Treatment of refractoriness to platelet transfusion by protein A column therapy

Ten thrombocytopenic patients (platelets < 10–24 × 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/− 11 × 10(9) per L as compared with counts of 16 +/− 7 × 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/− 810 and 10,010 +/− 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/− 9 and 13 +/− 10 × 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/− 1410 and 1520 +/− 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastroesophageal Reflux,Motility Disorders,and Psychological Profiles in the Etiology of Globus Pharyngis

The aim of this study was to investigate the origin of globus pharyngis with particular reference to esophageal disorders such as gastroesophageal reflux disease (GERD), motility disorders, structural abnormalities, other gastrointestinal tract diseases, and psychological profile. Previous studies on this subject using 24-hour pH monitoring give conflicting results and are hampered by the high background prevalence of asymptomatic GERD in the normal Western population. The local Chinese population is known to have a very low background level of GERD and therefore is an ideal study population. Twenty-six patients with globus pharyngis underwent 24-hour ambulatory pH monitoring, esophageal manometry, and esophagogas-troduodenoscopy with lower esophageal biopsy. A control group of 20 patients presenting with non-ulcer dyspepsia was similarly investigated. Personality profiles of the globus pharyngis subjects and an appropriate control group were assessed. Eight of the globus pharyngis group (30.7%) had evidence of GERD, whereas only one of the controls (5%) demonstrated GERD on 24-hour esophageal pH monitoring (P < 0.05). The manometric and personality profile studies did not show significant differences between study and control groups. We concluded that the finding of GERD in patients with globus pharyngis is not a coincidental finding but that there is a true association between GERD and globus pharyngis.     

Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody.

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.     

Adenosine receptor-induced cyclic AMP generation and inhibition of 5-hydroxytryptamine release in human platelets.

1. We have assessed the effects of adenosine receptor agonists and antagonists on collagen-induced 5-hydroxytryptamine (5-HT) release and cyclic AMP generation in human platelets. 2. 5'-N-ethylcarboxamidoadenosine (NECA) and CGS 21680 elicited accumulations of cyclic AMP with mean EC50 values of 2678 and 980 nM, respectively. The maximal response to CGS 21680 was approximately half that of the response to 10 microM NECA. 3. NECA and CGS 21680 inhibited collagen-induced 5-hydroxytryptamine release with mean EC50 values of 960 and 210 nM, respectively. The maximal response to CGS 21680 was approximately 25% of the response to 10 microM NECA. 4. The A1/A2a-selective adenosine receptor antagonist PD 115,199 was more potent as an inhibitor of NECA-elicited responses than the A1-selective antagonist DPCPX with calculated Ki values of 22-32 nM and > 10 microM, respectively. 5. In the presence of a cyclic AMP phosphodiesterase inhibitor, the effects of CGS 21680 on cyclic AMP accumulation and 5-HT release were enhanced to levels similar to those elicited by 10 microM NECA. In the absence of phosphodiesterase inhibition, CGS 21680 did not antagonise the effects of NECA. Furthermore, endogenous adenosine did not contribute to the effects of CGS 21680 when phosphodiesterase was inhibited. 6. We conclude that an A2a adenosine receptor appears to be involved in the NECA-elicited increases in cyclic AMP levels and inhibition of 5-HT release in human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Concurrent systemic cryptococcosis and haemangiosarcoma in a dog

A young dog with progressive neurological signs was humanely killed by the injection of barbiturate for postmortem examination. Lesions in the nose, lung, pancreas, lymph nodes, kidneys and the meninges were heavily infiltrated with Cryptococcus neoformans. In addition, haemangiosarcoma was detected in the right atrium. The finding of systemic mycosis and neoplasia together in a young dog suggests an immunosuppressed state.     

Transplacental passage of mifepristone and its influence on maternal and fetal steroid concentrations in the second trimester of pregnancy

The maternal and fetal endocrine effects of the maternal administration of the anti-progestin mifepristone in mid-pregnancy have been investigated. Mifepristone and the metabolite RU 42,633 were detected in the fetal circulation and in the amniotic fluid 4, 24 and 48 h after oral ingestion. Maximum fetal plasma concentrations of mifepristone occurred 4 h after treatment indicating rapid placental transfer of the drug. No significant changes in progesterone, cortisol, oestradiol or aldosterone concentrations were detected in the maternal circulation after mifepristone treatment. No significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations, but a significant increase in fetal aldosterone occurred 4 and 24 h after treatment. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour.     

Injury Type, Injury Severity, and Repeat Occurrence of Alcohol-Related Trauma in Adolescents

Injury associated with alcohol use is a significant problem among adolescents; however, routine evaluation of alcohol use in this population is not conducted. The purpose of this study was to compare injured adolescents presenting to an emergency room with a positive serum alcohol concentration (SAC+) with those injured adolescents wlth a negative serum alcohol concentration (SAC-). Data were collected retrospectively on 176 injured patients, between the ages of 13 and 18, consecutively admitted to a university hospital from January 1, 1989-December 31, 1990. Information collected included mechanism and severity of injury, outcome, SAC, length of stay, prychiatric history, prior or subsequent admission for injury, and hospital charges. Of those tested with an SAC, more than one-third had a positive SAC. Patients with positive SACs had a greater probability of having a psychiatric history and more frequently had a prior or subsequent injury. Furthermore, only 34% of SAC+ patients were referred for counseling. The results indicate that a SAC should be obtained on all adolescents admitted for trauma, that adolescents presenting with injuries and a positive SAC should be referred for alcohol and psychiatric assessment, and that injured adolescents may be at increased risk for repeat injuries in the future.     

Vincristine potentiates cytochalasin B-induced DNA fragmentation in vitro

Summary The cytochalasins are fungal metabolites that have previously been shown to have some chemotherapeutic potential. When various cell types are treated in vitro with both cytochalasin B and vincristine, the resultant DNA fragmentation is greater than the sum of that caused by each agent alone. The levels necessary to achieve this potentiation are obtainable in vivo. DNA fragmentation induced by cytochalasin E, an actin-specific agent, is potentiated by vincristine. Pretreatment of the mastocytoma line P815 with vincristine results in an enhancement of the ability of cytochalasin B to fragment DNA. These results inducate that cytochalasin B might be effective as a chemotherapeutic agent in the presence of vincristine.This work was supported in part by the Women's Cancer Association and by the Sylvester Comprehensive Cancer Center     

A prospective comparison of laparoscopic versus open cholecystectomy.

In one surgical unit, 115 patients undergoing cholecystectomy were studied to compare patient recovery, subjective and objective pain experienced and complications after laparoscopic and open cholecystectomy. The data were collected prospectively where allocation to open or laparoscopic cholecystectomy was by consecutive attendance. Laparoscopic cholecystectomy was feasible in 90% of patients presenting with symptomatic gallstones. Compared with the open operation, laparoscopic cholecystectomy was safe with less peroperative and postoperative morbidity, was more cost-effective and was associated with faster patient recovery as documented by less postoperative pain, earlier return to diet, earlier full mobilisation and discharge home. Laparoscopic cholecystectomy is superior to open cholecystectomy and should be available to all patients requiring elective cholecystectomy.     

Autologous Fat Injection for Vocal Cord Medialization in the Canine Larynx

This study examined the use of autologous fat as an alternative to Teflon® and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show moderate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation.