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Biomedical subjects

B Flynn

Publications and source records attributed to B Flynn.

At least 19 recordsLinked to original sources
PubMed1997

Weaning of immunosuppression in liver transplant recipients.

Immunosuppression has been sporadically discontinued by noncompliant liver allograft recipients for whom an additional 4 1/2 years of follow-up is provided. These anecdotal observations prompted a previously reported prospective drug withdrawal program in 59 liver recipients. This prospective series has been increased to 95 patients whose weaning was begun between June 1992 and March 1996, 8.4+/-4.4 (SD) years after liver replacement. A further 4 1/2 years follow-up was obtained of the 5 self-weaned patients. The prospectively weaned recipients (93 livers; 2 liver/kidney) had undergone transplantation under immunosuppression based on azathioprine (AZA, through 1979), cyclosporine (CsA, 1980-1989), or tacrolimus (TAC, 1989-1994). In patients on CsA or TAC based cocktails, the adjunct drugs were weaned first in the early part of the trial. Since 1994, the T cell-directed drugs were weaned first. Three of the 5 original self-weaned recipients remain well after drug-free intervals of 14 to 17 years. A fourth patient died in a vehicular accident after 11 years off immunosuppression, and the fifth patient underwent retransplantation because of hepatitis C infection after 9 drug-free years; their allografts had no histopathologic evidence of rejection. Eighteen (19%) of the 95 patients in the prospective series have been drug free for from 10 months to 4.8 years. In the total group, 18 (19%) have had biopsy proved acute rejection; 7 (7%) had a presumed acute rejection without biopsy; 37 (39%) are still weaning; and 12 (13%, all well) were withdrawn from the protocol at reduced immunosuppression because of noncompliance (n=8), recurrent PBC (n=2), pregnancy (n=1), and renal failure necessitating kidney transplantation (n=1). No patients were formally diagnosed with chronic rejection, but 3 (3%) were placed back on preexisting immunosuppression or switched from cyclosporine (CsA) to tacrolimus (TAC) because of histopathologic evidence of duct injury. Two patients with normal liver function died during the trial, both from complications of prior chronic immunosuppression. No grafts suffered permanent functional impairment and only one patient developed temporary jaundice. Long surviving liver transplant recipients are systematically overimmunosuppressed. Consequently, drug weaning, whether incomplete or complete, is an important management strategy providing it is done slowly under careful physician surveillance. Complete weaning from CsA-based regimens has been difficult. Disease recurrence during drug withdrawal was documented in 2 of 13 patients with PBC and could be a risk with other autoimmune disorders.

Adult↗
PubMed1995

Weaning of immunosuppression in long-term liver transplant recipients.

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.

Adolescent↗
PubMed1992

Clustering of adverse drug events: analysis of risk factors for cerebellar toxicity with high-dose cytarabine.

BACKGROUND: Cerebellar toxicity is a severe, therapy-limiting adverse reaction of cytarabine given in high doses. The Food and Drug Administration received a report of an increased frequency of cerebellar toxicity at the University of Wisconsin Hospital and Clinics after a switch from the product (Cytosar-U) manufactured by The Upjohn Co., Kalamazoo, Mich., to the generic form made by Quad Pharmaceuticals, Inc., Indianapolis, Ind. PURPOSE: To compare the incidence of cerebellar toxicity in Quad-treated patients with Upjohn-treated patients, a record-based cohort study was conducted at the University of Wisconsin Hospital and Clinics between January 1986 and August 1989. METHODS: The incidence of cerebellar toxicity was studied in 63 leukemia patients according to the manufacturer of the product received (34 Upjohn only, 25 Quad only, and four both manufacturers). The relative risk of cerebellar toxicity was adjusted for other known risk factors. RESULTS: Patients in the manufacturer-defined treatment groups did not differ significantly with respect to age, sex, type of leukemia, disease stage, calculated creatinine clearance, presence of abnormal liver function tests, or total dose received. The crude relative risk of cerebellar toxicity comparing the Quad product with the Upjohn product was 5.0 (95% confidence interval = 1.8-13.7). Adjustment for potential confounders did not alter the association. Other risk factors for cerebellar toxicity, independent of manufacturer, were age greater than 50 years, type of leukemia, disease stage, total dose greater than or equal to 20 g/m2, abnormal pretreatment liver function, and reduced creatinine clearance. CONCLUSION: This study found a significantly higher incidence of cerebellar toxicity with high-dose cytarabine manufactured by Quad Pharmaceuticals when compared with the incidence of cerebellar toxicity with the Upjohn product. Further research at independent institutions would be necessary to allow generalization of this finding. In addition, our findings suggest that a dose reduction in high-dose cytarabine therapy may be indicated for patients with reduced glomerular filtration rates.

