Genetic analysis of de novo CD5+ diffuse large B-cell lymphomas suggests an origin from a somatically mutated CD5+ progenitor B cell

CD5(+) diffuse large B-cell lymphomas (DLBLs) have recently been described as a particular subgroup of DLBLs. Classical banding and interphase cytogenetic analyses targeting ATM, TP53, and P16(INK4a) genes and the D13S25 locus from 13 CD5(+) DLBLs were compared with 55 CD5(-) DLBLs. Additionally, analysis of somatic mutations of the immunoglobulin heavy chain variable region (IgVH) genes were performed in CD5(+) DLBLs. CD5(+) DLBLs were somatically mutated (7 of 8 cases) and were negative for t(11;14)(q13;q32) and t(14;18)(q32;q21), whereas t(3;14)(q27;q32) was found in only one tumor. Trisomy 3 and gains on chromosomes 16/16p and 18/18q were significantly overrepresented in CD5(+) DLBLs. No ATM deletions were detected. The prevalence of deletions at the D13S25 locus was significantly higher in CD5(+) DLBLs (4 of 12 [33%]) compared with CD5(-) DLBLs (4 of 42 [10%]), as were p16(INK4a) deletions (33% versus 8%). On the basis of these findings, CD5(+) DLBLs are likely to arise from the same progenitor cell as the mutated variant of CD5(+) lymphocytic lymphoma/B-cell chronic lymphocytic leukemia (B-CLL).     

Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy

BACKGROUND: It is unclear what anticopper drug to use for patients with Wilson disease who present with neurologic manifestations because penicillamine often makes them neurologically worse and zinc is slow acting. OBJECTIVE: To evaluate the frequency of neurologic worsening and drug adverse effects with ammonium tetrathiomolybdate. DESIGN: Open-label study of 55 untreated patients (22 of them new) presenting with neurologic Wilson disease treated with tetrathiomolybdate varying from 120 to 410 mg/d for 8 weeks and then followed up for 3 years. Neurologic function was assessed with scored neurologic and speech tests. SETTING: A university hospital referral setting. PATIENTS: All untreated, newly diagnosed patients with neurologic Wilson disease. INTERVENTION: Treatment with tetrathiomolybdate. MAIN OUTCOME MEASURES: Neurologic function was evaluated by neurologic and speech examinations. Drug adverse effects were evaluated by complete blood cell counts and biochemical measures. RESULTS: Only 2 (4%) of 55 patients treated with tetrathiomolybdate showed neurologic deterioration, compared with an estimated 50% of penicillamine-treated patients. Five of the 22 new patients exhibited bone marrow suppression and 3 had aminotransferase elevations. These numbers are higher than in the original 33 patients and appear to be due primarily to a more rapid dose escalation. CONCLUSIONS: Tetrathiomolybdate shows excellent efficacy in patients with Wilson disease who present with neurologic manifestations. With rapid escalation of dose, adverse effects from bone marrow suppression or aminotransferase elevations can occur.     

Alzheimer disease in the US population: prevalence estimates using the 2000 census

CONTEXT: Current and future estimates of Alzheimer disease (AD) are essential for public health planning. OBJECTIVE: To provide prevalence estimates of AD for the US population from 2000 through 2050. DESIGN: Alzheimer disease incidence estimates from a population-based, biracial, urban study, using a stratified random sampling design, were converted to prevalence estimates and applied to US Census Bureau estimates of US population growth. SETTING: A geographically defined community of 3 adjacent neighborhoods in Chicago, Ill, applied to the US population. PARTICIPANTS: Alzheimer disease incidence was measured in 3838 persons free of AD at baseline; 835 persons were evaluated for disease incidence.Main Outcome Measure Current and future estimates of prevalence of clinically diagnosed AD in the US population. RESULTS: In 2000, there were 4.5 million persons with AD in the US population. By 2050, this number will increase by almost 3-fold, to 13.2 million. Owing to the rapid growth of the oldest age groups of the US population, the number who are 85 years and older will more than quadruple to 8.0 million. The number who are 75 to 84 years old will double to 4.8 million, while the number who are 65 to 74 years old will remain fairly constant at 0.3 to 0.5 million. CONCLUSION: The number of persons with AD in the US population will continue to increase unless new discoveries facilitate prevention of the disease.     

