Hepatitis C virus infection: review and implications for the orthopedic surgeon.

Hepatitis C virus (HCV), a single-stranded ribonucleic acid virus identified in 1989, is estimated to have infected 1%-2% of the United States population. The incidence of HCV in patients requiring orthopedic surgery may be as high as 5%. Surgeons and operating room personnel are at risk for blood-borne diseases transmitted during surgery. The orthopedic surgeon must be aware of viral infection with this pathogen for the safety of the entire operating room team. Further, screening for HCV is routinely done when a patient donates autologous blood prior to elective surgery, and the orthopedic surgeon is often the first or only physician informed of a positive result. The surgeon should know how to interpret the result, advise the patient, and incorporate the diagnosis of HCV into the plan for the proposed surgery. We will review the natural history, transmission, evaluation of, and current treatment for infection with this blood-borne virus.

Suppressor T-cell deficiency in primary sclerosing cholangitis. Case and family study.

Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters.

An immunogenetic study of suppressor cell activity in autoimmune chronic active hepatitis.

Some patients with autoimmune chronic active hepatitis as well as their disease-free first degree relatives show decreased suppressor cell activity of peripheral blood T lymphocytes. Studies were therefore undertaken in families ascertained by the presence of a single chronic active hepatitis patient to determine if this abnormality of immune regulation represents a genetic phenotype simply controlled by a gene or genes at a putative disease susceptibility locus and, further, if this locus showed linkage to either the HLA or the immunoglobulin constant region loci. In addition to determining circulating autoantibody status and genotyping for HLA and immunoglobulin allotypes, suppressor T cells were evaluated by surface markers and by determining their ability to suppress IgG secretion in vitro. The results suggest that immunoregulatory dysfunction in autoimmune chronic active hepatitis is a familial abnormality, but that this abnormality occurs independent of circulating autoantibody status and of the segregation of genes for HLA or immunoglobulin allotypes.

Immunogenetic studies of autoimmune chronic active hepatitis: HLA, immunoglobulin allotypes and autoantibodies.

The strategy of assigning a surrogate phenotype, defined as the presence of antinuclear and/or antismooth muscle antibodies to disease-free first degree relatives of index cases was used to search for a postulated disease susceptibility gene in autoimmune chronic active hepatitis. In addition to determining circulating autoantibody status, 10 patients, 51 first-degree relatives and 6 spouses of index chronic active hepatitis patients, each ascertained by the single patient, were genotyped for HLA (A, B and DR loci) and immunoglobulin allotype (G1m, G2m, G3m and A2m loci) haplotypes. Among the 10 chronic active hepatitis patients, 6 had HLA haplotypes B8 and DR3, and 3 of these patients had, in addition, the immunoglobulin allotype haplotype Gm a,x;g. Circulating autoantibodies defining the surrogate phenotype was found in 39% of the first-degree relatives. However, segregation analysis offered no support for either single autosomal dominant or recessive inheritance for the autoantibody-positive phenotype. Linkage between the postulated disease susceptibility locus and either the HLA (Chromosome 6) or immunoglobulin (Chromosome 14) locus was excluded by several analyses. Furthermore, logistic regression indicated that neither immunogenetic marker was statistically associated with autoantibody positively in these families. Therefore, despite the occurrence of autoantibody positivity in first-degree relatives of autoimmune chronic active hepatitis patients, we found no evidence that this trait has a simple genetic basis, or that it is an alternative manifestation of a postulated disease susceptibility gene for chronic active hepatitis.

Changes in distal esophageal function in response to cooling.

The effects upon esophageal motility of water at room temperature and 0 degrees C, taken as repeated small boluses and as 200-ml volumes swallowed as rapidly as possible, were compared before and after pretreatment with isosorbide denitrate 5 mg sublingually, in nine young healthy subjects and two patients with esophageal spasm. Iced water caused reduced strength, increased duration, and reduced velocity of distal esophageal contractions. It also reduced the force of lower esophageal sphincteric contraction, an effect that was more transient than that seen in the esophageal body, but it did not alter the magnitude of sphincteric relaxation. Esophageal responses in normal subjects with water at the two temperatures were not affected by isosorbide denitrate. The responses to iced water in the two patients with esophageal spasm were qualitatively similar to those in normal subjects. These findings indicate that cooling brings about a transient state of relative paralysis in the distal esophagus and lower esophageal sphincter. Taken in conjunction with other observations, they are consistent with the notion that cold-induced chest pain, whether in normal subjects or in patients with esophageal motor disorders, is related to esophageal distension.

HLA typing and autoantibodies in hepatitis B surface antigen-negative chronic active hepatitis.

HLA types, serum autoantibodies and serum globulin levels were surveyed in 46 patients with HBsAg-negative chronic active hepatitis. Patients with chronic active hepatitis with viral risk factors were less likely than those without viral risk factors to be HLA type B8 (10% vs 44%) or to have autoantibodies (antinuclear and/or anti-smooth muscle antibodies) (38% vs 84%). Thirty patients (10 with and 20 without viral risk factors) were treated with glucocorticosteroids. Of the 11 patients who were HLA-B8, 100% responded to treatment. Of the 20 patients who were ANA positive, 80% responded. The data suggest that the presence of HLA-B8 may be a useful predictor of response to anti-inflammatory treatment and may define a genetic subset of HBsAg-negative chronic active hepatitis that will benefit from glucocorticosteroid therapy.

Thymosin effects on immunoglobulin synthesis and suppressor T cell activity in normal subjects and patients with primary biliary cirrhosis.

Peripheral blood lymphocytes from patients with primary biliary cirrhosis previously have been reported to demonstrate reduced pokeweed mitogen-stimulated immunoglobulin synthesis and diminished function of suppressor T cells. To determine whether thymic hormone preparations reverse these immunologic defects in vitro, the effects of thymosin fraction 5 and thymosin alpha 1 on immunoglobulin synthesis and concanavalin A-induced suppression of immunoglobulin synthesis were investigated in normal subjects and patients with primary biliary cirrhosis. In normal subjects, no effects of thymosin were observed on unstimulated and pokeweed mitogen-stimulated immunoglobulin synthesis, nor on Con A-induced suppressor cell activity. Lymphocytes from patients with PBC synthesized less IgG and IgM than normals when stimulated by pokeweed mitogen, and this difference was enhanced by both thymosin fraction 5 and thymosin alpha 1. Con A suppression of immunoglobulin synthesis was abnormal in only one PBC subject so that thymosin effects on impaired suppressor T cell activity could not be tested.

Pleural and mediastinal changes following endoscopic injection sclerotherapy of esophageal varices.

Postero-anterior and lateral chest radiographs of patients undergoing endoscopic injection sclerotherapy of esophageal varices were reviewed. Radiographs were obtained prior to and within 48 hours of treatment. Following sclerotherapy, pleural effusions and densities were commonly seen at the azygoesophageal reflection and the posterior wall of the bronchus intermedius; however, on follow-up they had resolved. Most patients were asymptomatic, and morbidity was low. These findings suggest that inflammation developing after endoscopic injection sclerotherapy extends beyond the esophageal wall into the mediastinum and pleural space.