Inhibition of synovial plasma extravasation by preemptive administration of an antiinflammatory irrigation solution in the rat knee.

UNLABELLED: Inflammation and hyperalgesia during surgical procedures are caused by the local release of multiple inflammatory mediators. We used a rat knee joint model of acute inflammation (synovial plasma extravasation) to determine whether preemptive intraarticular irrigation of the antiinflammatory drugs ketoprofen, amitriptyline, or oxymetazoline, alone or in combination, can reduce inflammatory soup-induced plasma extravasation. These three drugs were selected because of their abilities to collectively inhibit the inflammatory effects of biogenic amines, eicosanoid production, and the release of neuropeptides from C-fiber terminals. Synovial perfusion of each one of the three drugs 10 min before, and then in combination with, the inflammatory soup (bradykinin, 5-hydroxytryptamine, and mustard oil) did not reduce plasma extravasation. Similarly, two-drug combinations did not significantly reduce inflammatory soup-induced plasma extravasation. The combination of all three drugs (amitriptyline, ketoprofen, and oxymetazoline) produced a dramatic inhibition of plasma extravasation and was more effective than any of the two-drug combinations. A comparison between the preemptive (10 min before inflammatory soup perfusion) and postinflammatory administration (10 min after inflammatory soup perfusion) showed that the postinflammatory administration of the three-drug solution lost all ability to inhibit inflammatory soup-induced plasma extravasation. We conclude that acute synovial inflammation, which is induced and maintained by multiple mediators, can be substantially inhibited only by the preemptive administration of a drug combination that targets multiple inflammatory mediators. IMPLICATIONS: Preemptive, intraarticular irrigation of a combination of multiple antiinflammatory drugs is a novel and potentially effective method for reducing the synovial inflammatory response, such as that during arthroscopy. In this study, a three-drug combination infusion was statistically superior to one- or two-drug infusions in a rat model.

Role of radionuclide imaging in the diagnosis of acute osteomyelitis.

Over the last decade, the role of nuclear medicine studies in the diagnosis of acute osteomyelitis has been discussed in depth in the literature. Yet, the respective roles played in this setting by each of the commonly used radionuclide studies often are confusing. In an attempt to develop a cogent diagnostic strategy, we reviewed the literature published within the last 12 years pertaining to the use of radiophosphate bone scintigraphy as well as gallium and indium WBC imaging in the diagnosis of this condition. Based on our findings, we propose an alternative approach to the evaluation of a patient with suspected acute osteomyelitis.

A chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch.

Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control gamma-to-beta switching, we analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome-i.e., chromosome 11--sufficient for expression of human fetal globin and the subsequent gamma-to-beta switch. The results suggest that the gamma-to-beta switch is controlled either cis to the beta-globin locus or by a trans-acting mechanism, the genes of which reside on human chromosome 11.