[Injury of polyester grafts by vascular clamps]. / Schädigung von Polyestergefässprothesen durch Gefässklemmen.

UNLABELLED: Protected vascular clamps are not new. Clamp associated damage of human arteries has already been published over 20 years ago. The necessity of protective clamps seems to have been forgotten. In our explant archive (230 explants) we have observed an accumulation of graft ruptures in the groin (13 of 25 ruptures). We presume a multifactorial process. Clamp damage could be part of it. The aim of this study is to prove the clamp induced damage of polyester vascular grafts and to examine whether protected clamps can reduce this. METHOD: Five unprotected (Aesculap(R) FB512R, FB502, FB517, Ulrich CC1235, CV3535) and 5 protected vascular clamp types (Aesculap(R) FB667, FB668, Edwards(R) - formally Baxter(R) - Fogarty(R) CV5050, CV5201, Edwards(R) Cosgrove(R) CV1033) were tested. A longitudinal burst test was performed after maximal clamp closure on 6 different, multifilament polyester yarns of 2 different vascular grafts manufacturers (B. Braun(R), Edwards(R)). RESULTS: The yarn tests with protected clamps showed no difference to those of the unclamped yarns. After clamping with unprotected vascular clamps the stress-strain-diagrams differed significantly. The mean, maximum burst strength was up to 75 % lower. Video documentation revealed filament ruptures. Damage of the yarn surface was seen on a simple woven graft in scanning electron microscopy (SEM). DISCUSSION: The application of unprotected vascular clamps on polyester vascular grafts is common in Germany (56 %). The observed damage of multifilament polyester yarns makes it necessary to re-consider the use of unprotected vascular clamps. The benefit for biological vessels has already been shown.

[Late complications after alloplastic vascular replacement]. / Spätkomplikationen nach alloplastischem Gefässersatz.

The follow-up of 273 AAA patients operated 1981-1985 showed a mean dilation of polyester grafts of 17.4% in 12 days and 34.8% in 3 years. This early dilation is due to mesh expansion of the warp knitted grafts. It has no clinical relevance. In contrary the late dilation after approximately 10 years is due to degradation. The evaluation of 436 explanted grafts attained from 75 hospitals showed graft rupture to be the cause of the explanation for 42/255 (16%) polyester grafts and 2/42 (5%) PTFE grafts. The most ruptures were observed in the surrounding of the inguinal ligament after 10 to 20 years of duration. In comparison to modern endovascular grafts the conventional polyester and PTFE grafts still are the gold standard of durability.

A new pyrrolyl-quinoxalinedione series of non-NMDA glutamate receptor antagonists: pharmacological characterization and comparison with NBQX and valproate in the kindling model of epilepsy.

Antagonists at the ionotropic non-NMDA [AMPA (amino-methyl proprionic acid)/kainate] type of glutamate receptors have been suggested to possess several advantages compared to NMDA (N-methyl-D-aspartate) receptor antagonists, particularly in terms of risk/benefit ratio, but the non-NMDA receptor antagonists available so far have not fulfilled this promise. From a large series of pyrrolyl-quinoxalinedione derivatives, we selected six new competitive non-NMDA receptor antagonists. The basis of selection was high potency and selectivity for AMPA and/or kainate receptors, high in vivo potency after systemic administration, and an acceptable ratio between neuroprotective or anticonvulsant effects and adverse effects. Pharmacological characteristics of these novel compounds are described in this study with special emphasis on their effects in the kindling model of temporal lobe epilepsy, the most common type of epilepsy in humans. In most experiments, NBQX and the major antiepileptic drug valproate were used for comparison with the novel compounds. The novel non-NMDA receptor antagonists markedly differed in their AMPA and kainate receptor affinities from NBQX. Thus, while NBQX essentially did not bind to kainate receptors at relevant concentrations, several of the novel compounds exhibited affinity to rat brain kainate receptors or recombinant kainate receptor subtypes in addition to AMPA receptors. One compound, LU 97175, bound to native high affinity kainate receptors and rat GluR5-GluR7 subunits, i.e. low affinity kainate binding sites, with much higher affinities than to AMPA receptors. All compounds potently blocked AMPA-induced cell death in vitro and, except LU 97175, AMPA-induced convulsions in vivo. In the kindling model, compounds with a high affinity for GluR7 (LU 97175) or compounds (LU 115455, LU 136541) which potently bind to AMPA receptors and low affinity kainate receptor subunits were potent anticonvulsants in the kindling model, whereas the AMPA receptor-selective LU 112313 was the least selective compound in this model, indicating that non-NMDA antagonists acting at both AMPA and kainate receptors are more effective in this model than AMPA receptor-selective drugs. Three of the novel compounds, i.e. LU 97175, LU 115455 and LU 136541, exerted potent anticonvulsant effects without inducing motor impairment in the rotarod test. This combination of actions is thought to be a prerequisite for selective anticonvulsant drug action.

