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Biomedical subjects

G Arnold

Publications and source records attributed to G Arnold.

At least 19 recordsLinked to original sources

Do NMDA receptor antagonists protect against MPTP-toxicity? Biochemical and immunocytochemical analyses in black mice.

We investigated whether excitatory amino acids acting at the N-methyl-D-aspartate (NMDA) subtype of the L-glutamate receptor contribute to the dopaminergic neurotoxicity induced by systemic administration of the Parkinson's syndrome-inducing toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl/6 mice. The MPTP-regimen chosen (30-40 mg/kg body weight subcutaneously) resulted a 60-70% depletion of striatal dopamine (DA) content and a 20% reduction of tyrosine hydroxylase immunoreactive (TH-IR) cells in the substantia nigra pars compacta 20 days after administration. Repeated systemic coadministration of the non-competitive NMDA receptor antagonist MK-801 or of the novel competitive NMDA receptor antagonist CGP 40116 did not protect against MPTP-induced striatal DA depletion 20 days after toxin administration. Additionally, no short-term protective effects of MK-801 on striatal DA content were observed 24, 48, and 96 h, respectively, after exposure to MPTP. A slight and non-significant attenuation (approximately 10%) of the MPTP-induced decrease in the number of nigral TH-IR cells was observed after MK-801- and CGP 40116-treatment. We conclude that neurotoxicity of systemically administered MPTP is not substantially antagonized by NMDA receptor antagonists in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Apomorphine test for dopaminergic responsiveness in patients with previously untreated Parkinson's disease.

We prospectively examined the predictive value of the apomorphine test for the therapeutic efficacy of sustained oral levodopa treatment in 62 patients with de novo Parkinson syndrome (no additional neurological deficit) who had not previously been treated with dopaminergic medication. Patients received 2 to 5 mg of apomorphine hydrochloride subcutaneously and a subsequent trial of oral levodopa of at least 3 months' duration. In three patients, response to apomorphine could not be evaluated owing to side effects experienced during the test. In the remaining 59 patients, the best predictor of response to oral levodopa was the apomorphine-induced relative decrease in the scores on the motor examination part of the Unified Parkinson Disease Rating Scale (UPDRS). At a cutoff value of 20% improvement in UPDRS scores, the test predicted the response to levodopa correctly in 50 patients (85%). The sensitivity of the test was 90%, specificity 88%. The positive predictive value was 95%. However, seven of 19 apomorphine test-negative patients experienced a good (n = 4) or partial (n = 3) improvement with levodopa therapy. Thus, the negative predictive value was only 63%. We conclude that response to apomorphine has a high predictive value for response to sustained oral levodopa treatment in most previously untreated patients, but a negative test should not preclude an adequate trial of oral levodopa.

Adult

Marked reduction of striatal dopamine D2 receptors as detected by 123IBZM-SPECT in a Wilson's disease patient with generalized dystonia.

[123I]iodobenzamide-single photon emission computed tomography (IBZM-SPECT) was employed to study the distribution of dopamine D2 receptors in a patient with biochemically proven Wilson's disease presenting with generalized dystonia. IBZM is a dopamine D2 receptor antagonist with high affinity and specific binding to basal ganglia detectable by SPECT. IBZM-SPECT in this patient (age, 20 years) displayed a striatum to frontal cortex ratio of 1.2 compared to 1.55 +/- 0.05 (mean +/- SD) in normal controls (n = 7; mean age, 53.3 years). In parallel with this finding, MRI with heavily T2-weighted sequences showed atrophy and low signal intensity changes of the basal ganglia. There was no improvement of dystonia after a subcutaneous injection of apomorphine. In contrast, IBZM-SPECT of a neurologically asymptomatic Wilson's disease patient (age, 21 years) displayed a striatum to frontal cortex ratio of 1.6. The MRI scan of this patient was normal. It is suggested that the observed apomorphine-unresponsive generalized dystonia in this Wilson's disease patient is related to striatal lesions proven by IBZM-SPECT and MRI.

Adult

Folinic acid therapy fails to improve early Parkinson's disease: a two week placebo controlled clinical trial.

Folinic acid (15 mg bid, po) was administered in a two week, double-blind, placebocontrolled, cross over clinical trial in 5 patients with Parkinson's disease (Hoehn and Yahr stage I or II). 4 patients had not been on L-dopa treatment prior to entering this trial and one patient was on a small dose of L-dopa. No significant improvement could be detected in this pilot study by clinical evaluation and motor performance assessed by a computer assisted motor performance test.

Adult

The competitive NMDA antagonist CGP40.116 enhances L-dopa response in MPTP-treated marmosets.

Experiments in MPTP-treated non-human primates testing potential antiparkinsonian action have shown both, beneficial and adverse effects of gutamate receptor antagonists. To investigate this matter further, the novel competitive NMDA antagonist CGP40.116 was administered systemically to three adult MPTP-treated marmosets. When coadministered subcutaneously with a subthreshold dose of L-DOPA, 2 mg/kg, CGP40.116 25-250 micrograms/kg, increased locomotor activity. However, when administered alone, CGP40.116 had no effect on locomotor activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

123I-iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism.

