Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes.

We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC. Beta-adrenergic stimulation with salbutamol resulted in a significant increase in glucose turnover from 12.1 +/- 1.1 mumol/kg/min to 13.4 +/- 0.9 mumol/kg/min (p less than 0.02), and the rates of appearance (Ra) of both alanine and free fatty acids (FFAs) also increased. Alanine Ra increased from 11.7 +/- 2.5 mumol/kg/min to 12.8 +/- 3.0 mumol/kg/min, and the corresponding values for FFA turnover were 7.6 +/- 1.1 mumol/kg/min and 10.3 +/- 2.1 mumol/kg/min (p less than 0.03), respectively. Salbutamol infusion did not result in any significant change in the rate of NPC.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute septic arthritis in infancy and childhood

Despite intensive study of acute septic arthritis in infancy and childhood, poor outcomes continue to occur. Failures are often due to delayed diagnosis and inadequate therapy, but can be due to factors beyond physicians' control such as associated osteomyelitis and occurrence during infancy. Recent advances in the understanding and management of septic arthritis include: (1) demonstration of beneficial effects of continuous passive motion in rabbits; (2) identification of inflammatory mediators of cartilage destruction and their respective sources; (3) recognition of changing patterns of pathologic organisms; (4) evolution of new antibiotics and standards for oral and home intravenous therapy; (5) development of arthroscopic debridement of septic knees; and (6) further refinement of indications for aspiration-irrigation versus open surgical drainage of septic joints. Permanent sequelae from septic arthritis can only be prevented by early diagnosis and aggressive treatment.     

Buserelin in premenstrual syndrome.

Buserelin, a luteinizing hormone releasing hormone agonist was administered nasally in doses of 900 micrograms daily to inhibit the ovarian cycle. Of 16 patients recruited, ten completed the treatment. Daily symptoms were measured on the Visual Analogue Scale and Trigg's trend analysis utilized for the analysis. The peak severity of symptoms (ESAmax) and the maximum global scores (Gmax) reduced on buserelin treatment. The minimum global scores (Gmin) and the minimum score for each symptom (ESAmin) increased, suggesting worsening of underlying symptoms. The difference between ESAmax and ESAmin (ESAdelta) and Gmax and Gmin (Gdelta) were calculated to determine the degree of symptom change. The delta scores for symptoms of depression, bloatedness and breast symptoms, and Gdelta were significantly reduced (p less than 0.05) on buserelin, whilst the latter significantly worsened in the follow-up months. Side-effects may limit the place of buserelin in the long-term treatment of premenstrual syndrome, although combination of additional hormonal treatment may facilitate long-term treatment.     

Distinct p53/56lyn and p59fyn domains associate with nonphosphorylated and phosphorylated Ig-alpha.

Among the earliest detectable events in B-cell antigen receptor-mediated signal transduction are the activation of receptor-associated Src-family tyrosine kinases and the tyrosine phosphorylation of Ig-alpha and Ig-beta receptor subunits. These kinases appear to interact with resting B-cell antigen receptor complexes primarily through the Ig-alpha chain antigen receptor homology 1 (ARH1) motif. Recent studies showed a dramatic increase in the amount of Src-family kinase p59fyn bound to Ig-alpha when ARH1 motif tyrosines were phosphorylated. To explore the submolecular basis of these interactions, we conducted mutational analysis to localize sites in p53/56lyn and p59fyn that bind nonphosphorylated and phosphorylated Ig-alpha. Here we report that distinct regions within these kinases bind nonphosphorylated and phosphorylated Ig-alpha ARH1 motifs. The N-terminal 10 residues mediate binding to the nonphosphorylated Ig-alpha ARH1 motif. Association with the phosphorylated Ig-alpha ARH1 motif is mediated by Src homology 2 domains. These findings suggest a mechanism whereby ligand-induced Ig-alpha tyrosine phosphorylation initiates a change in the orientation of an associated kinase that may alter its activity and/or access to substrates and other effectors.     

Effect of Rb+ on cromakalim-induced relaxation and ion fluxes in guinea pig trachea.

