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Biomedical subjects

G Arnold

Publications and source records attributed to G Arnold.

At least 109 records · Page 6Linked to original sources

3H-spiperone binding to lymphocytes fails in the differential diagnosis of de novo Parkinson syndromes.

In order to investigate the diagnostic value of 3H-spiperone binding capacity to lymphocytes in the differential diagnosis of de novo Parkinson's disease (idiopathic Parkinson syndrome, PD), we performed a double blind prospective study of spiperone binding capacity of 123 patients and 23 healthy control persons, belonging to different diagnostic groups (PD, Parkinsonian syndrome due to vascular lesions, multiple system atrophy [MSA], essential tremor). Diagnoses were based on medical history, clinical examination, CT or MRI scan, acute response to dopamimetic drugs, one year follow up, and long term response to L-DOPA treatment. Spiperone binding was assayed using ten different concentrations (0.03-3 nmol) in absence or presence of 1 mumol (+)-butaclamol to determine nonspecific binding. There was no significant difference in spiperone binding between patients with PD not treated with L-DOPA, and patients with other basal ganglia disorders including parkinsonian syndrome due to vascular lesions, multiple system atrophy, or progressive supranuclear palsy, and age matched controls. Binding was significantly higher in parkinsonian patients with PD treated with L-DOPA and patients with essential tremor. It is concluded that at present 3H-spiperone binding gives no further information in the differential diagnosis of de novo Parkinson's disease.

Adult↗

[In vitro diagnosis of coronary plaque morphology with intravascular ultrasound: comparison with histopathologic findings].

The aim of this study was to validate the accuracy of a commercially available intravascular ultrasound system in diagnosing plaque composition in human coronary arteries. Thirty-five coronary arteries of 18 human autopsy hearts were perfused with NaCl under a pressure of 100 mmHg and examined using a Diasonics ultrasound system and 4.8 F 20 MHz catheters. An ultrasound diagnosis was made of 139 coronary sections using previously published standard criteria and compared with histologic findings. In addition, the influence of the histologic pattern of lipid and calcific deposits on the accuracy of the ultrasound diagnosis was evaluated. Of the 25 sections with a histologically normal intima, 14 (56%) were correctly identified by ultrasound, whereas fibrotic thickening was diagnosed in the remaining 11 sections. There were 114 plaques by histology which were correctly visualized by ultrasound as plaques in all instances. Plaque calcification was correctly diagnosed in 54 of 63 (86%) sections, but massive calcifications were more reliably identified by ultrasound than small speckled calcifications (43/44 = 98% vs 11/19 = 58%, p < 0.001). Fibrosis was present in all 114 plaques and was correctly visualized by ultrasound in all instances. When lipid was diagnosed by ultrasound as a homogeneous zone of low signal intensity within a fibrous plaque as suggested in the literature, lipid accumulations were identified with a sensitivity of 26% (16/62) and a specificity of 92% (71/77). When lipids were diagnosed if more than a quarter of the plaque area showed lower signal intensity than the tissue surrounding the vessel, the sensitivity of ultrasound was improved to 73% (45/62) but specificity fell to 30% (23/77). The entire histologic composition of a section was correctly diagnosed by ultrasound in only 42% of the 139 sections. Further technical improvements are therefore mandatory before intracoronary ultrasound will be able to provide a reliable analysis of plaque composition, especially of the lipid content.

Adult↗

123I-iodobenzamide-SPECT in 83 patients with de novo parkinsonism.

Single photon emission computed tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) was used in a prospective study to investigate 83 patients with parkinsonism (Hoehn and Yahr stages I to III) who had not been previously treated with dopamimetic drugs. All patients had clinical signs that were compatible with Parkinson's disease. An additional 13 patients had clinical signs of another basal ganglia disorder, such as progressive supranuclear palsy or multisystem atrophy. 123I-IBZM-SPECT results were compared with clinical responses to subcutaneous injections of the D1/D2-receptor agonist apomorphine (83 patients) and to long-term oral dopamimetic therapy (62 patients). Results from 123I-IBZM-SPECT predicted a positive or negative response to apomorphine in 69 of 76 patients (apomorphine responses were equivocal in 7 patients) and a response to dopamimetic therapy in 54 of 62 patients. All patients with a clinical diagnosis of progressive supranuclear palsy or multisystem atrophy had reduced 123I-IBZM binding. In six of these patients, the response to apomorphine was negative, and none clearly benefited from long-term oral levodopa therapy. Imaging of dopamine D2 receptors with 123I-IBZM-SPECT appears to distinguish between patients with de novo parkinsonism that is levodopa-responsive (probably Parkinson's disease of Lewy body type) and that which does not respond to levodopa therapy.

Adult↗

IBZM-SPECT as predictor for dopamimetic responsiveness of patients with de novo parkinsonian syndrome.

IBZM-SPECT is useful as a predictor for the responsiveness to oral L-DOPA therapy in de novo parkinsonian patients. A reduction of postsynaptic dopamine D2 receptors in de novo parkinsonian patients makes the diagnosis of Parkinson's disease rather unlikely. Normal IBZM binding does not prove the diagnosis of Parkinson's disease; however, together with a positive apomorphine test, it strongly supports the clinical diagnosis. At present the combination of IBZM-SPECT and apomorphine testing appears to be a useful procedure for selecting de novo patients for clinical trials with new anti-parkinsonian therapy.

Administration, Oral↗

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↗