A dose response study of hepatitis A vaccine in healthy adults who are > or = 30 years old and weigh > or = 77 kg.

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels.

Viral hepatitis. What have we learned about risk factors and transmission?

Understanding of transmission of viral hepatitis continues to improve. Patients with certain behaviors (eg, injecting drug use, male homosexual activity) are at risk of infection with multiple hepatitis viruses. However, a significant proportion of patients who become infected have no identifiable risk factor for hepatitis. Many who contract hepatitis B or C are unaware of their infection. Therefore, patients often present with serologic evidence of previous infection but have no knowledge of a previous infection or recognizable risk factors.

Gastrointestinal histoplasmosis presenting as hematochezia in human immunodeficiency virus-infected hemophilic patients.

Two hemophiliacs infected with human immunodeficiency virus (HIV) presented with hematochezia secondary to gastrointestinal involvement with Histoplasmosis capsulatum. In one patient who was already receiving fluconazole, the diagnosis was obscured. Both patients responded to amphotericin B followed by intraconazole, with no recurrence of bleeding.

Sjögren's syndrome without mixed cryoglobulinemia is not associated with hepatitis C virus infection.

OBJECTIVES: Hepatitis C virus infection has been associated with the formation of autoantibodies. Furthermore, several autoimmune and immune-complex mediated disorders have been proposed to be associated with hepatitis C virus infection. The best documented of these associations is between hepatitis C virus infection and essential mixed cryoglobulinemia. Essential mixed cryoglobulinemia is itself frequently associated with Sjögren's syndrome, and hepatitis C virus infection has been reported to be accompanied by lymphocytic sialadenitis and by xerophthalmia. We therefore searched for hepatitis C virus RNA and antibodies in 48 patients with SS-A/SS-B autoantibodies. METHODS: Patients with both SS-A and SS-B autoantibodies were included if stored serum samples and medical records were available. No patients had clinically apparent chronic liver disease, and no patients had cryoglobulinemia. Six patients (group 1) had abnormally high aminotransferase values on one or more occasion, a history of acute hepatitis, or blood product exposure through transfusion or intravenous drug use. In 18 cases (group 2) no liver disease could be established, but there was insufficient information to exclude it. The 24 remaining patients (group 3) had no risk factors for liver disease, no known history of acute or chronic liver disease, a normal physical examination for signs of chronic hepatitis, and repeatedly normal aminotransferase values. Antibody to hepatitis C virus was determined by RIBA-2 (Chiron Corp, Emeryville, CA). The samples were tested for hepatitis C virus RNA after polymerase chain reaction amplification. RESULTS: No patient had detectable antibody to hepatitis C virus; 47 were negative, and one sample from group 1 was indeterminate. No patients were positive for hepatitis C virus RNA. CONCLUSIONS: We conclude that our patients with Sjögren's syndrome, without cryoglobulinemia and with detectable SS-A/SS-B autoantibodies, do not have clinically apparent liver disease, hepatitis C viremia by polymerase chain reaction, or antibodies to hepatitis C virus by second-generation testing using RIBA-2.

Peptide immunogen mimicry of putative E1 glycoprotein-specific epitopes in hepatitis C virus.

Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B hepatitis with serious consequences that may lead to hepatocellular carcinoma. The putative envelope glycoproteins (E1 and E2) of HCV probably play a role in the pathophysiology of the virus. In order to map the immunodominant domains of the E1 glycoprotein, two epitopes from amino acid residues 210 to 223 (P1) and 315 to 327 (P2) were predicted from the HCV sequence. Immunization of mice with the synthetic peptides conjugated to bovine serum albumin induced an antibody response, and the antisera immunoprecipitated the E1 glycoprotein (approximately 33 kDa) of HCV expressed by recombinant vaccinia virus. A panel of HCV-infected human sera was also tested with the synthetic peptides by enzyme-linked immunosorbent assay for epitope-specific responses. Of 38 infected serum samples, 35 (92.1%) demonstrated a spectrum of reactivity to the P2 peptide. On the other hand, only 17 of 38 (44.7%) serum samples were reactive to the P1 peptide. Strains of HCV exhibit a striking genomic diversity. The predicted P1 epitope showed localization in the sequence-variable region, and the P2 epitope localized in a highly conserved domain. Results from this study suggest that the E1 glycoprotein of HCV contains at least two potential antigenic epitopes. Synthetic peptides corresponding to these epitopes and antisera to these peptides may serve as the monospecific immunological reagents to further determine the role of E1 glycoprotein in HCV infection.

