Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET.

The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. METHODS: Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. RESULTS: PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.     

Geriatric competencies for RNs in hospitals.

Nurses in staff development are responsible for assuring nurses' competence in the delivery of care. Older patients are the predominant population in hospitals, yet there are no instruments that specifically assess the competency of nurses to deliver care to older patients. This article reports on the development and testing of an instrument, Geriatric Competencies for RNs in Hospitals, and makes recommendations as to how staff development educators can use the geriatric competency instrument with staff nurses.     

Polyamines and cardiovascular hypertrophy in experimental hypertension

Biochemical mechanisms which control cardiac and vascular response to hypertension are still unclear. Modifications of polyamines (putrescine, spermine, spermidine) may play a role in this phenomenon, since these molecules have been shown of importance in the control of tissue growth. Ornithine Decarboxylase (ODC) catalyses the first and probably the rate limiting step in the biosynthesis of the polyamines. We thus attempted to detect modification of ODC activity in renovascular hypertension in the rat (G1K-1C) and tried to correlate hypertrophic response and ODC activity in the aorta (Ao), the left (LV) and the right (RV) ventricles. In this experimental model, the aortic ODC activity increased at day 1 and 2, after clipping the renal artery, whereas in the LV the ODC activity increased after day 3 but stay high at least until day 7. The peak of ODC activity comes before the increase in DNA synthesis which occurs at day 4 in Ao, and the increase in protein turnover observed at day 7 in LV. No significant variation of ODC activity neither changes in DNA or protein biosynthesis rate are observed in the RV. In parallel with changes in ODC activity, an increase in spermidine and spermine content and mainly in the spermidine/spermine ratio is observed in the Ao and the LV confirming stimulation in polyamine biosynthesis in hypertensive tissues. In conclusion: increase in ODC activity is observed only in these tissues that will develop hypertrophy or hyperplasia and this modification is observed before any increase in nucleic acids or protein tissues content or turnover rate.     

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.      

Effects of the irreversible α-adrenoceptor antagonists phenoxybenzamine and benextramine on the effectiveness of nifedipine in inhibiting α 1- and α 2-adrenoceptor mediated vasoconstriction in pithed rats

Summary In pithed normotensive rats, i.v. injection of the selective ₁-adrenoceptor agonist cirazolien produced vasoconstriction which was largely resistant to inhibition by nifedipine. On the other hand, the pressor effects of the selective ₁-adrenoceptor agonists St 587 and Sgd 101/75 were much more effectively blocked by nifedipine, although not as effectively as the pressor effects to the selective ₂-adrenoceptor agonist B-HT 920. The sensitivity to inhibition of vasoconstriction in pithed rats to the different agonists increased in the order cirazoline St 587 ₁-, but not to ₂-adrenoceptor activation was dose-dependently enhanced. The potency of nifedipine to inhibit ₁-vasoconstriction by cirazoline, St 587 and Sgd 101/75 was increased maximally to the level of efficacy at which nifedipine antagonized B-HT 920-induced vasoconstriction. The dose of phenoxybenzamine required to maximally increase the potency and efficacy of nifedipine to antagonize vasoconstriction of the ₁-adrenoceptor agonists was inversely related to the level of sensitivity to blockade by nifedipine of the vasoconstriction they produced. In contrast, pretreatment of rats with the irreversible antagonist, benextramine (10 mg/kg, i.v., –100 to –60 min) did not increase the potency or efficacy of nifedipine to antagonize vasoconstriction to cirazoline, St 587, Sgd 101/75 or B-HT 920, despite irreversible blockade of ₁- and ₂-adrenoceptors. These data suggest that phenoxybenzamine, but not benextramine, selectively inhibits the ₁-adrenoceptor mediated vasoconstrictor mechanism that is independent of influx of extracellular calcium. Moreover, the results show that the existence of receptor reserve or the number of ₁-adrenoceptors activated does not determine the relative contribution of calcium influx-independent mechanisms in ₁-adrenoceptor-mediated vasoconstriction.Preliminary data were communicated at the Joint Meeting of the French and German Pharmacological and Toxicological Societies, Freiburg i. Br., September 19–22, 1983 (Timmermans et al. 1983a) and at the Winter Meeting of the British Pharmacological Society, London, January 1984 (De Jonge et al. 1984)     

Interactions between the putative calcium entry promotor Bay k 8644 and pressor responses produced by α-1 and α2-adrenocepter agonists in the pithed normotensive rat

Summary Interactions between the putative calcium entry promotor Bay k 8644 and both -₁ and ₁-adrenocepter mediated increases in diastolic pressure were studied in the pithed normotensive rat. The ₁-adrenocepter mediated pressor responses elicited by B-HT920, TL-99, DP-6,7-ADTN and B-HT958 were potentiated by Bay k 8644, reflected by a leftward shift and an increase in the maximum of the log dose-pressor respinse curves. The -₁-adrenocepter effects elicited by cirazoline, methoxamine, (–)-amidephrine, St 587, (–)-phenylephrine and Sgd 101/75 were less enhanced by Bay k 8644. Only a leftward shift of the dose-response curves was observed, which was most pronounced for (–)-phenylephrine and Sgd 101/75. The -₁ and ₂-adrenocepter pressor components of (–)-noradrenaline were similarly distinguished by Bay k 8644 as observed for the selective -₁ or ₂-adrenocepter agonists.Effects of Bay k 8644 on the increase in diastolic pressure mediated by B-HT 920, St 587 and cirazoline were also studied after pretreatment with the calcium entry blocker nifedipine. After additional pretreatment with nifedipine the potentiation by Bay k 8644 observed for B-HT 920 and St 587 was more pronounced. The presence of nifedipine had no effect on the interaction between Bay k 8644 and cirazoline.It is concluded that Bay k 8644 behaves as a mirror image of nifedipine. The observation that Bay k 8644 enhances ₂-adrenocepter mediated pressor effects more effectively than ₁-adrenocepter increases in diastolic pressure is in accordance with the hypothesis of the more pronounced calcium dependency of ₂-adrenocepter mediated pressor responses. The data obtained for ceptor mediated pressor responses. The data obtained for St 587 and (–)-phenylephrine are in apparent contradiction to the finding that the pressor responses to the former drug are more markedly inhibited by calcium entry blockade than those of the latter. It is suggested that St 587 employs calcium channels which are already maximally modulated and that (–)-phenylephrine makes use of calcium channels which are in a rather inactive state. The hypothesis is put forward that the intrinsic activity of ₂-adrenocepter agonists reflects their ability to bring calcium channels in an active state.