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Biomedical subjects

B R Cofer

Publications and source records attributed to B R Cofer.

17 recordsLinked to original sources

Laparoscopic nephrectomy in children.

BACKGROUND: Laparoscopic nephrectomy in the adult population is reported with increased frequency. We present our initial experience with laparoscopic nephrectomy in children. METHODS: Over a 2-year period, 11 nephrectomies were performed in nine children aged 16 months to 16 years (mean, 6.5 years). All patients were referred due to complications of a nonfunctioning kidney. Seven patients had recurrent urinary tract infections, and two had refractory hypertension. Two patients underwent bilateral laparoscopic nephrectomy. The operation was performed using four access ports measuring 3.5 to 10 mm. RESULTS: All kidneys were removed successfully using a laparoscopic technique. The average length of the operation was 163 min per kidney (range, 90-420). The estimated blood loss was <10-150 ml (mean, 45). No patient required transfusion. Seven patients were discharged home by postoperative day 2. The two patients with the longest operating times were discharged home on postoperative days 4 and 5 due to delay in return of bowel function. Narcotic use was minimal, and all patients enjoyed a rapid return to full activity. CONCLUSION: Laparoscopic nephrectomy is a viable alternative to open nephrectomy in children. Further experience with this technique is required to establish its efficacy and reduce the operating time

Adolescent↗

A multicenter trial of 6-aminocaproic acid (Amicar) in the prevention of bleeding in infants on ECMO.

BACKGROUND/PURPOSE: Intracranial hemorrhage (ICH), is a major source of morbidity and the leading cause of death in neonates treated with extracorporeal membrane oxygenation (ECMO). Anecdotal reports have suggested that epsilon-aminocaproic acid (EACA) can decrease the risk of ICH. The purpose of this study was to evaluate, in a multiinstitutional, prospective, randomized, blinded fashion, the effect of EACA on the incidence of hemorrhagic complications in neonates receiving ECMO. METHODS: All neonates (except congenital diaphragmatic hernia) who met criteria for ECMO at three institutions were eligible for enrollment. EACA (100 mg/kg) or placebo was given at the time of cannulation followed by 25 mg/kg/h for 72 hours. Bleeding complications, transfusion requirements, and thrombotic complications were recorded. Post-ECMO imaging included head ultrasound scan computed tomography (CT) scan, and duplex ultrasound scan of the inferior vena cava and renal vessels. RESULTS: Twenty-nine neonates were enrolled (EACA, 13 and placebo, 16). Five (17.2%) patients had a significant (grade 3 or larger) ICH. There was no statistical difference in the incidence of significant ICH in patients who received EACA (23%) versus placebo (12.5%). Septic patients accounted for all of the ICH in the EACA group. Thrombotic complications (aortic thrombus and SVC syndrome) developed in two patients from the placebo group. There was no difference in thrombotic circuit complications between groups. CONCLUSIONS: Our results suggest that the use of EACA in neonates receiving ECMO is safe but may not decrease the overall incidence of hemorrhagic complications.

Aminocaproic Acid↗

Infantile fibrosarcoma: complete excision is the appropriate treatment.

BACKGROUND: Infantile fibrosarcoma and its pathological variants are unusual childhood tumors. During the past 25 years, 18 children with these lesions were seen at our institution. METHODS: These patients' records were analyzed to determine clinical and pathological findings and outcome. RESULTS: The mean age at diagnosis was 7 months. There were 16 boys and 2 girls. The sites of tumor at presentation were: Extremity, head, trunk, and pelvis. Pathological findings were: fibrosarcoma, myofibroma, and fibromatosis. Histologic characteristics varied from benign hypocellular to more cellular pleomorphism. The initial surgical procedure was a complete excision in 16. Of those patients with complete removal, 6 recurred and all had secondary reexcision. In addition to excision, 3 patients received adjunctive therapy; chemotherapy in all 3 and radiation in 2. Sixteen (89%) children survived, including 4 of 6 with recurrent tumor and 2 of 2 with incomplete initial resection. Two children ages 6 and 9 months at diagnosis died of progressive recurrent tumor at 1 month and 6 years from initial diagnosis, despite operative therapy, chemotherapy, and radiation therapy. Both had paraspinal tumors that were removed completely. Pathological examination revealed spindle cell tumors infiltrating muscle. Neither clinical nor histologic findings distinguished surviving from nonsurviving patients. CONCLUSIONS: Fibrosarcoma occurring in infants has an excellent outcome despite histologic findings. Initial complete excision should be attempted in all children. Recurrence indicates a more aggressive variant and warrants more aggressive complete reexcision wherever possible. Adjunctive therapy probably has no benefit. The occasional death indicates the need for close follow-up.

