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Biomedical subjects

H L Sharp

Publications and source records attributed to H L Sharp.

At least 37 records · Page 2Linked to original sources
PubMed1987

Fatal liver disease associated with alpha 1-antitrypsin deficiency PiM1/PiMduarte.

A 53-yr-old man with a rare form of partial alpha 1-antitrypsin deficiency, PiM1/PiMduarte, died of endstage cirrhosis. Typical cytoplasmic alpha 1-antitrypsin globules were present in the hepatocyte cytoplasm. Initial protease inhibitor phenotyping on the patient was reported as normal PiM1 in more than one laboratory. This case emphasizes the diagnostic importance of alpha 1-antitrypsin and illustrates the point that protease inhibitor phenotyping without family genotyping may be misleading in heterozygous patients with liver disease.

Cytoplasm↗
PubMed1987

Contribution of extrahepatic tissues to biochemical abnormalities in hereditary tyrosinemia type I: study of three patients after liver transplantation.

Three patients with hereditary tyrosinemia type I were examined before and after liver transplantation to assess the role of extrahepatic tissues in the biochemical disorders of this disease. Before transplantation the three patients excreted excessive amounts of succinylacetoacetate (SAA), succinylacetone (SA), tyrosyl acidic compounds, and 5-aminolevulinate (ALA). The activity of 5-aminolevulinate dehydratase (ALA-D) in red blood cells was markedly inhibited (1% to 5% of control) in the three patients. Successful liver transplantation resulted in decreased excretion of urinary SAA plus SA, tyrosyl acidic compounds, and ALA. Two of the patients continued to excrete significant amounts of SAA plus SA, whereas those compounds were undetectable in the urine of the third patient. Tyrosine loading resulted in increased excretion of SAA plus SA in two patients, but those compounds remained undetectable in the third. All three patients continued to excrete higher than normal amounts of ALA, but the activity of ALA-D in red blood cells returned to normal after transplantation, indicating marked clearance of SA from the blood. Liver transplantation may not totally correct the biochemical abnormalities of hereditary tyrosinemia. It is likely that the kidney is the source of persistent biochemical aberrations in the urine without significant effects on the blood. Our results suggest the existence of heterogeneity for renal involvement in hereditary tyrosinemia.

Acetoacetates↗
PubMed1987

Liver allograft rejection. An analysis of the use of biopsy in determining outcome of rejection.

Two-hundred-seventy biopsy specimens from 47 patients undergoing liver transplants at the University of Minnesota were analyzed to determine if histological features could predict the eventual outcome of rejection episodes. Thirty-six patients (76.6%) rejected the transplant. Of these, five either suffered acute liver failure due to rejection (two cases) or developed chronic rejection (three cases). Features of significance in predicting such a bad outcome were arteritis, bile duct paucity, or simultaneous hepatocellular ballooning and hepatocellular dropout and necrosis. Other features, such as type and intensity of infiltrate, degree of bile duct damage, or simple presence of hepatocellular necrosis, were not predictive of outcome. Our conclusion is that biopsy is useful in predicting outcome. Since many of the histologic findings of predictive value were not present in initial pretreatment biopsy specimens, follow-up biopsies of patients being treated for rejection are recommended to assess efficacy of therapy.

Adolescent↗
PubMed1987

Hepatic regenerating nodules in hereditary tyrosinemia.

Hereditary tyrosinemia is an autosomal recessive, enzymatic disorder that results in micro- and macronodular cirrhosis in early childhood. Hepatocellular carcinoma occurs in approximately one-third of affected children. We evaluated the imaging studies performed in five children with this disorder. Pathologic examination of all five of the livers revealed cirrhosis and multiple regenerating nodules; hepatocellular carcinoma was present in two of the five livers. All five patients had high-attenuation or high- and low-attenuation foci within the liver. These high-attenuation foci were not apparent as focal lesions in three of four hepatic sonograms or in one of two hepatic nuclear scans. Angiography showed tumor vascularity in one patient with a focal hepatocellular carcinoma, but was indeterminate in a second patient with severe cirrhosis and multifocal hepatocellular carcinoma. Children with cirrhosis due to tyrosinemia may develop regenerating nodules that appear as high-attenuation hepatic foci on CT scans. It is difficult to differentiate regenerating nodules from multifocal hepatocellular carcinoma in these patients.

Amino Acid Metabolism, Inborn Errors↗
PubMed1987

Positive effect of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation.

In a randomized trial we studied the impact of providing total parenteral nutrition (TPN) to bone marrow transplant (BMT) patients during their cytoreductive therapy, and for 4 weeks following BMT, on 8 parameters of outcome. A total of 137 patients over 1 year of age and with normal nutritional status were randomized either to receive TPN starting one week prior to transplant or to receive hydration with a 5% dextrose solution containing electrolytes, minerals, trace elements, and vitamins. TPN was ultimately required by 40 of the 66 control patients when nutritional depletion was documented. Average total calorie and protein intake was significantly higher for the TPN group than for the control group. Minimum follow-up was 1 year and median was 2 years. Overall survival, time to relapse, and disease-free survival were significantly improved in the TPN group. Engraftment, duration of hospitalization, and incidences of acute and chronic graft-vs.-host disease and bacteremia were not different. Thus TPN during BMT had a positive effect on long-term outcome. Prophylactic nutritional therapy appears to be indicated even for well-nourished individuals during cytoreduction and BMT.