We used 123I-iodobenzamide-single photon emission computed tomography (IBZM-SPECT) in a prospective study to investigate 38 patients with parkinsonism (Hoehn and Yahr stage I to III) not previously treated with dopamimetic drugs. Thirty-four patients only showed symptoms of Parkinson's disease, and four patients showed, in addition, subtle clinical signs of progressive supranuclear palsy or multisystem atrophy. IBZM is a dopamine D2 receptor antagonist detectable by SPECT. We compared IBZM-SPECT results with clinical response to subcutaneous injections of the D1/D2 dopamine receptor agonist apomorphine (38 patients) and long-term dopamimetic therapy (31 patients). IBZM-SPECT results predicted a positive or negative response to apomorphine in 30 of 34 patients (apomorphine response in four patients was equivocal) and response to dopamimetic therapy in 27 of 31 patients. Thus, imaging of dopamine D2 receptors using readily available IBZM-SPECT seems to distinguish between L-dopa-responsive (most likely Parkinson's disease of Lewy body type) and L-dopa-unresponsive parkinsonism in patients not previously treated with dopamimetic drugs.

Adult

[Peri-graft reaction. A complication after implantation of a prosthesis shunt in children with congenital cyanotic heart defects].

Two different clinical manifestations of perigraft-reactions complicating the implantation of prosthetic aortopulmonary shunts in children with cyanotic congenital heart disease are described and discussed. The incidence of this complication in the past 5 years in our own patients was 3%. The appearance of a localized mass on the chest film surrounding the prosthesis requires the exclusion of a hematoma, aneurysm or inflammation. In the case of a massive serous pleural effusion examination of the ingredients leads to diagnosis. Concerning our own patients the fluid is identical with serum; the leakage through the prosthesis can therefore be called plasmapheresis. The claimed pathogenetic causes are discussed intensively, including a chylothorax promoting this complication in the second case. Local variations in porosity and structure of the implanted prosthesis may play a critical role in the pathogenesis of perigraft-reaction, as indicated by both our reported cases. In the event of unsuccessful observation of a localized perigraft seroma or of unsuccessful chest drainage of a massive pleural serous effusion, graft replacement and placement of a different graft material are found to have the best results.

Blood Vessel Prosthesis

Pressure induced hypertrophy in the hearts of growing dwarf pigs.

The left ventricles of 8 sibling dwarf pigs were stressed by banding the aorta ascendens for 7 to 49 days. There was no developmental retardation. Neither light nor electron microscopic controls showed signs of insufficiency. 3.7 X 10(7) Bq/kg (1 mCi/kg) body weight (3 H-)methyl thymidine had been applied as pulse at the end of the experiment. The 3 H-index (LI) of the left ventricular wall increases with the pressure registered (r = 0.95). At the same time the values for the right ventricular wall and the left atrium showed an inverse tendency corresponding to the fact that all indices decrease during normal growth. The relation of the indices is two to one for each atrium and its corresponding ventricle, as well as for the stressed left ventricular wall to the right one. The 3 H marked cells are found in groups with constant distances (75-85 microns). High LI are the consequences of the enlargement of these groups. There is no detectable relation to an anatomic structure. Some rare mitoses could be seen, especially in the left ventricular wall. Signs of a high biochemical activity are accumulations of mitochondria, high number of polysomes and large Golgi areas as well as laminas of ergastoplasm. The nuclei are extremely invaginated.

Animals

[Acute tonsillitis: clinical symptoms; bacteriologic culture and rapid test as deciding criteria for the use of antibiotics].

In order to prevent late sequelae from an untreated streptococcal pharyngitis all patients with streptococcal tonsillitis/pharyngitis have to be treated with antibiotics, preferably penicillin. A correct diagnosis by clinical criteria is only achievable in 72% of patients with streptococcal pharyngitis. Additional criteria such as diagnosis by culture are, therefore, mandatory. Time is a major disadvantage of traditional culture methods. Slide agglutination tests show an acceptable sensitivity of 92% and a specificity of 93%. Due to the possibility of false negative test results, with consequent withholding of adequate antimicrobial chemotherapy, these test results should be used only as a valuable guide. Decision to administer an antibiotic should still be based on clinical criteria.

Adolescent

[Saccular initial segments of the lymphatic vessel system].

It is commonly said that the lymphatic system begins "blindly" as saccular outpocketings. In order to examine these saccular outpocketings, 120 injections into the conjunctival lymphatics of 60 bovine postmortem eyes were carried out, measuring the level of injection pressure and simultaneously documenting the various filling stages photographically. 20 trials were selected for further analysis. We recorded low initial pressures when the tip of the needle was situated close to a larger lymphatic vessel and the coloured solution (1% aqueous Berliner Blue) as possibly applied intravascularly. Higher initial pressures were seen on positioning inside fine networks of vessels. Extremely high initial pressures without any visible filling of vessels but in the presence of simultaneously increasing depots of dye were probably caused by absent or insufficient connection between the tip of the needle and a vessel. During lymphography numerous coarser and finer, tube-like projections (saccular outpocketings) filled, from which further progression of the coloured solution could only be observed when higher injection pressures were applied. We were able to prove that such segments had connections to neighbouring vessels as well as forming plexus of their own. Based on our findings we have reason to doubt the existence of tube-like initial segments in the lymphatic system. Rather in the conjunctiva of the bovine eye this system has the structure of a fine network where tube-like segments can be demonstrated as temporary filling stages.

