Summary YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three hundred and forty patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B, 19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted for age). Analysis of serum YKL-40 as a continuous variable showed an association between increased serum YKL-40 and short survival (P < 0.0001). Patients with high preoperative serum YKL-40 concentration had significantly shorter survival than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3-2.1, P < 0.0001). Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age and gender showed that high YKL-40 was an independent prognostic variable for short survival (HR = 1.4; 95% CI: 1.1-1.8, P = 0.007). These results suggest that YKL-40 may play an important role in tumour invasion.Keywords: carcinoembryonic antigen; colorectal cancer; metastasis; tumour invasiveness; YKL-40/HC gp-39 1494British Journal of Cancer (1999) 79(9/10), 1494-1499 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received 20 May 1998 Revised 30 September 1998 Accepted 14 October 1998Correspondence to: HJ Nielsen *YKL-40 has been named after its molecular weight (40 kDa) and the one letter code for its three N-terminal amino acids (Johansen et al, 1992). The protein is also called human cartilage glycoprotein-39 (HC gp-39) (Hakala et al, 1993).
Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with unknown aetiology. Even though ASDs are suggested to be among the most heritable complex disorders, only a few reproducible mutations leading to susceptibility for ASD have been identified. In an attempt to identify ASD susceptibility genes through chromosome rearrangements, we investigated a female patient with childhood autism and high-grade myopia, and an apparently balanced de novo translocation, t(5;18)(q34;q12.2). Further analyses revealed a 3.2 Mb deletion encompassing 17 genes at the 18q break point and an additional deletion of 1.27 Mb containing two genes on chromosome 4q35. Q-PCR analysis of 14 of the 17 genes deleted on chromosome 18 showed that 11 of these genes were expressed in the brain, suggesting that haploinsufficiency of one or more genes may have contributed to the childhood autism phenotype of the patient. Identification of multiple genetic changes in this patient with childhood autism agrees with the most frequently suggested genetic model of ASDs as complex, polygenic disorders.
Objective The purpose of the present study was to compare the dosage requirements of recombinant human erythropoietin (rHuEPO) administered subcutaneously (SC) either one or three times weekly. Design A randomized, prospective study. .Setting: The patients were recruited from two university hospitals and five county hospitals. Patients Thirty-three anemic patients on continuous ambulatory peritoneal dialysis (CAPD) treatment for endstage renal failure completed the study. Interventions Initially, all were treated with rHuEPOSC three times a week until hemoglobin blood levels (Hb) remained constant between 105 and 121 g/L for three months. Following randomization, 17 patients continued the same treatment schedule (group A), while 16 patients received the same dose, but administered only once weekly for three months (group B). Main Outcome Measures The Hb levels and rHuEPO doses at the start and at the end of the three-month study period. Results In group A the median Hb at randomization was 118 g/L (109 -119) (25 -75 percentiles) and, after three months, was 113 g/L (106 -119) (p = 0.13), while in group B the median Hb was 114g/L (108–119) and 114 g/L (106 -120), respectively (p = 0.50). In group A the weekly dose of rHuEPO remained virtually unchanged during the study period, 65 (55 -86) and 66.3 (55 -95) U/kg/week, respectively, while in group B it was increased from 60.2 (46–88) to 77 (60 90) U/kg/week. The 22% increase (p = 0.03) took place during the last two weeks. Conclusions Our findings indicate that a once-weekly SC dosing regimen of rHuEPO in anemic CAPD patients was equally effective in maintaining a stable hemoglobin level as a thrice-weekly dosing regimen.
Advanced renal failure is often accompanied by secondary and tertiary hyperparathyroidism. In tertiary hyperparathyroidism it is necessary to reduce the gland mass. The present study describes the response to treatment with percutanous injection of ethanol of enlarged parathyroid nodules in 9 uremic patients. All had hypercalcemia, severely elevated serum levels of parathyroid hormone and ultrasonically detectable enlarged parathyroid glands. Three patients did not respond to the treatment. In the remaining 6 patients, serum values of total and ionized calcium were normalized and the serum values of parathyroid hormone were reduced at least 30% after 18 months. Seven of the patients experienced an improvement of symptoms. No complications were seen. We conclude that treatment with ethanol injection can be used as an alternative to conventional parathyroidectomy to improve parathyroid status in selected patients.
Summary:In a double-blind, placebo-controlled study, 273 patients with suspected acute myocardial infarction (AMI) were randomized to receive either 48-h magnesium (Mg) or placebo therapy intravenously, initiated immediately on admission to hospital. We describe the results from a 1-year survey in 270 of the patients, who were available for follow-up. Patients were equally divided: 135 received Mg and 135 received placebo. Mg treatment was associated with a marked reduction in 1-year death rate from 32% in the placebo group to 20% in the Mg group (p=O.O18). If only death from ischemic heart disease is considered, the figures were 28% in the placebo group as opposed to 15% in the Mg group (p=0.006). This reduction was mainly due to a reduction in mortality during the initial 30 days after inclusion in the study (17% vs. 7%), after which the difference in mortality between the two groups did not reach statistical significance (1 8 % vs. 15%, p=0.56). The beneficial effect of Mg on mortality was partly linked to a reduced incidence of arrhythmias (27% vs. 16%), and partly to a reduced incidence of infarction (63% vs. 48%) during the initial hospitalization. However, factors unknown to us were also involved, as revealed by a remaining statistically significant partial regression coefficient, when sex, age, cardiovascular history, development of AMI, and development of arrhythmias were considered. It is concluded that intravenous Mg treatment is beneficial to patients with acute ischemic heart disease and should be adopted as part of the routine treatment of these patients.
Summary: To evaluate the effect of intravenous magnesium (Mg) treatment on the inotropic state of the heart and maximal work capacity, 9 healthy volunteers were entered in a double-blind, placebo-controlled, cross-over study. Separated by an interval of three weeks, the volunteers were tested twice, each time randomly allocated to receive either an intravenous injection of 10 mmol magnesium chloride dissolved in 100 ml isotonic sodium chloride or placebo of isotonic sodium chloride only. Before and after each infusion myocardial inotropism was evaluated by echocardiography . Mitral-septal distance (MSA) was used as a measure for ejection fraction. On each test day an ergometer bicycle exercise test was performed, and maximal work capacity was calculated. Magnesium treatment reduced the MSA (from 4.2 to 2.9 mm, p=0.07), while no difference was found after placebo treatment. Likewise, a tendency toward increasing fractional shortening after magnesium treatment was detected, although this difference was not statistically significant (p=O.l). No difference in maximal work capacity between the magnesium and placebo periods was found. Serum magnesium concentrations rose significantly after the infusions (from 0.82 to 1.38 mmol/l, p
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