Adolescent↗
PubMed1991

A randomized, controlled trial of the use of music during laceration repair.

STUDY OBJECTIVES: To determine whether music significantly reduces the pain and anxiety associated with laceration repair in the emergency department. PARTICIPANTS AND SETTING: Adult patients presenting to the ED at an urban teaching hospital for laceration repair. Exclusion criteria included patients less than 18 years old, having received analgesics, with suspected alcohol or substance intoxication, and in whom laceration repair was complicated by treatment of a more serious medical condition. DESIGN AND INTERVENTIONS: This was a randomized, controlled trial. After giving informed consent, patients were randomly assigned to receive standard laceration repair without music (control) or standard laceration repair with music. Patients assigned to the music group chose an audio tape from 50 available styles and artists. Patients received the music through a headset, and they controlled the volume. Intradermal lidocaine was used in all patients. Data were collected on heart rate, blood pressure, and respirations just before and immediately after wound repair. Psychological variables included the state subscale of the Spielberger State Trait Anxiety Inventory (STAI), a visual analog pain scale rating, and a brief questionnaire. STAI and pain scale ratings were analyzed with Wilcoxon's rank-sum test with an alpha error of .05. RESULTS: Thirty-eight patients (19 per group) completed the protocol. Pain scores were significantly (P less than .05) lower in the music group (mean, 2.09) than in controls (mean, 3.31). Anxiety after the procedure was reduced in both groups, but STAI reduction scores were not significantly different between groups (music, 17.7; control, 18.5). Seventeen of 19 patients (89%) rated music "very beneficial," and 100% said they would use music again. CONCLUSION: Music provides a safe, inexpensive, and effective adjunct for the management of pain in the ED but does not significantly affect anxiety.

Adult↗
PubMed1990

A comparative study of temporomandibular symptoms following mandibular advancement by bilateral sagittal split osteotomies: rigid versus nonrigid fixation.

Rigid fixation to attach proximal and distal segments during bony healing of osteotomy sites has become increasingly popular. The effects of rigid fixation on the temporomandibular joints have been questioned. The purpose of this study was to evaluate the effects of rigid fixation after bilateral sagittal split osteotomies on temporomandibular dysfunction symptoms. Forty patients who had mandibular advancement surgery were evaluated for temporomandibular joint dysfunction. Twenty had received rigid fixation, and twenty had received nonrigid fixation. It was determined that there was no statistically significant difference in temporomandibular signs or symptoms between patients who were treated with rigid internal fixation for bilateral sagittal split osteotomies for mandibular advancement and those patients who were treated with nonrigid wire fixation.

Adolescent↗
PubMed1989

Comparison of technetium-99m MIBI and thallium-201 chloride myocardial scintigraphy in infants.

Myocardial perfusion scintigraphy was performed with both 201Tl and a new six coordinate monocationic isonitrile complex of 99mTc, [99mTc]2-methoxyisobutylisonitrile (MIBI), on 11 infants who had undergone the arterial switch procedure for transposition of the great arteries. Unlike 201Tl which can show rapid and variable rates of washout from myocardium, 73% of the initial first-pass activity of the isonitrile complex in the myocardium remains 1 hr after intravenous administration. The images obtained with [99mTc]MIBI required a shorter recording time, entailed less radiation exposure to the patient, and were qualitatively at least as good as those obtained with 201Tl. No infant had perfusion abnormalities. The potential applications of the isonitrile complexes for myocardial perfusion scintigraphy in children are discussed.

Female↗
PubMed1985

Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection.

A total of 41 patients with hematologic malignancies (other than acute leukemia in relapse) received allogeneic bone marrow transplants at the University of Wisconsin from 1 April 1980 through 31 March 1984. In an effort to minimize graft-versus-host disease, marrow was depleted of T-lymphocytes in vitro with monoclonal anti-T-cell antibody and complement prior to infusion for seven of 19 recipients of marrow from HLA-identical, MLC-nonreactive siblings, and for all 22 recipients of marrow from MLC-reactive HLA-haploidentical donors. The recipients of HLA-identical T-depleted marrow all showed excellent engraftment following standard pre-BMT conditioning with cyclophosphamide and total body irradiation. In contrast, five of five recipients of T-depleted haploidentical marrow failed to engraft following this same conditioning regimen. The addition of cytosine arabinoside to the pretransplant conditioning appeared to correct this problem, allowing engraftment in 14 of 17 subsequent patients. These clinical results, coupled with prior in vitro data, demonstrate the need to adequately suppress residual host-versus-graft immunity in order to prevent the rejection of T-cell-depleted HLA-haploidentical bone marrow.

