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Biomedical subjects

D P Ryan

Publications and source records attributed to D P Ryan.

At least 19 recordsLinked to original sources
PubMed2005

Proteasome inhibition with bortezomib (PS-341): a phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle.

PURPOSE: We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. PATIENTS AND METHODS: Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m2 on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. RESULTS: On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses > or = 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m2; 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. CONCLUSION: Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea.

Adult↗
PubMed2005

Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study.

PURPOSE: To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. RESULTS: One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = -0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. CONCLUSION: ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.

Adult↗
PubMed2004

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.

Adult↗
PubMed2003

Effect of offering rumen-protected fat supplements on fertility and performance in spring-calving Holstein-Friesian cows.

The objective of this study was to evaluate the effect of two different rumen-protected fat supplements, on reproductive performance and milk production, in grass-based spring calving cows. Two hundred and one Holstein-Friesian cows with an average lactation number of 3.6 (20% first lactation, 16% second lactation and 64% third lactation or greater) were grouped into blocks of three on the basis of calving date, lactation number and previous lactation milk yield for cows of second lactation or greater and on the basis of calving date for first lactation animals. From within-blocks individual animals were assigned at random, within 10 days post-calving, to one of the following three treatments: (1) Megalac Plus 3% (MP; 0.4kg/day, containing Ca salt of palm fatty acids and Ca salt of methionine hydroxy analogue), (2) Megapro Gold (MPG; 1.5kg/day, containing Ca salt of palm fatty acids, extracted rapeseed meal and whey permeate), and (3) Control (C; unsupplemented). Cows were supplemented for on average 103 days (range 54-134 days). The average milk yield over the first 12 weeks of lactation was higher (P<0.05) for both fat supplements compared to C and was higher for MP compared to C over the full lactation. Both supplements reduced (P<0.05) milk protein concentration over the first 6 weeks of lactation. MPG increased (P<0.05) conception rate to first service compared to C. Conception rate to first service was similar (P=0.14) on MP compared to C. For pregnancy to second service, C had a higher (P<0.05) conception rate than MP. There were no significant differences between treatments in overall pregnancy rate, services per conception, number of cows served in the first 3 weeks of the breeding season or the 6-weeks in-calf rate. Comparing the combined fat treatments to C resulted in a higher (P<0.05) conception rate to first service for the fat treatments but no significant difference in overall pregnancy rate. In conclusion, fat supplements increased conception rate to first service but did not significantly affect the proportion of cows pregnant at the end of the breeding season.

Animals↗
PubMed2001

Tracheal resection and reanastomosis in the neonatal period.

BACKGROUND/PURPOSE: Severe congenital tracheal stenosis is rare. Most of these can be managed conservatively before elective repair. Focal tracheal stenosis has been treated with resection of the involved trachea and primary reanastomosis in older infants. The authors found no reports of repair of this lesion in neonates. Two patients are presented with severe respiratory failure on the first day of life that required extracorporeal life support (ECLS) who underwent successful tracheal resection and reanastomosis (TRR) during the first week of life. METHODS: A retrospective review was conducted. RESULTS: Both babies had severe pulmonary hypertension and carbon dioxide retention despite maximal therapy and were placed on ECLS shortly after transfer. One had an isolated stenosis of the upper trachea, and the other had agenesis of the right lung, esophageal atresia with tracheoesophageal fistula, and a tracheal stenosis at the end of a short trachea with a long, narrow left bronchus. Both underwent diagnostic studies and had surgical repair while on ECLS at day 3 and 7 of life without bleeding complications. They were weaned off ECLS 1 and 8 days after surgery. One patient was extubated and did well. The other was extubated transiently, but required a tracheostomy because of left mainstem bronchomalacia. Both are alive and well at 18 and 38 months of age, with no narrowing of the repairs. CONCLUSION: In the setting of severe respiratory failure requiring ECLS support, TRR can be performed safely and successfully in the neonate with focal tracheal stenosis.

Anastomosis, Surgical↗
PubMed2001

Evaluation of suspected appendicitis in children using limited helical CT and colonic contrast material.

