Musculoskeletal manifestations and autoantibody profile in 90 hepatitis C virus infected Israeli patients.

OBJECTIVES: Recent interest has been expressed in rheumatic manifestations in hepatitis C virus (HCV)-infected populations. The aim of this study was to determine the prevalence and characteristics of the musculoskeletal manifestations and serological markers of autoimmunity in HCV-infected patients in Israel. METHODS: Ninety anti-HCV-positive patients were consecutively interviewed and examined. The prevalence of autoantibodies and their association with rheumatologic symptoms were also determined. RESULTS: Rheumatic manifestations were found in 28 subjects (31%), and included arthralgias (9%), arthritis (4%), cryoglobulinemia (11%), sicca symptoms (8%), cutaneous vasculitis (2%), polymyositis (1%), and antiphospholipid syndrome (1%). Rheumatic complications were not associated with liver disease severity, or subjects' gender. In addition, myalgia was reported by 22 patients (24%), and fibromyalgia was diagnosed in 14 (16%). Sixty-nine percent of the patients had at least one autoantibody detected in their serum, the most prevalent being rheumatoid factor (RF), 44%; antinuclear antibody (ANA), 38%; and IgM and IgG anticardiolipin antibodies (ac1), 28% and 22%, respectively. The frequency of autoantibodies was not associated with liver disease severity or rheumatic disorders. CONCLUSIONS: Musculoskeletal manifestations and autoimmune markers are common in HCV infection. An investigation of risk factors for HCV infection is pertinent in a patient presenting new rheumatic manifestations and should be included in the history of present illness. Future studies of these disorders may uncover the full spectrum of these associations and provide new insights into their operating mechanisms.

Maternal serum CA 125 is of prognostic value in patients with uterine bleeding in the detection of small-for-gestational-age neonates.

OBJECTIVE: The purpose of this study was to investigate whether maternal serum CA 125 determination in women with uterine bleeding has a prognostic value in the detection of women at risk for delivering a small-for-gestational-age neonate. STUDY DESIGN: The patients population consisted of women with uterine bleeding at a gestational age greater than 20 weeks. Patients with abruptio placentae, placenta previa, fetal distress and history of coagulopathy were excluded. Maternal serum CA 125 was measured at admission. Receiver operating characteristics curve analysis and logistic regression were used for statistical purposes. RESULTS: Fifty-nine women were enrolled into the study. Six of these had a small-for-gestational-age neonate, 8 had premature rupture of membranes and 33 delivered preterm. No relationship was found between maternal serum CA 125 concentrations and preterm delivery or PROM. Women who delivered a small-for-gestational-age infant (10.1%) had lower maternal serum CA 125 levels than those who delivered an appropriate-for-gestational-age infant (P < 0.02). Patients with uterine bleeding and serum CA 125 < or = 10 U/ml had a twofold risk to deliver a small-for-gestational-age neonate. Sensitivity, specificity, positive and negative predictive values were 66.6%, 79.2%, 26.6% and 95.4%, respectively. CONCLUSION: Our results show that a decreased maternal serum CA 125 concentration in women with uterine bleeding during the second half of pregnancy is of prognostic value in identifying those who will deliver a small-for-gestational-age infant.

Effect of prolonged use of inhaled steroids on the cellular immunity of children with asthma.

BACKGROUND: Systemic corticosteroids may affect the cellular immunity, but there is no available controlled data on such effects associated with a prolonged use of inhaled corticosteroids. OBJECTIVE: The investigation was designed to study the effect of long-term inhaled beclomethasone dipropionate in daily doses of up to 600 micrograms on cellular immune functions. METHODS: Twenty-four children with asthma treated with inhaled beclomethasone dipropionate for a mean of 22.6 months were compared with 16 children with asthma not treated with an inhaled steroid and with 20 healthy adults. Cellular immune parameters included differential white blood count, T- and B-cell numbers, T helper and suppressor counts, T-cell mitogenic transformation, and interleukin-1 and interleukin-2 secretion. RESULTS: There was no difference in any of the studied cellular immune functions among the three study groups. CONCLUSION: Long-term use of inhaled beclomethasone dipropionate by children with asthma, at daily doses of up to 600 micrograms, has no effect on certain parameters of cellular immunity.

