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Biomedical subjects

B Fyfe

Publications and source records attributed to B Fyfe.

At least 19 recordsLinked to original sources

Simulect induction facilitates Neoral-based steroid-free immunosuppression in primary kidney transplant recipients.

This study compares outcomes of kidney transplantation with two distinct induction protocols Basiliximab (Simulect) versus Muromonab (OTK 3) in the setting of cyclosporine (Neoral)-based immunosuppression. Postinduction protocols included either total prednisone avoidance or prednisone sparing versus standard prednisone dosing. Two hundred forty five adult patients receiving kidney transplantation between 1995 and 2000 were included in the study. Treatment in group 1 was OKT 3 + Neoral + adjunct + standard prednisone; group 2, Simulect + Neoral + adjunct + steroid sparing; group 3, Simulect + Neoral + adjunct + no prednisone. The demographics between all groups were similar. The mean (+/- SD) trough cyclosporine levels at 1 month were 276 +/- 128 versus 291 +/- 180 versus 398 +/- 365 (P=.020); at 3 months were 261 +/- 120 versus 280 +/- 152 versus 399 +/- 408 (P=.32); at 12 month were 235 +/- 144 versus 245 +/- 154 versus 234 +/- 132 (P=.96). Creatinine clearance at 1 month was 59 +/- 24 versus 58 +/- 18 versus 47 +/- 23 mL/min (P=.004); at 3 months was 66 +/- 28 versus 62 +/- 22 versus 53 +/- 25 mL/min (P=.007); at 12 months was 68 +/- 38 versus 65 +/- 22 versus 64 +/- 29 mL/min (P=.556). Serum creatinine at 1 month was 1.8 +/- 0.9 versus 1.6 +/- 1.2 versus 2.8 +/- 2.21 mg/dL (P=.005); at 3 months was 1.7 +/- 0.6 versus 1.9 +/- 1.0 versus 2.3 +/- 1.3 mg/dL (P=.007); at 12 months was 1.9 +/- 1.3 versus 2.1 +/- 1.0 versus 2.3 +/- 1.7 mg/dL (P=.179). The incidence of acute rejection within 1 year in the respective groups were 28% versus 15% versus 16%. Therefore, we conclude that using Simulect in transplant recipients results in long-term patient and graft survival similar to those achieved with OKT 3. The use of Simulect resulted in significant reduction in clinical rejection incidence within the first year regardless of steroid use. Thus, the use of Simulect allows complete steroid avoidance in Neoral-based immunosuppression regimen.

Antibodies, Monoclonal↗

Annexin-V imaging for noninvasive detection of cardiac allograft rejection.

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

Adult↗

Salvage of free flaps after secondary venous ischemia by local delivery of heparin.

Recent studies have demonstrated that heparin may protect against reperfusion injury through a direct effect on the microvascular endothelium that is independent of its effect on systemic coagulation. The purpose of this study was to determine whether local delivery of low-dose heparin has a role in the salvage of musculocutaneous flaps after secondary venous ischemia and revascularization. Cutaneous maximus musculocutaneous flaps were transplanted to the contralateral groin in adult Sprague-Dawley rats. All flaps were subjected to 2 hours of primary arteriovenous ischemia followed by 20 hours of reperfusion. The flaps were then subjected to a 6-hour secondary venous ischemic insult followed by anastomotic revision and reperfusion. Animals in group I received no adjunctive treatment. Those in group II were treated with low-dose heparin (5-6 U per kilogram per hour) infused systemically via the inferior epigastric vein. Those in group III received the same dose of heparin infused locally into the flap via the inferior epigastric artery. The dose of heparin used in groups II and III was insufficient to prolong the activated partial thromboplastin time above normal values. At 7 days, mean flap necrosis was 60.8% in group I and 62.1 in group II. Local heparin delivery (group III) resulted in complete survival of all flaps. Histological examination after 48 hours of reperfusion demonstrated improved microvascular patency and reduced neutrophilic infiltration in the flaps of group III animals. Thus, local infusion of low-dose heparin resulted in significantly improved flap salvage through a mechanism independent of its effect on systemic coagulation.

Animals↗

Intrapericardial yolk sac tumor associated with acute myocarditis.

An occult intrapericardial yolk sac tumor occurred in a 3-year-old girl with a fatal outcome. At autopsy, a 5.5-cm mass surrounded the base of the heart and compressed the left atrium posteriorly. Histologically, the tumor was a pure yolk sac tumor. Postmortem chemical analyses of the blood revealed an alpha-fetoprotein level greater than 7000 microg/L. Acute myocarditis of both ventricles was also found.

