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Biomedical subjects

S Hunt

Publications and source records attributed to S Hunt.

At least 109 records · Page 6Linked to original sources

Retransplantation for severe accelerated coronary artery disease in heart transplant recipients.

Development of accelerated coronary artery disease (CAD) in the cardiac allograft is one of the major causes of late graft failure in heart transplant recipients. At the Stanford University Medical Center 356 heart transplant procedures were performed in 329 patients by the end of January 1985. Eighty-nine of these patients developed evidence of transplant CAD. Twenty retransplant procedures, including 2 third transplants, were performed in 19 of the 89 patients because of transplant CAD. The graft survival rates after the second transplant were 55%, 25% and 10% after 1, 2 and 5 years, respectively. Nine of these retransplant patients currently survive, the longest for 5.5 years. To examine potential risk factors for development of severe transplant CAD, these 20 retransplant procedures were compared with 113 transplant recipients who had no evidence of transplant CAD on annual coronary arteriograms. An excess of rejection episodes (3 +/- 2 vs 2 +/- 1 episodes/patient, p = 0.02), elevated total cholesterol (266 +/- 78 vs 225 +/- 47 mg/dl, p = 0.002) and higher low-density lipoprotein levels (176 +/- 88 vs 137 +/- 46 mg/dl, p = 0.009) were noted in the transplant CAD retransplant group. Five of 11 retransplant recipients who survived greater than 1 year again developed transplant CAD. Characteristic morphologic features and rapid progression of CAD in the second graft were similar to those in the primary graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Electron probe X-ray microanalysis of the composition of hyaline articular and non-articular cartilage in young and aged rats.

Blocks of articular cartilage were taken from tibiae of young adult (8 week) and aged adult (50-60 week) rats; xiphisternal cartilage was obtained from young adult rats. Specimens were quench-frozen in nitrogen slush, freeze-fractured and examined by low-temperature scanning electron microscopy. The results of X-ray microanalysis of frozen-hydrated bulk cartilage are semi-quantitative. The composition of chondrocyte nuclei and cytoplasm are only marginally different. Xiphisternal chondrocytes contain lipid inclusions which show an absence of element peaks and are designated as being neutral lipid. Intra- and extracellular Na, P, S, Cl, K and Ca count rates are significantly different. Cartilage from older rats contains more S and Ca, and less K and Cl in the intercellular matrix than that from young rats. Intracellular K levels are lower in aged than in young rats. The intercellular matrix of xiphisternal cartilage contains larger amounts of S, Na and K, and a smaller amount of Cl compared to that of tibial articular cartilage.

Aging↗

Cation movement in rat articular and non-articular cartilage and in isolated chondrocytes: calcium influx and efflux.

1. Calcium ion influx varies between different types of young adult rat cartilage. Sternal cartilage accumulates significantly less Ca2+ than other cartilage types. 2. Influxes of Ca2+ into young adult and ageing tibial cartilage display no significant differences. 3. Efflux of Ca2+ from sternal and tibial cartilage resolves into exponential phases indicative of three compartments. Tracheal cartilage displays two compartment behaviour only. 4. Efflux of Ca2+ from isolated chondrocytes has different characteristics to cartilage efflux with the third slow compartment reduced. 5. Modification of Ca2+ efflux by lanthanum and barium is suggestive of an exchange of strongly bound extracellular calcium during the slow phase of the efflux from young adult tibial cartilage. 6. The metabolic inhibitor 2,4-dinitrophenol is without effect on the efflux of Ca2+ from tibial articular cartilage. 7. The degree of calcium binding exhibited during efflux depends upon cartilage type. Non-articular sternal cartilage binds calcium more strongly than articular tibial, both binding more strongly than non-articular tracheal cartilage. 8. In articular cartilage calcium binding shows an age-related increase.

2,4-Dinitrophenol↗

Regulation of o(2) concentration in soybean nodules observed by in situ spectroscopic measurement of leghemoglobin oxygenation.

A fiber optic spectrophotometric system was used to monitor the in vivo oxygenation of leghemoglobin in intact, attached soybean root nodules (Glycine max L. Merr. x USDA 16 Bradyrhizobium japonicum) which were flattened during development by growth in narrow, glass-walled cuvettes. When equilibrated at an external pO(2) of 20 kilopascals, leghemoglobin was 36.6 +/- 5.4% oxygenated, a value estimated to represent an infected cell O(2) concentration of 21.5 nanomolar. Increasing the external pO(2) from 20 to 25 kilopascals caused a rapid increase in leghemoglobin oxygenation, followed by a recovery to the initial level, all within 7.5 minutes. At 25 kilopascals O(2), the rates of H(2) and CO(2) evolution were similar to those at 20 kilopascals. Since respiration had not increased, the results support the proposal that nodules adapt to increased external pO(2) by regulating their resistance to O(2) diffusion.