OBJECTIVE: Colonic contrast material evaluation of suspected appendicitis in pediatric patients is technically more challenging than in adults because less intraabdominal fat is present. To determine the accuracy and feasibility of focused CT for pediatric patients, we carried out this retrospective investigation. MATERIALS AND METHODS: Between November 1995 and July 1999, 199 pediatric patients (1-18 years old; mean age, 12 years) were examined with focused CT in the emergency division for suspected appendicitis. The findings on CT were compared with the findings at surgery, pathology, and clinical follow-up. RESULTS: There were 64 true-positive CT scans, two false-negative, 128 true-negative, one false-positive, and four indeterminate. Seventy-four patients underwent appendectomy, with a negative appendectomy rate of 9%. One hundred twenty-five patients without appendicitis were treated nonoperatively. The true-positive rate was 32%, true-negative rate was 64%, sensitivity was 97%, specificity was 99%, positive predictive value was 98%, negative predictive value was 98%, and overall accuracy was 96%. Pediatric patients tolerated the procedure well. Colonic contrast material saved time and provided improved identification of the cecum and appendix. In 62 patients without appendicitis, focused CT provided alternative diagnoses. CONCLUSION: Focused CT appears to be nearly as accurate in pediatric patients as in adults. Focused CT provided alternative diagnoses in 48% of the patients for whom CT findings were negative for appendicitis.

Administration, Rectal↗
PubMed2001

Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies.

Ecteinascidin 743 (ET-743) is a cytotoxic tetrahydroisoquinoline alkaloid that covalently binds to DNA in the minor groove. The in vitro chemosensitivity of cancer cells to ET-743 is markedly enhanced by prolonging the duration of exposure to the drug. A Phase I study of ET-743 given as a 72-h continuous i.v. infusion every 21 days was performed. Characteristics of the 21 adult patients with refractory solid tumors enrolled in the study were as follows: (a) 12 men; (b) 9 women; (c) median age, 59 years; (d) Eastern Cooperative Oncology Group performance status < or = 1, 20 patients; and (e) two prior regimens of chemotherapy, 7 patients. Dose limiting toxicity (DLT) was defined by typical criteria, except that grade 3 transaminitis did not constitute a DLT. There were no DLTs in the six patients evaluated at the first two dose levels of 600 and 900 microg/m2. Reversible grade 4 transaminitis occurred in two of nine patients after treatment with the first cycle of therapy at the third dose level of 1200 microg/m2. Another patient experienced grade 4 rhabdomyolysis, renal failure requiring hemodialysis, grade 4 neutropenia, and grade 3 thrombocytopenia during the second cycle of therapy with this dose. The maximum tolerated dose was 1200 microg/m2, and an additional six patients were enrolled at an intermediate dose level of 1050 microg/m2. This well-tolerated dose was established as the recommended Phase II dose. The disposition of ET-743 was distinctly biexponential, and a departure from linear pharmacokinetic behavior was evident at the 1200-microg/m2 dose level. Pharmacokinetic parameters determined at 1050 microg/m2 were (mean +/- SD): maximum plasma concentration, 318 +/- 147 pg/ml; initial disposition phase half-life, 9.0 +/- 10.3 min; terminal phase half-life, 69.0 +/- 56.7 h; and total plasma clearance, 28.4 +/- 22.5 liters/h/m2. Prolonged systemic exposure to concentrations of the agent that are cytotoxic in vitro were achieved. Toxicity of the drug is clearly schedule-dependent, because increasing the duration of infusion from 3 or 24 h to 72 h results in decreased myelosuppression and comparable hepatotoxicity. Although there were no objective responses to therapy, clear evidence of antitumor activity was observed in a patient with epithelioid mesothelioma, as confirmed by positron emission tomography studies. A Phase II trial to assess the efficacy of ET-743 against this highly refractory neoplasm has been initiated on the basis of this observation. The therapeutically optimal administration schedule remains to be established, inasmuch as there have been indications of activity against a variety of tumors during Phase I studies when the drug was infused over times ranging from 1 to 72 h. Characterizing the pharmacokinetics of ET-743 during the course of Phase II trials and Phase I combination studies is recommended to assure that this promising new anticancer drug can be used with an acceptable margin of safety.

Adult↗
PubMed2000

Carcinoma of the anal canal.

Despite the rarity of carcinoma of the anal canal, remarkable progress has been achieved during the past 30 years in understanding its pathogenesis and improving treatment. Largely because of the rigorous collection of data and the treatment of patients in clinical trials, it is now widely accepted that the majority of cases are caused by human papillomavirus and can be cured by combination therapy. Concomitant treatment with external-beam radiation therapy and chemotherapy with fluorouracil and mitomycin represents the standard approach to combination treatment. Appropriate cytologic screening of high risk populations and the integration of platinum compounds into treatment regimens will most likely reduce mortality from this disorder even further.

