Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma.

Renal insufficiency (RI) is a frequent complication of multiple myeloma (MM) with negative consequences for patient survival. The improved clinical outcome with successive Total Therapy (TT) protocols was limited to patients without RI. We therefore performed a retrospective analysis of overall survival, progression-free survival and time to progression (TTP) of patients enrolled in TT2 and TT3 in relationship to RI present at baseline and pre-transplant. Glomerular filtration rate was graded in four renal classes (RCs), RC1-RC4 (RC1 ⩾90 ml/min/1.73 m(2), RC2 60-89 ml/min/1.73 m(2), RC3 30-59 ml/min/1.73 m(2) and RC4 <30 ml/min/1.73 m(2)). RC1-3 had comparable clinical outcomes while RC4 was deleterious, even after improvement to better RC after transplant. Among the 85% of patients with gene expression profiling defined low-risk MM, Cox regression modeling of baseline and pre-transplant features, which also took into consideration RC improvement and MM complete response (CR), identified the presence of metaphase cytogenetic abnormalities and baseline RC4 as independent variables linked to inferior TTP post-transplant, while MM CR reduced the risk of progression and TTP by more than 60%. Failure to improve clinical outcomes despite RI improvement suggested MM-related causes. Although distinguishing RC4 from RC<4, 46 gene probes bore no apparent relationship to MM biology or survival.

Application of Corynebacterium cutis lysate as an immune stimulant in cattle.

An ultrasonicated lysate of Corynebacterium cutis (Ultracorn, Virbac, France) was administered to 10-day-old calves, 5-month-old calves, and pregnant dams kept under Egyptian environmental conditions. Ninety-five calves and 50 dams were used in the study. All animals were treated with 2 ml/100 kg body weight of killed C cutis. Its effects on body weight gain and on calf mortality and morbidity were recorded. The results obtained showed that treated calves had greater weight gains, reduced susceptibility to common viral pathogens, and lower mortality. When given simultaneously with rinderpest vaccine, an immunopotentiating or adjuvant effect was seen. Thus, treated calves had higher neutralizing antibody titers to rinderpest as compared with untreated calves. When administered to pregnant cows in the last month of pregnancy, the offspring of these animals had higher birth weight, better weight gain, and reduced morbidity.

Pain threshold changes in adjuvant-induced inflammation: a possible model of chronic pain in the mouse.

A chronic hyperalgesic condition was induced in mice by the injection of Freund's complete adjuvant (FCA) into the lower lumbar region or directly into the hind footpads. Although little or no visible inflammation was observed after a single intradermal injection of FCA into the lower lumbar area of rats or mice, significant alterations in nociceptive thresholds occurred in each species as determined by decreases in response latency in tail-flick and hot-plate assays. Unilateral intraplantar administration of FCA in mice resulted in visible inflammation in the area of the tibiotarsal (ankle) joint. Changes in the response latency to a noxious stimulus in the areas surrounding the inflamed joint were similar to those observed in non-inflamed limbs, suggesting that changes in sensitivity to noxious stimuli were not merely the result of local hypersensitivity of the inflamed tissue, but may also be due to alterations in nociception at the level of the central nervous system (CNS). When the chronic inflammatory condition induced in the mouse tibiotarsal joint was evaluated by histological and morphological techniques, it was found to have the same characteristics as described in the early stages of FCA-induced arthritis in rats. The similarities between the response to FCA in rat and mouse suggest that injection of FCA in mice may prove to be a useful model for the study of chronic pain in mice as well as in rats.