Journal Article↗

Steady and nonsteady state gas exchange characteristics of soybean nodules in relation to the oxygen diffusion barrier.

An open gas exchange system was used to monitor the nonsteady state and steady state changes in nitrogenase activity (H(2) evolution in N(2):O(2) and Ar:O(2)) and respiration (CO(2) evolution) in attached, excised, and sliced nodules of soybean (Glycine max L. Merr.) exposed to external pO(2) of 5 to 100%. In attached nodules, increases in external pO(2) in steps of 10 or 20% resulted in sharp declines in the rates of H(2) and CO(2) evolution. Recovery of these rates to values equal to or greater than their initial rates occurred within 10 to 60 minutes of exposure to the higher pO(2). Recovery was more rapid at higher initial pO(2) and in Ar:O(2) compared to N(2):O(2). Sequential 10% increments in pO(2) to 100% O(2) resulted in rates of H(2) evolution which were 1.4 to 1.7 times the steady state rate at 20% O(2) in Ar. This was attributed to a relief at high pO(2) from the 40% decline in nitrogenase activity that was induced by Ar at a pO(2) of 20%. Changes in nodule respiration rate could not account for the nodules' ability to adjust to high external pO(2), supporting the hypothesis that soybean nodules have a variable barrier to O(2) diffusion which responds slowly (within minutes) to changes in pO(2). Nodule excision and slicing resulted in 45 and 78% declines, respectively, in total specific nitrogenase activity at 20% O(2). In contrast with the result obtained with intact nodules, subsequent 10% increases in pO(2) in Ar:O(2) did not result in transient declines in H(2) evolution rates, but in the rapid attainment of new steady state rates. Also, distinct optima in nitrogenase activity were observed at about 60% O(2). These results were consistent with an increase in the diffusive resistance of the nodule cortex following nodule excision or nodule slicing. This work also shows the importance of using intact plants and continuous measurements of gas exchange in studies of O(2) diffusion and nitrogenase activity in legume nodules.

Journal Article↗

Administration of MPTP to the common marmoset does not alter cortical cholinergic function.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits and decreased concentrations of dopamine, homovanillic acid, and 3,4-dihydroxy-phenylacetic acid (DOPAC) and [3H]dopamine uptake in the caudate-putamen. There was an 80% reduction in tyrosine hydroxylase immunoreactive cells in substantia nigra. At 10 days following the start of MPTP administration, the activity of choline acetyltransferase in the thalamus and frontal cortex was unchanged compared with control animals. Similarly, specific [3H]QNB binding was unaltered. At 4-6 weeks following the start of MPTP treatment, choline acetyltransferase activity and [3H]QNB binding in the frontal cortex and thalamus remained unaffected. There was no evidence for cell loss in the nucleus basalis of Meynert or alteration in the intensity of staining for acetylcholinesterase. MPTP treatment of the common marmoset produces a nigrostriatal lesion. In contrast, MPTP did not alter cortical cholinergic function and was not neurotoxic to the cholinergic cells in the nucleus basalis of Meynert.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Severe illness caused by the products of bacterial metabolism in a child with a short gut.

An 8-year-old boy with a short gut had six episodes of metabolic acidosis and neurological dysfunction over a 1 month period. The neurological features consisted of a depressed conscious state, confusion, aggressive behaviour, slurred speech and ataxia. The organic acid profile of urine demonstrated increased amounts of lactic, 3-hydroxypropionic, 3-hydroxyisobutyric, 2-hydroxyisocaproic, phenyllactic, 4-hydroxyphenylacetic and 4-hydroxyphenyllactic acids. Of the lactic acid 99% was D-lactic acid. The anaerobic gut flora consisted almost entirely of Lactobacilli in unusually large numbers. A course of vancomycin prevented further episodes. A urinary organic acid profile may be diagnostic when a person with a short gut develops metabolic acidosis or an unusual encephalopathy and bacterial metabolites should be considered in other patients with unusual combinations of organic acids in the urine.

Acidosis↗

The mechanisms of ventricular tachycardia in humans determined by intraoperative recording of the electrical activation sequence.

