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Biomedical subjects

J A Sanchez

Publications and source records attributed to J A Sanchez.

At least 55 records · Page 3Linked to original sources
PubMed1992

The heart in Tangier disease. Severe coronary atherosclerosis with near absence of high-density lipoprotein cholesterol.

Cardiac necropsy findings are described in a 72-year-old man with Tangier disease whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level was 1.4 mg/dL, and who had coronary artery bypass grafting for severe atherosclerotic coronary artery disease. At necropsy, 24 of the 72 (33%) 5-mm segments of the 4 major (right, left main, left anterior descending, and left circumflex) native coronary arteries and 4 of the 27 (15%) 5-mm segments of the saphenous vein aortocoronary bypass conduits were narrowed by more than 75% in cross-sectional area by atherosclerotic plaques. The plaques were composed primarily (91% to 97%) of fibrous tissue. Oil red O staining, polarized light microscopy, and electron microscopy revealed cholesterol deposits in the plaques and in the walls of coronary arteries, saphenous vein grafts, and aorta. Such deposits also were found in foam cells of histiocytic origin, fibroblasts in all four cardiac valves, and in Schwann cells of cardiac nerves.

Aged↗
PubMed1992

The efficiency and timing of plasmid DNA replication in Xenopus eggs: correlations to the extent of prior chromatin assembly.

Injection of the circular plasmid FV1 (derived from type I bovine papilloma virus) into Xenopus eggs before the start of the first cell cycle dramatically increases the efficiency of plasmid replication once eggs are chemically activated. We call this the preloading effect and report kinetic and quantitative characterization of this phenomenon here. The timing and the amount of FV1 synthesis were measured by both BrdUTP density labelling and an optimized method of selective enzymatic digestion of replicated and unreplicated molecules using the three methyladenosine-sensitive isoschizomers, DpnI, MboI and Sau3a. DpnI in 100 mM NaCl proved particularly useful for distinguishing and quantitating unreplicated, once-replicated, and repeatedly replicated molecules accumulated over several cell cycles. Our results reveal that both the amount of DNA replicated and the timing of synthesis during the first S-phase correlate with the length of the preloading period. Longer preloading leads to larger amounts of DNA being replicated sooner. In fact, up to 30-50% of 1 ng injected plasmid can replicate in a semiconservative cell cycle-dependent manner during the first S-phase. But such high levels of synthesis during the first cell cycle appear to limit the egg's ability to rereplicate this material in subsequent cell cycles. The preloading effect does not depend on synthesis of either viral or egg proteins, but does appear to correlate with the extent of plasmid assembly into chromatin before the start of the cell cycle. We postulate that each plasmid molecule must achieve a critical degree of chromatin assembly before it can proceed along the replication pathway. These observations illuminate some of the difficulties inherent in building a vector for gene insertion into Xenopus embryos, but also suggest an experimental strategy toward this aim.

Animals↗
PubMed1992

The implantable defibrillator: an electronic bridge to cardiac transplantation.

BACKGROUND: Sudden cardiac death (SCD) is common among patients awaiting heart transplantation. Medical management of SCD may fail due to lack of efficacy or adverse side effects. The implantable cardioverter-defibrillator (ICD) may extend patient survival until a donor heart is available. METHODS AND RESULTS: We reviewed 16 patients listed for transplantation between November 1988 and October 1991 who underwent ICD implantation for ventricular arrhythmias refractory to medical management. Mean age was 51.4 +/- 11.4 years (range, 19-66 years), mean ejection fraction was 15.4 +/- 3.0% (range, 10-21%), and underlying cardiomyopathy was ischemic (12 patients), valvular (one patient), or dilated (three patients). There was no mortality from ICD insertion. Fourteen patients were discharged before transplantation, and two patients remained in the hospital until transplantation. Twelve patients underwent transplantation after a mean of 155.7 +/- 113.7 days (range, 3-319) on the transplant list. The ICD delivered shocks for tachyarrhythmia associated with near syncope in 15 of 16 patients. ICD shocks numbered > 10 in five patients, 5-9 in three patients, and 1-4 in seven patients. There was no morbidity or mortality attributed to patch electrode removal. CONCLUSIONS: We conclude that the ICD can be implanted with minimal morbidity in transplant candidates, allowing the patients to be ambulatory and to leave the hospital while awaiting heart transplantation. In patients at risk of SCD, the ICD is an effective electronic bridge to transplantation.

Anti-Arrhythmia Agents↗
PubMed1992

Cardiac transplantation after prolonged graft preservation with the University of Wisconsin solution.

We tested the ability of University of Wisconsin solution to extend hypothermic preservation of the nonperfused heart during orthotopic baboon allotransplantation. Seven baboons received hearts after cardioplegia and storage (4 degrees C) with University of Wisconsin solution, with a preservation time of 14.2 +/- 1.6 hours. One animal died as a result of a technical error. Six survivors were immunosuppressed for 45 days and then put to death. Preservation did not alter heart weight or histologic features according to light and electron microscopy. Animals were weaned from bypass and returned to their cages without intravenous support within 3.9 +/- 0.8 hours. Weekly biopsies, electrocardiograms, enzyme analyses, echocardiograms, and right heart catheterizations demonstrated excellent cardiac function. University of Wisconsin solution can extend hypothermic cardiac preservation and has no deleterious effects on long-term myocardial function (up to 45 days). This study validates the rationale for human trials with preservation and storage in University of Wisconsin solution toward the goal of improving and prolonging donor heart preservation.

