Evidence for a bimodal relation between serum lysozyme and prognosis in 232 patients with acute myeloid leukaemia

Lysozyme values are sometimes used as an aid for diagnostic subtyping of acute myeloid leukaemia (AML), since monocytic forms often show high levels. We wanted to study if pretreatment serum lysozyme has any relation to prognosis in AML. For this purpose, 232 adult AML patients who had received remission induction therapy at two hospitals were reviewed retrospectively. Their median age was 65.5 yr. Sixty-three patients were FAB classified as "monocytic" AML (M4, M5) and 169 as "non-monocytic" AML (M0, M1, M2, M3, M6). A linear relation was rejected, and a bimodal relation was found between lysozyme and prognosis where values below 20 or above 80 mg L-1 were indicative of better outcome than values in the range 20-80 mg L-1. Analysed in three categories with cut-off levels at 20 and 80 mg L-1, lysozyme showed an independent effect on complete remission (CR) frequency (P = 0.0003), overall survival (P < 0.0001), and CR duration (P = 0.0005) in multivariate analysis. The hazard ratios (HR) for lysozyme <20, 20-80, and >80 mg L-1 regarding overall survival were 1.0, 3.3, and 0.7. Influence of lysozyme on survival was bimodal both in "non-monocytic" AML (HR 1.0, 3.0, and 0.1) and M4-M5 (HR 1.0, 10.1, and 1.2). Our finding of a bimodal relation between serum lysozyme and prognosis in AML should be regarded as a new hypothesis and controlled in other studies.     

Response to methimazole in Graves' disease

OBJECTIVE A variety of regimens continue to be used In the treatment of Graves' disease with antithyrold drugs. We have lnvestigated the factors which determine the initial response to methimazole (time until euthyroidism Is achieved) In Graves' disease. PATIENTS Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months. MEASUREMENTS Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary Iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, Index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase. RESULTS Within 3 weeks, 40.2% of patients responded to 10mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroldism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), Index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed In patients with large goitres, iodine excretion of ≧ 100μg/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyrold within 3 weeks when urinary Iodide was <50μg/g of creatinine, and only 27% when iodide was above 100μg/g. By stepwise logistic regression, the main factors for the response to methimazole were dally dose, pretreatment T3 levels, and goitre size. CONCLUSION Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole In Graves' disease, at least In areas comprising low, subnormal and normal iodine supply.     

Gammalinolenic acid treatment of fatigue associated with primary Sjögren's syndrome

OBJECTIVE: To evaluate the efficacy of the essential omega-6 fatty acid Gammalinolenic acid (GLA) on fatigue associated with primary Sj?gren's syndrome. METHODS: Ninety patients with primary Sj?gren's syndrome (with or without signs of autoimmunity) entered a 6-month double blind placebo-controlled randomised trial with high dose GLA (extracted from Evening Primrose Oil) or corn oil. The primary outcome parameter was fatigue; secondary endpoints were eye dryness, mouth dryness, muscle and joint pain. RESULTS: No statistically significant improvement was found in fatigue assessed by Visual Analogue Scale (VAS) or in the time needed for sleeping/resting during a 24-hour period. No differences were found between the treatment and placebo group. The same applies to the secondary endpoints: no differences in VAS for eye and mouth dryness or pain, no significant changes in Schirmer-1-test, van Bijsterveld score, unstimulated whole sialometry (UWS), or use of artificial tears or analgesics. Only mild side effects were observed. CONCLUSION: According to our study results GLA (Evening Primrose oil) treatment for fatigue in primary Sj?gren's syndrome is ineffective.     

Surgical treatment of cytomegalovirus enterocolitis in severe human immunodeficiency virus infection