Hepatitis C virus. What recent studies can tell us.

Hepatitis C virus (HCV) is responsible for most cases of non-A non-B hepatitis and is primarily spread by a parenteral route, although familial, sexual, and maternal transmission may occur rarely. Second-generation assays and the polymerase chain reaction facilitate detection of HCV infection. The association between HCV infection and hepatocellular cancer is well established, whereas the links between HCV infection and essential mixed cryoglobulinemia, porphyria cutanea tarda, membranoproliferative glomerulonephritis, and idiopathic pulmonary fibrosis remain to be defined more clearly. Standard therapy for chronic HCV infection remains interferon alfa-2b (Intron A), although other agents may have potential. We eagerly await additional clarifying studies.

Hepatitis C testing: interpretation, implications, and counseling.

New molecular biology techniques recently identified hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis. Serologic assays for HCV specific antibodies are a significant advance, but they require cautious interpretation due to problems with the tests' sensitivity and specificity. Patients with suspected HCV infection should be thoroughly evaluated to verify the presence of infection, to exclude other forms of chronic liver disease, and to determine the extent of liver damage prior to considering treatment.

Nosocomial infection rate as a function of human immunodeficiency virus type 1 status in hemophiliacs.

As part of a prospective cohort study initiated in 1983, the human immunodeficiency virus type 1 (HIV-1) status has been periodically determined for patients with clotting disorders (hemophilia A or B, von Willebrand's disease, miscellaneous). The University of North Carolina Hospitals has conducted comprehensive surveillance for nosocomial infections (NI) using modified Centers for Disease Control criteria since 1980 and entered this information in a computerized data base. Cross-matching of our NI data base and hemophiliac/HIV-1 study data base for the time period 1980-1989 revealed that 13 NI occurred in 11 patients during 659 hospitalizations (5,723 hospital days). NI rates per 100 admissions (per 1,000 hospital days) by HIV-1 status were as follows: HIV-1 negative = 0.91 (1.18), HIV-1 positive pre-AIDS = 1.65 (1.84), and AIDS = 6.67 (6.48). NI occurred with a similar frequency in HIV-1 positive pre-AIDS hemophiliacs and HIV-1 negative hemophiliacs (Fisher's exact test, p greater than 0.10). However, NI occurred more frequently in hemophiliacs with AIDS versus HIV-1 positive or negative hemophiliacs (Fisher's exact test, p less than 0.05). We conclude that HIV-1 infection does not appreciably alter the risk of developing a NI, but that patients who have progressed to AIDS are at significantly increased risk of developing a NI per hospital day or per hospitalization.

Human immunodeficiency virus-1 disease progression in hemophiliacs.

A retrospective study of 153 hemophiliacs infected with human immunodeficiency virus-1 (HIV-1) was performed to determine the clinical and immunological consequences of HIV-1 infection and the markers and cofactors associated with these changes. Nearly 80% of HIV-1-infected hemophiliacs have developed a significant reduction in their CD-4+ counts (less than 400 CD-4+ cells/mm3) with 40% having less than 200 CD-4+ cells/mm3 by the end of 1987. The rate of CD-4+ cell count decline was slightly greater in patients who have already developed the acquired immunodeficiency syndrome (AIDS) compared to those who have not (50 vs. 31 cells/mm3/6 months). Thrombocytopenia and older age were associated with a more rapid CD-4+ count deterioration, but the quantity of clotting factor utilized did not affect immunologic progression. In patients with less than 200 CD-4+ cells/mm3, the incidence of AIDS was significantly higher in adults (greater than 21 years old) compared to children/adolescents. Cytomegalovirus (CMV) seroprevalence increased with age but did not correlate with the amount of concentrated clotting factor used. Although there was no relationship between CMV status and progression to AIDS, CMV-seropositive patients were older and had a lower CD-4+ count. Thus the majority of HIV-1-infected hemophiliacs are developing progressive immune dysfunction measured by CD-4+ count decline. This drop in CD-4+ count significantly correlates with a risk for the development of AIDS in adults but not in children (less than 21 years old).

