Search PubMed⌕ Search

Biomedical subjects

J H Lewis

Publications and source records attributed to J H Lewis.

At least 109 records · Page 6Linked to original sources

Prognostic importance of antibodies to human immunodeficiency virus by recombinant immunoassay and Western blot techniques in HIV antibody-positive hemophiliacs.

Antibodies to specific HIV viral antigens were measured by ELISA recombinant proteins representing gag and env amino acid sequences of human immunodeficiency virus (HIV) (E. I. du Pont de Nemours, Wilmington, DE) and by a Western blot system using biotinavidin detection (Biotech Research Labs, Rockville, MD) on 36 HIV antibody-positive hemophiliacs (HTLV-III ELISA, du Pont) on whom date of seroconversion was known and on whom serial samples where available between 1977 and 1986, representing 2-8 years following seroconversion. The 36 included 9 acquired immunodeficiency syndrome (AIDS) and 27 non-AIDS (7 AIDS-related complex (ARC); 4 other HIV class IV, 16 asymptomatic) patients. The development of AIDS was preceded 1-4 years by loss or lack of antibody to gag (p15, 24, or 55) and/or to pol (p31, 53, or 64), each p less than 0.001, compared with non-AIDS patients. Correlation between Western blot and recombinant assays was good except in one Western blot p24 (gag) only seroconverter who showed strong reactivity to env by recombinant assay. In conclusion, HIV antibody patterns appear to show prognostic significance in HIV-infected hemophiliacs.

Antibodies, Viral↗

The effect of the Garren-Edwards Gastric Bubble on solid and liquid gastric emptying.

To determine the effect of the Garren-Edwards Gastric Bubble (GEGB) on gastric emptying, radionuclide solid and liquid gastric emptying in 12 obese patients prior to insertion of the GEGB was studied. Four were restudied at one and seven days and ten patients were restudied at twelve weeks with the GEGB in place. There were no significant differences in liquid gastric emptying at one and seven days nor in solid and liquid gastric emptying at twelve weeks. Solid gastric emptying was significantly decreased from a mean of 63% to 31% after one day (P less than 0.05) and returned to preplacement baseline by seven days. These results indicate that gastric emptying is not significantly changed after twelve weeks with the GEGB in place. Therefore, the mechanism of action for weight reduction with the GEGB is not likely to be mediated by an effect on gastric emptying. However, the solid food-induced dyspeptic symptoms commonly noted 1-3 days after placement of the GEGB, which resolve within seven days, are probably explained by transiently delayed solid gastric emptying.

Adolescent↗

Basal gastric acid secretion in children with atypical epigastric pain.

We investigated basal acid output (BAO) by nasogastric aspiration in 28 children with atypical recurrent abdominal pain, defined as subxyphoid or epigastric pain of more than 3 months duration, associated with vomiting, anorexia, failure to thrive, and/or nocturnal awakening. Twenty-one children had normal upper endoscopies with no esophageal mucosal disease on biopsy, and seven had acid-peptic mucosal disease seen either on endoscopy or on esophageal biopsy. Mean BAO in the children with acid-peptic mucosal disease (6.8 +/- 4.3 mEq/h) was significantly higher than the mean BAO in the children with no mucosal disease (2.4 +/- 1.7 mEq/h) (p less than 0.02). Gastric volumes were also significantly greater in the children with acid-peptic mucosal disease than in children with no mucosal disease (p less than 0.001). There was no significant correlation between body weight and either BAO or basal volume output. Three of seven children with acid-peptic mucosal disease had a BAO greater than two standard deviations above the mean for the group with no mucosal disease. Two of these three had a BAO of more than 10.0 mEq/h (defined as gastric acid hypersecretion in adults), and required higher than usual doses of H2 blocker therapy. These results indicate that the values for BAO in children (greater than 2 yr) are comparable to values recorded in adults. Moreover, measurement of BAO may define a subgroup of children with atypical abdominal pain who are hypersecretors of acid and who require higher doses of antisecretory agents in order to achieve an optimal clinical response.

Abdomen↗

1986 update of HIV seroprevalence, seroconversion, AIDS incidence, and immunologic correlates of HIV infection in patients with hemophilia A and B.