Adenosine↗
PubMed1992

Laser activation of tissue sealant in hand-sewn canine esophageal closure.

UNLABELLED: Dehiscence rates of esophageal anastomoses are between 5% and 20%. Because small leaks between sutures might promote microabscess formation and lead to dehiscence, we postulated that a better initial physical seal might be beneficial. Reinforcement with laser activation of tissue sealant (LATS) is a new technique that has been shown to increase the bursting strength of anastomoses in other tissues. The tissue sealant is composed of 0.4 ml of hyaluronic acid and 0.2 ml of albumin, to which 3 drops of indocyanine green dye are added to give the sealant a peak absorbance of 805 nm, matching the wavelength (808 nm) of a small, hand-held diode laser. Since tissues do not absorb at this wavelength, laser energy is focused in the sealant, minimizing collateral thermal damage. To extend this concept, we assessed LATS in a canine model of esophageal closure. The esophagus was exposed via a right thoracotomy in 20 dogs, and two transverse incisions, 2 cm in length, were made in each esophagus (n = 40 closures). Both sites were closed with a single layer of interrupted 4-0 polyglycolic acid suture. Either the proximal or distal incision was randomly chosen to receive laser activation of tissue sealant. Tissue sealant was applied to the reapproximated edges of the hand-sewn closure, which was then exposed to diode laser energy. The end point was visible shrinking and desiccation of the sealant, which required about 2 minutes. Each esophagus was recovered at 0, 2, or 7 days postoperatively (n = 10, 5, and 5 dogs, respectively), bursting pressure was measured, and the closures were examined histologically. At all three time points LATS closures had significantly higher bursting pressures than control closures (time 0: 251 +/- 87 versus 105 +/- 46, p less than 0.0001; time 2 days: 296 +/- 36 versus 121 +/- 14, p less than 0.0013; time 7 days: 318 +/- 72 versus 197 +/- 60, p less than 0.0021). Histologic study revealed trace thermal injury, with regeneration of intact mucosal lining by 7 days. CONCLUSION: laser activation of tissue sealant is a simple technique that significantly increases the strength of esophageal closure and may reduce the prevalence of dehiscence.

Adhesives↗
PubMed1992

Genetic differentiation among natural European populations of Atlantic salmon, Salmo salar L., from drainages of the Atlantic Ocean.

Previously published allelic frequencies at four polymorphic protein coding loci were used as a basis for examining genetic relationships among 19 European populations of Atlantic salmon, Salmo salar L.--exclusive of Baltic drainages--from the Barents Sea to Spain. The data did not support a model of distinct ancestral (e.g. Boreal and Celtic) origins, but were consistent with all populations descending from a single ancestral group within this region with genetically diverged populations drawn together through limited local migrations.

Alleles↗
PubMed1992

University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial.

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.

Adenosine↗
PubMed1991

University of Wisconsin solution for human donor heart preservation: initial clinical experience.

Although in vitro and primate orthotopic transplant experiments have suggested the superiority of University of Wisconsin solution (UWS) compared with crystalloid cardioplegia and saline solution storage for hypothermic heart preservation, concerns about the viscosity and the high potassium concentration of UWS have precluded its use in human cardiac transplantation. To test the safety and efficacy of UWS, 16 patients received hearts arrested with, flushed with, and stored in UWS at 4 degrees C for a mean ischemic time of 153.3 +/- 30.7 minutes. After reperfusion, the hearts contracted vigorously and attained a stable sinus rhythm within 4.0 +/- 2.4 minutes, and the patients were weaned from bypass in 24.5 +/- 8.0 minutes. There was no evidence of acute or chronic ischemic myocardial injury by enzymatic analysis, electrocardiography, or biopsy specimen histology. The results suggest UWS can be safely used, within currently accepted limits of donor ischemic time, to arrest and preserve human hearts for transplantation. Further studies of preservation are required to compare UWS with crystalloid cardioplegia and saline solution storage and to test the ability of UWS to prolong the period of safe donor hypothermic ischemia in clinical heart transplantation.

Adenosine↗
PubMed1991

Binding of preformed xenoantibodies to porcine bioprosthetic valves.

We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials.

Animals↗
PubMed1991

Effect of AICD patch electrodes on the diastolic pressure-volume curve in pigs.

Although the automatic implantable cardioverter defibrillator (AICD) is effective against malignant ventricular arrhythmias, the effects of AICD patches on left ventricular diastolic properties have not been defined. Accordingly, extrapericardial (group E, n = 5) or intrapericardial (group I, n = 6) AICD patches were implanted through a median sternotomy in 11 anesthetized pigs. Six weeks later, using a left thoracotomy, the hearts were arrested with hypothermic cardioplegia. A balloon catheter was inserted into the left ventricle through the aortic root, and pressure-volume curves were measured before and after sequential removal of patches and pericardium. A dense intrapericardial fibrotic reaction in group I was not present in group E. Normalized left ventricular filling volumes in group E were significantly larger at pressures of 5.1 to 10, 15.1 to 20, and 20.1 to 28 mm Hg compared with group I (p less than 0.05). We conclude that intrapericardial AICD patches adversely affect left ventricular diastolic pressure-volume relations and recommend that AICD patches be placed in the extrapericardial location clinically whenever possible.

