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Biomedical subjects

J Schwarz

Publications and source records attributed to J Schwarz.

At least 145 records · Page 8Linked to original sources

Near-tetraploid poorly differentiated acute myeloid leukemia M0 diagnosed by short-term cultures with a phorbol ester TPA.

Leukemic blasts of two patients with acute leukemia exhibited similar characteristics. They were heterogeneous in size with a diameter of 14-30 microns in smears and unclassifiable by morphological, cytochemical, immunophenotypic and ultrastructural examinations. Cytogenetic examinations of both revealed a near-tetraploid karyotype. Blasts from both patients differentiated into macrophages in cultures with 10 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) which is a feature specific for myeloid blasts and the cases were thus classified as poorly differentiated acute myeloid leukemias (AML M0). Near-tetraploid poorly differentiated acute myeloid leukemias M0 seem to be a special category of AML in the morphologic, immunologic and cytogenetic (MIC) classification. The presence of very large blasts in the heterogeneous blast population in acute unclassified leukemias could be a morphological sign of near-tetraploid leukemias AML M0.

Aged↗

Comparison of 123I-IBZM SPECT and 11C-raclopride PET findings in patients with parkinsonism.

We compared the results of 123I-iodobenzamide (123I-IBZM) single photon emission computed tomography (SPECT) and 11C-raclopride positron emission tomography (PET) in 22 patients with parkinsonism. Nineteen patients were clinically diagnosed as having Parkinson's disease, two patients presented with atypical parkinsonism (i.e. clinical signs of Parkinson's disease and a subsequent poor response to dopamimetic drugs) and one patient was diagnosed as having Wilson's disease. All patients were drug naive. The SPECT data were semiquantitatively evaluated by calculating the ratios of striatal (basal ganglia, BG) IBZM binding to IBZM binding in various reference areas, i.e. the frontal cortex (BG/FC), the occipital cortex (BG/OC) and the cerebellum (BG/CE). In PET studies similar regions of interest were derived and ratios of striatal to cerebellar raclopride activity were determined. 123I-IBZM SPECT results significantly correlated to specific 11C-raclopride binding. This correlation was not significantly different when the frontal cortex (P = 0.05, r = 0.42), occipital cortex (P < 0.05), r = 0.44) or cerebellum (P 0.05, r = 0.45) were used as reference regions for non-specific IBZM binding. In comparison to PET ratios the SPECT BG/CE showed a higher variance (S.E.M. = 0.1) than BG/FC (S.E.M. = 0.05) and BG/OC (S.E.M. = 0.06) ratios. Thus, for the calculation of specific striatal IBZM binding one would prefer the frontal or occipital cortex as reference. However, when only those 19 patients with a clinical diagnosis of Parkinson's disease and increased specific 11C-raclopride binding were considered, no significant correlation was obtained. Qualitative changes of dopamine D2 receptor binding, such as asymmetry, were equally recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

D2-dopamine receptor occupancy differs between patients with and without extrapyramidal side effects.

To investigate whether the occurrence of extrapyramidal side effects was related to D2 dopamine receptor occupancy, iodobenzamide single positron emission computed tomography was carried out in 27 schizophrenic patients and 10 controls. Eighteen patients were treated with haloperidol; 9 patients were treated with clozapine. Our data suggest a relationship between D2 receptor occupancy and extrapyramidal side effects as well as the existence of a neuroleptic threshold of a striatal:frontal cortex ratio of 1.2, below which drug-induced exptrapyramidal side effects can be expected.

Adult↗

Treatment with D-penicillamine improves dopamine D2-receptor binding and T2-signal intensity in de novo Wilson's disease.

We report the results of in vivo striatal dopamine D2-receptor binding assessed by PET using 11C-raclopride (only one patient) and by single-photon emission computed tomography (SPECT) using 123I-iodobenzamide (123I-IBZM) and the findings of T2-weighted MRIs in two de novo Wilson's disease patients before and 4 months after initiation of D-penicillamine treatment. Before treatment, specific 11C-raclopride binding (only patient 1) was markedly reduced, with a putamen to cerebellum ratio of 1.99 (controls: 3.99 +/- 0.55, n = 15) and a caudate to cerebellum ratio of 2.52 (controls: 3.65 +/- 0.59, n = 15). Specific 123I-IBZM binding was reduced in both patients, with a basal ganglia to frontal cortex ratio of 1.25 (patient 1) and of 1.41 (patient 2) controls: 1.57 +/- 0.04, n = 5). After 4 months of therapy, 11C-raclopride-PET improved to a putamen to cerebellum ratio of 2.52 and a caudate to cerebellum ratio of 3.06 (patient 1). 123I-IBZM-SPECT revealed an increase of basal ganglia to frontal cortex ratios of 1.34 (patient 1) and 1.55 (patient 2). On heavily T2-weighted MRI sequences, hyperintense signal changes before therapy within the putamen (both patients), brainstem (only patient 1), and caudate (only patient 2) greatly diminished after treatment. Reduced striatal dopamine D2-receptor binding in these Wilson's disease patients improved under therapy, suggesting, in part, a reversible defect of striatal neurons.