Effects of valproic acid,carbamazepine, and phenobarbitone on the fatty acid composition of erythrocyte membranes in children

PURPOSE: To investigate a possible relation between antiepileptic drugs (AEDs) and the fatty acid composition of membranes. METHODS: Fatty acid (FA) composition of erythrocytes was studied in children with epilepsy receiving AED monotherapy. Children taking valproate (VPA, n = 28), carbamazepine (CBZ, n = 17), or phenobarbitone (PB, n = 14) were compared with healthy controls (n = 25). FAs were measured by capillary-gas chromatography (GC-FID). RESULTS: Significant changes (p < 0.05) in the FA composition of membranes were found. In children treated with VPA, C13:0 was decreased (8.2 +/- 2% vs. 10.7 +/- 4% in controls) and C14:0 increased (1.4 +/- 0.5% vs.1 +/- 0.5% in controls). C17:0 again was reduced (9.9 +/- 4% vs. 13.2 +/- 6% in controls), whereas the long-chained acids were enhanced: C18:2n-6 (6 +/- 2.4% vs. 3.9 +/- 2.5% in controls), and C20:4n-6 (1.9 +/- 1.7% vs. 1.4 +/- 0.5% in controls). The nonidentified FAs also increased with VPA therapy: 2.5 +/- 0.8% versus 1.7 +/- 0.9% in controls. Children treated with CBZ showed only minimal changes of FA composition: C13:0 was decreased compared with controls (8 +/- 2% vs. 10.7 +/- 4%). No changes were seen in patients taking PB. The mean corpuscular volume (MCV) showed important differences between the study groups: MCV was 84.7 +/- 6.0 fl during VPA therapy (p < 0.001) and 85.7 +/- 4.1 fl with CBZ (p < 0.001). During PB, the MCV increased to 82.87 +/- 3.29 fl compared with controls (78.73 +/- 4.92 fl; p < 0.01). CONCLUSIONS: VPA therapy is associated with changes of the FA composition of membranes, which is not the case with PB therapy. The implications of this finding remain to be established.     

Medical care of injuries caused intentionally by domestic violence

OBJECTIVE: To describe and analyze the causes of emergency care services for intentional injuries, especially those caused by domestic violence, at four public hospitals in Mexico City. MATERIAL AND METHODS: A cross-sectional study was conducted between January and April 1998, which included variables related with the victim, the aggressor, and the medical care provided to the victim. A questionnaire was applied to individuals who had been injured intentionally. Statistical analysis of data consisted of simple frequencies, the chi 2 test, and odds ratios (OR) with 95% confidence intervals (CI). A logistic regression model was also used to adjust for variables associated with the injury requiring emergency medical care. RESULTS: A total of 598 cases of intentional injuries were analyzed, 16% of which were due to domestic violence. Females were the most frequent victims (76%), followed by young people between 15 and 29 years old (46%). Variables associated with medical care due to injuries by domestic violence were: age 30 or older (OR 2.36, 95% CI 1.13-4.90), female gender (OR 8.60 95% CI 4.25-17.40), history of injuries (OR 4.93 95% CI 2.03-11.95), home as place of occurrence (OR 36.25 95% CI 16.59-79.18), and low education level (OR 2.33 95% CI 1.03-5.26). CONCLUSIONS: Study findings are consistent with those from other studies and call for enforcement of the Mexican Official Norm for Medical Care of Domestic Violence (Norma Oficial Mexicana para la Atención Médica de la Violencia Familiar) established in March 2000.     