PURPOSE: The aim of this study was to describe our experiences of surgical removal of inflamed bowel in cytomegalovirus enterocolitis. METHODS: Eight homosexual males with a mean age of 41 years (range, 29–59 years) and a mean CD4 count of 21×10 ⁶/1 (1–60× 10⁶/1)with advanced human immunodeficiency virus infection and severe cytomegalovirus enterocolitis were treated with ileocecal resection (4 patients) or right-sided hemicolectomy (4 patients). Symptoms were lower abdominal pain, severe diarrhea, fever, and weight loss, unrelieved by anticytomegalovirus therapy. Radiologic examination showed that ulcerative inflammation was limited to the right colon and terminal ileum. Microscopic examination confirmed the cytomegalovirus enterocolitis. Intermittent cytomegalovirus treatment, usually with foscarnet for 10 to 14 days every 4 to 6 weeks was given postoperatively. RESULTS: Two minor postoperative complications occurred: a lesser wound infection and a moderate bleeding from the abdominal wound edges. One patient died after three weeks because of gastrointestinal bleeding from an ulcerating Kaposi's sarcoma lesion and another patient died from unrelated causes three weeks after discharge from the hospital. The remaining 6 patients experienced complete or partial palliation of the abdominal symptoms for a mean of 14 months (range, 5–35 months) until death or the end of observation time. One patient is still alive two years after the operation. The overall mean survival was 12 months (range, 0.5–35 months). Recurrent or persistent symptoms and/or signs of cytomegalovirus enterocolitis occurred in four patients after a mean of seven months. CONCLUSION: Resection of inflamed bowel combined with postoperative anticytomegalovirus treatment leads to excellent palliation and a relatively favorable survival in AIDS patients with cytomegalovirus enterocolitis.     

Influence of oxygen on perfused capillary density and capillary red cell velocity in rabbit skeletal muscle

The pattern of capillary blood flow changes was investigated in rabbit tenuissimus muscle as a function of oxygen tension in the solution suffusing the muscle. The density of perfused capillaries decreased from 269 ± 22 (mean ± SD) to 6 ± 10 cap/mm² when ambient pO₂ was elevated progressively from 5 to 100 mm Hg. In the same pO₂ range capillary red cell velocity decreased from 0.29 ± 0.14 (mean ± SD) to 0.18 ± 0.06 mm/sec in the capillaries which were perfused. During exposure of the muscle to atmospheric oxygen tension (pO₂ = 150 mm Hg) there were no capillaries perfused and hence flow velocity was zero in all capillaries. The results demonstrate that oxygen influences capillary blood flow over an extensive range of oxygen tensions. The anatomical structures responsible for the alterations in both capillary density and capillary flow velocity are the arterioles. This site of control determines actively the total blood flow through the capillary bed, whereas passive factors seem to determine the distribution of the flow between specific capillaries. The results do not support the existence of precapillary sphincters controlling perfused capillary density.     

Stage-specific regulation of adhesion molecule expression segregates epithelial stem/progenitor cells in fetal and adult human livers

Purpose Regulated expression of cell adhesion molecules could be critical in the proliferation, sequestration, and maintenance of stem/progenitor cells. Therefore, we determined fetal and adult stage-specific roles of cell adhesion in liver cell compartments. Methods We performed immunostaining for the adhesion molecules, E-cadherin and Ep-CAM, associated proteins, β-catenin and α-actinin, hepatobiliary markers, albumin, α-fetoprotein, and cytokeratin-19, and the proliferation marker, Ki-67. Expression of albumin was verified by in situ mRNA hybridization. Results In the fetal liver, hepatoblasts showed extensive proliferation with wide expression of E-cadherin, β-catenin, and α-actinin, although Ep-CAM was expressed in these cells less intensely and focally in the cell membrane to indicate weak cell adhesion. Hepatoblasts in ductal plate and bile ducts showed less proliferation and Ep-CAM was intensely expressed in these cells throughout the cell membrane, indicating strong adhesion. In some ductal plate cells, β-catenin was additionally in the cytoplasm and nucleus, suggesting active cell signaling by adhesion molecules. In adult livers, cells were no longer proliferating and E-cadherin, β-catenin, and α-actinin were expressed in hepatocytes throughout, whereas Ep-CAM was expressed in only bile duct cells. Some cells in ductal structures of the adult liver with Ep-CAM coexpressed albumin and cytokeratin-19, indicating persistence of fetal-like stem/progenitor cells. Conclusions Regulated expression of Ep-CAM supported proliferation in fetal hepatoblasts through weak adhesion and helped in biliary morphogenesis by promoting stronger adhesion in hepatoblasts during this process. Restriction of Ep-CAM expression to bile ducts in the adult liver presumably facilitated sequestration of stem/progenitor cells. This stage-specific and cell compartment-related regulation of adhesion molecules should be relevant for defining how liver stem/progenitor cells enter, exit, and remain in hepatic niches during both health and disease.     

Tuberculosis Risk in Ankylosing Spondylitis,Other Spondyloarthritis,and Psoriatic Arthritis in Sweden: A Population‐Based Cohort Study

Objective

Rheumatoid arthritis is a risk factor for tuberculosis (TB), particularly following treatment with biologic agents. Since these therapies are increasingly used in ankylosing spondylitis (AS), other types of spondyloarthritis (SpA), and psoriatic arthritis (PsA), we investigated the corresponding TB risks in these patients.

