Simultaneous en bloc transplantation of liver, small bowel and large bowel in pigs--technical aspects.
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Anastomosis, Surgical↗
Biomedical subjects
J Fryer
Publications and source records attributed to J Fryer.
Endotoxemia during small bowel transplantation in pigs.
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Animals↗
Etoposide plus cisplatin followed by thoracic radiation for stage IIIB non-small cell lung cancer: MAOP study 2188.
Thirty-five patients with stage III B non-small cell lung cancer were treated with the combination of cisplatin (CDDP) 30 mg/M2/day and etoposide (VP16-213) 75 mg/M2/day administered as a 72-hour infusion. Twenty evaluable patients (67%) received subsequent thoracic radiation as definitive regional therapy following a clinical response or stable disease status. Complete plus partial responses to chemotherapy were observed in 15 patients (5CR and 10PR or 44%). Of the 20 patients who received radiation, six responded with five transitioning from stable disease to partial (2) or complete (3) responses. The overall response rate to the combined sequential chemotherapy plus radiation was therefore 20/35 or 59% with eight complete responders. Histopathology influenced the response rate to chemotherapy (53% versus 30% for epidermoid versus adenocarcinomas, respectively), but following radiation, the response rates were similar for the two pathologic subtypes (73% versus 71%). Median overall survival was 363 days with 20% of patients alive at 13 to 45 months. The response rate for CDDP plus VP16-213 chemotherapy administered as a 72-hour infusion was superior for stage III B non-small cell lung cancer compared with stage IV disease as previously reported by the Mid Atlantic Oncology Program (44% versus 25%). This difference between stage III B and stage IV was also reflected in median survival (363 days versus 190 days). The sequential addition of radiation therapy to this chemotherapy regimen is feasible in stage III B disease with a small proportion of patients demonstrating long-term survival.
Adenocarcinoma↗
Kidney transplant outcome with and without right renal vein extension.
Use of the vena cava to extend the right renal vein for cadaver transplantation is controversial. Right renal vein extension permits an easier anastomosis and possibly better positioning of the kidney, but may create a low flow or turbulent state. We studied whether use of a vein extension had an impact on outcome. Between January 1986 and April 1993, 305 cadaver transplant recipients received a right kidney. Of these, 76 received a graft with vein extension. None of the 76 experienced technical vascular complications versus 5 of the 229 (2.2%) without vein extension. There was no difference in 1- and 2-year graft survival for those with versus without extension. We conclude that there is no increased risk with use of the vena cava extension and recommend that the donor team routinely provide the right kidney with the vena cava attached. This allows the recipient team to determine whether an extension is appropriate for the particular recipient.
Anastomosis, Surgical↗
Comparison of the effect of rapamycin and FK506 on release of prostacyclin and endothelin in vitro.
Alterations in mesangial and endothelial cell production of vasoactive substances may be a contributing factor to the decreased renal blood flow and glomerular thrombosis associated with FK506 nephrotoxicity. In preliminary studies Rapamycin (RAPA) appears to induce fewer renal side-effects than FK506, although further documentation is required. In this study, the effects of FK506 and RAPA on release of prostacyclin, a vasodilator, and endothelin, a vasoconstrictor, were investigated in cultured rabbit mesangial and endothelial cells. In general, the effects of both RAPA and FK506 on the basal or stimulated release of prostacyclin (as measured by release of its stable metabolite, 6-keto-PGF1 alpha) or endothelin from mesangial cells and endothelial cells were similar with the following exceptions: RAPA resulted in a significant (p < 0.05) increase in the release of prostacyclin (PGI2) from endothelial cells, while in contrast, FK506 resulted in a significant decrease in the release of this analyte from these cells. The similar effects both drugs have on release of vasodilatory and vasoconstrictor substances in vitro does not explain the differences in renal side-effects of the drugs in vivo.
6-Ketoprostaglandin F1 alpha↗
The relationship of blood concentrations of rapamycin and cyclosporine to suppression of allograft rejection in a rabbit heterotopic heart transplant model.