Adolescent↗

[11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors.

We studied cerebral dopamine D2-receptor binding using [11C]raclopride and PET in 18 previously untreated patients with Parkinson's disease (PD) and 14 healthy volunteer subjects. Sixteen patients were scanned before and after 3 to 4 months of stable oral therapy with either L-dopa (300 mg/d) (n = 7) or lisuride (0.8 to 1.2 mg/d) (n = 9). Two additional patients were investigated before and after a continuous IV infusion of L-dopa. In addition, we studied the effect of acute IV L-dopa and lisuride administration on [11C]raclopride binding in a healthy rhesus monkey. At baseline, PD patients showed higher uptake values in the putamen than did healthy subjects (p < 0.0001). Oral lisuride treatment lowered [11C]raclopride uptake in the putamen (-19%) and in the caudate nucleus (-15%) compared with baseline, but the difference did not reach significance upon Bonferroni correction for multiple comparisons. However, putamen tracer uptake returned to baseline in two patients when we repeated [11C]raclopride scans 4 days after lisuride withdrawal. Oral L-dopa treatment did not induce changes in the putamen or caudate nucleus indices. Acute lisuride (25 micrograms) administration in a healthy monkey reduced striatal uptake values, but acute injection of L-dopa (300 mg) did not. The results suggest that lisuride blocks [11C]raclopride binding at dopamine D2-receptor sites and demonstrate that 3 to 4 months' oral therapy with L-dopa or lisuride does not change striatal dopamine D2-receptor density in PD patients.

Adult↗

[Late and slow diagnosis of acute promyelocytic leukemias--the main cause of early death].

Acute hypergranular promyelocytic leukemia (AML M3) belongs to malignant diseases leading very rapidly to death. Immediate treatment based on early diagnosis may cure one third of patients. The typical finding in peripheral blood of patients is pancytopenia with or without atypical promyelocytes. In published studies only 15-25% patients exhibit leukocyte counts above 10 x 10(9)/l. Five of our ten patients studied had leukocyte count above 10 x 10(9)/l. The difference might be in connection with late and slow diagnosis of AML M3. AML is not taken into consideration during medical examination even if the disease occurs in medical family. Thus we describe clinical signs of AML M3 that could be divided into three main groups: bleeding, infections and anemia. In patients with bleeding or anemia or with infections repeating within a short period or with an infection and concurrent signs of bleeding or anemia the complete blood cell count should be examined immediately. If blood cell count abnormalities are found the patient should be sent immediately to hematology unit for further examination and treatment. Early diagnosis enables to start "differentiation therapy" with all-trans retinoic acid that could be administered as monotherapy only in patients with leukocytes below 5 x 10(9)/l. Early diagnosis of AML M3 might ameliorate the fate of patients, since four of our five patients referred to us with elevated leukocyte counts expired in the first five days.

Adult↗

[Extrapulmonary tuberculosis with involvement of the reticuloendothelial system and secondary lupus vulgaris].

The authors describe a case of extrapulmonary tuberculosis with affection of the reticuloendothelial system in a 59-year-old female patient. After successful treatment the findings in the spleen, bone marrow and the laboratory results had normal levels. The authors draw attention to the diagnostic difficulties. They were able to confirm the diagnosis only by histological examination of biopsy from the pelvic bone. An interesting finding was eruption of lupus vulgaris on the legs in the course of treatment. The authors discuss some aspects of the disease and its differential diagnosis.

Bone Marrow Diseases↗

Reversible hyperkinesia in a patient with autoimmune polyglandular syndrome type I.