Optical coherence tomography in contact dermatitis and psoriasis

Optical coherence tomography (OCT) is a new noninvasive imaging technique. In this study, it was used for the investigation of contact dermatitis and psoriasis. In these common inflammatory skin diseases the value of OCT for quantification and monitoring of the changes in comparison with other bioengineering methods was evaluated. Repeated measurements were performed in healthy volunteers after experimental induction of irritant contact dermatitis and in patients with psoriasis. In the OCT images, the thickness of the epidermis and the signal attenuation coefficient in the upper dermis were evaluated. The changes were compared with measurements of transepidermal water loss, hydration, skin colour and surface roughness, and with high-frequency ultrasound measurements. In irritant dermatitis and psoriasis, thickening of the epidermis was detected and could be monitored over time. The light scattering in the upper dermis was lower than in healthy skin. This was interpreted to be due to the inflammation and oedema, leading to a less-dense arrangement of the collagen fibres. The changes in the OCT images did not significantly correlate with the changes shown by the other methods. OCT is an interesting tool for investigation of inflammatory skin diseases. It is a simple method for determination of epidermal thickness and therefore provides, in addition to other methods, information on the severity of the disease and on treatment effects.     

Difference between real and perceived power of dermoscopical methods for detection of malignant melanoma

Clear proceedings in detection of malignant melanoma and monitoring of melanocytic nevi (MN) have been achieved by dermoscopy in recent years: sensitivity to 95% is possible for experts. Does patients' confidence in methods for detection of malignant melanoma most important for adherence in follow-up reflect this diagnostic power? A self-administered survey was performed in 210 consecutive patients at 13 private dermatological practices and the department of Dermatology of the University of Regensburg. Confidence was assessed by a 5-step ordinal scale ranging from 1 to 5 (higher values indicate higher confidence) and willingness-to-pay (wtp) as health-economic instrument for naked-eye inspection (NEI), handheld dermoscopy (HHD), digital dermoscopy (DD), and teledermoscopy (TD); additional, wtp for a hypothetical method promising 100% accuracy. Data of 143 patients (response rate 69.5%; mean age 37 years, 58% female) could be analysed. Mean confidence was 1.9 0.9 for NEI, 2.8 0.9 for HHD, 4.5 0.7 for DD, and 4.7 0.5 for TD. Mean wtp per examination was 0.64% 1.1 of monthly income for NEI, 1.1% 1.9 for HHD, 2.8% 3.3 for DD, 3.1% 4.6 for TD, and 5.0% 7.8 for hypothetical method. Differences between methods were statistically significant. Compared to the hypothetical method, NEI achieved only 14.9%, HHD 24.8%, DD 58.4%, and TD 60% of maximum confidence. This study was performed without any influence on routine information for patients. Results therefore represent patients' actual knowledge of dermoscopical methods in daily dermatological practices. Patients' confidence was highest for TD, HHD was clearly underestimated. Willingness-to-pay in HHD, DD, and TD was at least 40% below a hypothetical method promising 100% accuracy. Better information about diagnostic accuracy of methods available is necessary to increase patients' knowledge and confidence.     

Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis

We conducted a double-blind, placebo-controlled, multicenter, randomized trial to test the hypothesis that 300 mg of tobramycin solution for inhalation administered twice daily for 28 days would be safe and result in a profound decrease in Pseudomonas aeruginosa (Pa) density from the lower airway of young children with cystic fibrosis. Ninety-eight subjects were to be randomized; however, the trial was stopped early because of evidence of a significant microbiological treatment effect. Twenty-one children under age 6 years were randomized (8 active; 13 placebo) and underwent bronchoalveolar lavage at baseline and on Day 28. There was a significant difference between treatment groups in the reduction in Pa density; no Pa was detected on Day 28 in 8 of 8 active group patients compared with 1 of 13 placebo group patients. We observed no differences between treatment groups for clinical indices, markers of inflammation, or incidence of adverse events. No abnormalities in serum creatinine or audiometry and no episodes of significant bronchospasm were observed in association with active treatment. We conclude that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis.     

Executive function assessed by memory updating and random generation in schizotypal individuals

Individuals scoring high (N=32) and low (N=27) on the unusual experiences (UnEx) scale of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) were selected from a large sample (N=265) of normal volunteer undergraduates. The high- and low-UnEx groups were compared on two tasks, random generation and memory updating, which target executive functions that inhibit prepotent responses and update current information. The groups differed only on the R measure of random generation that assesses inequality in the relative frequencies of response alternatives, a result attributed to superstitious behaviour rather than to executive deficit. The results suggest that the executive impairments previously observed in high schizotypal individuals using the Wisconsin Card Sorting Test and other measures are selective rather than global.