Effects of the skin mitogens tumor-promotor 12-O-tetradecanoylphorbol 13-acetate and divalent-cation-ionophore A23187 on ion fluxes and membrane potential in a murine epidermal cell line (HEL30) and in 3T3 fibroblasts.

The transmembrane potential of HEL30 keratinocytes and 3T3 fibroblasts has been determined by measuring the distribution of labelled triphenylmethylphosphonium bromide. The tumor-promotor 12-O-tetradecanoylphorbol 13-acetate (1-5 microM) induces hyperpolarization in 3T3 cells but does not exert any effect on the membrane potential of keratinocytes, whereas the divalent cation ionophore A23187 (0.5 - 1 microM) hyperpolarizes keratinocytes and probably also 3T3 cells. Studies on Na+ and Rb+ fluxes, as well as with different inhibitors, indicate that the hyperpolarizing effect is the consequence of an increased Na+ influx which in turn stimulates the Na+/K+-dependent ATPase. No causal relationship seems to exist between the change of the membrane potential and arachidonic acid release (and subsequent prostaglandin synthesis) which is induced by both drugs in both cell lines. Since the induction of the arachidonic cascade (by both agents) as well as the stimulation of Na+ influx (by A23187) are found to be critically dependent on extracellular Ca2+ and are inhibited by 'Ca2+-blockers', it is concluded that both reactions are triggered by the same event (Ca2+ translocation) but proceed independently of each other. The release of arachidonic acid is already stimulated under conditions where a measurable influx of Ca2+ is not yet observed. This indicates a local mobilization of Ca2+, perhaps across the plasma membrane. It is concluded that monovalent cation fluxes and changes of the membrane potential are not critically involved in the stimulation of the arachidonic acid cascade and cellular proliferation by agents which induce epidermal hyperplasia in vivo.

Adult GM2 gangliosidosis masquerading as slowly progressive muscular atrophy: motor neuron disease phenotype.

Ultrastructural and biochemical studies were performed on postmortem material of a 67-year-old woman presenting with proximal muscle weakness in the legs, slurred speech, and mental subnormality. The symptoms began at age 19 and showed extremely slow progression, mimicking progressive muscular dystrophy. A brother suffered from a similar chronic neuromuscular disease, and two sisters died at an early age from unknown "nervous" diseases. Autopsy disclosed abundant lipid accumulation in CNS neurons and severe cerebellar cortical atrophy of the granule cell type. Skeletal muscle showed a terminal stage of denervation atrophy with severe lipomatosis; intrafusal fibers of muscle spindles contained lipid deposits. Complex lamellar cytoplasmic inclusions often resembling membranous cytoplasmic bodies or stacked membranes were seen in cells of the brain. In addition, there were various lipopigment bodies, fingerprint profiles, rare polyglucosan bodies, rodlike structures, and filamentous sheaves, particularly in substantia nigra. Accumulation of gangliosides GM2 and GA2 in the cerebral cortex was demonstrated by thin-layer chromatography. Determination of hexosaminidase activity was not possible (formalin-fixed material). This observation, in addition to the cases reported by Navon et al. [1981] and Johnson [1982], is suggested to represent a new phenotype of adult-onset GM2 gangliosidosis referred to as motor neuron disease phenotype, which can be differentiated from other adult-onset lipidoses and motor neuron disorders. Our paper emphasizes the importance of ultrastructural demonstration of lamellar inclusions for the differential diagnosis of ceroid lipofuscinosis, and the value of biochemical studies in the diagnostic clarification of atypical neuromuscular disorders.

[Problems in water bed therapy from the point of view of the neurologist (author's transl)]. / Die Wasserbetttherapieproblematik aus neurologischer Sicht.

Patients suffering from various diseases are hospitalized in water beds for therapeutical reasons. By means of a detailed report on the course of the disease in 3 characteristic cases it can be shown, that water bed therapy is an useful additional therapeutic measure in critical situations. Thrombotic attacks, which take place as side-effects in some cases, seem to be caused by a retardation of the bloodstream and have to be treated with conventional antithrombotic therapy. Apart from hemodynamic factors also the temperature of the water might take part in provoking thrombotic attacks.

Benign and malignant types of Parkinson's disease: clinical and patho-physiological characterization.

Parkinson's disease (P.D.) is characterized by two different types, a benign form found in 85% of patients and a malignant type in 15%. Computer tomography shows malignant patients, in the end stage of the disease process, to exhibit hydrocephalus internus and externus. Such patients exhibit early EEG-deterioration and pharmacotoxic psychosis. The application of neuroleptics to patients with P.D. is associated with an increase in the urinary excretion of acidic metabolites especially of 5-hydroxyindoleacetic acid. It is suggested, that this treatment might also be a useful therapeutic approach to optimizing the residual neuronal function in Parkinson's disease.

