Cytokines Expressed in Multinucleated Cells: Paget's Disease and Giant Cell Tumors versus Normal Bone

Human osteoclasts are well characterized multinucleated cells whose function is the directed resorption of normal bone (NB). Osteoclastic bone destruction accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of bone and giant cell tumors of bone (GCTB). The mechanism of this stimulation of osteoclastic bone resorption is unknown. This study was designed to detect cytokines present in the multinucleated cells of PD and GCTB in order to determine whether cytokine abnormalities exist to account for bone lysis. Nine cytokines, representing the functions of bone resorption, angiogenesis, tumor necrosis, bone cell proliferation, and osteoblast–osteoclast coupling, were examined by immunohistochemistry using tissue samples from 15 NB, 17 PD, and 19 GCTB patients. Standard nonparametric statistical analysis showed a significant increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB for interleukin-6 (Il-6), tumor necrosis factor beta (TNFβ), epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). There was a statistically significant decrease in immunostaining of giant cells of GCTB as compared with NB for transforming growth factor beta (TGFβ), but no other differences from normal osteoclasts. The increase in staining of PD osteoclasts over the giant cells of GCTB was significant (P < 0.01) for Il-6, TNFβ, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P < 0.05) for Il-1 and EGF. It was concluded that marked cytokine differences exist in vivo between osteoclasts of NB and PD lesions consistent with stimulated resorption. Alternatively, ``osteoclastoma' cells in the center of the tumor did not overexpress the cytokines associated with bone lysis, suggesting some other mechanism for stimulated resorption. Received: 12 February 1996 / Accepted 31 December 1996     

Anorexia nervosa as a compulsive behaviour disease.

A number of anorexic young women develop bulimia, a condition in which binge eating is driven so intensely they cannot resist it. Although this drive has the character of a compulsion the patients do not as a rule suffer from obsessional-compulsive neurosis. A questionnaire was developed and used to determine whether similar compulsive drives manifest themselves in restricting anorexics and whether there are compulsive features resembling patients with compulsive personality disorder (as described in DSM-III) in eating disorders. A total of 162 patients were studied, comprising 42 controls, 30 depressed patients, 34 non-bingeing anorexics, 28 bingeing anorexics and 28 compulsive patients. The questionnaire was shown to be a stable instrument and, on the compulsion scale, the anorexics, bulimics and compulsive patients all scored very highly (mean +/- S.E.; 32.1 +/- 1.9, 35.8 +/- 1.9, 28.0 +/- 2.2, respectively) compared to the controls (13.1 +/- 1.1, p < 0.005). The compulsive patients did not have anorexia-type eating disorders. It was concluded that many of the factors which underlie compulsive personality disorder are present in primary eating disorders and the compulsive nature of anorexia could not be ignored when treatment was considered. The difference between compulsive behaviour and addiction is discussed in the light of the failure of long-term naloxone infusion to cure severe anorexia, even though some patients had dramatic weight gains associated with the antilipolytic action of naloxone.     

General Ultrasound in the Critically Ill. D. A. Lichenstein. Published by Springer-Verlag, Berlin. Pp. 199; indexed; illustrated. Price {pound}77.00. ISBN 3-540-20882-4

Bedside ultrasound with ‘point of care machines’is now a reality for any critical care department. Often thesemachines are primarily used by visiting radiologists to preventwear and tear on less portable equipment. However, there ispotential benefit to be gained by the critical care physicians     

Role of group II and group III metabotropic glutamate receptors in spinal cord injury.

Spinal cord injury (SCI) produces an increase in extracellular excitatory amino acid (EAA) concentrations that results in glutamate receptor-mediated excitotoxic events. An important class of these receptors is the metabotropic glutamate receptors (mGluRs). mGluRs can activate a number of intracellular pathways that increase neuronal excitability and modulate neurotransmission. Group I mGluRs are known to modulate EAA release and the development of chronic central pain (CCP) following SCI; however, the role of group II and III mGluRs remains unclear. To begin evaluating group II and III mGluRs in SCI, we administered the specific agonists for group II, APDC, or group III, L-AP4, by interspinal injection immediately following SCI. Contusion injury was produced at spinal segment T10 with a New York University impactor (12.5-mm drop, 10-g rod 2 mm in diameter) in 30 adult male Sprague-Dawley rats (175-200 g). Evoked and spontaneous behavioral measures of CCP, locomotor recovery, changes in mGluR expression, and amount of spared tissue were examined. Neither APDC nor L-AP4 affected locomotor recovery or the development of thermal hyperalgesia; however, L-AP4 and APDC attenuated changes in mechanical thresholds and changes in exploratory behavior indicative of CCP. APDC- and L-AP4-treated groups had higher expression levels of mGluR2/3 at the epicenter of injury on post contusion day 28; however, there was no difference in the amount of spared tissue between treatment groups. These results demonstrate that treatment with agonists to group II and III mGluRs following SCI affects mechanical responses, exploratory behavior, and mGluR2/3 expression without affecting the amount of tissue spared, suggesting that the level of mGluR expression after SCI may modulate nociceptive responses.     

Renin correlates with blood pressure reactivity to stressors

This study examines the relationship between renin levels and physiologic reactivity to stressors. Seventy-five normotensive and mildly hypertensive men were studied on a high salt diet (200 mEq/day Na) and on a low salt diet (10 mEq/day Na). Renin, plasma catecholamines, heart rate, and blood pressure were examined at rest, after standing in place for 8 minutes, and after a brief mathematics task. Renin levels increased in response to the stressor tasks, particularly on the low salt diet. The change in diastolic pressure in response to the stressor tasks was correlated with the change in renin (r = 0.45, p less than 0.001) but not with the change in norepinephrine. The combination of change in renin and norepinephrine levels accounted for 21% of the variance in predicting diastolic pressure reactivity (p less than 0.0015).     

Substrate inhibition of adenosine phosphorylation in adenosine deaminase deficiency and adenosine-mediated inhibition of PP-ribose-P dependent nucleotide synthesis in hypoxanthine phosphoribosyltransferase deficient erythrocytes

Summary The metabolism of adenosine and its effects on phosphoribosylpyrophosphate, PP-ribose-P, dependent nucleotide synthesis were studied using erythrocytes from patients with adenosine deaminase and hypoxanthine phosphoribosyltransferase deficiency as models. The phosphorylation of adenosine was progressively inhibited by concentrations of adenosine greater than 1 µmol L^–1 for control and ADA deficient erythrocytes. There was essentially no initial rate of phosphorylation at 30 µmol L^–1 adenosine. Adenosine, 1 µmol L^–1, also caused a 60% reduction in PP-ribose-P concentration in ADA deficient erythrocytes. For HPRT deficient erythrocytes in which ADA activity was blocked by coformycin, 10 µmol L^–1 inosine stimulated PP-ribose-P dependent nucleotide synthesis from adenine, whereas, 10 µmol L^–1 adenosine inhibited nucleotide synthesis. These observations suggest that adenosine phosphorylation and PP-ribose-P dependent nucleotide synthesis are inhibited under conditions in which adenosine accumulates, such as in hereditary or pharmacologically induced ADA deficiency.