefore not always be identified by their pattern of oscillatory firing. Alternating long and short oscillation periods (T) could be measured in an oscillatory firing alpha 1 (T = 125 ms) and alpha 2-motoneuron (T = 150 ms). In both cases the average difference between the alternating oscillation periods was 5 ms. Tremor, alternating long and short oscillation periods, cellular oscillator properties, and recurrent excitation and inhibition are discussed with respect to the oscillator theory of the functioning of the human central nervous system. Mathematical predictions from populations of interacting biological oscillators are compared to measurements on neuronal network data.

Action Potentials↗
PubMed1995

Classification of human peripheral nerve fibre groups by conduction velocity and nerve fibre diameter is preserved following spinal cord lesion.

(1) Single nerve fibre action potentials (APs) of lower sacral nerve roots were recorded extracellularly with two pairs of wire electrodes during an operation in which an anterior root stimulator for bladder control was implanted in 9 humans with a spinal cord lesion and dyssynergia of the urinary bladder. Roots that were not saved and that were used to record from were later used for morphometry. (2) Nerve fibre groups were identified by conduction velocity distribution histograms of single afferent and efferent fibres and partly by nerve fibre diameter distribution histograms, and correlation analysis was performed. Group conduction velocity values were obtained additionally from compound action potentials (CAPs) evoked by electrical stimulation of nerve roots and the urinary bladder. (3) The group conduction velocities and group nerve fibre diameters had the following pair-values at 35.5 degrees C: Spindle afferents: SP1 (65 m/s/13.1 microns), SP2 (51/12.1); touch afferents: T1 (47/11.1), T2 (39/10.1), T3 (27/9.1), T4 (19/8.1); urinary bladder afferents: S1 (41 m/s/-), ST (35/-); alpha-motoneurons: alpha 13 (-/14.4), alpha 12 (65m/s/13.1 microns), alpha 11 (60?/12.1)(FF), alpha 2 (51/10.3)(FR), alpha 3 (41/8.2)(S); gamma-motoneurons: gamma beta (27/7.1), gamma 1 (21/6.6), gamma 21 (16/5.8), gamma 22 (14/5.1); preganglionic parasympathetic motoneurons: (10 m/s/3.7 microns). (4) The values of group conduction velocity and group nerve fibre diameter measured in the paraplegics were very similar to those obtained earlier from brain-dead humans and patients with no spinal cord lesions. Also, the number and the density of myelinated fibres were preserved in the roots. Thus, the classification and identification of nerve fibre groups remained preserved following spinal cord lesion. A direct comparison can thus be made of natural impulse patterns of afferent and efferent nerve fibres between paraplegics (pathologic) and brain-dead humans (supraspinal destroyed CNS, in many respects physiologic). (5) When changing the root temperature from 32 degrees C to 35.5 degrees C, the group conduction velocities changed in the following way in one case: SP2: 40 m/s (32 degrees C) to 50 m/s (35.5 degrees C), S1: 31.3 to 40, ST: 25 to 33.8, M: 12.5 to 13.8; alpha 2: 40 to 50, alpha 3: 33 to 40. The group conduction velocities showed different temperature dependence apart from SP2 fibres and alpha 2-motoneurons. (6) Upon retrograde bladder filling the urinary bladder stretch (S1) and tension receptor afferent (ST) activity levels were undulating and increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Enhancement of nerve fibre regeneration by nucleotides after peripheral nerve crush damage. Electrophysiologic and morphometric investigations.

The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using both morphometric and electroneurophysiologic techniques. After a standardized localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UMP), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of nerve regeneration for comparison with age-matched crushed or nonoperated controls. Electroneurophysiologic studies of right sural nerves were performed as single fibre measurements. Morphometry was performed on semithin transverse sections of the right common peroneal nerve with a fully automatic interactive image analysis system. Forty days after crush injury the single fibre conduction velocity of all type II afferents in the UMP/CMP treated group was significantly accelerated. There was a trend (10% greater than or equal to p greater than or equal to 5%) to increase of mean efferent single nerve fibre function at this time. Morphometry of nerve fibres revealed a trend to enlargement of mean fibre area and mean fibre diameter related to increased myelin area and myelin thickness. After 60 days, there was a trend to increase of single fibre conduction velocity of all type II afferents in the UMP/CMP treated group. Automated morphometry revealed a significant increase for the following parameters: fibre area, fibre diameter, myelin area, myelin thickness and axon area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Mucopolysaccharidoses. Genetics, clinical pathology, therapeutic regimes].