Wound infection rates after invasive procedures in HIV-1 seropositive versus HIV-1 seronegative hemophiliacs.

One-hundred and two patients with hemophilia A, hemophilia B, or acquired antibody to factor VIII who had undergone invasive procedures were cross referenced with patients participating in an ongoing prospective natural history study of HIV-1 infection in hemophiliacs. Matching revealed that HIV-1 status was known for 83 patients (83%) who had undergone 169 procedures between July 1979 and April 1988. Invasive procedures were classified as clean in 108 patients (63.9%), clean-contaminated in 45 (26.6%), contaminated in 2 (1.2%), and infected in 14 (8.3%). Wound infection rates by HIV-1 status were as follows (95% confidence intervals): HIV+ 1.4% (0% to 5%), HIV- 0% (0% to 9%), and procedure before testing HIV+ 1.5% (0% to 6%). There were no significant differences between the wound infection rates of HIV-positive and HIV-negative hemophiliacs nor in the wound infection rate among all three subgroups of patients (p greater than 0.5, Fisher's Exact Test). We conclude that surgery in HIV-1-infected patients who have not progressed to AIDS does not entail an increased risk of postoperative wound infections.

Haemophilus influenzae pericarditis successfully treated by catheter drainage.

Surgical drainage together with antibiotic therapy is generally considered the treatment of choice for purulent pericarditis. A case of culture-proven Haemophilus influenzae pericarditis is described in a young, previously healthy adult. Successful management of his illness included placement of an indwelling pericardial catheter and intravenous antibiotics. Pericardial catheter drainage may be an alternative to surgical drainage in some cases of purulent pericarditis.

Regulation of prostaglandin synthesis mediated by thrombin and B2 bradykinin receptors in a fibrosarcoma cell line.

The murine fibrosarcoma cell line HSDM1C1 synthesizes prostaglandin E2 in response to thrombin and bradykinin, two products of the coagulation pathway. These physiologic effectors interact with two independent cell-surface receptor systems whose properties we have characterized. HSDM1C1 cells possess a B2 bradykinin receptor, a type more sensitive to native bradykinin than to related peptides, including Met-Lys- and desArg9-bradykinin. A period of bradykinin desensitization follows the initial response. Recovery occurs within 1 hr by a process independent of serum factors. The thrombin-mediated pathway differs in several respects. The maximum amount of prostaglandin E2 synthesized is 40% lower. Prolonged desensitization of the thrombin response occurs after an initial exposure; recovery requires at least 3 hr and depends strictly on the presence of serum. Antithrombin III and hirudin, two proteins that specifically inactivate thrombin, act in serum-free medium to relieve thrombin desensitization. Thrombin's prolonged desensitization thus suggests a persistent ligand-receptor association. The expression of receptor-mediated prostaglandin synthesis governed by multiple physiologic effectors in the same cell may reflect environmental conditions, such as the relative proportions of each effector and the presence of exogenous factors that modulate the ligand-receptor interaction.

Increased neurite development and plasminogen activator expression by exposure of human neuroblastoma cells to plasminogen-deficient growth medium.

Growth of human neuroblastoma strain SK-N-SH in a plasminogen-deficient medium results in about a 40% increase in the number of differentiated cells (cells with a neurite-like process at least 50 micrometers in length) and about a five-fold increase in the amount of plasminogen activator liberated per cell. Plasminogen deficiency has no effect on the growth rate of SK-N-SH cells. These results are consistent with the hypothesis that plasminogen activator is involved in neuroblast development.