We recorded ventricular activation sequence during ventricular tachycardia in 76 patients who underwent surgical therapy of refractory ventricular tachycardia. Ventricular tachycardia arose from a discrete site (focal origination) in 28 patients (37%) or resulted from reentry around scar (macroreentry) in 22 patients (29%). The mechanism responsible for ventricular tachycardia was not discernable in the remaining 26 patients (34%), usually because of inadequacy of activation data. We conclude: (1) although focal originating of ventricular tachycardia is common, more frequently the mechanism is either macroreentry or uncertain, as assessed by conventional recording techniques; thus, a search for the "site of earliest activation" during ventricular tachycardia frequently may fail to direct rationally the operative procedure; (2) conventional techniques for intraoperative study of electrical activation during ventricular tachycardia are inadequate.

Cardiac Pacing, Artificial↗

Heart and lung transplantation for pulmonary hypertension.

Seventeen patients received combined heart and lung transplants at Stanford University between March 1981 and December 1983. All recipients were suffering from end-stage pulmonary hypertension. Five patients died within the first few postoperative weeks, but the remainder were well between 2 and 35 months after operation. Immunosuppression consisted of cyclosporine with an initial course of rabbit antithymocyte globulin, and azathioprine was given for the first 2 postoperative weeks. Maintenance immunosuppression was achieved with cyclosporine and prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with intravenous methylprednisolone. The functional status of the survivors has been good, and upon discharge from the hospital, all returned to normal activity. Our preliminary experience indicates that cardiopulmonary transplantation represents a realistic therapeutic approach for patients with end-stage pulmonary disease.

Adult↗

Chitin helicoids accompany protein helicoids in the periostracum of a whelk, Buccinum.

The periostracum of the marine gastropod Buccinum has a helicoidal arrangement of its principal constituent which is a fibrous protein (Hunt and Oates, 1978). Chitin, chemically and physically identified, is present at a concentration of about 6% of the dry weight and can be seen in dispersates of whole periostracum as long fibrils and ribbons between 3 and 14 nm diameter. Deproteinization with hot alkali removes all protein leaving a chitinous 'ghost' of the periostracum. Dispersates, examined negatively stained, show only chitin fibrils and ribbons while sectioned material demonstrates a tenuous, part orthogonal, part helicoidal, architecture based on the chitin residue. The relative roles of the protein and polysaccharide components is speculated upon and comparisons with arthropod cuticle drawn.

Amino Acids↗

Heart-lung transplantation for irreversible pulmonary hypertension.

Combined heart and lung transplantation was carried out in 17 patients at Stanford University between March, 1981, and December, 1983. The recipients were between 22 and 45 years old. All patients had end-stage pulmonary hypertension; 10 had Eisenmenger's syndrome and the remaining 7, primary pulmonary hypertension. Five patients died within the first few postoperative weeks. The remainder are well between four weeks and 33 months from operation. The immunosuppressive protocol has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin. Azathioprine also was given for the first two weeks and then was replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with high doses of methylprednisolone. Modifications of technique that have developed include the removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. Rejection occurred in 6 of the 12 survivors. Infections developed in 9 patients, but only one resulted in a fatal outcome (Legionella). Thus, the results of clinical heart-lung transplantation have been considerably superior to clinical efforts in lung transplantation. It is suggested that the combined operation is preferable for the following reasons: (1) all diseased tissue is removed, thus eliminating recurrent infection and ventilation/perfusion disparity; (2) transplantation of the entire heart-lung block preserves coronary-bronchial vascular anastomoses and makes airway dehiscence less likely; and (3) to date, diagnosis of rejection by cardiac biopsy has appeared to be a satisfactory method of diagnosing and treating pulmonary rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical heart-lung transplantation.

Combined heart and lung transplantation was carried out in thirteen patients at Stanford University between March 1981 and May 1983. The recipients were between 22 and 45 years old. All patients were suffering from end-stage pulmonary hypertension; nine patients had Eisenmenger's syndrome; the remaining four were transplanted for primary pulmonary hypertension. Three patients died within one month of surgery. The remainder are well at between 22 months and three weeks from operation. The duration of stay in the hospital for the surviving patients ranged from 38 to 85 days. The immunosuppressive protocol has been essentially the same for all recipients, and has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin (RATG) with azathioprine given for the first two weeks, and then replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with pulses of methylprednisolone. Early complications included bleeding that necessitated reexploration (five patients); damage to the vagus, recurrent laryngeal, or phrenic nerves (three patients); and failure of the donor lungs (one patient). Modifications of technique that have developed include removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. The results of this operation are considerably superior to clinical efforts in lung transplantation. The combined operation may be preferable for the following reasons: All diseased tissue is removed, thus eliminating recurrent infection, and also perfusion/ventilation disparity. Transplantation of the entire heart and lung block preserves coronary-tracheal vascular anastomoses and makes airway dehiscence less likely. Diagnosis of rejection by cardiac biopsy seems to be a satisfactory method of diagnosis and treatment of pulmonary rejection.

Adult↗