Female↗

Indefinite allograft survival induced by the combination of multiple donor-specific transfusions, cyclosporine, and an anti-T cell monoclonal antibody in a protocol relevant to cadaveric organ transplantation. The importance of prolonged posttransplant cyclosporine coverage.

A single donor specific transfusion (DST) 24 hr pretransplant and Cyclosporine (CsA) are synergistic in inducing prolongation of allograft survival. This synergy was further potentiated by giving 3 additional DSTs at weekly intervals posttransplant, or by the additional administration of a small dose of the anti-T cell monoclonal antibody OX-52 24 hr pretransplant to the above protocol. This study determined whether indefinite survival can be achieved in the ACI-to-Lewis heart allograft model by combining an anti-T cell monoclonal antibody, 4 DSTs given once 24 hr pretransplant and weekly 3 times posttransplant, and CsA. CsA was given daily for 28 days or 60 days posttransplant. The dose consisted of CsA 5 mg/kg/day starting 24 hr pretransplant and continuing until day 7 posttransplant and followed by 2.5 mg/kg/day for either 21 more days (total CsA days = 28 days) or 53 days (total CsA days = 60 days). The anti-T cell monoclonal antibody OX52 (200 micrograms i.v.) was given once 24 hr pretransplant. DST (1 ml) was given 24 hr pretransplant and on days 7, 14, and 21 posttransplant. Low-dose CsA for 28 days never induced indefinite allograft survival. CsA for 60 days, however, resulted in the occasional indefinite allograft survival (> 1 year) even in this difficult model. The addition of DST 24 hr pre- and posttransplant on days 7, 14, and 21 to both 28 days and 60 days of CsA further prolonged allograft survival. The best survival was seen in the group given DST 24 hr pre- and on days 7, 14, and 21 posttransplant and 60 days of CsA, with all the allografts surviving beyond 100 days of CsA, with all the allografts surviving beyond 100 days and more than 50% surviving indefinitely (> 1 year). The addition of a single dose of OX52 24 hr pretransplant to the multiple DSTs and 28 days of CsA protocol significantly improved indefinite allograft survival but its influence was less dramatic when given to the multiple DSTs and 60 days of CsA protocol. This beneficial interaction between CsA, DST, and an anti-T cell MoAb offers a clinically applicable protocol for both living donor and cadaveric organ transplantation in inducing donor-specific hyporesponsiveness, and further investigations are warranted.

Animals↗

The significant relationship between platelet count and haemorrhagic complications on ECMO.

Haemorrhagic complications, which occur in up to 35% of infants during extracorporeal membrane oxygenation (ECMO), often produce devastating sequelae. Although many complex factors interact to control haemostasis, platelet number and function has significant impact on the development of primary haemostasis. The optimum platelet count on ECMO, however, has not been defined. At our institution prior to August 1987, platelet counts were maintained at greater than 100,000/mm3. After August 1987, however, platelet counts of greater than 200,000/m3 were maintained. In a retrospective study, patients were randomly chosen from these two treatment periods: group 1--March 1986 to July 1987; and group 2--June 1988 to June 1989. The average platelet count, platelets administered, hours on ECMO, and bleeding complications were compared to each other and to the July 1992 ELSO Registry. There was a significant difference in average platelet counts between group 1 and group 2. However, the amount of platelets administered per kg per day was similar. There was a significant difference in overall bleeding complications between Group 2 (12%) and the ELSO Registry (35%) (p < 0.01). There was a trend towards decreased complications in all subgroups, although sample size precluded significance. We conclude that increasing platelet counts to greater than 200,000/mm3 decreases the overall bleeding complication rate. This advantage is achieved without a continuous need for increased platelet administration once the desired level is reached and without an increase in perfusion time, mechanical complications, or mortality.

Extracorporeal Membrane Oxygenation↗

Extracorporeal membrane oxygenation in the management of cardiac failure secondary to myocarditis.