In recent years, several clinical and biochemical studies have been published contributing to better understanding of mucopolysaccharide storage diseases. Our purpose, therefore, is, to give an updated survey of this group of lysosomal diseases for diagnostic orientation to the pathologist. The present classification of mucopolysaccharidoses is based on a mixture of clinical symptoms, demonstration of enzyme defects, analysis of urinary excretion of glycosaminoglycans (mucopolysaccharides) and historical eponyms. A broad heterogeneity has been revealed: identical enzyme defects may lead to severe mental and physical deterioration and death during childhood or to mild forms with normal adult height, intelligence, and life expectancy. Conversely, identical phenotypes may result from mutations of different genes. Various types of mucopolysaccharidoses are mostly characterized by quantitative differences of main symptoms (coarse facial features, various skeletal abnormalities, hepatosplenomegaly, corneal clouding, mental retardation, and cardiac failure). Morphologically, storage material can be observed practically in all tissues by light and/or electron microscopy. Until recently, no more than palliative treatment could be offered. In the last decade, bone marrow transplantation has become available and may have beneficial effects in selected cases. The genes of several lysosomal enzymes have been identified, and comprehensive studies to introduce the gene into defective cells are currently undertaken. However, substantial efforts are still necessary until gene transfer will become available for patients with mucopolysaccharidoses.

Brain↗
PubMed1992

Acceleration of nerve and muscle regeneration by administration of nucleotides--electroneurophysiological and morphometrical investigations.

The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using morphometric techniques. In addition morphometrical investigations of peroneal and soleal muscles were performed at different times. After a localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UM), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of common peroneal nerve regeneration for comparison with age-matched crushed or nonoperated controls. Forty days after daily UMP/CMP administration the single fibre conduction velocity of all type II afferents was significantly accelerated. There was a trend towards increased mean fibre area related to increased myelin area. Mean diameter of type II muscle fibres was increased. After 60 days, there was a trend to increase of single afferent fibre conduction velocity in the UMP/CMP group. In the same group automated morphometry revealed a significant increase of nerve fibre area, myelin area and axon area. At this time an increase was found of type I and/or type II muscle fibres in all animal groups. The present results suggest that both axons (neurons) and myelin sheaths (Schwann cells) of regenerating nerve fibres and regenerating muscle fibres are influenced by nucleotide administration.

Animals↗
PubMed1991

[Acceleration of muscle regeneration by nucleotide administration. Experimental morphometric studies].

Morphometric studies of the peroneus longus muscle as well as of the soleus muscle were performed 20, 40 and 60 days after crush injury of sciatic nerve and continuous administration of nucleotides. 96 female Wistar rats were used in the experiments. Under ether anesthesia a crush injury was performed on the right sciatic nerve. 53 rats were injected daily with nucleotides (uridine monophosphate [UMP], cytidine monophosphate [CMP] or UMP plus CMP [UMP/CMP], respectively), and 43 control animals were given injections of saline. Morphometric studies of right peroneus longus and soleus muscles were performed with the aid of a semiautomatic technique to measure muscle fibre diameters. After 20 days there were no differences between mean muscle fibre diameters. 40 days after the beginning of the experiments semiautomated morphometry revealed an increase of type II fibre diameters in the UMP/CMP group. There were enlargements of type II fibres in the UMP and the CMP group after 60 days. At the same time larger diameters of type I fibres were found in the UMP/CMP group (trend) and in the UMP group. In conclusion the results presented here indicate, that the administration of nucleotides possibly represents a new opportunity for the treatment of traumatic nerve and muscle lesions.

Animals↗
PubMed1991

[Alcoholic encephalopathies in autopsy material].

A report is given on incidence, complications, causes of death, and morphological diagnosis of chronic alcoholism in autopsy material. Chronic alcoholism was registered in 8.4% of all autopsies. The average age at death of alcoholics, particularly female, was significantly lower than that of all autopsy material. Pneumonia was the most frequent direct cause of death (21.1%). Acute ethanol intoxication was in second position (15.8%). Wernicke's encephalopathy was observed in 0.6% of all autopsies (18% of alcoholics), cerebellar atrophy occurred in 0.4% (12%), and central pontine myelinolysis was found in 0.2% (7%). The mean brain weight of alcoholics was 1310 g as compared with 1400 g of controls. Problems of clinical and postmortal diagnosis as well as medical and social consequences are discussed.

Adult↗