Animals↗
PubMed1991

The interaction of cefotaxime with the serum albumin of several mammalian species.

1. The interaction of cefotaxime with the serum albumin of several mammalian species; horses, swine, sheep, dogs and rabbits, was studied comparatively. The technique of ultrafiltration and spectrophotometric determination of the free antibiotic in the filtrate was used. 2. Binding percentages, which vary according to the species studied, were found to be higher in swine and rabbit albumins (between 92 and 81%) and lower for sheep, dog and horse albumins (between 67 and 52%). 3. The number of binding sites is usually close to 2; in the case of the horse it is 2.43. The apparent binding constants are: swine, 1.61 x 10(4) M-1; rabbit, 1.19 x 10(4) M-1; sheep, 2.33 x 10(3) M-1; dog, 2.00 x 10(3) M-1; horse, 1.42 x 10(3) M-1. The Scatchard model was used for data analysis. 4. Possible consequences of this interaction regarding clinical use of cefotaxime on different species are discussed.

Animals↗
PubMed1991

The effect of amiloride on the resting potential and the electrical constants of frog skeletal muscle fibres.

1. The effects of amiloride on the membrane potential of frog skeletal muscle fibres were investigated with a single intracellular microelectrode. Two microelectrode current- and voltage-clamp experiments were also performed to determine the effects of amiloride on the electrical constants and membrane current near the resting potential. 2. Amiloride reversibly hyperpolarized muscle fibres up to ca 12 mV in 2.5 mM-K+, in a concentration-dependent manner, with a half-maximum effect at 0.2 mM. Amiloride (0.4 mM) also significantly increased the membrane resistance of muscle fibres. 3. The effects of amiloride were consistent with the classical theory of the resting potential and could be described by assuming that it removes the Na+ permeability factor in the Goldman-Hodgkin-Katz equation for [K+]o > or = 2.5 mM. 4. Replacement of [Na+]o by N-methyl-glucamine, choline or Mg2+ produced smaller effects on the resting potential and on membrane resistance than those induced by amiloride. 5. It is concluded that an amiloride-sensitive poorly selective conductance continuously depolarizes the cellular membrane thus playing a role in the resting potential of frog skeletal muscle.

Amiloride↗
PubMed1991

Improved heart preservation with University of Wisconsin solution: experimental and preliminary human experience.

We tested the ability of University of Wisconsin solution (UWS) to extend hypothermic nonperfused heart preservation in baboons and then proceeded to human transplantation. Orthotopic transplantation was performed in five baboons (UWS cardioplegia and storage [4 degrees C]; preservation time 10.3 +/- 0.6 hours). Four survivors were immunosuppressed for 45 days and killed. One animal died from disruption of the aortic anastomosis due to technical error. Preservation did not alter histology under light and electron microscopy or heart weight (at harvest, 51.4 +/- 11.6 g; before implant, 52.5 +/- 11.1 g). Animals were weaned from bypass (mean, 23 +/- 12 minutes) and returned to their cages without intravenous support within 3.6 +/- 0.6 hours. Weekly biopsy, electrocardiogram, enzyme analysis, echocardiogram, and right heart catheterization demonstrated excellent cardiac function. Following success in baboons, UWS was applied to human transplantation (n = 2, UWS cardioplegia and storage [4 degrees C]; preservation time 4.2 and 2.1 hours). The hearts returned to sinus rhythm within 4 minutes of reperfusion without defibrillation, and enzymatic and hemodynamic data reveal excellent heart preservation. Preliminary data suggest the ability of UWS to prolong heart preservation in baboons and be used safely in humans. Further studies are required to compare UWS with crystalloid cardioplegia and saline storage and to prolong donor heart preservation in humans.

Adenosine↗
PubMed1991

Resection of a granular cell tumor at the hepatic confluence. A precarious location for a benign tumor.

Granular cell tumors are lesions that account for less than 10 per cent of benign biliary tumors and only 1 per cent occur in the biliary tract. Since the first description, 45 other cases have been described to which we add a case. In reviewing the literature, a striking predominance in black females is evident. The most frequent location of these tumors in the biliary tree appears to be the common bile duct (50%), followed by the cystic duct (37%), the hepatic ducts (15%), and the gallbladder (4%). Most patients have been treated with resection followed by restoration of biliary continuity using biliary enteric diversion. In the case presented, the tumor was located at the hepatic confluence with extension into the hepatic substance requiring segmental duct cholangiojejunostomy after resection. This resulted in fulminant sepsis and death despite adequate preoperative biliary decompression and the lack of signs or symptoms of infected bile. Alternative forms of management in the treatment of this benign condition at this location are discussed.

Adult↗