Adolescent↗
PubMed1983

HLA identical leukemia cells and T cell growth factor activate cytotoxic T cell recognition of minor locus histocompatibility antigens in vitro.

Lymphocytes from a healthy HLA-identical bone marrow transplant donor were tested for their ability to destroy her brother's acute myelogenous leukemia blasts in vitro. Primary mixed lymphocyte culture (MLC) and cell-mediated lysis (CML) responses between the patient's remission (pretransplant) and donor's lymphocytes were negative. Stimulation of donor lymphocytes for 7 d in vitro with irradiated leukemia cells, leukemia cells plus allogeneic irradiated lymphocytes, or a pool of irradiated lymphocytes from 10 donors, did not activate any cytotoxic cells able to destroy the HLA identical leukemic blasts. Further culturing for 7 additional d in T cell growth factor (TCGF) generated lymphocytes that induced effective cytotoxicity against the leukemic blasts, but not against autologous lymphocytes. Effective killing against the leukemia was observed only in cultures initially stimulated with the irradiated leukemia cells. These cytotoxic cells were maintained in TCGF and mediated persistent killing against the leukemic target cells. They were also able to destroy lymphocytes from the patient's mother and father, but not from an unrelated cell donor. This suggested specific recognition of non-HLA antigens inherited by the patient, that were foreign to the HLA identical bone marrow donor. These lymphocytes were cloned by a limiting dilution technique and one clone maintained cytotoxicity to the AML blasts and the father's lymphocytes, but not lymphocytes from the mother or an HLA-identical donor. This cytotoxicity was inhibited by a monoclonal anti-HLA antibody. Thus, in vitro sensitization of this sibling's lymphocytes with AML blasts followed by TCGF expansion, and cloning, enabled the detection of HLA-restricted cytotoxic cells that recognize minor locus histocompatibility antigens. This immune recognition may be relevant to the "graft vs. leukemia" effect that has been observed in leukemic animals and patients following histocompatible hematopoietic transplants.

Adult↗
PubMed1981

Thymic dysfunction in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is, in the great majority of cases, a neoplastic proliferation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigation of B cells. The associated immunologic dysfunction accounts for many of the clinically associated phenomenon such as infection and second malignancies. Much of this dysfunction has been attributed to poor B-cell function. Functional impairment of the T-cell component is currently being elucidated. In the investigations reported herein, we further demonstrate the immune deficiency of CLL by measuring proliferation and immunoglobulin synthesis in response to mitogens. Stimulation of various cell fractions indicates that in certain cases there is deficient T-helper, while others T function appears intact. In 2 of 4 cases tested there was augmentation of ig synthesis when the CLL cells were cocultured with thymic epithelium. The implications of such in vitro modulation are discussed.

Aged↗
PubMed1978

Cytosine arabinoside modulation of the mitotic index in treatment of adult acute leukemia.

Twenty-three unselected adult acute leukemic patients were treated with an initial intravenous pulse of cytosine arabinoside (Ara-C) 5 mg/kg. The mean mitotic index dropped from 7.7/1,000 to 2.8/1,000 at 4 hours after Ara-C pulse and rebounded to 6.7/1,000 at 18 hours. Infusions of Ara-C 7--10 mg/kg were given for 9 or 12 hours, depending on changes in the mitotic index. The group of responders (M1 or M2 marrows) could be predicted by the initial blast count in the marrow and the change in the mitotic index 18 hours after the Ara-C pulse. There were 9 (39%) complete and partial remissions. Six patients remained in remission more than 200 days. Since the changes in the mitotic indices induced by Ara-C were indistinguishable from those of another more successful trial, we infer that factors other than modulation of the cell cycle are critical to the success of this mode of therapy.

Acute Disease↗
PubMedDate not supplied

Community development through faculty practice in a rural nurse-managed clinic.

This article describes a community-academic partnership that led to the development of a nurse-managed clinic (NMC) in 1996 in a rural Indiana area designated by the state as a medically underserved area (MUA) and a health professional shortage area (HPSA). Application of the community development model in faculty practice is described in relation to the clinic. The project is ongoing; lessons learned to date, which have implications for others involved in faculty practice, are described.

Community Health Centers↗