Growth plate injury of the long bones in treated β-thalassemia

In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50–80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded.     

Unicentric osteosarcoma of bone with subsequent skeletal metastases

Five cases of unicentric osteosarcoma with subsequent skeletal metastases are reviewed. Skeletal metastases may occur prior to pulmonary metastases in such patients. Initial and periodic bone scanning is therefore justified since early detection of distant bone lesions may have important therapeutic implications. A classification of multiple site osteosarcoma based upon clinical, pathologic, and radiologic characteristics is proposed.     

Single-dose tolerance to the behavioral effects of dibutyryl cyclic AMP in mice

The behavioral effects of varying doses of intraperitoneally administered dibutyryl cyclic AMP, cyclic AMP, adenosine, 5-AMP, and butyric acid were studied in male ICR mice. Behavioral parameters 25 min following treatment included measurement of spontaneous locomotor activity (SLMA) and rotarod performance, the latter providing an indication of neuromuscular coordination. Dibutyryl cyclic AMP produced a dose-related inhibition of SLMA with the largest dose, 75 mg/kg, decreasing activity by 89%. Adenosine and 5-AMP produced maximal inhibition of approximately 50–80% of SLMA at doses ranging from 75–250 mg/kg, while cyclic AMP decreased SLMA by 58% at only the highest dose, 250 mg/kg. Butyric acid failed to produce alterations in SLMA at doses ranging from 25–250 mg/kg. No compound altered neuromuscular coordination. Single-dose tolerance to the inhibitory effect of dibutyryl cyclic AMP on SLMA developed within 3 h and lasted at least 7 days. Adenosine failed to produce tolerance while cyclic AMP and 5-AMP exhibited only a slightly reduced effect following a second injection at intervals of 4 and 24 h. These results suggest that exogenous administration of dibutyryl cyclic AMP and its metabolites exert centrally mediated behavioral effects with selective development of single-dose tolerance to the dibutyryl derivative.     

The functional pool of brain catecholamines: Its size and turnover rate

Behavioral data are reviewed that give evidence for an indiscriminate involvement of brain catecholamines (CA), especially dopamine (DA), in nervefunction, regardless of the time elapsed from their synthesis. Critical analysis of biochemical and pharmacological studies shows that a clear-cut distribution of brain catecholamines in two compartments [newly synthesized (NS) and main storage] is not at all established, and moreover that there is no adequate proof that the difference in turnover rates attributed to these two supposed pools is due to a preferential extraneuronal release of NS-CA during nerve function rather than to a preferential (nonfunctional) intraneuronal deamination of NS-CA, or at least of NS-DA.     

Differential actions of dopamine agonists and antagonists on the γ-butyrolactone-induced increase in mouse brain dopamine

-Butyrolactone (GBL) increased the dopamine concentration in the forebrain of the mouse. Apomorphine dose-dependently antagonized the GBL effect, while piribedil was less effective. Haloperidol prevented the antagonism of GBL by apomorphine but pimozide was ineffective in blocking apomorphine. After chronic treatment with haloperidol or pimozide, there was no alteration of the maximum GBL-induced increase in dopamine nor was there any significant change in the antagonism by apomorphine, although a trend toward increased sensitivity to apomorphine was noted in the group withdrawn from haloperidol. These results suggest that in the mouse, haloperidol is a more effective antagonist of presynaptic dopamine autoreceptors than pimozide, while apomorphine is a better presynaptic agonist than piribedil.     

Aktivierungsverhalten bei sensumotorischer regeltätigkeit in abhängigkeit von der leistung

Zusammenfassung Mit 40 Versuchspersonen wurde Kompensationstracking durchgeführt. Anhand des Leistungsparameters Regelfehler wurden 2 Gruppen gebildet, bei denen untersucht wurde, ob sie sich im Aktivierungsverhalten unterscheiden. Es wurde gefunden, daß die Herzfrequenz- und Atemfrequenzsteigerungen in allen Versuchsabschnitten bei der Gruppe mit guter Trackingleistung signifikant höher waren. Die Streuung der Herzfrequenz war bei der schlechten Gruppe geringer.Die Aktivierungsvariablen Herz- und Atemfrequenz unterscheiden sich am deutlichsten in der jeweils ersten Belastungsminute der Versuchsabschnitte, dabei spiegelt die Herzfrequenz die Aufgabenschwierigkeit besser wider als die Atemfrequenz.Die Untersuchung der Korrelation zwischen dem Leistungsparameter Regelfehler und Herzfrequenzanstieg ergibt bei der Gruppe mit schlechterer Trackingleistung immer negative Werte für r, die in 3 Belastungsabschnitten signifikant sind. Bei der Gruppe mit guter Trackingleistung besteht eine positive Korrelation zwischen Herzfrequenzanstieg und Regelfehler bei geringerer statistischer Sicherheit.Die Ergebnisse werden diskutiert und Schlußfolgerungen für die psychophysiologische Eignungsbeurteilung werden abgeleitet.     

