Malignancies, prothrombotic mutations, and the risk of venous thrombosis

Context  Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. Objective  To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. Design, Setting, and Patients  A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations. Main Outcome Measure  Risk of venous thrombosis. Results  The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer. Conclusions  Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.      

Simultaneous measurement of 25 inflammatory markers and neurotrophins in neonatal dried blood spots by immunoassay with xMAP technology

BACKGROUND: Inflammatory reactions and other events in early life may be part of the etiology of late-onset diseases, including cerebral palsy, autism, and type 1 diabetes. Most neonatal screening programs for congenital disorders are based on analysis of dried blood spot samples (DBSS), and stored residual DBSS constitute a valuable resource for research into the etiology of these diseases. The small amount of blood available, however, limits the number of analytes that can be determined by traditional immunoassay methodologies. METHODS: We used new multiplexed sandwich immunoassays based on flowmetric Luminex xMAP technology to measure inflammatory markers and neutrophins in DBSS. RESULTS: The high-capacity 25-plex multianalyte method measured 23 inflammatory and trophic cytokines, triggering receptor expressed on myeloid cells-1 (TREM-1), and C-reactive protein in two 3.2-mm punches from DBSS. It also measured 26 cytokines and TREM-1 in serum. Standards Recovery in the 25-plex method were 90%-161% (mean, 105%). The low end of the working range for all 25 analytes covered concentrations found in DBSS from healthy newborns. Mean recovery of exogenous analytes added at physiologic concentrations in DBSS models was 174%, mean intra- and interassay CVs were 6.2% and 16%, respectively, and the mean correlation between added and measured analytes was r2 = 0.91. In DBSS routinely collected on days 5-7 from 8 newborns with documented inflammatory reactions at birth, the method detected significantly changed concentrations of inflammatory cytokines. Measurements on DBSS stored at -24 degrees C for >20 years showed that most cytokines are detectable in equal concentrations over time. CONCLUSIONS: The method can reliably measure 25 inflammatory markers and growth factors in DBSS. It has a large potential for high-capacity analysis of DBSS in epidemiologic case-control studies and, with further refinements, in neonatal screening.     

Medical treatment of ventricular tachycardia: Considerations in the selection of patients for surgical treatment

The decision of when and how to treat ventricular tachycardia is primarily determined by the type and severity of concomitant heart disease. After the ventricular origin of the tachycardia is established, extensive investigation into this problem is mandatory. Long-term medical treatment in patients with ventricular tachycardia in the setting of coronary artery disease is unsatisfactory. Although drug selection with the use of programmed cardiac stimulation seems logical and promising, the long-term value of this method remains to be demonstrated. The extensive myocardial damage present in most patients with coronary artery disease and ventricular tachycardia makes it unlikely that drug therapy will be the ultimate answer. These considerations justify careful evaluation of the long-term efficacy of surgical therapy of symptomatic ventricular tachycardia, especially in patients with arrhythmia in the subacute or chronic phase of myocardial infarction.     

Differential diagnosis of low-attenuation splenic lesions on computed tomography

A retrospective computed tomography evaluation of proved low-attenuation splenic lesions in nontraumatic cases was done. Computed tomography was able to distinguish cystic from solid lesions. Although computed tomography examination is sensitive in the detection of low-attenuation lesions, the computed tomography findings alone are not helpful in differentiation of different low-attenuation lesions. Associated computed tomography findings in other organs and clinical findings are more helpful than the size, shape, and computed tomography attenuation of the lesions. Splenic lesions may be the only metastatic manifestation in some cancer patients. A thin needle aspiration may be done to document the nature of the pathologic lesion in problematic cases.     

Magnetic resonance imaging of discrete and conglomerate retroperitoneal lymph node masses

In the identification of discrete and conglomerate retroperitoneal lymph node masses, MRI and CT performed equally well. No specific MRI characteristics were identified.     

P-100 in the treatment of Ménière's disease: a clinical study

Patients suffering from Ménière's disease are particularly sensitive to negative pressure in the middle ear. For example, attacks of vertigo can be triggered by a descent in an aircraft when ventilation of the middle ear can become critical. Positive-pressure pulse treatment has been shown to have a beneficial effect on the symptomatology and is now a true alternative in the treatment of Ménière's disease. In this study, we compared two devices that produced positive-pressure pulses delivered to the inner ear via the external ear canal and after the insertion of a middle-ear ventilation tube. Both devices (Meniett and P-100) were equally successful and confirmed that positive-pressure pulse treatment is a true alternative to current treatment modalities. However, the P-100 is the preferred device, particularly for its convenience of use and its cost, which is considerably lower.     

Short-term exogenous galactose supplementation does not influence rate of appearance of galactose in patients with classical galactosemia

INTRODUCTION: Recently, evidence has been presented that adult patients with classical galactosemia have higher than expected galactose tolerance. This may be caused by a decrease of endogenous galactose production with ageing. Alternatively, suppression of endogenous galactose production by exogenous galactose might be implicated. The aim of this study was to determine if the rate of appearance of galactose is suppressed by exogenous galactose. MATERIALS AND METHODS: Two adult patients with classical galactosemia and three healthy control subjects were given a primed continuous infusion of D-[1-13C]galactose to determine the rate of appearance of galactose (GAR, expressed as micromol/kg/h) before and during additional galactose supplementation. After initial assessment of GAR (GAR1), GAR was determined during doubled (GAR2) or quadrupled (GAR4) galactose infusion. RESULTS: GAR1 was 2.48 and 2.44 in patients 1 and 2, and 0.46, 0.34, and 0.39 in control subjects 1, 2, and 3, respectively. GAR(2) was 2.43 and 2.13 in patients 1 and 2, and 0.57, 0.38, and 0.47 in control subjects 1, 2, and 3, respectively. In patient 1 the experiment was repeated during quadrupled galactose infusion. Here GAR1 was 3.01 and GAR4 was 3.26. CONCLUSIONS: No significant differences between GAR before and during additional galactose infusion were found in patients and in control subjects. GAR1 was significantly higher in patients than in control subjects. We conclude that the rate of appearance of galactose is not influenced by exogenous galactose, at least under short-term conditions, in patients with classical galactosemia and in control subjects.