A cohort of 181 patients with hemophilia A (149) and hemophilia B (32) cared for at the Hemophilia Center of Western Pennsylvania was followed to determine human immunodeficiency virus (HIV) seroprevalence, seroconversion rate, and clinical and immunologic correlates of HIV infection. By December 1986, 82 (45%) were HIV seropositive, and of these, ten (12%) had developed AIDS, 28 (34%) had symptomatic HIV infection (CDC class III, IV), of whom 14 (17%) had AIDS-related complex (ARC), and 44 (54%) had asymptomatic HIV infection (CDC class II). The HIV seropositive group included 82% of those treated with factor VIII concentrate (97% severe, 5% moderate), 48% of those treated with factor IX concentrate (92% severe, 8% moderate), 10% of those treated with cryoprecipitate (67% severe, 33% moderate), and none of those treated with fresh frozen plasma. Based on 77 serially sampled HIV seropositive hemophiliacs (1977 to 1986), peak seroconversion occurred in 1982, with 14% (11 of 77) occurring since 1984. With increasing time from seroconversion, both T4 lymphocyte number and function (the latter measured by growth in soft agar [T colony assay]) progressively declined; T4 number declined to 135 +/- 26/mm3 (SEM), and colony count declined 1193 +/- 537 (control 3851 +/- 387) by 5 years after seroconversion. In those developing AIDS, total T4 fell below 100/mm3 (33 +/- 8/mm3) at diagnosis. In this cohort, the overall AIDS incidence is 5.5% (12% among the HIV seropositive) and in those seropositive 5 or more years, the AIDS incidence approaches 32%.

Acquired Immunodeficiency Syndrome↗

Hepatic effects of drugs used in the treatment of peptic ulcer disease.

Although one member of the H2 blocker family (oxmetidine) proved to be intrinsically hepatotoxic, overt hepatic injury attributable to cimetidine and ranitidine is decidedly rare, given the tens of millions of patients who have received these medications. Even considering the fact that serious adverse reactions may be underreported by as much as a factor of 100, the number of reports submitted to the FDA-DDE of possible hepatic toxicity associated with these agents supports this low incidence. Whether or not a similarly low incidence will be seen with famotidine and the newer H2 receptor antagonists still under investigation must await additional clinical experience. The major effect of cimetidine on the liver is inhibition of the mixed function oxidase system responsible for the metabolism of many drugs and other compounds. Ranitidine and famotidine at usual doses do not appear to share the same drug interaction potential. Although cimetidine may potentiate the action of several medications with a narrow therapeutic range, possibly leading to clinical toxicity, its inhibitory effect on oxidative metabolism also appears to be the basis for its unique, potentially hepatoprotective role against injury due to acetaminophen and certain other hepatotoxins. Whether or not cimetidine will become clinically useful in the setting of acute acetaminophen overdose remains speculative at this time. The investigational drug, omeprazole, a substituted benzimidazole, is also capable of inhibiting the cytochrome P-450 system. Antacids, sucralfate, and other coating agents are devoid of any hepatotoxic potential, as they are essentially nonsystemic compounds. E-type prostaglandins currently under investigation for treatment of peptic ulcer disease do not appear to be intrinsically hepatotoxic, and, in fact, may have important hepatoregulatory and hepatoprotective properties.

Aged↗

Liver transplantation in hemophilia A.

Four patients with hemophilia A have undergone liver transplantation in our institution, three successfully. The first was a 21-year-old man with chronic active hepatitis (CAH) in whom the effects of previous abdominal operations prevented the satisfactory technical insertion of the new liver. He died intraoperatively. The second patient was a 15-year-old boy with CAH who began to synthesize factor VIII coagulant activity (F VIII:C) within 18 hours of successful liver transplantation and has continued to do so for almost 2 years (F VIII:C range 0.89 to 3.20 U/mL). The first 2 months of his postoperative course were complicated by infections, but since that time he has done well and has returned to school. The third patient was a 48-year-old man with portal fibrosis and severe ascites. He synthesized F VIII:C (range 0.96 to 1.50 U/mL) within six hours after reestablishment of circulation through the new liver. His postoperative course was complicated by numerous infections, and he died with sepsis and an acquired immunodeficiency-like syndrome 4 months after transplantation. The fourth patient was a 47-year-old mild hemophiliac with CAH who produced adequate factor VIII:C levels following transplantation (range 0.79 to 2.80 U/mL). These patients demonstrate that liver transplantation in hemophiliacs with end-stage liver disease may be lifesaving and results in correction of the F VIII:C deficiency and associated hemorrhagic tendency.

Adolescent↗

Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation.

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F less than 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with epsilon-aminocaproic acid (0.09%) and an untreated sample. Blood treated with epsilon-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of epsilon-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, epsilon-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with epsilon-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 +/- 29.5% to 94.8 +/- 7.4% (mean +/- SD, P less than 0.001). None of the treated patients had hemorrhagic or thrombotic complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antibody responses to immunization of patients with hemophilia with and without evidence of human immunodeficiency virus (human T-lymphotropic virus type III) infection.

