Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus: correlation with anemia

OBJECTIVE: To investigate the existence of circulating autoantibodies to erythropoietin (EPO) in sera from patients with systemic lupus erythematosus (SLE), and to correlate their presence with anemia and clinical activity. METHODS: Ninety-two consecutive patients with SLE, 80 patients with rheumatoid arthritis, and 42 normal individuals were studied. The patients with SLE were categorized into 3 groups according to hemoglobin (Hgb) level: group A (45 patients with Hgb > 12 gm/dl), group B (26 patients with Hgb 10.1-12 gm/dl), and group C (21 patients with Hgb < or = 10 gm/dl). In all patients with SLE, the disease activity was evaluated using the European Consensus Lupus Activity Measurement scale. Antibodies to EPO were detected using an enzyme-linked immunosorbent assay and purified recombinant human EPO as antigen. The specificity of the method was evaluated with homologous and cross-reactive inhibition assays. RESULTS: Antibodies to EPO were found in 15.2% of the SLE patient sera. The distribution of these antibodies among the 3 groups of SLE patients was as follows: 8.8% (4 of 45) from group A, 15.4% (4 of 26) from group B, and 28.6% (6 of 21) from group C. The prevalence of antibodies to EPO in patients with severe anemia (group C) was statistically significantly higher compared with patients without anemia (chi(2) = 4.31, P < 0.05). Patients with antibodies to EPO had higher disease activity scores (P < 0.005) and lower levels of the C4 component of complement (P < 0.05) compared with patients without antibodies to EPO. CONCLUSION: In this study, the presence of antibodies to EPO in the sera of SLE patients is demonstrated for the first time. The presence of these antibodies is associated with severe anemia and active disease.     

Adult height and risk of breast cancer among white women in a case-control study

Data from a hospital-based case-control study were analyzed to evaluate the relation of adult height to the risk of breast cancer among white women. The authors compared 5,358 newly diagnosed breast cancer cases and 4,555 controls interviewed from 1976 to 1992 in hospitals located mainly in the United States. Overall, there was no association between stature and risk of breast cancer. In comparison with women whose heights were less than 62 inches (< 158 cm), the adjusted odds ratios were 1.1 (95% confidence interval (Cl) 0.9-1.2), 1.0 (95% Cl 0.9-1.2), 1.0 (95% Cl 0.9-1.1), and 1.0 (95% Cl 0.8-1.2) for women with heights of 62-63, 64-65, 66-67, and > or = 68 inches (equivalent to 158-160, 163-165, 168-170, and > or =173 cm), respectively. There was no consistent evidence of modification of the effect of height by other risk factors. The results suggest that adult stature in white women is not related to the risk of breast cancer.     

Petrosectomies for invasive tumours: surgery and reconstruction

Tumours involving the temporal bone have historically carried a bad prognosis. The only prospect of cure is radical en bloc resection. Temporal bone resection for malignancies is, however, such a formidable undertaking that many centres label such tumours as unresectable. Additionally, the enormity of the surgical defect poses a major reconstructive challenge. A review of 14 petrosectomies (in 12 males and 2 females) performed for extensively invasive neoplasms in and around the ear is presented. All underwent immediate reconstruction, the majority (12/14) with free tissue transfers. 9 of the 14 patients (64%) are still alive after a mean follow-up of 70 months (range 4-8 years). With the use of free tissue transfers, an aggressive approach with regard to the resection margins can safely be adopted in the full knowledge that the eventual size of the defect need not compromise tumour clearance. Additionally, free flaps provided a reliable dural seal. This approach of radical en bloc resection with free flap reconstruction has decreased the mortality (compared to the literature), while largely reducing the morbidity to that of unavoidable cranial nerve resection.     

Excess prevalence of fasting and postmethionine-loading hyperhomocysteinemia in stable renal transplant recipients

Hyperhomocysteinemia, either fasting or after methionine loading, may contribute to the increased incidence of cardiovascular disease events experienced by renal transplant recipients. Limited data are available on fasting homocysteine (Hcy) levels, and none on postmethionine-loading Hcy levels, in these patients. We assessed the prevalence and potential determinants of fasting and postmethionine-loading hyperhomocysteinemia in 29 stable renal transplant recipients and 58 age- and sex-matched, population-based controls free of renal disease with serum creatinine levels of 1.5 mg/dL or less. Total (t) plasma Hcy was determined fasting and 2 hours after methionine loading, along with fasting determinations of the B-vitamin cofactors/substrates for Hcy metabolism, ie, pyridoxal 5'-phosphate, B-12, and folate and serum creatinine. Geometric mean fasting (18.1 versus 9.8 microM, P < .001) and postmethionine-loading increase (22.0 versus 15.2, P = .001) in tHcy levels were significantly greater in the renal transplant recipients, as were the prevalence odds (with 95% confidence intervals) for fasting [14.8 (3.4-64.7)], postmethionine loading [6.9 (1.5-32.8)], combined fasting and postmethionine-loading [18.0 (2.3-142.1)] hyperhomocysteinemia, and inadequate circulating folate [4.2 (1.1-16.5)] or pyridoxal 5'-phosphate [3.2 (0.9-11.0) status. Correlation analyses suggested important potential relationships between creatinine and both fasting (+0.64, P < .001) and postmethionine-load increase (+0.38, P = .045) in tHcy, folate and fasting (-0.41, P = .025) tHcy, and pyridoxal 5'-phosphate and postmethionine-loading increase (-0.33, P = .091) in tHcy. We conclude that there is an excess prevalence of fasting and postmethionine-loading hyperhomocysteinemia in stable renal transplant recipients. Renal function is related to both fasting and postmethionine loading-hyperhomocysteinemia, inadequate folate status is associated with fasting hyperhomocysteinemia, and inadequate vitamin B-6 status may be related to postmethionine-loading hyperhomocysteinemia in this patient population.     