Methods

We identified individuals with AS/SpA/PsA, and non‐AS/SpA/PsA comparators by linking Swedish national patient, population, TB, and rheumatology registers, and followed them for TB occurrence. Incidence rates were estimated for biologic‐naive and biologic‐exposed patients and the comparators. We calculated hazard ratios (HRs), adjusted for age, sex, and country of birth.

Results

Included in this study were 38,702 patients with AS/SpA/PsA, and 200,417 persons from the general population. Among the patients, 11 active TB cases were identified, with an incidence rate (per 10⁵) of 22 (95% confidence interval [95% CI] 8.3–59.2) for biologic‐exposed patients, 2.7 (95% CI 1.3–5.6) for biologic‐naive patients, and 2.4 (95% CI 1.8–3.3) for non‐AS/SpA/PsA comparators. The adjusted HR comparing biologic‐naive patients to the general population was 1.2 (95% CI 0.5–2.7), and 7.5 (95% CI 1.9–29) comparing biologic‐exposed to biologic‐naive patients.

Conclusion

Biologic‐naive AS/SpA/PsA patients are not at an increased TB risk in Sweden. Following treatment with biologic agents, the risk increased, but the absolute TB risk was low.

     

Protein Electrophoretic Profiles and the Origin of the B Genome of Wheat

Protein electrophoretic profiles cast doubt upon the prevalent theory that the B genome of the polyploid wheats was derived from a species of Aegilops. They suggest, instead, that the wild tetraploid wheats comprise a complex, whose components were derived from various combinations of diploid Triticum types, which evidently include the B-genome type.     

B-type natriuretic peptide and its precursor in cardiac venous blood from failing hearts

BACKGROUND: Plasma concentrations of B-type natriuretic peptide (BNP-32) and its precursor (proBNP) are increased in chronic heart failure. Accordingly, BNP-32 and proBNP are both being implemented as clinical markers. AIM: To determine the molar relation of BNP-32 and proBNP in different cardiovascular regions. METHODS AND RESULTS: Blood samples were obtained from different cardiovascular regions during right heart catheterization in heart failure patients, and from normal subjects. Plasma BNP-32 and proBNP concentrations were measured using sequence-specific radioimmunoassays. Patients with severe left ventricular dysfunction (n=21) displayed increased peripheral plasma concentrations of both BNP-32 (four-fold, P=0.0008) and proBNP (seven-fold, P=0.0002) compared with normal subjects. Moreover, the peripheral concentrations were highly correlated with the corresponding concentrations in the coronary sinus (BNP-32: r=0.97, P<0.0001; proBNP: r=0.94, P<0.0001). Despite comparable peripheral concentrations of BNP-32 and proBNP, the BNP-32 concentration was higher than the proBNP concentration in the coronary sinus (median 126 pmol/l (21-993) vs. 103 pmol/l (16-691), P=0.035). CONCLUSIONS: The BNP-32 and proBNP concentrations are closely related in venous cardiac blood. The findings suggest an overall constitutive secretion of processed proBNP, i.e. an N-terminal precursor fragment and BNP-32, in chronic heart failure.     

Synthesis of Complementary RNA Sequences During Productive Adenovirus Infection

Liquid RNA.DNA hybridization with separated strands of adenovirus type 2 DNA revealed that late nuclear RNA can hybridize to about 85% of the 1-strand and 10-15% of the h-strand, whereas late cytoplasmic RNA hybridizes to 65-70% and 25% of the l- and h-strand, respectively. With separated strands from the six EcoRI fragments of adenovirus type 2 DNA as probes, it was shown that late nuclear RNA hydridizes to 85-90% of the l-strand from all six EcoRI fragments. Since late cytoplasmic RNA hybridizes to 40-50% of the h-strand from both fragments EcoRI-B and EcoRI-C, complementary viral RNA sequences are synthesized during adenovirus infection. Complementarity between nuclear and cytoplasmic RNA could also be demonstrated by showing that late cytoplasmic RNA which had been preincubated with late nuclear RNA hybridized to a smaller fraction of the h-strand of fragment EcoRI-C than without preincubation. Double-stranded RNA which contains sequences that correspond to at least 60% of the viral genome was isolated from infected cells. However, less than 2% of the newly synthesized late RNA became double-stranded after incubation under annealing conditions, which suggests that RNA derived from one of the strands is present at a low concentration. Accordingly, it was shown that nearly all viral cytoplasmic RNA which is synthesized late after infection is derived from the l-strand.