Institutional review boards: changing with the times?

Institutional Review Boards (IRBs) are responsible for safeguarding the rights and welfare of human research subjects. This article describes the changes in the conduct of research and the increasing pressure to conduct more research. Some institutions have not ensured that their IRBs have kept pace with the changing complexity of the research scene. The article discusses the need for a system to protect human subjects that is just as sophisticated as the research enterprise itself. This is increasingly important to justify the public's trust in the research system.

Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone.

Matrix metalloproteinases (MMPs) play an important regulatory role in tissue morphogenesis, cell differentiation, tumor invasion and metastasis. Several authors have reported a direct correlation between the production of 72 kDa (MMP-2) and 92 kDa (MMP-9) type IV collagenases/gelatinases and the metastatic potential of cancer cells. Recently, we have identified the expression of both MMP-2 and MMP-9 in primary cultures of human giant cell tumor (GCT) of bone in vitro, and in tissue extracts in vivo. Interestingly, MMP-9 is not secreted by late-passaged GCT cells. It is possible that the production of MMP-9 is regulated by certain factor(s) secreted by the multinucleated giant cells in the primary culture. In order to test this hypothesis, the effect of primary-culture-conditioned medium on the expression of MMP-9 by late-passaged mononuclear stromal cells was examined. Adding conditioned medium from the primary GCT culture to the late-passaged stromal cells induced MMP-9, as evidenced by the presence of lytic bands at M(r) 92,000 and 72,000 on a gelatin zymogram. These enzyme activities were inhibited by EDTA, a well-known inhibitor of the MMPs. We confirmed these results by Western blotting using specific antibodies and RT-PCR for MMP-2 and MMP-9. Immunofluorescence studies with specific antibodies to MMP-9 further confirmed its expression by the passaged stromal cells cultured in the primary-culture-conditioned medium. The data indicate that MMP-2 and MMP-9 are produced by the mononuclear stromal cells when cultured in GCT primary-culture-conditioned medium. This suggests that multinucleated giant cells in primary cultures secrete a factor(s) that stimulates stromal cells to produce MMP-9, which, in turn, may contribute to the aggressive behavior of GCT.

Optimum concentration of bupivacaine for combined caudal--general anesthesia in children.

Caudal epidural anesthesia has become widely accepted as a means of providing postoperative pain relief and intraoperative supplementation to general anesthesia for children. To determine the best concentration of bupivacaine for combined general-caudal anesthesia in children, 122 children aged 1-8 yr scheduled for outpatient inguinal herniorrhaphy were randomized to receive, in a double-blind fashion, caudal anesthesia with bupivacaine in one of six concentrations (0.125, 0.15, 0.175, 0.2, 0.225, or 0.25%). After incision, a programmed reduction in inspired halothane resulted, if tolerated by the subject, in an inspired halothane concentration of 0.5% 10 min after incision. End-tidal halothane concentration at hernia sac ligation for subjects receiving 0.175% bupivacaine (0.55 +/- 0.03%) was less than that for subjects receiving 0.15% bupivacaine (0.75 +/- 0.05%; P less than 0.05). Subjects receiving 0.175% bupivacaine also were discharged earlier from the postanesthesia care unit (PACU) (27 +/- 1 min) than were subjects receiving 0.15% bupivacaine (38 +/- 5 min; P = 0.05). Children receiving greater than or equal to 0.2% bupivacaine tended to complain more of leg weakness after surgery; however, the difference did not reach statistical significance (39 of 67 vs. 16 of 47; P = 0.057). The incidence of complaints of leg weakness and paresthesia was positively correlated with bupivacaine concentration (r = 0.706; P = 0.05). Subjects receiving 0.125% bupivacaine had higher pain scores on arrival to the PACU than did those receiving 0.2% bupivacaine (P = 0.05); there were no other differences in pain scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Caudal epidural anesthesia in conscious premature and high-risk infants.

Twenty premature or high-risk infants received caudal epidural anesthesia for inguinal herniorrhaphy, orchiopexy, and circumcision. Mean gestational age at surgery was 48 +/- 12 weeks; mean weight at surgery was 4,100 +/- 1,400 g. Caudal anesthesia, performed with 1 mL/kg of 0.375% bupivacaine, was successful in 19 of 20 infants. Onset of anesthesia occurred in 14 +/- 1 minutes; duration of surgical anesthesia was 89 +/- 8 minutes. Surgical conditions were generally excellent and the infants tolerated anesthesia and surgery well. No postoperative complications were observed. Caudal epidural anesthesia is an acceptable alternative to general or spinal anesthesia in premature and high-risk infants.

Haemodialysis related osteomalacia: a staining method to demonstrate aluminium.

A slight modification in tissue processing and staining technique enables a previously described method for staining aluminium to be used to demonstrate aluminium in osteomalacia associated with haemodialysis. The stain appears to be accurate in diagnosing this condition and may assist in establishing the diagnosis before severe osteomalacia develops.

Ectopic adrenocorticotrophic hormone production and neoplasm.

Three patients presented with severe hypokalaemic, hypochloraemic alkalosis, muscle weakness and later cutaneoud pigmentation. There were few signs of Cushing's syndrome. Two had bronchial and one pancreatic neoplasm. Plasma cortisol and urinary steroid metabolites were extremely elevated and synacthen stimulation showed significant adrenal capacity even with adrenal metastases. Aminoglutethamide reduced plasma cortisol in two patients.