Bone Marrow Transplantation↗
PubMed1985

Persistent succinylacetone excretion after liver transplantation in a patient with hereditary tyrosinaemia type I.

A liver transplant was performed on a 4-year-old female in liver failure caused by hereditary tyrosinaemia, with hepatocellular carcinoma following a negative evaluation for metastases. However, serum alpha-fetoprotein levels never returned to normal after the surgery. Urinary succinylacetone (SA) was detected in her urine prior to transplantation despite strict adherence to a low-tyrosine diet. Other patients with severe liver disease awaiting liver transplantation do not excrete SA in the urine. She continued to excrete SA during the postoperative period despite normal liver functions. Oral tyrosine loading resulted in significant elevation of SA excretion. Possible explanations for this observation and clinical and therapeutic relevance are discussed.

Carcinoma, Hepatocellular↗
PubMed1984

Total parenteral nutrition in bone marrow transplantation: a clinical evaluation.

Bone marrow transplantation (BMT) is associated with severe metabolic stress secondary to anorexia, mucositis, enteritis, and infection. We compared nutritional parameters and clinical outcomes of 22 patients who received prophylactic total parenteral nutrition (TPN) to those of 22 controls, matched for age and diagnosis, who received nutritional support ad libitum. Over the 5-week study period, the TPN group averaged caloric intakes greater than 1.5 X basal energy expediture (BEE) per day and gained 2.5% of body weight; the control group averaged less than 0.9 X BEE and lost 3.7% of body weight. Visceral protein status as reflected by serum albumin was not different. Engraftment of donor marrow cells was 3 days earlier (p less than 0.01) in the TPN group than in the controls, despite there being no significant difference in the number of marrow cells each group received. There was no difference in the two groups' clinical outcomes; mortality, duration of hospital stay, and incidences of sepsis, graft-versus-host disease, and return of malignancy were equivalent. Thus, patients who received prophylactic TPN engrafted sooner than patients who did not; however, overall clinical outcome was unaffected by TPN. Controlled studies of prophylactic TPN are indicated for the BMT patient population.

Adolescent↗
PubMed1983

Graft-versus-host disease of the intestine: a protein losing enteropathy characterized by fecal alpha 1-antitrypsin.

Severe hypoproteinemia often accompanies the development of graft-versus-host disease of the intestine in allogeneic bone marrow transplant patients. To determine whether or not protein loss occurs across the intestinal mucosa in this severe diarrheal illness, we measured fecal alpha 1-antitrypsin once per week in 24-h stool specimens from 25 consecutive patients during hospitalization for bone marrow transplantation. The mean alpha 1-antitrypsin concentration and serum clearance for these patients before transplantation were below 2.6 mg/g stool and 13.0 ml/day (upper limits for normals). Values for all patients increased moderately after pretransplant conditioning. Values for patients who did not develop graft-versus-host disease of the intestine returned to baseline levels; however, those for patients with graft-versus-host disease of the intestine became markedly and persistently elevated (concentration ranged from 16.6 to 51.1 mg/g, clearance from 66.6 to 384.5 ml/day). We conclude that mucosal protein exudation contributes to the hypoproteinemia of graft-versus-host disease of the intestine and that measurement of fecal alpha 1-antitrypsin can be used as a marker for this disease.

Adolescent↗
PubMed1982

Alpha-1-antitrypsin: an ignored protein in understanding liver disease.

alpha 1AT should no longer be ignored by hepatologists with regard to its role in protecting the liver from injury. This protective role needs further definition with regard to protease inhibition, immunologic control, and functional inactivation. Severe deficiency of alpha 1AT clearly predisposes to definable types of liver disease not only in infants and children, but at the other end of the spectrum in elderly adults. It is unfortunate that the pathophysiology of human and animal alpha 1AT related liver injury is not as readily apparent as in pulmonology conditions. However, it is time to digest the tremendous progress that has evolved in that field in relating alpha 1AT to emphysema. Cirrhosis of the liver should be studied in relationship to the pathophysiology demonstrated by our colleagues to be important in "cirrhosis of the lung." The diagnosis of alpha 1AT deficiency and the course of the associated liver disease have been reviewed and updated. Prevention and cure have been demonstrated to be possible but neither method has universal applicability. In contrast, other potential therapeutic endeavors, although not presently proved to be efficacious, with time and research will provide methodologies for the treatment of this disorder as well as insight into mechanisms of general liver injury not previously appreciated.

Adult↗
PubMed1982

Sclerosing cholangitis associated with inflammatory bowel disease.

The asymptomatic course of two adolescents with hepatobiliary complications of inflammatory bowel disease are reported. As has previously been documented in adult patients, liver biopsy and cholangiography of the biliary tree are indicated procedures when the cholestatic enzymes are elevated in children with colonic involvement.

Adolescent↗
PubMed1982

Acute viral enteritis and exacerbations of inflammatory bowel disease.

In order to determine whether or not acute viral gastroenteritis predisposes to exacerbations of inflammatory bowel disease, patients with Crohn's disease and ulcerative colitis were observed longitudinally. Assessment of disease activity was correlated with evidence for viral infection by serology and stool antigen testing. Disease exacerbations were rarely associated with rotavirus, Norwalk agent, or adenovirus infection, primarily because these infection rates were very low. However, the few patients having these viral infections often had relapse symptoms.

Acute Disease↗