Hereditary cerebellar atrophy (Holmes type) with optic atrophy: a clinico-pathological study of four generations in a family.

A family with a dominantly inherited progressive cerebellar ataxia is described; four members of successive generations were affected. Neuropathological examination of one family member classified this disorder as hereditary cerebellar atrophy of Holmes type. An associated optic atrophy has not been previously reported in this disease.

[Familial striatal degeneration (author's transl)]. / Familiäre Striatumdegeneration.

An extrapyramidal disorder occurring in three generations of a family (only males) is described The clinical features were progressive dementia and extrapyramidal signs without choreiform hyperkinesia. The youngest patient (onset of disease at the age of 22 years) showed tremor, rigidity, ataxia, convulsions, and myoclonus. The neuropathologic findings were characterized by isolated symmetrical degeneration of the corpus striatum and diffuse cortical atrophy without affecting other cerebrospinal neuronal systems. The clinical features of this familial disorder and its relation to other types of familial striatal degeneration and to the juvenile form of Huntington's chorea are discussed.

Amphetamine and 2-phenylethylamine in post-mortem Parkinsonian brain after (-)deprenyl administration.

Deprenyl is an inhibitor of monoamine oxidase type B, the enzyme responsible for 2-phenylethylamine oxidation, and is used in conjunction with L-Dopa therapy in Parkinson's disease. Post-mortem studies in human brain tissue have shown that after (-)deprenyl administration to parkinsonian patients amphetamine is present in concentrations up to 56 ng/g. It also could be shown that phenylethylamine concentrations are substantially increased in such patients. Phenylethylamine and amphetamine have been investigated using a gas chromatographic technique.

CNS Modulation of adrenal tyrosine hydroxylase in Parkinson's disease and metabolic encephalopathies.

Tyrosine hydroxylase (TH) activity was assayed radioenzymatically in various regions of post-mortem brains of human individuals without neurologic disorders (controls), with Parkinson's disease, senile dementia, hypertensive encephalopathy, hepatic and diabetic coma, liver cirrhosis without coma, and hepatic coma treated with parenteral administration of L-valine. In addition TH activity of the post-mortem adrenal medulla was assayed in controls, in Parkinson's disease, senile dementia and hypertensive encephalopathy. In Parkinson's disease TH activity was significantly decreased in the nigrostriatal system, and less severe in other brainstem areas, while the raphé-reticular formation and limbic system showed normal values. In addition, there was significant decrease in the TH activity of the adrenal medulla, suggesting that Parkinson's disease is a generalized disorder not limited to distinct CNS areas, and that impairment of the dopaminergic niggro-striatal system may involve the TH activity in the adrenal medulla, thus inducing disorders of the peripheral sympathetic system. Senile brain atrophy showed no definite changes in brain, except the striatum, and adrenomedullary TH, while in one case of hypertensive encephalopathy due to long-term corticosteroid treatment normal TH activity in the adrenal medulla was opposed by decreased striatal TH activity, probably due to cerebral ischemia. TH activity in the caudate nucleus of individuals with both hepatic and diabetic coma were within normal ranges, suggesting a sufficient energy supply of the brain during such metabolic catastrophes, while reduced brain TH activity in patients with hepatic coma who died of acute gastrointestinal bleeding is probably due to severe final cerebral ischemia. No correlative data on brain and adrenomedullary TH activities in metabolic encephalopathies are available so far.

Brain-noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson's syndrome.

1. Significantly reduced values of noradrenaline in Parkinson's disease were observable in all brain areas which were studied. 2. A topographic distribution of free 3-methoxy-4-hydroxyphenylglycol (MHPG) can be demonstrated in the human brain. As MHPG in the various brain areas shows a different pattern of concentration it seems that this metabolite of noradrenaline is of physiological significance and is able to reflect noradrenaline turnover. The highest values of free MHPG were found in the hypothalamus, n. accumbens, thalamus and n. ruber. 3. In a limited series of patients with Parkinson's disease post mortem analysis indicated lower values of MHPG in caudate n., putamen, s. nigra, red nucleus and n. accumbens. All other brain areas did not show significant alterations. 4. Parkinsonian patients who died during Madopar therapy demonstrated a significant increase of MHPG in caudate n., putamen, s. nigra, n. ruber, n. amygdalae and n. accumbens when compared to the untreated group, indicating an enhanced turnover of noradrenaline in these areas. 5. Bound MHPG has been estimated in various brain areas as to be in the range of 13--38 percent of free MHPG.