Antineoplastic Agents↗
PubMed2000

A phase I study of gemcitabine and docetaxel in patients with metastatic solid tumors.

BACKGROUND: A Phase I study was initiated to determine the maximum tolerated dose of weekly gemcitabine combined with monthly, fixed-dose docetaxel. METHODS: Patients with metastatic solid tumors were treated with docetaxel, 60 mg/m(2), on Day 1 every 28 days. Gemcitabine was administered on Days 1, 8, and 15 and underwent dose adjustment in cohorts of 3-6 patients. At the maximum tolerated dose, 11 additional patients were enrolled. RESULTS: Twenty-six patients received 85 cycles of therapy. At the first dose level, the planned gemcitabine dose on Days 1, 8, and 15 was 800 mg/m(2). Two of the 6 patients treated at this dose level experienced dose-limiting toxicities (DLTs) requiring the reduction of gemcitabine to 600 mg/m(2) per dose and the administration of ciprofloxacin, 500 mg orally twice daily, on Days 8-18. At the second dose level the first 3 patients experienced no DLTs and the dose of gemcitabine was increased to 700 mg/m(2). Two of the 6 patients treated at the 700 mg/m(2) dose level experienced DLTs. Eleven additional patients were enrolled at the recommended Phase II dose of gemcitabine (600 mg/m(2)). At this dose level, Grade 3/4 (according the National Cancer Institute's common toxicity criteria) neutropenia and thrombocytopenia occurred in 12.5% and 2.1% of cycles, respectively. Grade 3 and 4 nonhematologic toxicities were uncommon. Three of seven evaluable patients with pancreatic carcinoma had evidence of significant antineoplastic activity (three partial responses). In addition, two complete responses (one patient with gastric carcinoma and one patient with ovarian carcinoma) and one partial response (patient with hepatocellular carcinoma) were noted in patients with other solid tumors. CONCLUSIONS: The regimen comprised of docetaxel, 60 mg/m(2), on Day 1 and gemcitabine, 600 mg/m(2), on Days 1, 8, and 15 with ciprofloxacin on Days 8-18 every 28 days is safe, well tolerated, and active.

Antimetabolites, Antineoplastic↗
PubMed2000

Anal carcinoma: histology, staging, epidemiology, treatment.

Our understanding of the pathogenesis and management of squamous cell carcinoma of the anal canal has undergone profound change over the last 30 years. Epidemiologic studies have demonstrated that infection with human papillomavirus is most likely responsible for the majority of cases. Primary treatment with concomitant chemotherapy and radiation cures the majority of patients without the need for an abdominoperineal resection. Recent series have demonstrated that approximately one half of patients with a local recurrence after chemoradiation will be cured with salvage surgery. The incorporation of cisplatin into the primary chemoradiation treatment of patients with carcinoma of the anal canal is the focus of current studies.

Adenocarcinoma↗
PubMed2000

Congenital caudal vertebral malformations in the alpaca (Lama pacos).

OBJECTIVE: To assess radiologically the caudal vertebrae of a male alpaca with an abnormal tail, and nine of his offspring. PROCEDURE: Right lateral and ventrodorsal radiographs were taken of the caudal vertebrae. RESULTS: The caudal vertebral abnormalities in these alpacas included vertebral subluxation, hemivertebrae, wedge hemivertebrae and block vertebrae. CONCLUSION: These malformations in offspring of one sire suggest a hereditary basis for congenital caudal vertebral malformations in the alpaca.

Animals↗
PubMed2000

Rectal cancer: integrating oxaliplatin into chemoradiation studies.

The current standard of care for patients with stage T3 rectal cancer is adjuvant combined-modality treatment with radiation and fluorouracil (5-FU)-based chemotherapy. Although data from randomized phase III trials comparing preoperative and postoperative combined-modality therapy are lacking, preoperative therapy is an option in T3 disease and can be considered the standard of care for T4 disease. Given its effects in reducing systemic disease in stage IV rectal cancer and its potential for radiosensitization of target tumors, oxaliplatin (Eloxatin), a new cytotoxic agent from the diaminocyclohexane platinum family, is being evaluated in preoperative combined-modality regimens in a Cancer and Leukemia Group B (CALGB) phase I/II study (protocol 89901) in T4 disease and an Eastern Cooperative Group (ECOG) phase I study (E-1297) in locally advanced T3 or T4 disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Comparison of oestrous synchronization regimens for lactating dairy cows.