While most patients with viral myocarditis have a relatively uncomplicated clinical course, a small number of patients will present with cardiogenic shock unresponsive to standard medical therapy. We describe the clinical course of three patients who developed profound cardiac failure secondary to a documented viral myocarditis. Each patient was managed using venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support using the right common carotid artery/internal jugular vein for cannulation. While undergoing ECMO support, each patient developed elevated left-sided cardiac chamber pressures with resultant pulmonary edema. This was managed by balloon atrial septostomy in two cases and combined blade/balloon atrial septostomy in one case. Excellent decompression of the left heart was achieved in each patient. Two patients were successfully weaned from ECMO and are currently alive, with one demonstrating residual cardiac dysfunction. One patient developed global myocardial necrosis and ultimately died. This small series demonstrates a role for ECMO in the management of cardiac failure due to acute viral myocarditis unresponsive to medical therapy. Our experience also suggests that balloon atrial septostomy may be useful to decompress the left atrium and ventricle of patients with acute myocarditis while on ECMO.

Acute Disease↗

Effect of a short course of rapamycin, cyclosporin A, and donor-specific transfusion on rat cardiac allograft survival.

The interactions of rapamycin (Rapa), CsA, and donor-specific transfusion (DST) were examined in an ACI to Lewis rat heterotopic cardiac allograft model. Survival data were truncated at 175 days for the purpose of statistical comparisons. Vehicle (Veh)-treated animals rejected at a mean of 7.3 +/- 0.2 days. Treatment with a DST on the day before transplantation (d-1) resulted in a decreased survival of 5.5 +/- 0.3 days (P < 0.05). An 8-day course of low-dose CsA (d-1 to d6) in Veh-treated animals prolonged allograft survival to 10.3 +/- 0.5 days (P < 0.05). The addition of a DST d-1 to the Veh/CsA-treated animals resulted in a synergistic prolongation of survival to 45.7 +/- 12.5 days (P < 0.05). Rapa proved to be a potent immunosuppressive agent in this model, with an 8-day course of Rapa (d-1 to d6) at 0.5 mg/kg/day (R1) or 1.5 mg/kg/day (R2), resulting in mean allograft survivals of 24.2 +/- 5.0 and 67.3 +/- 20.9 days, respectively (P < 0.05 vs. Veh or Veh/CsA). Rapa demonstrated synergy with CsA by further prolonging allograft survival to 115.9 +/- 27.9 days (R1/CsA, P < 0.05 vs. Veh/CsA, R1) and 164.6 +/- 10.4 days (R2/CsA, P < 0.05 vs. Veh/CsA). The extended graft survival using a combination of Rapa and DST, compared to Rapa alone, did not prove to be statistically significant. When all three treatments were combined (Rapa/DST/CsA), no significant benefit to survival was seen over Veh/DST/CsA (45.7 +/- 12.5 days vs. R1/DST/CsA, 81.9 +/- 18.4 days; R2/DST/CsA, 98.5 +/- 21.3 days; P > 0.05). If Rapa was withheld until postoperative day 1 (Rapa, 1.5 mg/kg/day on d1 to d6/DST/CsA), enhancement of the DST/CsA effect was seen with a mean survival of 170.2 +/- 4.8 days (P < 0.05). This suggests that the timing of Rapa administration may significantly impact its interaction with DST/CsA treatment and merits further investigation.

Animals↗

Effects of pre- and postengraftment donor-specific transfusions and cyclosporine on the enhancement of experimental allograft survival.

The tolerogenic effects of immediate pretransplant donor-specific transfusion (DST) with cyclosporine (CsA) have been well described. The purpose of this study was to determine if these effects could be improved upon by the administration of post-transplant DSTs. When added to a 29-day course of CsA, a single DST given 24 hr pretransplant improved graft survival compared to CsA alone (84.9 +/- 12.3 vs 40.0 +/- 8.8 days; P less than 0.05). The administration of an additional DST on post-transplant Days 7, 14, and 21 further improved this survival to 152 +/- 28 days, with 45% of grafts surviving greater than 200 days, until sacrifice. The donor specificity of this effect was demonstrated by the increased survival of second ACI grafts transplanted into Lewis recipients with existing "tolerant" ACI allografts (long-term survivors, or LTS); third-party Buffalo rat hearts transplanted into LTS rats in a similar manner were rejected normally. Loss of graft antigenicity was not seen, as retransplanted ACI hearts obtained from LTS Lewis rats were rejected in a first-order manner. From this we conclude that (1) the addition of multiple post-transplant DSTs improve the enhancement seen with preoperative DST and CsA, (2) loss of graft antigenicity does not contribute to this improved enhancement, and (3) this effect appears to be donor antigen specific.

Animals↗

Efficacy of a single pretransplant donor-specific transfusion and cyclosporin A administered 24 to 48 hours before one-haplotype-mismatched living related donor kidney transplant.