Acute Disease↗

Posttransplant lymphoproliferative disease presenting as sudden respiratory arrest in a three-year-old child.

Posttransplant lymphoproliferative disease (PTLD) is an occasional complication of pediatric organ transplantation that, heretofore, has not been associated with airway obstruction. We report the first documented case of PTLD associated with complete airway obstruction resulting in sudden respiratory arrest and death in a 3-year-old child. This is contrasted to a subsequent case of PTLD wherein heightened clinical suspicion and prompt tonsillectomy resulted in a definitive diagnosis and improved outcome. The early clinical hallmarks of PTLD are a mononucleosis-like syndrome, tonsillar enlargement, and positive Epstein-Barr virus seroconversion. The potential for a fatal outcome of PTLD involving Waldeyer's ring components warrants early recognition and aggressive treatment.

Adolescent↗

Heart transplantation-associated perioperative ischemic myocardial injury. Morphological features and clinical significance.

BACKGROUND: The frequency and clinical significance of perioperative ischemic myocardial injury (PIMI) after heart transplantation and the diagnostic features distinguishing PIMI from rejection are not well defined. METHODS AND RESULTS: We evaluated PIMI in the first four weekly endomyocardial biopsies and/or autopsy myocardium from 140 consecutive orthotopic heart transplantation recipients (1984 to 1991) by grading the severity of coagulative myocyte necrosis (CMN) as absent, 0; mild-focal, 1; moderate-multifocal, 2; or severe-confluent, 3, and determining the evolution of morphological features of its healing. CMN (often with contraction bands) was noted in 124 patients (89%); 24 patients (17%) had grade 3 CMN, of which 4 died within 30 days of transplantation. Nevertheless, at 1 year after surgery, survival was similar in patients with and without severe injury. Increased cold ischemic time but neither donor age nor intensity of inotropic support correlated with more severe early ischemic injury. PIMI inflammation was characterized by a predominantly polymorphonuclear/histiocytic infiltrate that contained lymphocytes and plasma cells, expanding the interstitium but not encroaching upon and separable from adjacent viable myocytes. Histological features of PIMI developed and resolved more slowly than those of typical myocardial infarct necrosis in nonimmunosuppressed patients; at 4 weeks, CMN persisted in 20% of patients and residual healing in nearly half. Diagnostic rejection was observed concurrently with PIMI in 54 of 533 biopsies (10%). CONCLUSIONS: Diagnosed by conventional histological criteria, PIMI is prevalent early after heart transplantation and has a protracted healing phase that can mimic or coexist with rejection. Extensive PIMI has deleterious impact on short-term survival, but the long-term impact of PIMI remains to be established.

Adolescent↗

Sarcoidosis involving a paratesticular adenomatoid tumor.

Adenomatoid tumor is a common paratesticular neoplasm which may occur at any age and can involve the epididymis, testes, spermatic cord, and ejaculatory duct. Sarcoidosis of the genitourinary tract is exceedingly rare with approximately 30 cases of epididymal sarcoidosis reported. We report the first case of an epididymal adenomatoid tumor involved by classic sarcoid granulomata in a patient with systemic sarcoidosis.

Adenomatoid Tumor↗

Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G).

Mutation of mitochondrial (mt) DNA at nucleotide (nt) 8993 has been reported to cause neurogenic weakness, ataxia, retinitis pigmentosa (NARP), or Leigh syndrome (LS). We report a family in whom the mutation was expressed clinically as LS and hypertrophic cardiomyopathy (CMP) in a boy who presented with a history of developmental delay and hypotonia, and who had recurrent lactic acidosis. The mother's first pregnancy resulted in the birth of a stillborn female; an apparently healthy older brother had died suddenly (SIDS) at age 2 months. MtDNA analysis identified the presence of the T8993G point mutation, which was found to be heteroplasmic in the patient's skeletal muscle (90%) and fibroblasts (90%). The identical mutation was present in leukocytes (38%) isolated from the mother, but not from the father or maternal grandmother. Our findings expand the clinical phenotype of the nt 8993 mtDNA mutation to include hypertrophic cardiomyopathy and confirm its cause of LS.

Acidosis, Lactic↗

The value of polyclonal carcinoembryonic antigen immunostaining in the diagnosis of microvillous inclusion disease.