The National Cancer Data Base report on non-Hodgkin's lymphoma

BACKGROUND: The National Cancer Data Base (NCDB) has reported on many malignancies occurring in men and women in the U. S. from >1400 contributing hospitals. The current report on non-Hodgkin's lymphoma (NHL) is a companion to an upcoming Patient Care Evaluation study of this relatively common and serious cancer. METHODS: This report is comprised of all NHL cases submitted to the NCDB divided into two diagnostic-year groups: 1985-1988 and 1990-1993. Variables routinely collected by hospital cancer registries have been analyzed to report on patterns of diagnosis and treatment. RESULTS: High grade NHL cases were more likely to be Stage IV (40.8%) than were low or intermediate grade cases (34.8% and 32.5%, respectively). Patients with NHL arising from lymph node sites tended to present with more advanced disease (55.8% with Stages III and IV disease), whereas patients with NHL arising from extranodal sites and non-lymph node nodal sites presented at an earlier stage (64.7% and 74.0%, respectively, with Stage I or Stage II disease). Approximately 67% of all patients underwent chemotherapy, whereas only 25% underwent surgery or radiation. By histology, 5-year survival was 68.8% for low grade disease, 51.9% for intermediate grade disease, and 45.8% for high grade disease; by stage, survival rates ranged from 73.5% for Stage I to 42.9% for Stage IV disease. CONCLUSIONS: To the authors' knowledge, the 91,306 cases in this study represent the largest contemporary sample of NHL patients. The material reported here may serve as a reference with which to compare local patterns with national data. The Working Formulation's ability to stratify patients' survival rates confirms its utility for NHL. Stage according to the American Joint Committee on Cancer also was accurate in predicting survival.     

Intravenous immunoglobulin prophylaxis in neonates on artificial ventilation

The efficacy of the prophylactic use of intravenous immunoglobulin (Ig) was evaluated in a double-blind placebo-controlled trial of 21 pairs of ventilated neonates weighing more than 1,500 g. Each infant received 0.4 g/kg/day of intravenous Ig or a similar volume of placebo daily for 5 days. Criteria used to assess the efficacy of intravenous Ig were the number of infections, the duration of ventilation therapy and time to clinical recovery. There were no significant differences in the treated and placebo groups with regard to the frequency of positive blood cultures (28.6% and 14.3%), endotracheal cultures (57.1% and 66.7%) and abnormal white cell counts (52.4% and 57.1%). On entry to the study there was no significant difference in IgG levels between the treated (974.5 mg/dl; SD 575.3) and placebo groups (818 mg/dl; SD 516.9). However, on day 6 the treated group had a mean level of 1,400.3 mg/dl (SD 426.7) versus 710.9 mg/dl (SD 377.4) in the placebo group (P < 0.05). Clinical improvement occurred within 3 days in both groups. Ventilatory support was required for 11.8 days (SD 8.3) in the treated and 11.8 days (SD 7.3) in the placebo group. Both groups required 3-4 antibiotic treatments over a period of 14-15 days. Two patients died in the treated and 4 in the placebo group, with 1 infant in each group developing bronchopulmonary dysplasia. The patients who recovered did so within 14 days. Analyses of subgroups of patients with different diagnoses revealed no differences except a trend suggesting fewer infections in term babies treated with intravenous Ig. The organisms cultured in the intravenous Ig groups were Pseudomonas, Klebsiella, Escherichia coli and Staphylococcus and in the placebo group Pseudomonas, Klebsiella and Enterobacter. The above has shown that, except for a trend in the older neonates, intravenous Ig is not of prophylactic benefit in ventilated neonates. Newer adjuncts in immunotherapy such as hyperimmune gammaglobulin or monoclonal antibodies may prove of greater value in the treatment of neonatal sepsis.     

Evaluating multiple alternative hypotheses for the origin of Bilateria: an analysis of 18S rRNA molecular evidence

Six alternative hypotheses for the phylogenetic origin of Bilateria are evaluated by using complete 18S rRNA gene sequences for 52 taxa. These data suggest that there is little support for three of these hypotheses. Bilateria is not likely to be the sister group of Radiata or Ctenophora, nor is it likely that Bilateria gave rise to Cnidaria or Ctenophora. Instead, these data reveal a close relationship between bilaterians, placozoans, and cnidarians. From this, several inferences can be drawn. Morphological features that previously have been identified as synapomorphies of Bilateria and Ctenophora, e.g., mesoderm, more likely evolved independently in each clade. The endomesodermal muscles of bilaterians may be homologous to the endodermal muscles of cnidarians, implying that the original bilaterian mesodermal muscles were myoepithelial. Placozoans should have a gastrulation stage during development. Of the three hypotheses that cannot be falsified with the 18S rRNA data, one is most strongly supported. This hypothesis states that Bilateria and Placozoa share a more recent common ancestor than either does to Cnidaria. If true, the simplicity of placozoan body architecture is secondarily derived from a more complex ancestor. This simplification may have occurred in association with a planula-type larva becoming reproductive before metamorphosis. If this simplification took place during the common history that placozoans share with bilaterians, then placozoan genes that contain a homeobox, such as Trox2, should be explored, for they may include the gene or genes most closely related to Hox genes of bilaterians.