Nodular regenerative hyperplasia of the liver in a case of myelofibrosis with extramedullary hematopoiesis and secondary portal venous hypertension.

Nodular regenerative hyperplasia of the liver was identified at autopsy in a patient with myelofibrosis with extramedulary hematopoiesis, an association not previously reported. Portal venous hypertension, documented during the patient's terminal hospitalization, was ascribed, in part, to a high rate of blood flow through the enlarged spleen. Possible mechanisms accounting for the development of nodular regenerative hyperplasia of the liver, and evidence provided by this case pertinent to these mechanisms, are discussed.

The transmission of hepatitis B by renal transplantation.

A case of a renal transplant is reported with hepatitis B infection acquired directly from the cadaveric kidney of a previously unrecognized hepatitis B carrier. In retrospect, the recipient's serum became reactive for the virus 6 days postoperatively which was not recognized for ten weeks thereby placing at risk for secondary transmission almost 100 health care deliverers. Of interest, the other kidney from the same donor caused only antibody conversion in its recipient. This kidney was mechanically perfused prior to implantation while the infected recipient's transplant was cold stored.

The current status of non-A, non-B viral hepatitis.

It is probable that two or more different viruses account for non-A, non-B hepatitis throughout the world, with a third agent causing epidemic hepatitis in India and neighboring countries. NANB virus(es) is the major cause of transfusion-associated hepatitis, and is responsible for roughly 20% of sporadic hepatitis cases. NANB postransfusion hepatitis progresses to chronic hepatitis in half or more of cases. This form of chronic hepatitis, while usually minimally symptomatic, causes progressive liver destruction and eventual cirrhosis in a significant proportion of cases. To date, the NANB virus(es) has not been specifically identified, either serologically or by electron microscopy. When developed, serologic assays will find their most immediate application in the identification of NANB virus carriers among blood donors, thereby being applied to the prevention of post-transfusion hepatitis. No specific therapy is available for NANB virus infection. Gamma globulin is of uncertain prophylactic efficacy.

Veterans Administration cooperative study on hepatitis and dentistry.

Personnel in the VA dental facilities were screened for the detection of viral hepatitis and identification of factors implicating infectivity. A total of 963 personnel from 126 dental facilities throughout the United States voluntarily participated in the study. The rate of seroconversion for any hepatitis B markers was approximately 1% per year. Serial positive tests for antibody to hepatitis B core antigen or antibody to hepatitis B surface antigen (or both) were present in 16.2% of dentists and 13.0% of dental auxiliary personnel. Oral and maxillofacial surgeons composed the highest prevalence occupation (24.0%), and clinical personnel composed the lowest prevalence occupation (8.9%). There was a significant association between years in dental environment and serological positivity for viral B infection. The dentists and dental auxiliary personnel had significant linear trends of increasing serological positivity with years in the dental environment. Although a majority of personnel reported wearing gloves while treating high-risk patients or performing invasive procedures, inadequate prophylactic measures were exercised for most patients undergoing a variety of less invasive procedures. The results of the study show the need for an active immunization program against type B viral infection for dental and dental auxiliary personnel, preferably before the initial exposure to the professional environment.

A new hepatitis B virus surface antigen.

A new determinant of hepatitis B surface antigen (HBs Ag), g, which is distinct from the previously identified determinants a, d, y, w, and r, was studied. This new antigen tended to be associated with the d antigen; it was found in 97% of ad specimens and in 15% of ay specimens. With few exceptions, the atypical subtypes, adg- and ayg+, were identified in sera from blood donors, but not in sera from patients with acute viral hepatitis; this finding possibly reflects a reduced tendency of these viral strains to evoke a host immune response. The ability to identify g represents a refinement of HBs Ag serotyping that may be of value in the study of the epidemiology of hepatitis B virus.

Reexamination of hepatitis B virus subtypes and e-antigen expression by radioimmunoassays.

Radioimmunoassay methods were used to determine both the hepatitis B virus (HBV) subtype and hepatitis B e antigen (HBeAg) and antibody (anti-HBe) status of a group of hepatitis B surface antigen (HBsAg)-positive blood donors. The study involved sera containing HBV of the three major occidental subtypes, adw2, ayw3, and ayw2. The previously reported association of the y-type virus with HBeAg and the d types with anti-HBe was again observed. However, when the two y subgroups, ayw2 and ayw3, were considered individually, it was evident that the ayw3 specimens alone accounted for the association with HBeAg while the ayw2 sera were strongly associated with anti-HBe. The study also indicated that the prevalence of HBeAg declined and that of anti-HBe increased progressively with advancing age. On the average, ayw2 donors were significantly older than the adw2 donors, and donors from both of these groups were older than the ayw3 donors. It is postulated that the observed age differences account, at least in part, for the differing prevalence of e markers in the three HBV subtype groups, and that these age differences, in turn, may reflect a tendency for infections with the ayw2 viral strain to persist longer than adw2 infections, and both of these longer than ayw3 infections. Alternately, the three subtypes may represent epidemiologic shifts from remote ayw2 and adw2 infections to more recent ayw3 infections.