Heterotopic heart transplants were performed on 50 New Zealand white rabbits. Groups of 5 rabbits were randomly assigned to receive, through an intravenous route, rapamycin (RAPA) or cyclosporine at the following doses: RAPA (0.05, 0.1, 0.5, and 1.0 mg/kg/day); CsA (5.0, 10.0, and 15.0 mg/kg/day). Drug vehicle and saline controls were also included. Trough blood concentrations were monitored in both RAPA- and CsA-treated groups on a weekly basis throughout the study. Biochemical assessment of renal and liver function was performed at the beginning and end of the study. Animals receiving RAPA exhibited excellent allograft survival; only two animals in the lowest dosage group (0.05 mg/kg/day) rejected their grafts. In contrast, no rejection occurred in the CsA-treated groups. Animals that rejected their grafts were maintained on the drug until the endpoint of the study was reached at 60 days posttransplant to monitor drug induced side-effects. In some instances animals were sacrificed prior to this time due to infectious and other complications. No significant changes in renal or liver function were noted in the RAPA-treated group, while in the group of animals receiving the highest dose of CsA (15.0 mg/kg/day) a significant decrease in creatinine clearance was noted. A correlation was shown to exist between dose and the trough concentrations of both drugs. The whole-blood concentrations of RAPA that resulted in maximal efficacy with minimal toxicity was in the range of 10-60 micrograms/L. Rabbits having trough whole-blood concentrations of < 10 micrograms/L rejected their grafts. A much wider therapeutic range for CsA (50-300 micrograms/L) was noted. The results suggest that RAPA is as efficacious as CsA in prevention of allograft rejection in the animal model tested. The therapeutic monitoring of trough blood concentrations of RAPA, as with CsA, may be useful in guiding dosage adjustments to maximize the immunosuppressive efficacy while minimizing drug-induced side-effects.
Animals↗
Polyarteritis associated with Yersinia enterocolitica infection.
A patient developed polyarteritis, predominantly affecting the muscles, 10 days after a Yersinia enterocolitica O:3 infection. Immunoperoxidase staining showed Yersinia enterocolitica O:3 antigen in the subendothelial layer of the blood vessels. This suggests that vasculitis should be considered as a rare manifestation of Yersinia enterocolitica infection.
Adult↗
Pharmacokinetics of rapamycin: single-dose studies in the rabbit.
The pharmacokinetics of rapamycin was investigated in five New Zealand white rabbits following intravenous administration of 0.05 and 0.5 mg/kg rapamycin in a randomized crossover fashion. Whole blood concentrations of rapamycin were analyzed by high-performance liquid chromatography (HPLC). Model-dependent and -independent parameters were calculated. The volume of distribution at steady state and total body clearance increased significantly as the dose increased. Rapamycin pharmacokinetics appear to be nonlinear. The whole blood volume of distribution, especially at the higher dose, indicated distribution out of the blood component. The drug is not cleared rapidly, with a terminal half-life of > 13 hours as calculated by model-independent parameters. The 24-h whole blood trough concentrations of the drug are well within the analytical range of the HPLC procedure. This should permit trough level monitoring for therapeutic range studies involving the drug.
Animals↗
Continuous infusion 5-fluorouracil plus weekly cisplatin for pancreatic carcinoma. A Mid-Atlantic Oncology Program study.
Fifty-six previously untreated patients with biopsy-proven, locally advanced or metastatic and measurable adenocarcinoma of the pancreas were treated with the combination of a protracted intravenous infusion of 5-fluorouracil (5-FU) and low dose weekly bolus cisplatin administered continuously for 10 weeks followed by a 2-week rest period. The objective response rate was 16% with two patients (4%) achieving a complete response (confidence intervals, 8% to 29%). The median survival time for all treated patients was 5.8 months; however, 26% of all patients were alive at 1 year. Both median survival time and the proportion alive at 1 year exceed that of prior reports involving large patient groups, possibly due to better patient selection.
Adenocarcinoma↗
Detection of infectious immune complexes in human immunodeficiency virus type 1 (HIV-1) infections: correlation with plasma viremia and CD4 cell counts.
The detection of infectious immune complexes in plasma after human immunodeficiency virus (HIV) infection may be useful as a surrogate marker of progression of disease and may help in understanding the pathogenesis of AIDS. Polyethylene glycol (PEG) precipitates of plasma were tested for the presence of HIV p24 antigen and infectious virus. Results were compared with data from cell and plasma cultures, plasma p24 antigen, CD4 cell counts, and stage of disease. PEG precipitation increased the detection rate of the p24 antigen assay from 38.3% to 58.7%. There was a significant correlation between precipitable p24 antigen and plasma viremia, changes in CD4 cell counts, and progression of disease. The sensitivity of the PEG-precipitable p24 antigen assay versus traditional p24 antigen testing was 59.0% and the specificity 91.7%. The assay was reproducible and may be a useful determinant of viral load, clinical progression, and antiretroviral efficacy.
AIDS-Related Complex↗
Cerebral nocardiosis--clinical and pathological findings in three patients.
Cerebral nocardiosis is an uncommon but increasingly diagnosed infection in Australia. We report three cases. One occurred in an immunosuppressed male in whom the diagnosis was made at autopsy, one in an otherwise healthy elderly woman with subcutaneous nocardiosis, and the third was a posterior fossa nocardial abscess without systemic involvement occurring in a previously healthy woman after surgical excision of a meningioma. Primary cerebral nocardiosis is rare, with only two cases of primary posterior fossa nocardiosis reported. The cases highlight the difficulty of diagnosis and the need for aggressive treatment with a combined approach of surgical drainage and antibiotic therapy. The antibiotic regime of choice is the subject of controversy. Rifampicin, cephalosporins, imipenem, sulphonamides and other agents were used with varying success in our patients. Cerebral nocardiosis should be considered in any patient with a cerebral space occupying lesion.