The objective of this experiment was to evaluate various programmes for synchronization of oestrus. The focus of the study was to evaluate rates of detection of oestrus, synchrony of oestrus, pregnancy rate, and effect of ovarian status at initiation of the programmes on rates of detection of oestrus and pregnancy rate. Spring-calving, lactating dairy cows (n = 2009) were allocated at random to one of six treatments: (1) A (n = 335), progestogen (controlled intravaginal drug release; CIDR) inserted per vaginum 10 d before breeding season for 8 d, 10 microg of buserelin at CIDR insertion, PGF2alpha treatment on the day prior to CIDR removal, and AI of cows detected in oestrus within 6 d after CIDR withdrawal; (2) B (n = 330), as in A, plus 1 mg of oestradiol benzoate i.m. 10 h post CIDR withdrawal; (3) C (n = 347), as in A, except buserelin was replaced by 10 mg of oestradiol benzoate; (4) D (n = 335), as in A, plus PGF2alpha and oestradiol benzoate at CIDR insertion; (5) E (n = 332), CIDR containing a 10 mg oestradiol benzoate capsule inserted per vaginum for 12 d; or (6) F (n = 330), as in E, plus PGF2alpha on the day prior to CIDR withdrawal. The oestrous detection rate (number of cows detected in oestrus within 6 days of CIDR withdrawal as a proportion of the number of cows submitted for synchronization of oestrus) and oestrous synchrony (oestrous detection rate within 2 d of CIDR withdrawal), respectively, were greater (P<0.05) following B (95.7% of 330, 98.7% of 316) compared with any of the other programmes for synchronization of oestrus (A: 87.5 of 335, 79.4% of 293; C: 86.7% of 347, 80.0% of 301; D: 90.1% of 335, 89.8% of 302; E: 74.4% of 332, 70.4% of 247; F: 76.4% of 330, 78.5% of 252). The oestrous detection rate was reduced (P<0.05) among cows in metoestrus administered E (64.0% of 50) relative to similar cows administered F (82.8% of 64). Pregnancy rate was greater (P<0.05) following B (57.9% of 330) than A (48.9% of 335, P = 0.06), C (43.2% of 347), E (40.0% of 332), and F (35.1% of 330) but not D (59.3% of 302), when based on those cows presented for oestrous synchronization programmes. In conclusion, 1 mg of oestradiol benzoate administered 10 h post CIDR withdrawal (B) resulted in the best overall oestrous detection, oestrous synchrony, and pregnancy rates, which would be beneficial to a fixed-time AI program.

Administration, Intravaginal↗
PubMed1999

The ability of pressure-controlled discography to predict surgical and nonsurgical outcomes.

STUDY DESIGN: A multicenter, retrospective study of long-term surgical and nonsurgical patient outcomes, after lumbar discography. OBJECTIVES: To investigate the efficacy and surgical outcome predictive value of categorizing positive discography findings, using a pressure x pain provocation categorization system. BACKGROUND: With the use of pressure-controlled manometric discography, improved and more specific diagnostic categorization is possible. The literature suggests that more specific categorization of positive discographic findings may predict surgical and nonsurgical outcomes. Studies have shown that intertransverse fusions may not fully protect the disc from anterior loading. Consequently, in patients who have low-pressure-sensitive discs, surgery that includes interbody fusion should provide a more favorable long-term outcome than intertransverse fusion only. METHODS: Long-term outcome was ascertained in 96 patients who had lumbar discography and subsequently underwent interbody fusion alone, combined fusion, intertransverse fusion or no surgery. Patients were retrospectively placed into specific diagnostic categories, according to a four-point scale. Progressively restrictive subgroups, beginning with the entire sample and ending with the most sensitive group (chemically sensitive), were examined for long-term surgical outcome differentiation. RESULTS: There were no significant differences in long-term surgical outcome across the entire sample. However, significant outcome differences existed across the subgroup of patients with chemically sensitive discs. In this group, patients undergoing interbody/combined fusion had a significantly better outcome than patients who had intertransverse fusion. Nonsurgical patients had the worst outcome overall. CONCLUSIONS: Patients with highly (chemically) sensitive discs appear to achieve significantly better long-term outcomes with interbody/combined fusion than with intertransverse fusion. Patients without disc surgery have the least favorable outcome. Precise prospective categorization of positive discographic diagnoses may predict outcomes from treatment, surgical or otherwise, thereby greatly facilitating therapeutic decision-making.

