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Biomedical subjects

H Sharp

Publications and source records attributed to H Sharp.

At least 19 recordsLinked to original sources

Is Behçet's disease triggered by childhood infection?

In a comparison of 30 patients with Behçet's disease and 60 age and sex matched community controls an increased risk of Behçet's disease was associated with tonsillectomy, a history of cold sores, large sibship size, late birth order, travel to countries with high incidence of the disease, and first sexual intercourse before 16 years of age. These findings are consistent with a triggering of the disease by infection during childhood or adolescence in an immunogenetically predisposed host.

Adolescent

Obstetric anesthesia: a national survey.

To assess obstetric anesthesia in the United States, and to determine why more anesthesia personnel are not involved in this subspecialty, a questionnaire was sent to the heads of obstetric and anesthesia services in 1,200 hospitals. Both obstetric and anesthesia respondents agreed on several characteristics of obstetric anesthesia that inhibit more participation by anesthesia personnel. Among others, they identified that: the unpredictability of labor and delivery makes scheduling difficult; obstetricians tend to dictate type and timing of anesthesia; the risk of malpractice claims is increased for obstetric anesthesia; and, finally, larger obstetric services would make it more practical to provide anesthesia services. Regarding availability of personnel and procedures, obstetric units with less than 500 deliveries per year were considerably more under-staffed than the larger units in most areas studied. When general anesthesia was used for cesarean section in these units, it was provided by, or given under the direction of, an anesthesiologist only 44% of the time, whereas in the hospitals with more than 1,500 deliveries per year, an anesthesiologist was present 86% of the time. Likewise, in the small units, personnel classified as "others" were responsible for newborn resuscitation in 24% and 43% of instances after cesarean section and vaginal delivery, respectively. In the hospitals with more than 1,500 deliveries, comparable figures were 4% and 2%, respectively.

Anesthesia, Epidural

Metabolism during hepatic transplantation: indicators of allograft function.

In an attempt to determine the initial function of hepatic allografts, several metabolic indicators of hepatic function were studied intraoperatively in 12 cases of hepatic transplantation. The operation was divided into three sampling periods: baseline, anhepatic, and reperfusion. During the baseline period plasma lactate levels rose at 2.6 mmol/L/hr and continued to rise at a similar rate during the anhepatic period. Baseline period total free plasma amino acid levels (TFPAA) rose at a moderate rate of 0.4 mmol/L/hr. During the anhepatic period TFPAA levels rose at a fivefold greater rate than during baseline (p less than 0.01). The ability of the hepatic allograft to reduce abnormal levels of TFPAA and lactate during the reperfusion period was associated with reduced morbidity in the first 48 hours after transplantation. Intraoperative clearance of accumulated TFPAA is currently the best means of assessing initial allograft function. Elevated preoperative total serum bilirubin levels were also associated with increased early morbidity in hepatic transplant recipients.

Adult

Abnormal polyunsaturated fatty acid patterns of serum lipids in Reye's syndrome.

Fatty acid patterns of the serum lipids were measured in 17 children with Reye's syndrome (RS). Serial measurements of total serum free fatty acids (FFA) showed that levels were increased during RS and, after recovery, were significantly lower in the patients who survived. Fatty acid patterns of serum FFA, triglycerides, and phospholipids in patients with RS were significantly different from those in controls. In RS the polyunsaturated fatty acid content of phospholipids was less than control values; in the FFA, it was higher. This was consistent with the possible involvement of increased phospholipase activity. The increase in polyunsaturated fatty acids in FFA, the precursors of prostaglandins, suggests that a grossly disturbed prostaglandin pattern may occur in RS. These changes in lipid metabolism may be related to the abnormal hepatic and neurological functions observed in RS.

Fatty Acids, Nonesterified

The association of familial liver disease, subepidermal immunoproteins, and membranoproliferative glomerulonephritis.

Herein we report a new familial form of hepatic disease. Each of the four patients had splenomegaly, hypersplenism, a small liver, biochemical evidence of hepatic excretory dysfunction and hepatocellular damage, kidneys without demonstrable cysts, and normal blood pressue. An evaluation of serum immunoproteins, autoantibodies, histocompatibility antigens, and mixed lymphocyte reactivity further defined the immunologic features of this syndrome. Extrahepatic manifestations included a papulosquamous dermatitis with deposition of immunoglobulins and complement in both normal and abnormal skin, a membranoproliferative glomerulonephritis with subendothelial deposits, arthritis, and pericardial, pleural, and synovial effusions.