Antibody responses after immunization with 23-valent pneumococcal polysaccharide and trivalent influenza virus vaccines were evaluated in 30 adults with hemophilia and in 17 healthy controls. The 30 patients with hemophilia included 13 who were human immunodeficiency virus (HIV) antibody positive with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (group 1), 11 who were asymptomatic HIV antibody positive (group 2), and six who were asymptomatic HIV antibody negative (group 3). Sera were obtained before and 4 weeks after immunization, and levels of antibody were measured by enzyme-linked immunoassay or by hemagglutination inhibition assay. All three groups of patients with hemophilia showed significantly higher preimmunization geometric mean titers of antibodies (groups 1 and 2, fivefold, group 3, 2.8-fold higher), with little increase after pneumococcal vaccine, when compared with controls. Defective humoral responses were noted in groups 1 and 2, with depressed antibody responses after influenza vaccine, significantly elevated levels of IgG and IgM, and depressed blastogenic responsiveness to pokeweed mitogen. Group 3 demonstrated normal responses to pokeweed mitogen, normal antibody responses to influenza vaccine, and normal level of IgG and IgM, although levels of IgG and IgM were higher than those of controls. These data suggest that humoral immune abnormalities are found frequently in patients with hemophilia who are HIV antibody positive. Further, prolonged administration of blood products, regardless of the recipient's HIV status, appears to be associated with polyclonal activation of B cells for T-independent but not T-dependent antigens.

Acquired Immunodeficiency Syndrome↗

Hemostatic defects in response to aspirin challenge in hypothyroidism.

A patient with hypothyroidism had ingested aspirin and bled profusely following dental extraction. The only abnormalities noted on coagulation survey were a prolonged aspirin bleeding time and reduced retention of platelets on glass beads. Based on this index case, an additional 12 hypothyroid patients, on no medications, were evaluated for a mild bleeding disorder, including studies with aspirin challenge. The results indicate that thrombin-induced platelet serotonin release, following aspirin ingestion, was subnormal in most hypothyroid patients. However, only hypothyroid individuals with TSH levels of greater than 60 microU/ml have an increased hemostatic sensitivity to aspirin, as measured by the bleeding time test. These findings did not appear to result from decreased synthesis of the factor VIII-von Willebrand factor complex. As this drug is commonly ingested, the effects of aspirin on bleeding may explain the easy bruising and menorrhagia that occur in hypothyroid individuals.

Aspirin↗

Alpha-1-antitrypsin-Pittsburgh. A potent inhibitor of human plasma factor XIa, kallikrein, and factor XIIf.

Alpha-1-antitrypsin-Pittsburgh is a human variant that resulted from a point mutation in the plasma protease inhibitor, alpha 1-antitrypsin (358 Met----Arg). This defect in the alpha 1-antitrypsin molecule causes it to have greatly diminished anti-elastase activity but markedly increased antithrombin activity. In this report, we demonstrate that this variant protein also has greatly increased inhibitory activity towards the arginine-specific enzymes of the contact system of plasma proteolysis (Factor XIa, kallikrein, and Factor XIIf), in contrast to normal alpha 1-antitrypsin, which has modest to no inhibitory activity towards these enzymes. We determined the second-order-inactivation rate constant (k'') of purified, human Factor XIa by purified alpha 1-antitrypsin-Pittsburgh and found it to be 5.1 X 10(5) M-1 s-1 (23 degrees C), which is a 7,700-fold increase over the k'' for Factor XIa by its major inhibitor, normal purified alpha 1-antitrypsin (i.e., 6.6 X 10(1) M-1 s-1). Human plasma kallikrein, which is poorly inhibited by alpha 1-antitrypsin (k'' = 4.2 M-1 s-1), exhibited a k'' for alpha 1-antitrypsin-Pittsburgh of 8.9 X 10(4) M-1 s-1 (a 21,000-fold increase), making it a more efficient inhibitor than either of the naturally occurring major inhibitors of kallikrein (C-1-inhibitor and alpha 2-macroglobulin). Factor XIIf, which is not inhibited by normal alpha 1-antitrypsin, displayed a k'' for alpha 1-antitrypsin-Pittsburgh of 2.5 X 10(4) M-1 s-1. This enhanced inhibitory activity is similar to the effect of alpha 1-antitrypsin-Pittsburgh that has been reported for thrombin. In addition to its potential as an anticoagulant, this recently cloned protein may prove to be clinically valuable in the management of septic shock, hereditary angioedema, or other syndromes involving activation of the surface-mediated plasma proteolytic system.

Factor IX↗