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Biomedical subjects

A Hoffman

Publications and source records attributed to A Hoffman.

At least 109 records · Page 6Linked to original sources

The use of a pig liver xenograft for temporary support of a patient with fulminant hepatic failure.

A 26-year-old female patient with fulminant hepatic failure and a history of autoimmune hepatitis was heterotopically transplanted with a pig hepatic xenograft to provide temporary metabolic support prior to transplantation with a human donor organ. Circulating natural antipig antibodies were removed prior to transplantation by plasmapheresis and ex vivo en bloc perfusion of the donor pig kidneys. The liver xenograft functioned after transplantation as measured by active bile production, stabilization of prothrombin levels, and reduction in the circulating levels of lactic acid and the enzymes AST and ALT. Despite the removal of greater than 90% of the recipient's natural xenoantibodies prior to transplantation, the levels of antibody rapidly returned and were associated with antibody and complement-mediated rejection of the donor graft. Immunohistochemical evidence of graft rejection could be detected by the deposition of antibody, complement components including properdin, and endothelial swelling as early as 3 hr posttransplantation. These lesions progressed in severity and were accompanied by evidence of thrombosis and ischemic necrosis of the liver xenograft by 34 hrs posttransplantation. The main portal vein, hepatic artery, and vena cava were patent. The placement of the liver graft did not result in any improvement in the neurological status of the patient and she died 34 hr after xenografting due to irreversible brain damage. The information derived from this case has renewed interest in the clinical use of bioartificial devices and whole organ perfusion using xenogeneic tissue for temporary bridging of patients prior to allografting.

Adult↗

Acute limb ischemia due to malignant arterial embolism from a metastatic germ cell tumor.

Arterial tumor embolization is a rare but serious complication of neoplastic disease. The majority of these tumors are associated with primary or secondary lung malignancies, originating from pulmonary vein metastasis or from an atrial mass. Malignant germ cell tumors primarily disseminate to the retroperitoneal lymph nodes and lung, and to the brain and liver later in the course of the disease. A germ cell tumor metastasis embolizing to the iliac-femoral arterial system has not yet been reported. We report a metastatic embolism in a patient with disseminated embryonal cell carcinoma causing acute limb ischemia, managed by surgical embolectomy. The sudden development of limb ischemia in a patient with a germ cell tumor should alert the physician to the possibility of tumor embolism.

Echocardiography↗

Correlation of bone mineral density and femoral neck hardness in bovine and human samples.

Bone mineral density (BMD) is a predictor of fracture risk. The purpose of this study was to determine whether a correlation exists between femoral neck BMD and an indicator of mechanical bone strength in human and bovine samples. Human proximal femurs were obtained from seven men and two women undergoing total hip arthroplasty (THA), mean age 60.3 years. Preoperative BMD measurements of the femoral neck were obtained (Lunar DPX). A 3 cm2 area of interest on each excised femoral neck corresponding to the preoperative BMD measurement site was carefully marked and BMD was remeasured postoperatively. Ten excised bovine femoral necks were also measured for BMD. A bicortical core, each cortex 2.8 cm2 in area, containing the center of the area of interest was removed from the human and bovine femoral necks, cut into multiple 7-mm thick, multiple cross-sectional discs, and measured for hardness by indent depth (Rockwell International Hardness Tester, Wilson Mechanical Instruments, New York, NY). In vivo human femoral neck BMD measurements correlated with in vitro BMD measurements (r = 0.99). BMD measurements of human femoral necks were significantly lower than BMD measurements of bovine femoral necks (P < 0.05). Inverse relationships were found between in vivo and in vitro human BMD measurements and indent depth (r = -0.58 and -0.59, respectively). Bovine BMD measurements and indent depth were also inversely related (r = -0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Morphometric analysis of atrial natriuretic peptide-containing granules in atriocytes of rats with experimental congestive heart failure.