The effects of cromakalim, verapamil and salbutamol have been examined in guinea pig trachealis smooth muscle in both Krebs physiological salt solution and Krebs solution where K+ has been replaced by Rb+. Cromakalim-induced relaxation in the presence of Rb+ was reduced in extent and became transient, whilst the relaxation response to verapamil was enhanced and that to salbutamol unaffected. The transient relaxation occurring in Rb+ was blocked by quinidine and glibenclamide. The presence of extracellular Rb+ also prevented cromakalim-stimulated efflux of both 86Rb+ and 42/43K+. There was, however, no effect on cromakalim-stimulated 86Rb+ uptake. It is proposed that cromakalim is opening two populations of potassium channel in guinea pig tracheal smooth muscle, one of which is susceptible to blockade by Rb+ and one of which is not. The latter channel appears to play the dominant role in cromakalim-stimulated uptake, and is responsible for the transient relaxation response in the presence of rubidium, whilst the former is responsible for the maintained relaxation.     

The effect of monoclonal antibodies to calcitonin gene-related peptide (CGRP) on CGRP-induced vasodilatation in pig coronary artery rings.

1. The modification of the vasodilator effect of calcitonin gene-related peptide (CGRP) by a panel of monoclonal antibodies (MAbs), which map to discrete epitopes on the CGRP molecule, was investigated in pig coronary artery rings (PCA). The preparations were pre-constricted with acetylcholine (3 x 10(-7) M) and concentration-response curves to CGRP (2 x 10(-10)-2.56 x 10(-8) M) were obtained in the presence or absence of each MAb. 2. CGRP caused a concentration-dependent relaxation of PCAs which reached a maximum (98.2 +/- 4.8%, n = 25) at 1.28 x 10(-8) M and gave an EC50 of 3.8 +/- 0.8 x 10(-9) M. 3. Two MAbs which map to the N-terminal, CN1 and CRA3, did not affect the CGRP response whilst a third, CRA5, significantly inhibited its effect. 4. The C-terminal MAb, CRA2, did not modify the CGRP response whilst, in contrast, CB3 (C-terminal) potentiated its effect. A similar augmentation of the CGRP-induced vasodilatation was seen in the presence of the middle-region MAb, CRA8. 5. These results suggest that regional specific MAbs can modify the vasodilator effect of CGRP causing either inhibition (CRA5, N-terminal) or potentiation (CB3, C-terminal; CRA8, middle region).     

Do discrepancies in interpersonal perception predict relapse?: A comparison of remitted depressed patients and collaterals

In an effort to examine whether disturbed interpersonal relationships are associated with relapse in depression, discrepancies in self-ratings provided by formerly depressed patients and their collateral informants were compared. Thirty-eight remitted depressed patients and their collateral informants were asked to monitor moods, life events, and stress levels on a bimonthly basis for a 1-year period. It was hypothesized that patient/collateral dyads displaying a greater discrepancy in interpersonal perception would have a higher risk of relapse than dyads who showed more agreement in their ratings. Results indicated that while discrepancies in the perceptions of patients' life events were associated with the duration of a relapse once it occurred, discrepancies were generally not related to the emergence of new episodes of depressive disorder. The implications of these findings for models seeking to integrate cognitive and interpersonal models of depression, through the study of environmentally determined and personally appraised adversity, is discussed.This research was supported by grants to the first and third authors from the Canadian Psychiatric Research Foundation and the Laidlaw Foundation.     

Bremsstrahlung imaging using the gamma camera: factors affecting attenuation.

Quantitative imaging of bremsstrahlung from pure beta emitters is proposed as a means for in vivo management of antibody therapy. The method involves the use of high-energy collimation, an empirically selected broad photon energy window to enhance detector sensitivity, and a Wiener restoration filter to compensate for system blur. The measured and filtered data were obtained for an idealized scattering medium and isolated spherical sources. An effective linear attenuation coefficient of about 0.13 cm-1 was determined from the raw image data of 32P. A coefficient of 0.14 cm-1 was determined after the images were restored using the Wiener filter. The measured attenuation was not significantly dependent on the size of the region of interest or the size of the source. Its variation was within the experimental error of measurement (+/- 5%). The measured sensitivity (6 x 10(-6) cps/Bq) was sufficient for imaging therapy doses of 32P or 90Y.