Female↗
PubMed1999

Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure.

HYPOTHESIS: Extracorporeal membrane oxygenation (ECMO) is effective in nonneonatal acute respiratory failure under certain circumstances. DESIGN: Retrospective medical record review. SETTING: The intensive care unit of a tertiary care hospital. PATIENTS: Thirty-four nonneonatal patients (mean age, 22 years; range, 8 days to 56 years), with ratios of the PaO2 to the fraction of inspired oxygen persistently below 70, who were treated with ECMO after maximal ventilator therapy had failed (mean time of ventilator therapy, 6.9 days; range, 1-41 days). The mean ECMO duration was 304 hours (range, 56-934 hours). Patients were grouped into 7 categories based on their diagnosis: sepsis or sepsis syndrome (n = 3), bacterial or fungal pneumonia (n = 10), viral pneumonia (n = 5), trauma or burn (n = 2), inhalation injury without burn (n = 1), immunocompromised state (due to transplantation or chemotherapy) (n = 8), and acute respiratory failure of unknown origin (n = 5). MAIN OUTCOME MEASURE: Survival to hospital discharge following ECMO therapy. RESULTS: Overall survival was 53% (18 patients). All 6 patients (100%) with viral pneumonias or isolated inhalation injuries survived. Of 13 patients with bacterial pneumonia, sepsis, or sepsis syndrome not complicated by multiorgan failure, 10 (77%) survived. In contrast, all but 1 of the immunocompromised patients died. Survival in patients who were intubated for less than 9 days before ECMO was 64%, whereas survival fell precipitously to 22% for patients who experienced mechanical ventilation for 9 or more days before the implementation of ECMO. Finally, the proportion of patients who died while receiving ECMO therapy was greater when the ECMO duration exceeded 300 hours (62% vs. 38%; P<.05). CONCLUSIONS: Nonneonatal survival with ECMO therapy is strongly dependent on the diagnosis. Pre-ECMO intubation for less than 9 days had little effect on survival. Survival rates decreased when the length of time of receiving ECMO exceeded 300 hours.

Acute Disease↗
PubMed1999

Induction immunosuppression for lung transplantation with OKT3.

BACKGROUND: The use of OKT3, an anti-CD3 monoclonal antibody, for immunosuppressive therapy for lung transplantation has been restricted because of concerns regarding infectious risk and cardiopulmonary instability after its administration. METHODS: Fifty-two patients received OKT3 (5 mg/d intravenously for 10 days) for induction of immunosuppressive therapy, along with azathioprine (1.5 mg x kg(-1) x d(-1) intravenously) and enteral cyclosporine (12 mg x kg(-1) x d(-1)). Maintenance steroid therapy was begun on postoperative day 8. Prophylactic antifungal therapy (fluconazole or amphotericin B) and ganciclovir was used in all patients. Serial transbronchial biopsy and measurements of pulmonary function were used to assess patients for evidence of infection or rejection. Cytomegalovirus infection was diagnosed by biopsy or the presence of cytomegalovirus antigenemia. RESULTS: The 30-day mortality rate was 4%; the in-hospital mortality rate was 8%. Acute graft failure was seen in 6 patients. The median length of intubation was 5 days, and the median hospital stay was 30 days. Systemic and pulmonary artery systolic pressures, cardiac index, and ratio of arterial partial oxygen pressure to fraction of inspired oxygen showed no significant alteration after OKT3 dosage. Gram-negative pulmonary infections were identified in 12 patients. Aspergillus infection was seen in 7 patients. Cytomegalovirus infection in 8 patients responded to ganciclovir and did not affect mortality. Respiratory syncytial viral infection was seen in 7 patients. Acute rejection was never seen during OKT3 administration. No episodes of acute rejection were identified in 14 patients at any time postoperatively. In the remainder, episodes of acute rejection responded to steroid or antithymocyte globulin therapy. At a median length of follow-up of 31 months, freedom from obliterative bronchiolitis was 69%+/-9% at 36 months. The overall survival rate was 88%+/-5% at 12 months, 82%+/-6% at 24 months, and 74%+/-7% at 36 months after transplantation. CONCLUSIONS: OKT3 is a safe and effective agent for induction immunosuppressive therapy in lung transplant recipients that limits the incidence of acute rejection and may decrease the incidence of obliterative bronchiolitis.

Adolescent↗