The morphometric characteristics of atrial natriuretic peptide-containing granules were studied in atrial myoendocrine cells of rats with aorto-caval fistula, an experimental model of congestive heart failure. A total of 6680 granules of control and aorto-caval rats were analyzed by a computerized image analysis system that evaluated the number and sectioned surface area of granules and their subcellular location. Compared with control animals, rats with congestive heart failure displayed a slight increase in the number of peripheral granules, adjacent to the sarcolemma, but not centrally located in the Golgi areas. The mean sectioned surface area of granules in rats with congestive heart failure was about 50% of that in controls, both in the right and left atria. Rats with aorto-caval fistula had a higher percent of small granules and lower percent of large granules compared with controls. The data demonstrate different morphometric characteristics in atrial natriuretic peptide-containing granules in atriocytes in rats with experimental congestive heart failure; this may reflect the enhanced synthesis and release of atrial natriuretic peptide in heart failure.

Aldosterone↗

Angiotensin II stimulates macrophage-mediated oxidation of low density lipoproteins.

Increased incidence of myocardial infarction was found in hypertensive patients with high plasma renin activity and increased susceptibility to oxidation was demonstrated in low density lipoprotein (LDL) that was obtained from hypertensive patients. As lipid peroxidation was demonstrated in areas of the atherosclerotic lesion, we sought to analyze the effect of angiotensin II (AN-II) on LDL oxidation, both in vitro and in vivo. Preincubation of J-774 A.1 macrophage-like cell line or mouse peritoneal macrophages (MPM) with AN-II (10(-7) M) for 1 h at 37 degrees C, followed by the addition of LDL for a further 18 h of incubation, resulted in a substantial increase in macrophage-mediated oxidation of LDL (by 55% and 19%, respectively). Similarly, incubation of LDL with MPM harvested from AN-II-injected mice resulted in a substantially increased oxidation of the lipoprotein by up to 90% in comparison to saline-injected mice. Analysis of cellular lipid peroxidation in the MPM themselves, in both the in vitro and the in vivo studies, revealed a 25% or 90% increased macrophage lipid peroxidation, respectively. The mechanism of AN-II-mediated cellular lipid peroxidation involved AN-II binding to its receptor on macrophages as saralasin, an AN-II receptor antagonist, completely inhibited this effect. Inhibitors of phospholipases A2, C and D substantially reduced macrophage lipid peroxidation, suggesting the involvement of phospholipases A2, C and D substantially reduced macrophage lipid peroxidation, suggesting the involvement of phospholipid metabolites in AN-II-mediated macrophage lipid peroxidation, suggesting the involvement of phospholipid metabolites in AN-II-mediated macrophage lipid peroxidation. Extracellular calcium ions, which active phospholipases, were also essential for AN-II-mediated macrophage lipid peroxidation since calcium channel blockers substantially inhibited cellular lipid peroxidation. Finally, the nature of the oxidant and oxygenase involved in AN-II-mediated cellular lipid peroxidation was studied using oxygenase inhibitors. Angiotensin II-mediated macrophage lipid peroxidation was found to involve the action of cellular NADPH oxidase as well as 15-lypoxygenase. We conclude that AN-II stimulates macrophage-mediated mediated oxidation of LDL secondary to cellular lipid peroxidation, and this may have a role in the accelerated atherosclerosis found in hypertensive patients.

Angiotensin II↗

Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo.

Recently, a novel glial cell line-derived neurotrophic factor (GDNF) has been identified, cloned, and shown to have potent survival- and growth-promoting activity on fetal rat midbrain dopaminergic neurons in cell culture. In this study, we document marked and long-lasting effects on adult rat midbrain dopaminergic neurons in vivo after intracranial administration. A single injection of this factor into the substantia nigra elicited a dose-dependent increase in both spontaneous and amphetamine-induced motor activity, and a decrease in food consumption, lasting 7-10 days. Using immunocytochemistry, we found sprouting of tyrosine hydroxylase-positive neurites towards the injection site, and increased tyrosine hydroxylase immunoreactivity of the ipsilateral striatum was produced by GDNF. There was also a marked and dose-dependent increase in dopamine turnover in the substantia nigra and striatum, and in ipsilateral dopamine levels in the substantia nigra. Little or no effects of GDNF were seen on norepinephrine or serotonin levels. The neurochemical changes on dopaminergic afferents persist for at least 3 weeks after a single intracranial injection of 10 micrograms. Taken together, these data suggest that this glial cell line-derived factor has a potent influence on adult rat dopamine neurons and may have a potentially important role as a trophic factor for these neurons.

