A Call for a National Transplant Surgical Quality Improvement Program

The severity of illness in transplant patients and the complexity of transplant operations results in significant postoperative morbidity and mortality. Remarkable efforts have been made by transplant physicians to study and improve organ allocation, graft and patient survival, immunosuppression and the long-term management of post-transplant complications. Less effort has been spent studying the actual transplant operation and systems of acute transplant care. The National Surgical Quality Improvement Program (NSQIP) has provided a standardized approach to quality improvement and has demonstrated significant potential for a reduction in postoperative morbidity and mortality in other surgical disciplines. Medical centers are under increasing pressure to measure surgical quality and the nexus of transplant surgical quality improvement should not lie in the hands of CMS or JACHO, but rather it should be created and developed within the transplant community. The time has come for a national transplant surgical quality improvement program based on the NSQIP infrastructure. Such a proactive approach toward quality improvement from the transplant community is an excellent investment for patients, providers and health care payers.     

The effect of age, sex, weight and height on the plasma concentrations in healthy subjects of the acidic metabolites of some biogenic monoamines involved in psychiatric and neurological disorders.

1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply for both males and females but are significant only for males. 3. Homovanillic and vanillylmandelic acid concentrations in plasma increase with age. 4. The importance of using age, sex, weight and height matched groups in studies involving the plasma concentrations of some of the trace amine metabolites in psychiatric disorders has been demonstrated. This is particularly the case for phenylacetic acid, the major metabolite of phenylethylamine which is now thought to be a neuromodulator of catecholaminergic neurotransmission.     

Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas.

OBJECTIVE: To examine the relationship between growth rate of vestibular schwannomas and the expression of various growth factor receptors. STUDY DESIGN: Retrospective case review of clinical growth rate in conjunction with a histopathologic and immunohistochemical reexamination of archival specimens. SETTING: A tertiary referral neurotologic center. PATIENTS: Three groups: a historical group to act as controls, consisting of 30 patients with sporadic vestibular schwannomas removed before the unit adopted an initial interval scan policy; a group of 14 patients with sporadic vestibular schwannomas who had undergone an initial interval scan policy, showed radiologic evidence of growth, and therefore had their schwannoma removed; and a group of 16 schwannomas removed from 11 neurofibromatosis Type 2 patients. MAIN OUTCOME MEASURES: A comparison between the three clinical groups using immunohistochemical studies to determine the level of expression of the proliferation factor Ki-67, c-erbB-2, and c-erbB-3 receptors and fibroblastic growth factor receptors 1 and 4. RESULTS: The level of expression of the proliferation factor Ki-67 was very low and similar in all three groups. C-erbB-2 and c-erbB-3 receptors were not expressed in any of the groups. fibroblastic growth factor receptor 4 expression was not significantly different, but there was a variation in the expression of fibroblastic growth factor receptor 1 between the three groups that correlated well with the differing incidence of growth in the groups. The increase in expression of fibroblastic growth factor receptor 1 in the neurofibromatosis Type 2 group was not statistically significant, but the increase in expression of fibroblastic growth factor receptor 1 in the growing sporadic group was statistically significant when compared with the historical controls. The level of fibroblastic growth factor receptor 1 expression correlates significantly with the rate of growth as measured on interval magnetic resonance imaging. CONCLUSIONS: Overexpression of fibroblastic growth factor receptor 1 has a positive correlation with the incidence and the rate of growth of sporadic vestibular schwannomas.     

Recombinant granulocyte-macrophage colony-stimulating factor improves hematopoietic recovery after 5-fluorouracil

Antitumor chemotherapy is often limited by hematopoietic toxicity. In an attempt to determine if it is possible to attenuate the myelosuppressive effects of chemotherapy, we administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), a multilineage hematopoietic growth factor, to mice receiving 5-fluorouracil (5-FU). Mice receiving injection of 5-FU followed 24 hr later by a single 1-microgram injection of rmGM-CSF had significantly increased femoral bone marrow granulocyte-macrophage colony-forming cells (GM-CFC) 48 hr after 5-FU injection compared to animals receiving 5-FU alone. Animals receiving rmGM-CSF twice daily beginning 24 hr after 5-FU had significantly elevated white blood cell counts and increased granulocyte and monocyte counts at Day 7 following 5-FU injection, compared to those of 5-FU animals. The total reserve of GM-CFC was also expanded initially in the femoral marrow and later in the spleen of animals receiving rmGM-CSF following 5-FU. A means of accelerating bone marrow recovery and restoration circulating granulocytes and monocytes could allow more frequent doses of chemotherapy to be administered or shorten the time period that patients are leukopenic.     

Treatment of steroid-resistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin

The A chain of the toxin ricin has been conjugated by a disulfide bond to a murine monoclonal antibody that recognizes the CD5 (T,p67) antigen present on 95% of peripheral blood T lymphocytes. This immunotoxin was used to treat a patient with severe grade III-IV, steroid-resistant, acute graft-vs-host disease (GvHD) after an allogeneic, human leukocyte antigen-identical bone marrow transplant for acute myelogenous leukemia. Immunotoxin therapy produced a complete clinical response in the skin and gastrointestinal tract. The patient tolerated a 14-day course without symptoms or signs of toxic effects. After two days of therapy, circulating T cells could not be demonstrated by indirect immunofluorescence. After therapy, acute GvHD did not recur. However, seven months after therapy the patient demonstrated mild signs of chronic GvHD that were easily controlled with low-dose immunosuppressive therapy. These findings indicate that an anti-T-cell ricin A chain immunotoxin can be given safely for treatment of acute GvHD and may be an effective therapy for this significant posttransplant complication.