The expression of HLA class I antigen in prostate cancer in relation to tumor differentiation and patient survival.

The expression of HLA class I antigens was studied using the immunoperoxidase technique on 30 patients with prostate cancer and 29 patients with benign prostatic hypertrophy (BPH). Forty-three percent of the tumors stained positive, in contrast to 21% of the BPH. An inverse relationship was noted between class I expression and degree of tumor differentiation: 88% of the well-differentiated tumors (8/9) expressed class I antigen, compared with 33% (3/9) of the moderately differentiated and 16% (2/12) of the poorly differentiated tumors. No significant survival difference was found between those with class I-positive and -negative tumors. However, when both class I expression and degree of differentiation were considered, those with positive tumors at each level of differentiation had better survival than those with negative tumors. These data suggest that HLA class I expression may serve as a finite prognostic factor and may have relevance in future immunotherapy.

Relationship between C-reactive protein levels and intraamniotic infection in women with preterm labor.

The purpose of this study was to determine the relationship between C-reactive protein (CRP) levels and intraamniotic infection in 48 women presenting with preterm labor and intact membranes. Blood samples for CRP tests were obtained immediately before the performance of transabdominal amniocentesis. The prevalence of amniotic fluid cultures positive for organisms was 14.6%. In 16 women (33.3%) positive CRP levels were obtained. There were no significant differences in the prematurity rate or the prevalence of microbial invasion of the amniotic cavity between women with positive CRP levels and women with negative levels. The sensitivity, specificity, and positive and negative predictive values for the detection of amniotic infection were 71.5%, 73.2%, 31.3% and 93.8%, respectively. Based on these results, we suggest that in women with preterm labor and negative CRP levels, routine amniocentesis may not be essential to the initial workup.

[C-reactive protein as a marker of infection in women with preterm delivery].

There is a strong association between systemic and intrauterine infection and preterm delivery. C-reactive protein (CRP) is considered a nonspecific marker for intrauterine inflammation. We determined its blood level in 100 women who presented with preterm labor and intact membranes and delivered prematurely. CRP levels were used as a noninvasive marker for infection to compare clinical characteristics between women who delivered prematurely at 31-36 and 24-30 weeks of gestation. Women who delivered earlier than the 24th week of gestation had a higher rate of positive CRP levels than those who delivered later, 54% vs 24%, respectively (p < 0.0001). Moreover, women from the lower gestational age group with positive CRP levels had significantly different clinical characteristics than those in the same group but with negative CRP levels. There was a significant difference between Jewish and Bedouin women in cervical dilatation and time interval from hospitalization to delivery between those with positive CRP and those with negative CRP levels. We conclude that patients who delivered prematurely at 24-30 weeks had higher rates of an inflammatory etiology than women who also delivered prematurely, but at a more advanced gestational age.

[Pityriasis rosea-like eruption after anti-inflammatory and antipyretic medication].

We report 2 cases of a pityriasis rosea-like eruption after the use of the anti-inflammatory and antipyretic medications naproxen, acetaminophen, and a combination of acetylsalicylic acid and codeine phosphate. The role of these drugs in the induction of the eruption was supported by the results of macrophage migration inhibition factor and mast cell degranulation tests performed on the offending drugs.

Expression of class I histocompatibility antigens in transitional cell carcinoma of the urinary bladder in relation to survival.

The expression of class I histocompatibility antigens (HLA) in transitional cell carcinoma of the bladder was studied by the immunoperoxidase technique and correlated with tumor differentiation and survival. Tumors of 33 patients who underwent cystectomy were examined; 57% of the tumors expressed HLA class I antigens. Positive expression was observed in 5 of 6 cases with Grade 1 tumors, 8 of 13 with Grade 2, and 6 of 14 with Grade 3. The 5-year survival was significantly better in patients with HLA class I-positive tumors (74%) compared with those with negative tumors (36%, P less than 0.05). The expression of HLA class I on tumor cells may serve as a target for the immune response and control the metastatic potential of the tumor. These results suggest that HLA class I expression in bladder carcinoma is a prognostic indicator that should be considered in treatment planning.