Animals↗

Urinary neutral endopeptidase 24.11 activity: modulation by chronic salt loading.

Neutral endopeptidase (NEP) 24.11 is a zinc-metallopeptidase involved in the metabolism of several biologically active peptides including enkephalin, atrial natriuretic peptide, bradykinin, and endothelin. The enzyme is found in abundant amounts in the brush border of renal proximal epithelial cells. A soluble form of NEP was previously identified in human urine with characteristics similar to the renal enzyme. The present study further characterized the excreted form of NEP activity in urine of normal rats using a sensitive two-stage enzymatic assay. The response of urinary NEP to known inhibitors such as phosphoramidon and thiorphan, and its dependence on pH and salt concentration was studied. In addition, we evaluated the effects of acute and chronic changes in salt balance, induced by i.v. saline infusion and drinking of saline solution, on urinary NEP and on the activity of the enzyme in isolated proximal tubules. Our findings demonstrated that abundant NEP activity was detected in the urine of normal rats. Furthermore, chronic salt loading, but not acute salt infusion, was associated with increased activity of NEP in urine and in isolated proximal tubules, suggesting that the enzyme may be regulated by salt balance. Finally, the data suggest that urinary NEP may be used as an index of enzyme activity in the kidney.

Animals↗

Bone loss in patients with chronic renal disease: prediction with quantitative bone scintigraphy with SPECT.

PURPOSE: To determine whether quantitative bone scintigraphy (QBS) with single-energy photon emission computed tomography (SPECT) can help predict which patients with chronic renal disease will show bone mineral density (BMD) loss. MATERIALS AND METHODS: In 18 patients, the percentage of injected dose of technetium-99m methylene diphosphonate per cubic centimeter of bone was measured with QBS SPECT in the lumbar vertebrae and femoral neck. The differences in BMD over an average of 20 months were measured and compared with SPECT measurements. QBS values were also compared with serum bone turnover markers. RESULTS: There was a negative correlation (r = -.54, P < .05 for the lumbar spine and r = -.60, P < .01 for the femoral neck) between QBS values and bone loss. Positive and negative predictive values, sensitivity, and specificity of QBS for bone loss in the lumbar spine were 78%, 71%, 78%, and 71%, respectively, and in the femoral neck, 82%, 100%, 100%, and 78%, respectively. Differences between predictive values of serum bone turnover markers were not statistically significant. CONCLUSION: QBS with SPECT enabled prediction of rapid bone loss in patients with renal disease.

Absorptiometry, Photon↗

Portal vein patency in candidates for liver transplantation: MR angiographic analysis.

PURPOSE: To assess the accuracy of magnetic resonance (MR) angiography for evaluating portal vein patency in candidates for liver transplantation. MATERIALS AND METHODS: MR angiography was performed in the main portal vein and proximal confluence of the portal vein in 102 candidates for liver transplantation (64 male patients and 38 female patients aged 8 months to 74 years; mean age, 47 years). The MR angiographic results were compared with the surgical and histologic findings in the explanted liver and excised main portal vein. RESULTS: MR angiography depicted 10 portal vein clots, all of which were confirmed at transplantation. Ninety-two portal veins were patent at MR angiography, a finding that was confirmed at transplantation. One tiny chronic clot in a small, intrahepatic branch of the portal vein was not seen at MR angiography or transplantation. It was identified at histologic analysis of the explanted liver. CONCLUSION: MR angiography is accurate in the evaluation of portal vein patency.

Adolescent↗

Early clinical experience with a hybrid bioartificial liver.