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children

Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined -adrenoceptor blockade and a hyperresponsiveness of -andrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to -blockers, a reduced formation of cyclic AMP in response to -adrenergic stimulation and enhanced -adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled -and -adrenergic antagonists made it possible to study - and -adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed - and -receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases.Using ¹²⁵[I]-cyanopindolol (ICYP) and ³[H]-yohimbine (HYOH) as highly specific ligands for - and -adrenoceptors, the following results were obtained: (1) Lymphocytes and platelets from control subjects and asthamatics bound similar amounts of ICYP and HYOH and thus showed no differences either in the number or the affinity of - and -adrenoceptors. Lymphocytes and platelets of wheezing and nonwheezing infants also bound the same amounts of the radioligands. (2) In asthmatic children receiving 4×2 puffs salbutamol -adrenoceptor were down-regulated and this may mimic -adrenoceptor blockade. (3) When subjects were divided into four categories according to age (0–5, 5–10, 10–20 years, adults) the number of -adrenoceptor binding sites showed an age-dependent increase. The number and affinity of -adreneceptor binding sites on platelets was neither influenced by age nor disease.It is concluded that the - and -adrenoceptors of wheezing infants and asthmatic children at least on blood cells are normal. However the -adrenoceptors show an age-dependent maturation process, which may account for an unresponsiveness to -adrenoceptor agonists in wheezing infants.Supported by a grant from the Ministerium für Wissenschaft und Forschung, NRWPresented at the 19th Workshop for Pediatric Research, University of Göttingen, March 10–11, 1983     

T cells in patients with chronic Tγ lymphocytosis: Morphology,cytochemistry, ultrastructure and immunological characteristics

Summary We have studied the morphology and cytochemistry in relation to the immunological phenotyping and functional properties of T cells from eight patients with chronic T lymphocytosis. At the light microscopic level the morphology of the patients' lymphocytes was similar to that described for large granular lymphocytes. Ultrastructurally, a division into two groups could be made on differences in the amount of cytoplasm and the location and the more irregular form of the nuclei. The lymphocytes of one group (five patients) had in common the phenotype Fc+, T3+, T4–, T8+, Ia–, M1– and demonstrated (with the exception of one patient) the same functions: presence of K-cell activity, absence of NK, helper and suppressor cell activities. In the other group (three patients), the lymphocytes of one patient showed the same phenotype and functions as those indicated above. The other two patients both lacked the T8 antigen on their lymphocytes but were different with regard to other surface markers. In addition, their cells were functionally identical: both demonstrated NK- and K-cell activity. Thus in this group of eight patients with chronic T lymphocytosis, the immunological and functional subdivision paralleled in part a morphological division at the ultrastructural level.     

Relationship between blood flow and fatty acid metabolism in subacute myocardial infarction: a study by means of99mTc-Sestamibi and23I-β-methyl-iodo-phenyl pentadecanoic acid

Contradictory data have been published on the relative behaviour of fatty acids and flow tracers during the subacute stage of myocardial infarction. Therefore, the present study was set up (1) to investigate the potential occurrence of mismatches between -methyl-iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, and Sestamibi, and to describe their nature, and (2) to relate these mismatches to clinical characteristics such as whether or not thrombolysis or percutaneous transluminal coronary angioplasty (PTCA) had been performed. Twenty-six patients were studied within 2 weeks after myocardial infarction. Sestamibi and BMIPP single-photon emission tomography (SPET) were performed within 4 days of one another. Activity of both tracers was scored in 16 basal, 16 midventricular and 8 apical segments, using a four-point grading system: 3 = normal (65% of maximum activity), 2 = mildly decreased (45%–64%), 1 = moderately decreased (25%–44%), 0 = severely decreased (0%–24%). Coronary arteriography was obtained during the same hospital stay. Four hundred and seventy-seven segments out of 1040 studied were abnormal for at least one tracer: 197 with higher Sestamibi activity (group I), 226 with equal scores for Sestamibi and BMIPP (group II) and 54 with higher BMIPP activity (group III). Seventy-five percent of group I segments and 84% of group III segments were found in infarct-related artery territories. Group I segments were associated with acute thrombolysis and/or PTCA (P < 0.01), and with the absence of prior infarction in the territory of the infarct-related artery (P < 0.001). Group III segments were associated with the absence of thrombolysis or PTCA (P < 0.001), with occlusion of the infarct-related artery (P < 0.001), with previous infarction in the same territory (P < 0.001) and with a- or dyskinesia in this territory (P < 0.001). These data could support the interpretation that areas in which the uptake of BMIPP is more decreased than that of Sestamibi (group I) are due to delayed recovery of fatty acid metabolism after reperfusion, whereas those with higher BMIPP than Sestamibi activity (group III) are accounted for by the enhanced metabolism induced by passive systolic wall stretch.     

Ossification and pseudoepiphysis formation in the “nonepiphyseal” end of bones of the hands and feet

Metacarpals, metatarsals, and phalanges were studied to assess the developmental morphology of secondary ossification in the nonepiphyseal ends of these bones as well as the formation of the pseudoepiphysis as an epiphyseal ossification variant. Both direct ossification extension from the metaphysis into the epiphysis and pseudoepiphysis formation preceded, and continued to be more mature than, formation and expansion of the classic epiphyseal (secondary) ossification center at the opposite end of each specific bone. Direct metaphyseal to epiphyseal ossification usually started centrally and expanded hemispherically, replacing both physeal and epiphyseal cartilage simultaneously. In contrast, when remnants of physis were retained, while juxtaposed epiphyseal cartilage was replaced, a pseudoepiphysis formed. There were three basic patterns of pseudoepiphysis formation. First, a central osseous bridge extended from the metaphysis across the physis into the epiphysis and subsequently expanded to create a mushroom-like osseous structure. In the second pattern a peripheral osseous bridge formed, creating either an osseous ring or an eccentric bridge between the metaphysis and the epiphysis. In the third pattern, multiple bridging occurred. In each situation the associated remnant physis lacked typical cell columns and was incapable of significantly contributing to the postnatal longitudinal growth of the involved bone. Pseudoepiphyses were well formed by 4–5 years and coalesced with the rest of the bone months of years before skeletal maturation was attained at the opposite epiphyseal end, which ossified in the typical pattern (i.e., formation of a secondary center de novo completely within the cartilaginous epiphysis). This process may also affect the development and appearance of ossification within the longitudinal epiphyseal bracket (delta phalanx).