Autoimmune polyglandular syndrome is characterized by a failure of multiple endocrine organs and the presence of circulating organ-specific autoantibodies targeted against the failing organs. Here we describe a patient with autoimmune polyglandular syndrome type I with the endocrine manifestations of hypoparathyroidism, adrenocortical insufficiency, and insulin-dependent diabetes mellitus. Long-standing hypoparathyroidism led to extensive calcification of the basal ganglia which resulted in the clinical presentation of an extrapyramidal movement disorder (choreoathetotic and hemiballistic hyperkinesia of the left extremities). Interestingly, parallel to rehydration and the initiation of cortisol replacement therapy a complete reversion of the hyperkinetic signs was achieved. This case shows a rare multiendocrine organ failure with complex metabolic interactions resulting in marked neurological signs. Furthermore, this case demonstrates for the first time that a hyperkinetic syndrome--most likely due to hypoparathyroidism-induced basal ganglia calcification--can be reversed solely by adequate treatment of the concomitant endocrine failures.

Adrenal Cortex Diseases↗

Investigation of the origin of variant, truncated estrogen receptor-like mRNAs identified in some human breast cancer biopsy samples.

Variant, smaller sized, estrogen receptor-like mRNAs have been previously cloned and sequenced from human breast cancer biopsy samples. In this study we have found that one variant estrogen receptor-like mRNA, clone 24, which is expressed in only one tumor, consists of sequences from the normal ER gene which is found on chromosome 6 and sequences unrelated to the ER which are found normally on chromosome 12. A more commonly occurring variant estrogen receptor-like mRNA, clone 4, contains sequences from the normal ER gene and LINE-1 sequences. Similar but not identical LINE-1 sequences have been found in some of the intervening sequences of the normal ER gene. The generation of these transcripts may involve either alternative splicing or trans-splicing mechanisms.

Animals↗

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↗

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↗

Students can learn medicine with computers. Evaluation of an interactive computer learning package in geriatric medicine.

OBJECTIVE: To assess the effectiveness of a computer-aided learning program on dementia. DESIGN: Fourth year medical students were arbitrarily assigned to groups that used a computer-aided learning program (65) or had a tutorial covering similar material (73). These sessions were in addition to a base curriculum in a two-week course in geriatric medicine. MAIN OUTCOME MEASURES: The effectiveness of the teaching sessions was judged by the performance on a multiple choice questionnaire about dementia, given to the students on two occasions, one at the beginning and one at the end of the two-week course. RESULTS: Both groups of students scored significantly better on the second test (computer group, 66% [95% confidence interval, 64-69] to 81% [79-83] and tutorial group, 66% [63-67] to 74% [73-77]). The difference between the groups at the start of the course was not significant (F1,136 = 0.61, P = 0.61); however, there was a significant difference between the groups at the end of the course (F1,136 = 21.83, P < 0.001). CONCLUSION: Both groups improved their knowledge of dementia during the two-week course. Students who used the computer-aided learning programs showed a greater improvement in score. Computer learning programs are effective learning tools and are a useful addition to traditional teaching methods. Further study is required to assess the effects of computer-aided learning programs in long-term studies of dementia knowledge.

Computer Literacy↗

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↗

Decrease of D2 receptors indicated by 123I-iodobenzamide single-photon emission computed tomography relates to neurological deficit in treated Wilson's disease.

Single-photon emission computed tomography with 123I-iodobenzamide, a dopamine D2 receptor antagonist, was employed to study dopamine D2 receptor densities in 17 patients with biochemically proved Wilson's disease and stable neurological status with therapy and in 5 age-matched control subjects. Of the 17 patients with Wilson's disease, 5 were neurologically asymptomatic, 3 had cerebellar signs, 1 exhibited a mild parkinsonian syndrome, 7 showed a parkinsonian syndrome and cerebellar signs, and 1 had generalized dystonia and a parkinsonian syndrome. In 5 age-matched control subjects specific isotope binding as calculated by the basal ganglia to frontal cortex ratio was 1.57 +/- 0.04 (mean +/- standard deviation). The ratio in patients with Wilson's disease ranged from 1.56 +/- 0.05 (n = 5, asymptomatic patients) to 1.17 +/- 0.02 (n = 4, marked neurological impairment). We observed an almost linear correlation between the reduction of 123I-iodobenzamide (IBZM) binding and the severity of neurological signs at the time of IBZM-SPECT (correlation coefficient, -0.84; p < 0.01). We suggest that the reduction of postsynaptic striatal dopamine D2 receptors as detected by IBZM-SPECT reflects striatal neuronal damage in Wilson's disease.

Adolescent↗

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↗