Aged↗
Vasculitis presenting as chronic unilateral painful leg swelling.
We describe 2 patients who presented with chronic painful indurated swelling of one lower limb, thought at the time of referral to be due to chronic venous insufficiency. Reassessment because of marked periostitis of the tibia and fibula as well as laboratory indices consistent with an inflammatory process revealed acute necrotizing arteritis in one patient and granulomatous arteritis in the other. Clinicians should be aware of this unusual presentation of treatable vasculitic diseases.
Aged↗
Neoplastic angioendotheliosis.
Neoplastic angioendotheliosis is a rare disease in which malignant cells are found within numerous blood vessels throughout the body in the absence of any detectable extravascular primary malignancy. The disorder has a propensity for clinical neurological involvement despite pathological evidence of systemic spread. To date 23 patients with neurological involvement have been described. This report adds a further 3 cases. There was no definite evidence to support the theory that the malignancy arises in endothelial cells; no primary extravascular tumour was found. At present a definite conclusion about the cause of the disease cannot be made.
Aged↗
ACTH-releasing activity of urotensin I and ovine CRF: interactions with arginine vasotocin, isotocin and arginine vasopressin.
The release of ACTH from superfused dispersed goldfish anterior pituitary cells was examined to determine if the neurohypophyseal peptides arginine vasotocin (AVT), isotocin (IST) or arginine vasopressin (AVP) potentiate the ACTH-releasing activities of the structurally homologous peptides urotensin I (UI) or ovine corticotropin-releasing factor (CRF). The ACTH-releasing activities of the neurohypophyseal peptides and UI or CRF were additive. AVT, IST or AVP failed to potentiate the ACTH-releasing activity of UI or CRF. These results suggest that in teleost fishes neurohypophyseal peptides have intrinsic ACTH-releasing activity but, unlike mammals, do not potentiate the release of ACTH evoked by CRF, or by the piscian CRF-like peptide, UI.
Adrenocorticotropic Hormone↗
Intramedullary spinal cord glioma with intracranial seeding.
Two cases of intracranial dissemination of primary intramedullary spinal cord gliomas are reported, with a review of the literature. One patient had a post mortem confirmation and in the second, cerebral CT scan and CSF examination demonstrated the occurrence of intracranial dissemination. CSF protein was elevated on both patients and malignant cells were found late in only the one patient. Both patients had raised intracranial pressure. The mechanisms of dissemination and of raised intracranial pressure are discussed. Such dissemination may be more common than previously realised.
Adult↗
Neurohormones from fish tails. II: Actions of urotensin I in mammals and fishes.
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Adrenocorticotropic Hormone↗
Isolation, analysis of structure, synthesis, and biological actions of urotensin I neuropeptides.
The 41-residue neuropeptide urotensin I (UI), from the urophyses of two teleost fish species (Cyprinus carpio and Catostomus commersoni), was isolated and purified, and its amino acid sequence was determined and confirmed by synthesis of a fully active peptide. The UI peptide was found to be a close structural and biological homologue of the ovine hypothalamic corticotropin-releasing factor (CRF) and the frog skin peptide sauvagine; UI is, therefore, a phylogenetic prototype of this group of peptides. Extraction of urophyses in hot acetic or hydrochloric acid cleaves an amino terminal tripeptide yielding a fully active UI(4-41). The UI peptides are equipotent with the other two naturally occurring peptides (CRF and sauvagine) in the release of mammalian pituitary corticotropin (ACTH), but UI is several times more potent than the mammalian homologue in the stimulation of release of fish pituitary ACTH. The UI peptide and its mammalian or amphibian homologues have a long-lasting hypotensive action in mammals, via a uniquely selective vasodilatation in the superior (anterior) mesenteric vascular bed only. The significantly lower hypotensive vasodilatory action of the mammalian homologue (CRF) suggests a change in the unknown physiological role of the haemodynamic actions of the UI peptides in the mammalian gastrointestinal tract during phylogenetic progression from fishes to mammals.
Adrenocorticotropic Hormone↗
Urotensin I, a CRF-like neuropeptide, stimulates acth release from the teleost pituitary.
Intraperitoneal injections of urotensin I, a CRF-like neuropeptide isolated from the caudal neurosecretory system of the teleost Catostomus commersoni, ovine CRF and sauvagine all produced significant increases in circulating levels of plasma cortisol in goldfish in which endogenous ACTH secretion was suppressed with betamethasone. In vitro, urotensin I was 2-3 times more potent than CRF or sauvagine in stimulating ACTH release from a superfused goldfish anterior pituitary cell column. These results demonstrate that urotensin I stimulates ACTH release in the goldfish, which suggests that urotensin I or a urotensin I-like peptide may serve as a CRF in teleost fishes.
Adrenocorticotropic Hormone↗