BACKGROUND: Severe liver failure is associated with high mortality. Orthotopic liver transplantation (OLT) is the only effective therapeutic modality; there is a need for a 'bridge' system to support patients until an organ becomes available. METHODS: A bioartificial liver (BAL) was used to treat 10 patients with severe liver failure. A plasmapheresis system was used to pump patient plasma through a module with porcine hepatocytes. Each treatment lasted 6-7 h. RESULTS: All patients tolerated the procedure(s) well. Eight patients underwent OLT following BAL treatment(s). There were two late deaths after recovery from liver failure. Five patients with increased intracranial pressure (ICP) and decerebration had ICP normalization, increased cerebral perfusion pressure and full neurologic recovery after OLT. There was improvement in the level of encephalopathy and a significant decrease in serum ammonia after BAL treatment(s). CONCLUSIONS: BAL treatment is safe and beneficial and can be successfully used as a 'bridge' to transplantation.

Adult↗

Differential effect of endothelin-1 on renal regional blood flow: role of nitric oxide.

This study evaluated the effects of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively) and the interactions with other local vasoactive systems in the regulation of renal regional blood flow. CBF and MBF were measured simulataneously by laser-Doppler flowmetry in anesthetized Wistar rats. Administration of ET-1 (1.0 nmol/kg, i.v.) produced a decrease in CBF (delta = -20%) and at the same time increased MBF (delta = +24%). In the presence of nitric oxide (NO) blockade by L-NAME, the vasodilatory effect of ET-1 on MBF was completely blocked and actually reversed (delta = -19%), whereas the cortical vasconstrictor effect was potentiated (delta = -31%). Cycloxygenase inhibition with indomethacin attenuated the vasodilator effect of ET-1 on MBF (delta = +12%) but did not affect the changes in CBF. Therefore, ET-1 exerts a differential effect on intrarenal regional blood flow, i.e., a decrease in CBF and an increase in MBF. The medullary vasodilator action of the peptide is dependent on an intact NO system and, to a lesser extent, on prostaglandin synthesis.

Animals↗

Renal effects of big endothelin-1 in experimental congestive heart failure.

The present study was designed to evaluate the effects of big endothelin (ET) on renal hemodynamics and excretory functions in rats with experimental congestive heart failure (CHF) produced by aortocaval fistula. Clearance studies were performed in control and in chronic (7 day) CHF rats. Administration of bit ET (1 and 3 nmol/kg, i.v.) to control rats caused an increase (29%) in mean arterial pressure (MAP) associated with a decrease (38%) in renal blood flow (RBF) and a marked increase (130%) in renal vascular resistance (RVR). These changes were accompanied by a decrease in glomerular filtration rate (GFR) and a significant increase in sodium excretion. In contrast, the effects of big ET on MAP and renal hemodynamics were blunted in CHF rats, and sodium excretion increased only minimally in response to big ET despite a significant increase in GFR. The data suggest that rats with CHF have reduced sensitivity to the vascular and renal action of ET.

Animals↗

Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo.

Fischer 344 rats were unilaterally injected into the medial forebrain bundle with 6-hydroxydopamine (6-OHDA). Apomorphine-induced rotational behavior was used to select animals whose rotation exceeded 300 turns/h, corresponding to greater than 95% dopamine (DA) depletion in the ipsilateral striatum. Four weeks later, glial cell line-derived neurotrophic factor (GDNF) or vehicle was injected intranigrally ipsilateral to the lesion (0.1-100 micrograms). The highest dose of GDNF tested produced a marked decrease in rotational behavior. This dose also produced levels of DA in the ipsilateral substantia nigra (SN) which were not statistically different from the contralateral side. Vehicle-treated animals showed a marked DA depletion in the ipsilateral SN. These results demonstrate neurochemical and behavioral improvements in unilaterally DA-lesioned rats following intranigral administration of GDNF, suggesting that GDNF may develop into a useful therapy for Parkinson's disease.

Animals↗

Sanfilippo syndrome type A in two adult sibs.

We report on 2 adult sibs with Sanfilippo syndrome type A (MPS IIIA; deficiency of heparin sulfamidase) who were less functionally impaired than other reported individuals with this disorder. These individuals expand our understanding of the range of clinical expression that one may see in Sanfilippo syndrome type A.

Adult↗