Microvillous inclusion disease is a specific disorder recognized as a cause of intractable diarrhea of infancy. We studied three cases by light microscopy, electron microscopy, and immunostaining for polyclonal carcinoembryonic antigen (CEA). Histologically, all cases had villous atrophy and abnormal accumulation of periodic acid-Schiff-positive material in surface enterocytes. Ultrastructurally, poorly developed brush-border and intracytoplasmic inclusions lined by intact microvilli were present in surface enterocytes. Crypt cells showed well-preserved surface microvilli. Carcinoembryonic antigen immunostaining showed prominent intracytoplasmic reactivity in surface enterocytes and linear brush-border reactivity in crypt cells. Normal and diseased small bowel biopsy specimens used as controls revealed linear brush-border reactivity without intracytoplasmic staining. Intracytoplasmic positivity for carcinoembryonic antigen in microvillous inclusion disease is explained by its presence in the glycocalyx within the microvillous inclusions. The demonstration of a distinct staining pattern for polyclonal carcinoembryonic antigen in routinely processed small bowel biopsy specimens provides a new useful criterion that complements other established techniques for accurate diagnosis of microvillous inclusion disease.

Antibodies↗

Tissue factor is rapidly induced in arterial smooth muscle after balloon injury.

Tissue factor (TF) is a major activator of the coagulation cascade and may play a role in initiating thrombosis after intravascular injury. To investigate whether medial vascular smooth muscle provides a source of TF following arterial injury, the induction of TF mRNA and protein was studied in balloon-injured rat aorta. After full length aortic injury, aortas were harvested at various times and the media and adventitia separated using collagenase digestion and microscopic dissection. In uninjured aortic media, TF mRNA was undetectable by RNA blot hybridization. 2 h after balloon injury TF mRNA levels increased markedly. Return to near baseline levels occurred at 24 h. In situ hybridization with a 35S-labeled antisense rat TF cRNA probe detected TF mRNA in the adventitia but not in the media or endothelium of uninjured aorta. 2 h after balloon dilatation, a marked induction of TF mRNA was observed in the adventitia and media. Using a functional clotting assay, TF procoagulant activity was detected at low levels in uninjured rat aortic media and rose by approximately 10-fold 2 h after balloon dilatation. Return to baseline occurred within 4 d. These data demonstrate that vascular injury rapidly induces active TF in arterial smooth muscle, providing a procoagulant that may result in thrombus initiation or propagation.

Animals↗

Gastric syphilis. Primary diagnosis by gastric biopsy: report of four cases.

Gastric involvement in secondary or tertiary syphilis is rarely recognized clinically, and its diagnosis by examination of endoscopic biopsy specimens has been reported infrequently. We report four cases of gastric syphilis with the primary diagnosis made by gastric biopsy. The patients, all male, ranged in age from 38 to 78 years and presented with gastric complaints, the most common being upper gastrointestinal tract bleeding (three of four). Gastroscopy showed either erosive gastritis or gastric ulcers with heaped, nodular edges. The clinical diagnoses ranged from benign ulcer disease to infiltrating carcinoma and lymphoma. Gastric biopsy specimens in all cases showed a severe gastritis with dense plasmacytic infiltration, associated with varying numbers of polymorphonuclear leukocytes and lymphocytes, variable degrees of glandular destruction and reactive atypia, and a vasculitis without proliferative changes. Modified Steiner silver impregnation stain revealed numerous spirochetes in all four cases and associated Helicobacter pylori infection in one case. Serologic studies for syphilis were positive in all four cases (rapid plasma reagin test, fluorescent treponemal antibody absorption test). None of the patients were seroreactive for antibodies to human immunodeficiency virus. These recent cases of gastric syphilis emphasize the importance of remaining alert to the protean clinical manifestations of syphilis and aware of the histopathologic patterns of this disease.

Adult↗

Hypopharyngeal lipoma as a cause for sudden asphyxial death.

Lipomas of the hypopharynx are uncommon tumors that are rarely life threatening. When positioned in the hypopharynx, asphyxia may be the result of the tumor size or sudden displacement into the oropharynx. We present a case of a large hypopharyngeal lipoma, review the literature, and discuss mechanisms by which these lesions may cause sudden asphyxial death.

Aged↗

Thymic hyperplasia. A clue to the diagnosis of hyperthyroidism.

The association of simultaneous abnormalities of the thyroid and thymus is well documented, particularly in the case of Graves' disease. We present a case of a natural death following thyroid storm in which marked thymic hyperplasia was present. This finding can be helpful in determining the cause of death.

Female↗