Adolescent

Cytidine-5'-monophosphate-N-acetylneuraminic acid. Asialoglycoprotein sialic acid transferase activity in liver and serum of patients with juvenile hepatic cirrhosis and alpha-1-antitrypsin deficiency.

The molecular basis for the accumulation of a substance which displays the immunological reactivity of alpha-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum alpha-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine 5'-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with alpha-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with alpha-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients with liver disease. However, serum from family members homozygous for alpha-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialytransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialytransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuals with alpha-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of alpha-1-antitrypsin rather than the enzyme deficiency being the primary cause of the hepatic cirrhosis and alpha-1-antitrypsin deficiency.

Adolescent

Acute and chronic effects of methotrexate on hepatic, pulmonary, and skeletal systems.

With the progressive improvement in the survival of children with acute lymphocytic leukemia, the question of late effects of therapy on normal tissue becomes a more significant problem. In a review of a large number of children who have received long-term treatment with chemotherapy, especially methotrexate, a significant increase in the serious effects on hepatic, pulmonary, and skeletal tissue was noted. A review of the methotrexate-induced acute and chronic changes seen in these tissues is the basis for this report.

Bone and Bones

Absorption of vitamin A in patients with cystic fibrosis. Absorption is best with emulsified vitamin A alcohol.

Vitamin A absorption tests using vitamin A palmitate and alcohol separately in oil and oil-water emulsions were done on 43 patients with cystic fibrosis. Patients were given 7,000 units of vitamin A per kilogram of body weight with a fatty breakfast. Pancreatic enzymes were not given with the test meal and were withheld for five hours from start of test. Blood was drawn before administration of the vitamin and at three and five hours after administration. Serum vitamin A levels were estimated using the Carr-Price technique. The percentages of patients with normal vitamin A absorption were 85 with vitamin A alcohol in oil-water emulsion, 61 with vitamin A alcohol dissolved in oil, 64 with vitamin A palmitate in oil-water emulsion, and 19 with vitamin A palmitate in oil. The number of stools per day is an inverse indicator of retention time in the intestine. Absorption of fat soluble vitamins is always abnormal when a patient has four or more stools a day. The observations that cystic fibrosis patients with abnormal liver biopsies have poor absorption of vitamin A were not statistically significant. The question of the effect of cirrhosis in cystic fibrosis on vitamin A absorption remains unresolved.

Adolescent

The pH-dependence of the binding of competitive inhibitors to pepsin.

1. The pH-dependence of the binding to pepsin of four dipeptide competitive inhibitors is reported. Values of K(i) obtained from equilibrium-dialysis experiments agree closely with those from kinetic measurements. 2. The binding of uncharged N-acyl-dipeptide amides to pepsin is essentially independent of pH from 0.2 to 5.8. Values of K(i) for the corresponding N-acyl-dipeptide acids rise rapidly above pH3.5, and depend on the ionization of a group of apparent pK(a) 3.6. 3. The data indicate that pepsin does not undergo any gross conformation change (at least none that affects binding) over the whole pH range of its catalytic activity. The pH-dependence of the dipeptide acid inhibitors indicates that the acid anions do not bind to pepsin, presumably because of electrostatic repulsion between the inhibitor anion and a negative centre at or near the active site of the enzyme. 4. The binding of all four stereoisomers of N-acetylphenylalanylphenylalanine, of the depside analogues of the l-l- and d-l-compounds and of N-acetylglycyl-l-phenylalanine and N-acetyl-l-phenylalanylglycine was studied at pH2.2. 5. These results throw further light on the binding specificity of pepsin and on the charge nature of the active site of this enzyme.

Amides

The inhibition of pepsin-catalysed reactions by products and product analogues. Kinetic evidence for ordered release of products.

1. The inhibition of pepsin-catalysed hydrolysis of N-acetyl-l-phenylalanyl-l-phenylalanylglycine by products and product analogues was studied. 2. The non-competitive nature of the inhibition by the product N-acetyl-l-phenylalanine confirms an ordered release of products, and points to a common mechanism (involving an amino-enzyme) for pepsin-catalysed transpeptidation and hydrolysis reactions. 3. N-Acetyl-l-phenylalanine ethyl ester is also a non-competitive inhibitor, but here the inhibition is of the ;dead-end' type. No ethanol is detectable in reaction mixtures, indicating that this ester cannot act as an amino group acceptor in a transpeptidation process. 4. The same is true for N-methanesulphonyl-l-phenylalanine methyl and methyl thiol esters. No methanethiol is liberated when the methyl thiol ester is present as an inhibitor of the hydrolytic reaction, and the hope that such a thiol ester would effectively trap the amino-enzyme was not fulfilled.

Amino Acids