Hypocomplementemia with low Cls-Cl inhibitor complex in systemic lupus erythematosus

Ninety-three serum and plasma samples from 45 patients with systemic lupus erythematosus were analyzed for the complex formed by Cls and its inhibitor, as well as for C3, C4, C4a desarginine, and staphylococcal protein A-bound immune complexes. There were statistically significant correlations between Cls-Cl inhibitor complex and CH50, between Cls-Cl inhibitor complex and C4, and between Cls-Cl inhibitor complex and C4a desarginine. Serial studies were performed on 24 patients over a period of 6 months. Seven of 21 patients with hypocomplementemia had persistently normal levels of Cls-Cl inhibitor complex, 7 had transiently abnormal levels of Cls-Cl inhibitor complex, and 7 had sustained abnormal levels of Cls-Cl inhibitor complex. Two of 3 pregnant patients with normal levels of complement had abnormal levels of Cls-Cl inhibitor complex. Staphylococcal protein A-bound immune complexes demonstrated no correlation with any of the complement assays. Complement activation, as measured by Cls-Cl inhibitor complex, is often a transient phenomenon in systemic lupus erythematosus patients with persistent hypocomplementemia.     

The physiological regulation of toll-like receptor expression and function in humans

Eleven mammalian toll-like receptors (TLRs 1–11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14⁺ monocytes following activation with specific TLR ligands was greater ( P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34°C). Strenuous exercise resulted in a decrease ( P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14⁺ monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14⁺ monocytes following activation with specific TLR ligands was decreased ( P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.     

Abnormal hematological indices in cirrhosis

Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis.     

Prednisone does not prevent recurrent fetal death in women with antiphospholipid antibody

Effects of therapy, antibody titer, and pregnancy history on pregnancy outcome were evaluated in pregnancies of women with antiphospholipid antibody. Prior fetal death and a high antiphospholipid antibody titer (greater than 40 IgG phospholipid units) contributed independently, in an additive manner, to current fetal loss. Twenty-one pregnancies occurred in asymptomatic women who had both prior fetal death and a high IgG antiphospholipid antibody titer. In this very high-risk group, 9 of 11 (82%) of pregnancies treated with prednisone, 10 to 60 mg/day, ended in fetal death, compared with 5 of 10 (50%) not treated with prednisone (p approximately 0.01, life-table analysis). Of pregnancies treated with aspirin, 80 mg/day, 9 of 14 (64%) treated and 5 of 7 (71%) not treated with prednisone had a fetal death (difference not significant). Prednisone does not improve, and may worsen, current fetal outcome in asymptomatic pregnant women with a high antiphospholipid antibody titer and prior fetal death.     

A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension.

In a crossover design, control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension. Compliance with once daily felodipine was higher than with nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine, at 77.6 (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age) was lower for felodipine than for nifedipine: 43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though this did not reach statistical significance. These data suggest that once a day felodipine is effective in children with hypertension. This may be because of improved compliance.     

A retrospective analysis of long-term survival in severe aplastic anemia patients treated with allogeneic bone marrow transplantation or immunosuppressive therapy with antithymocyte globulin and cyclosporin A at a single institution

Severe aplastic anemia can be treated with either bone marrow transplantation (BMT) or immunosuppressive therapy (IST). A retrospective review of patients with severe aplastic anemia treated with both of these modalities was conducted. Fifteen BMT and 16 IST patients were available for analysis, and follow-up of 22 and 15 years was available for the BMT and IST groups, respectively. Median survival was limited to 4.3 months in BMT patients vs. 135.2 months in IST patients, despite the older median age of the latter (22 vs. 55 years). Actuarial survival at 1 and 5 years was 87% and 78% for the IST patients and 40% and 33% for the BMT patients. Hematologic response rates, as defined by achievement of transfusion independence, were similar for the two groups. Long-term responses and survival are possible with antithymocyte globulin/cyclosporin A.     

Mutational analysis of 9 different tumour-associated genes in human malignant mesothelioma cell lines

Seven tumour suppressor genes (Chk1, Chk2, Apaf1, Rb1, p53, p16(INK4a) and p14(ARF)) and two oncogenes (N-ras and BRAF) were screened in nine human malignant melanoma (HMM) cell lines for point mutations or small deletions/insertions by DGGE, TGGE and SCCP analysis. For the first time in human mesothelioma, Chk1 gene mutations were detected in two of the nine investigated HMM cell lines. P53 gene mutations were found in three cell lines and p16(INK4a) mutations in 5. Mutation of the Chk1 gene implies a novel disruption mechanism of the p53 pathway in HMM, without affecting p53 itself. According to our knowledge, this is the first mutation screening of Chk1, Chk2, Apaf1 and Rb1 in human malignant mesothelioma.     

Primary lymphedema tarda in an 88-year-old African-American male

Primary lymphedema tarda is considered to be a congenital disease with delayed manifestations. We report a case of isolated lymphedema of the left upper extremity in an 88-year-old African-American male. The diagnosis of lymphedema was confirmed by lymphoscintigraphy, and appropriate diagnostic studies were done to rule out other known causes of lymphedema. Lymphoscintigraphic findings were consistent with idiopathic primary lymphedema. During the course of investigations, the patient was found to have adenocarcinoma in situ of the sigmoid colon with no evidence of metastatic spread. Based on the available data, we were unable to establish a causative relationship between colonic carcinoma and lymphedema in our patient. Therefore, this case can best be described as a case of Idiopathic primary lymphedema tarda. We emphasize the use of histopathologic examination in the diagnostic algorithm to rule out underlying malignant process only in patients with radionuclide findings suggestive of secondary lymphedema with no obvious etiology.