Organ culture studies of rat antrum: evidence for an antral inhibitor of gastrin release.

The regulation of gastrin release in rodent antral mucosal organ cultures was investigated. The tissue was well preserved morphologically and medium gastrin concentration increased steadily throughout a 24-h culture period. The effects of peptone and a bovine serum albumin digest on gastrin release were independently investigated. During the periods these agents were in contact with the tissue, medium gastrin concentration did not differ from those of control cultures. However, treatment cultures released a significantly greater amount of gastrin into the medium than did control cultures during the two posttreatment periods. Prolongation of the period of exposure to peptone did not alter this secretory pattern. The rise in medium gastrin concentration that followed the removal of peptone was directly related to the medium peptone concentration and was partially inhibited by readdition of peptone to cultured antral explants. These results suggest that substances which stimulate gastrin release in vivo may cause the accumulation of an antral inhibitor of gastrin release when exposed to rat antral mucosa in culture.

Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke.

Hepatitis and pregnancy.

The maternal and fetal outcomes of 50 pregnancies complicated by acute viral hepatitis were examined. Twenty (40%) cases were due to type B hepatitis virus. The clinical course of the maternal hepatitis was unaffected by the pregnant state. Maternal hepatitis (type B or nontype B) had no effect on the incidence of congenital malformations, stillbirths, abortions, or intrauterine malnutrition; it did increase the incidence of prematurity (type B 31.6%; nontype B 25%; overall 27.6%) over that seen in the general delivery population (10 to 11%). Eight mothers acquired acute type B hepatitis during the third trimester; two of their infants (25%) were found to be chronic asymptomatic carriers of hepatitis B surface antigen and to have mild, persistent elevations of SGOT for up to 45 months.

Metabolic and functional characteristics of alveolar macrophages recovered from rats exposed to marijuana smoke.

Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge.

Hepatitis B viral antigenic structure: signature analysis by monoclonal radioimmunoassays.

An approach has been developed for the analysis of hepatitis B viral (HBV) antigenic structure that creates numerical "signatures" of HBV strains. This technique employs high-affinity IgM and IgG monoclonal antibodies (anti-HBsAg) directed toward distinct and separate determinants on hepatitis B surface antigen (HBsAg). Such antibodies have been used to develop sensitive and specific radioimmuno-assays for measurement of HBsAg-associated determinants in serum. In performing "signature" analysis separate binding curves for each monoclonal anti-HBsAg are generated by measuring immunoreactivity in serial dilutions of HBsAg-positive serum. Since the HBsAg concentration in serum is unknown, the binding profiles of groups of samples from the same "classic" HBV subtype are aligned by an iterative maximum likelihood procedure to give the numerical signature of that HBV subtype. By using this approach, HBsAg shows far more antigenic heterogeneity than previously recognized by polyvalent anti-HBsAg antibodies. Indeed, there are subgroups within the classic HBsAg subtypes. In addition, the a domain (common to all known subtypes or strains of HBV) has been shown to be multideterminant. Thus, these studies have demonstrated heretofore unrecognized differences in HBV subtypes. This approach also has broader significance for the study of subtle or major antigenic changes among other viral agents since it is not necessary to know the concentration of virus or viral protein in complex protein mixtures.

A prospective trial of steroid therapy in severe viral hepatitis. The prognostic significance of bridging necrosis.

A prospective, double-blinded, randomized trial of corticosteroid therapy in patients with severe acute viral hepatitis has been conducted. At the same time, we have examined the prognostic significance of the presence of bridging necrosis in liver biopsies obtained from such patients as well as the predictive value of certain serologic markers. Forty-two of the 77 patients admitted to the trial were shown to have bridging necrosis on their initial biopsies. Two patients progressed to death with massive hepatic necrosis, while 5 patients developed chronic liver disease. A complicated course could not be predicted by the initial biopsy findings nor by any of the serologic markers assessed. We could not identify any clinical or epidemiologic features with prognostic impact. No advantage was demonstrated to be associated with the use of corticosteroids early in the course of severe viral hepatitis.

Serum gamma-glutamyl transpeptidase activity in viral hepatitis: suppression in pregnancy and by birth control pills.

gamma-Glutamyl transpeptidase (GGT) activity in serum was increased in the majority of women with viral hepatitis occurring in the first half of pregnancy. By contrast, GGT activity was abnormal less frequently and the mean value was relatively depressed, even though hepatitis was as severe, in the second half of gestation. Mean GGT activity was also lower, and abnormal values were less frequent, in nonpregnant women with viral hepatitis who were taking birth control pills (BCP). Depressed GGT is not attributable to an inhibitor in serum in women in late pregnancy or taking BCP. The data suggest that estrogen and/or progestational compounds affect liver such that less GGT is released into blood with acute hepatocellular injury. In addition, hyperbilirubinemia was found to be associated with depressed serum GGT activity, and bilirubin added to serum in vitro interfered with measured activity of the enzyme.