Cellular B-2 microglobulin expression as a prognostic indicator in renal cell carcinoma.

The expression of B-2 microglobulin (B-2M) on tumor cells and their normal cell counterparts in 39 patients with renal cell carcinoma was studied and correlated to tumor stage and survival. The median survival time of patients with localized disease (stage I) whose tumors expressed B-2M was 10.2 years while the median survival time for patients whose tumors did not express B-2M was only 3.6 years (p less than 0.001). For patients with more advanced disease (stages II, III, IV) whose tumors expressed B-2M, median survival time was 3.6 years compared to 2.0 years in patients whose tumors did not express B-2M, a non-significant difference. It is suggested that the tumor cell membrane expression of B-2M may serve as an indicator of good prognosis in early renal cell carcinoma.

Characteristics of antineuronal antibodies in systemic lupus erythematosus patients with and without central nervous system involvement: the role of mycobacterial cross-reacting antigens.

Sera of 16 patients with systemic lupus erythematosus (SLE) and active involvement of the CNS were examined for the presence of antibodies to human brain neurons, using indirect immunofluorescence of human brain tissue sections. Thirteen of the 16 patients (81%) had high antineuronal titers, which declined during convalescence, compared with 18 of 105 (17%) SLE patients who had no CNS disease. Competition assays showed that the binding of the antineuronal antibodies was blocked by mycobacterial glycolipids and bovine brain extracts. This finding suggests an additional link between mycobacterial infection and SLE.

Variation of HLA-ABC surface antigen expression on adenocarcinoma of the colon in correlation with the degree of differentiation.

The expression of HLA class I antigens was tested on biopsy specimens originating from 90 patients suffering from adenocarcinoma of the colon. Three different samples were examined from each specimen: one from the tumor and the other two from the neighboring surrounding surgical margins. Twenty-seven out of 27 well-differentiated carcinomas were found highly positive for the presence of HLA class I antigens. Most of the moderately well differentiated tumors (37 out of 46) were weakly positive. None of the poorly differentiated tumors (n = 11) nor the mucin-producing tumors (n = 6) expressed HLA class I antigens. In 180 histologically normal colonic epithelia from patients suffering from adenocarcinoma of the colon (surgical edges free from tumorous tissue of the same specimens) no positive expressions were found. These results tend to suggest that class I HLA-ABC deficient, poorly differentiated tumors may possibly evade lethal immune aggression by HLA-restricted cytotoxic T cells and thus progress to overt malignancy. This negative expression may provide an explanation for the poorer prognosis observed among patients afflicted by a poorly differentiated adenocarcinoma or mucin-producing adenocarcinoma of the colon. Furthermore, these results tend to suggest that enhanced expression of HLA class I antigens on colonic epithelium could serve as a clinical laboratory indication for further examination looking for the possible emergence of neoplasm. If further verified, this may prove to serve as a predictive diagnostic tool for screening populations at risk.

Suppression of lymphocyte activation by a soluble factor released from the human placental chorionic membrane: chemical analysis and functional characterization.

A heat-resistant factor that markedly and reversibly inhibits human lymphocyte activation was discovered in culture medium of human placental chorion. The chorionic factor inhibits lymphocyte proliferation in response to polyclonal mitogens and in the mixed leukocyte response. The inhibitory action is most effective if the factor is added during the first 24 h of lymphocyte culture and is reversible. The chorionic factor is sensitive to proteinase K, pepsin and bovine pancreatic protease; its activity is completely lost after papain digestion and following treatment with trichloracetic acid (TCA). The factor prevents the expression of IL-2 receptors and class II MHC glycoproteins (HLA-DR) on phytohemagglutinin-stimulated PBMC but does not affect the expression of MHC class I molecules. It inhibits the replication of IL-2-dependent CTLD cells but is without effect on the growth of various human or murine cell lines or acute leukemic cells. Human placental chorion is thus capable of releasing in vitro a nontoxic heat-resistant factor with protein characteristics that reversibly inhibits processes associated with the early stages of lymphoid cell triggering. This factor may play a role in an immunoregulatory mechanism that prevents maternally mediated immune rejection of the conceptus.