During the 7-year period from March 1984 to June 1991, 86 haploidentical living related kidney recipients were entered into one of three donor-specific transfusion (DST) and cyclosporine treatment protocols: (1) Multiple pretransplant DSTs with cyclosporine begun after transplant, n = 34; (2) Multiple pretransplant DSTs with cyclosporine begun pretransplant, n = 31; and (3) a single DST 24 to 48 hours before transplant with intravenous cyclosporine initiated after the transfusion, n = 21. Triple immunosuppression (prednisone, azathioprine, and cyclosporine) was continued in all groups after transplant. The 1-year patient (97%, 97%, and 93%, p = not significant) and graft (91%, 90%, and 87%, p = not significant) survival were similar for the three groups. No differences were seen in the incidence of rejection at 1 year (61%, 45%, and 60%, p = not significant) or in the incidence of infectious complications (26%, 42%, and 47%, p = not significant). It is concluded that a single DST given 24 to 48 hours before operation followed by pretransplant cyclosporine is as effective as classic DST conditioning of recipients using either pretransplant or post-transplant cyclosporine. The single DST protocol has the advantage of not eliminating any donors because of sensitization and was less costly and easier to administer.

Adult↗

The induction of immunologic hyporesponsiveness by preoperative donor-specific transfusions and cyclosporine in human cadaveric transplants. A preliminary trial.

A prospective randomized preliminary trial was performed in patients undergoing cadaveric renal transplantation to determine the potential benefits, disadvantages, and logistic problems associated with the administration of donor-specific transfusions and cyclosporine initiated 24 hr before transplantation. Ten patients received DST followed by continuous intravenous CsA approximately 24 hr before cadaveric renal transplantation from the same donor. Twelve patients receiving sequential therapy with Minnesota antilymphoblast globulin, azathioprine, and steroids with subsequent conversion to CsA served as controls. Patient demographics and the donor characteristics were evenly matched in the two groups. While the study group had longer cold ischemia time and more evidence of renal dysfunction within the first two weeks, subsequent renal function was identical in the groups and there were fewer episodes of severe rejection requiring treatment with OKT3 within the first six months in the DST group (5 vs. 0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures against preserved donor-specific lymphocytes than did the control group (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05). The need for dialysis, incidence of infections and other complications, and subsequent immunosuppressive therapy were not different in the two groups. It is concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation are capable of inducing reduced immunologic responsiveness against the specific donor. Patients treated with this therapy should receive organs from "ideal" donors without risk factors and cold ischemia time should not exceed 30 hr. Further clinical studies of this approach are warranted.

Acquired Immunodeficiency Syndrome↗

Penetrating injury of a duplicated ureter: case report.

Duplications of the genitourinary tract are uncommon and may be a source of confusion in the early diagnosis of ureteral trauma when their presence is not suspected. We present a case of delayed diagnosis of a penetrating injury to a duplicated ureter and its management.

Adult↗

Reduced cardiac myofibrillar Mg-ATPase activity without changes in myosin isozymes in patients with end-stage heart failure.

In this study we tested the hypothesis that reduced myofibrillar ATPase activities in end-stage heart failure are associated with a redistribution of myosin isozymes. Cardiac myofibrils were isolated from left ventricular free wall from normal human hearts and hearts at end-stage heart failure caused by coronary artery diseases, cardiomyopathy or immunological rejection. The hearts had been excised in preparation for a heart transplant. Myofibrillar Ca2(+)-dependent Mg-ATPase and myosin Ca2(+)- and K+EDTA-ATPase activities were compared. Possible changes in myosin isozyme distribution in the diseased heart were investigated using polyacrylamide gel electrophoresis of native myosin in the presence of pyrophosphate. Significant reduction in myofibrillar Ca2(+)-dependent Mg-ATPase with no changes in the sensitivity of the myofibrils to Ca2+ was observed in heart with coronary artery diseases (25.2 to 27.1% at pCa 5.83 to pCa 5.05), cardiomyopathy (21.1 to 25.5% at pCa 5.41 to pCa 5.05), and in the immunologically rejected heart (18.4 to 22.8% at pCa 5.41 to pCa 5.05). Significantly lower myosin Ca2(+)-ATPase was observed with coronary artery diseases only and myosin K-EDTA activities did not differ in diseased and normal hearts. Polyacrylamide gel electrophoresis of native myosin from the normal and three models of end-stage heart failure revealed two distinct bands in the human left ventricle and one diffuse band in the human right atria. No apparent differences in myosin isoenzyme pattern were observed between the normal and diseased hearts. Further evaluation is needed to clarify the ATPase nature of the two bands.

Ca(2+) Mg(2+)-ATPase↗