Animals

[The significance of sonography and computed tomography for the diagnosis of the intraperitoneal spread of tumors. Findings in 307 cases of peritoneal carcinosis].

Taking the results of 307 cases with peritoneal carcinomatosis, the diagnostic value of ultrasonography and computerized tomography in the detection of peritoneal spread of gynaecological and gastrointestinal tumors is discussed. Ascites is the most important, though nonspecific, symptom which can be detected with the greatest accuracy. Peritoneal nodular lesions as well as omental and/or mesenteric involvement can easily be missed by both methods. Thus, staging-laparotomy cannot be replaced in the management of gynecologic malignancies.

Female

[Advantages of biplane transesophageal echocardiography].

Biplane transesophageal echocardiography (BTEE) was intraoperatively performed on 27 patients; ten patients with coronary artery bypass graft surgery, ten with aortic valve replacement, five with mitral valve replacement, one with reconstruction of complete AV-canal, and one with surgical repair of dissecting aortic aneurysm. Compared with the transverse views of the monoplane TEE, BTEE permits the following additional images of the heart: 1) Longitudinal "two-chamber-view" for assessment of left ventricular (LV) anterior, apical, and posterior wall motion, and for assessment of mitral valve anatomy and function (e.g., grading of color flow regurgitation). 2) Imaging of the right-ventricular outflow tract (RVOT) for evaluation of RVOT obstruction, including a crosswise imaging of aortic valve. 3) Proximal two-thirds of the aorta ascendens for the diagnosis of dissecting aortic aneurysm (de Bakey Types I and II). 4) Imaging of the superior vena cava, helpful for detecting transposition of pulmonary veins. 5) Apex of left ventricle, advantageous for detecting thrombus. 6) Longitudinal view of the descending aorta: from the origin of the left subclavian artery down to the origin of the coeliac artery (origins of both vessels, inclusively). We prepared post mortem sections of the heart corresponding to the longitudinal echocardiographic views and documented them by photography. In conclusion, the second plane provides an important improvement in semi-invasive imaging of the heart.

Adult

Organization of collagen and other extracellular material in anterior capsular cataract.

Capsular cataract takes the form of a white-grey opacity appearing under the anterior lens capsule (anterior subcapsular cataract). The capsule is wrinkled through the action of myofibroblast-like cells developed from the anterior lenticular epithelium. The myofibroblast-like cells also produce collagen that takes on a dysplastic appearance. Collagenous microfibrils accumulate to form fibre-like aggregations. These aggregations represent an abnormal collagen density (collagen condensation or attraction) in comparison to normal collagenous fibrils and fibres. Within the anterior capsular cataract 4 topological regions may be distinguished: Cell regions (1), stratification regions (2), aggregation regions (3), and intermediate regions (4). It is postulated that these regions represent different stages in the maturation and degradation of collagen, in the absence of phagocytic elements.

Cataract

[Life after urostomy. A retrospective study].

The study reported, which was based on a questionnaire and psychological tests, examined cystostomy patients with respect to the work-up and acceptance of their altered body. It was noted that 30% of the patients judged their situation as good, and 25% could accept the cystostomy, but a great many has to live with sexual disturbances, reduced social mobility, increased dependence, and psychic consequences; some had to give up their jobs. Sex, earlier psychosomatic diseases, developmental disorders in early childhood, which influence the personality, significantly affect the acceptance of the stoma. The problems are discussed. Suggestions are made, which include a plan for a holistic therapy.

Adaptation, Psychological

[Thermoanalytic studies of bundles of collagen fibers with biomechanical methods].

Thermomechanical experiments were performed on collagenous fibre bundles of tendons from cattle and man. Subsequent to extensions of fibre bundles the particular amount of length was kept constant (isometric conditions). At the end of the relaxation under approximative equilibrium conditions (mechanical steady state phase) the temperature was raised proportional to time (with linear temperature rate). In the range between 0 and 43 degrees Celsius the isometric force decreased in form of an approximately straight line. This line was declined at 43 degrees C (thermal depression region). After the thermal shrinkage region (62-64 degrees C) the isometric force increased considerably. In this ascending part of the isometric thermal mechanogram 2 domains of slope can be observed. They are designed as lower and upper thermal transition region. In the ascending part of the isometric thermal mechanogram an isothermal relaxation is to be seen under constant temperature conditions. The isothermal isorheological line and isothermal superelevation are described. The results are discussed in context with their meaning for functional anatomy, muscle physiology, supercoolings, and burnings.

Animals