Leishmania major: histopathological responses before and after topical treatment in experimental animals.

The cellular response in the cutaneous leishmaniasis lesion (CL), of BALB/c mice treated topically with an ointment composed of 15% paromomycin and 12% methylbenzethonium chloride (PR-ointment) was studied. In the infected, untreated control group, the lesion showed progressive necrosis with an increase in the number of parasites, macrophages, lymphocytes, and polymorphonuclear cells over a period of 18 weeks. In the PR ointment-treated group, complete healing of the lesion was observed 4 weeks after termination of treatment, but total elimination of the parasites from the lesion was observed only 2 weeks later. A marked reduction in the number of macrophages and polymorphonuclear cells was observed during the healing process. A similar phenomenon was observed with mice inoculated intraperitoneally with paromomycin alone, although total elimination of the parasites from the lesions of these mice was not demonstrated over a period of 18 weeks. Neither L3T4 helper T cells nor Ly2 cytotoxic suppressor T cells were detected in the CL lesion, either before or after treatment.

Nephrotic syndrome associated with transitional cell carcinoma of the bladder.

We describe the occurrence of a nephrotic syndrome in association with transitional cell carcinoma of the bladder. The proteinuria disappeared several weeks after removal of the tumor. Light and electron microscopy were compatible with a minimal-change lesion, but immunofluorescence showed linear immunoglobulin deposition. Immunoglobulins eluted from the tumor reacted specifically with the kidney and vice versa. We conclude that antibody formation against a specific component of basement membrane common to both kidney and tumor gave rise to the nephropathy in this case.

Cellular immunity and T-lymphocyte subsets in young children with acute measles.

The changes occurring in the T-cell subsets during acute symptomatic measles were examined in ten malnourished and 18 well nourished hospitalized children younger than 5 years of age (median age 14 months). A significant decrease in total lymphocyte count was observed, which was due mainly to a decrease in helper/inducer T lymphocytes, whereas the suppressor/cytotoxic T-lymphocyte subset remained unchanged. Consequently, helper/suppressor ratio decreased significantly during the acute phase of the disease. A reduced response to mitogens (PHA, Con A, PWM) was also observed. Malnourished infants showed a trend toward a deeper depression in both helper and suppressor T cells during the acute phase than well nourished children, whereas the helper/suppressor ratio remained similar in the two groups.

Effect of oral colchicine on T cell subsets, monocytes and concanavalin A-induced suppressor cell function in asthmatic patients.

Asthmatic patients have a deficiency of concanavalin A-(Con A) induced suppressor cell function. We tested whether oral colchicine 0.5 mg twice daily for 7 days could correct this immunoregulatory abnormality. Peripheral blood mononuclear cells were incubated with Con A and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. Sixteen asthmatic patients had significantly (P less than 0.002) decreased Con A-induced suppressor cell function (17.0 +/- 17.2%, mean +/- s.d.) as compared to 13 healthy volunteers (37.9 +/- 14.9%). Oral colchicine significantly (P less than 0.05) increased, though only partially corrected, these 16 asthmatic patients' Con A-induced suppressor cell function (28.1 +/- 14.3%). Asthmatic patients had an increased number of monocytes (691 +/- 289 vs 388 +/- 271/mm3 for normals, P less than 0.01) and a normal number of lymphocytes, Leu 4+ total T cells, Leu 3+ helper/inducer T cells, and Leu 2+ suppressor/cytotoxic T cells as well as a normal Leu 3/Leu 2 ratio. Oral colchicine significantly (P less than 0.005) decreased the number of monocytes (451 +/- 255/mm3) without significantly affecting the number of lymphocytes, Leu 4+, Leu 3+, or Leu 2+ T cells, or the Leu 3/Leu 2 ratio. These results are consistent with the hypothesis that the deficiency of Con A-induced suppressor cell function in asthmatic patients may be due, in part, to an increased number and/or abnormal activity of monocytes. If so, then oral colchicine may have partially corrected the deficiency of Con A-induced suppressor cell function by decreasing the number and/or modulating the activity of monocytes.