An institutional outbreak of hepatitis B related to a human biting carrier.

An outbreak of hepatitis B in a residential institution for the mentally retarded was studied. Initially one overt case of hepatitis was noted. A serologic screen of students and employees revealed a total of 12 individuals positive for hepatitis B surface antigen (HBsAg). Subtyping by radioimmunoassay subsequently demonstrated that the population of HBsAg-positive individuals could be subdivided into two groups, based on the HBsAg subtype: adw2 or ayw3. The five individuals with subtype adw2 all were carriers. The ayw3 group, in contrast, were acutely infected except for one carrier with persistent hepatitis B e antigen. Both the ayw3 carrier and several of the acutely infected individuals were aggressive biters. Human biting, a frequent occurrence in the classroom studied, was one probable mode of transmission in this outbreak. The resolution of the outbreak was achieved by rapid screening for HBsAg with subtyping of positive patients and careful observation of the setting for putative modes of transmission.

Value of screening for markers of hepatitis in dialysis units.

The value of monitoring the serum activity of SGOT, as well as markers of hepatitis B virus and hepatitis A virus infections, in the patients and staff of two dialysis units has been assessed retrospectively. Sera were checked each month for SGOT and HBsAg on 406 patients and 170 staff members over a 4-year period. Anti-HBc, anti-HBs, and anti-hepatitis A antibodies were assayed on the stored sera. Only 30% of the patients had normal SGOT values (less than 65 units per ml) on all occasions. Most of the abnormal values were less than 100 units per ml and could not be explained. Viral hepatitis was a reasonable explanation for only half of those instances where the SGOT value was greater than 100 units per ml. Hepatitis A virus contributed nothing to the problem of dialysis-associated liver disease. Testing for HBsAg alone missed approximately 40% of the hepatitis B events acquired in the unit. Only two of these episodes were of epidemiologic importance, however, because the rest were recognized only after there was serologic resolution of the infection. There was a high frequency of potentially "false positive" reactions with all the antibodies tested. It is not cost-effective to monitor dialysis patients and staff regularly with anti-HBc, anti-HBs, or antibodies against hepatitis A. Initial screening with anti-HBc and anti-HBs on entry to the unit is of value but weak positive results must be interpreted with caution since approximately half of such results will prove to be nonspecific.

Impact of interpreter services on delivery of health care to limited-English-proficient patients.

OBJECTIVE: To determine whether professional interpreter services increase the delivery of health care to limited-English-proficient patients. DESIGN: Two-year retrospective cohort study during which professional interpreter services for Portuguese and Spanish-speaking patients were instituted between years one and two. Preventive and clinical service information was extracted from computerized medical records. SETTING: A large HMO in New England. PARTICIPANTS: A total of 4,380 adults continuously enrolled in a staff model health maintenance organization for the two years of the study, who either used the comprehensive interpreter services (interpreter service group [ISG]; N = 327) or were randomly selected into a 10% comparison group of all other eligible adults (comparison group [CG]; N = 4,053). MEASUREMENTS AND MAIN RESULTS: The measures were change in receipt of clinical services and preventive service use. Clinical service use and receipt of preventive services increased in both groups from year one to year two. Clinical service use increased significantly in the ISG compared to the CG for office visits (1.80 vs. 0.70; P <.01), prescriptions written (1.76 vs 0.53; P <.01), and prescriptions filled (2.33 vs. 0.86; P<.01). Rectal examinations increased significantly more in the ISG compared to the CG (0.26 vs. 0.02; P =.05) and disparities in rates of fecal occult blood testing, rectal exams, and flu immunization between Portuguese and Spanish-speaking patients and a comparison group were significantly reduced after the implementation of professional interpreter services. CONCLUSION: Professional interpreter services can increase delivery of health care to limited-English-speaking patients.

Characterization of a postlavage, in situ pulmonary macrophage population.

A postlavage in situ subpopulation of pulmonary macrophages (PM), biochemically distinct from the lavaged population, has recently been isolated from rats. After exhaustive bronchopulmonary lavage to extract the free lung cells, the lungs were excised, homogenized, and filtered, and the resultant cell suspension was allowed to form a monolayer on plastic Petri dishes. Electron microscopic morphometry failed to indicate any morphologic differences in the two populations. The postlavage in situ PM were more active metabolically during phagocytosis of zymosan particles or stimulation by phorbol myristate acetate (PMA) than the corresponding lavage population, as evidenced by greater superoxide generation. Macrophages prepared by either method became more avidly phagocytic when incubated with cell-free medium isolated in the preparation of the situ population. Peroxidase, an enzyme absent from the granules of PM separated by lavage techniques, was found in a granule-rich fraction of the in situ macrophage. Catalase activity was found in similar amounts in both supernatants and granule-rich fractions of both populations. The results support the concept of subpopulations of PM and suggest that these subpopulations are distinguished by their biochemical properties and their functional abilities.