Systemic tuberculosis presenting as an epiglottic mass detected on F-18 FDG PET/CT

A 32-year-old man presented with asthenia, weight loss, cough, and dysphagia following a recent stay in Morocco. Endoscopy showed a bulky mass of the epiglottis suspected of being a malignant tumor. The patient underwent jointly an F-18 FDG PET/CT and a biopsy of the tumor. Against all expectations, biopsy revealed granulomatous inflammation with epitheloid giant cells and caeseating necrosis. These findings associated with the presence of acid-fast bacilli in the sputum smears were highly suggestive of laryngeal tuberculosis, which was confirmed later after cultivation of mycobacteria. F-18 FDG PET showed diffuse pharyngolaryngeal and lung uptake with bilateral cervical and abdominal nodes, but also one thoracic vertebral uptake. Lung CT could have revealed carcinomatous dissemination, but cavitary lesions in some pulmonary segments were more evocative of tuberculosis. Moreover, cerebral MRI showed brain tuberculomas not visualized on F-18 FDG PET/CT. The patient was treated with a 5-antituberculosis drug regimen, which improved clinical symptoms with epiglottis mass regression, and lung CT image reduction, clinching the systemic tuberculosis diagnosis. A control F-18 FDG PET/CT performed 5 months later showed disappearance of the pharyngolaryngeal and node uptake, with an improvement of lung uptake without normalization, arguing for persistent disease. Unexpected pathologic findings may be present in more than 3% of neck dissections. Although this is usually indolent, with the underlying SCC remaining the main prognostic determinate, it may significantly complicate postoperative management.     

Evaluating the potential impact of mismatches outside the antigen recognition site in unrelated hematopoietic stem cell transplantation: HLA-DRB1*1454 and DRB1*140101

DNA sequencing of 268 individuals drawn from four US populations carrying two unresolved DRB1*14 alleles differing only outside the antigen recognition site identified DRB1*1454 in the majority. A database of 4222 human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation donor–recipient pairs was queried to determine the number likely mismatched for DRB1*140101/DRB1*1454 but matched for class I loci. A power calculation suggests that more than 88,000 transplants among European Americans will be needed to identify sufficient 7/8 allele-matched pairs to evaluate the impact of the DRB1*140101/DRB1*1454 mismatch on transplant outcome. Molecular modeling of the HLA-DR interaction with the T-cell receptor and with CD4 suggests that the amino acid substitution distinguishing the two alleles will have minimal impact on allorecognition.     

Four-locus high-resolution HLA typing in a sample of Mexican Americans

Mexicans are the most common minority population of the United States. From a sample of 553 bone marrow donor registrants of self-described Mexican ancestry, human leukocyte antigen (HLA) loci A, C, B and DRB1 were typed by highresolution sequence based typing (SBT) methods. A total of 47, 34, 76 and 46 distinct alleles at A, C, B and DRB1 respectively were identified, including 3 new alleles. The four-locus haplotype frequency distribution was extremely skewed with only 53.9% of 1106 chromosomes present with more than one estimated copy. Haplotypes of Native American origin were identified. These data form an initial basis for determining the requirements for an adequate donor pool for stem cell transplantation in this population.     

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y₁, P2Y₁₂, CYP2C9, CYP3A4 and CYP3A5 genotypes.     

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.     

Integrative ecotoxicological assessment of sediment in Portmán Bay (southeast Spain)

Portmán Bay, southeast Spain, contains the most seriously metal-contaminated sediments of the Mediterranean Sea. From 1958 to 1991, approximately 50 million tons of mine tailings were dumped into the bay, completely filling up the bay and dispersing over an extensive area of the continental platform and continental slope. The objective of our study was to characterize the nature and extent of metal contamination and the responses of natural communities to it and to assess the toxicity of the sediment deposits 10 years after mining had ceased. We studied the physical and chemical characteristics of the sediments and toxicity (of the porewater and sediment–water interface) using two sea urchin species (Arbacia lixula and Paracentrotus lividus). Metal bioavailability and patterns of macroinvertebrate community composition along the contamination gradient were also studied. Univariate and multivariate analyses showed positive correlation between the sediment metal concentrations associated to the all biological effects (sea urchins toxicity tests and benthic indices). The effects of sediment contamination on the benthic community structure are visible among sampling stations.     

Bone mineral density in male adolescents with anorexia nervosa

OBJECTIVES: To determine the percentage of male adolescent patients with abnormal bone mineral density (BMD), to identify the variables related to BMD loss, and to study BMD change after follow-up. METHOD: Dual-energy-x-ray absorptiometry tests at the lumbar spine (L2-L4) and the femoral neck were administered in 20 male adolescents with anorexia nervosa (treated from 1997 until 2000 at the Department of Child and Adolescent Psychiatry and Psychology of the Hospital Clinic Universitari in Barcelona). Examinations were repeated in 15 patients after a follow-up of 6 to 24 months. RESULTS: Thirty-five percent of patients had osteopenia at the lumbar spine and femoral neck. The following variables were related to osteopenia: >12 months' duration of anorexia (p = .003), <3 hours/week of physical activity (p = .009), and calcium intake <600 mg/day (p = .015). In a stepwise logistic regression analysis to predict spinal BMD with the three variables mentioned above, only months of duration entered in the equation (beta = 3.5, SE = 1.3, p = .008) and correctly classified 85% of patients. At the follow-up, patients with only partial weight recovery had a BMD loss of 3.2% at lumbar spine and 6.4% at femoral neck, whereas patients with total weight recovery had an increase of 7.8% at lumbar spine and 6.7% at femoral neck. CONCLUSIONS: The risk of osteopenia in male adolescents with anorexia of more than 12 months' duration is high. In patients with total weight recovery, BMD increase is higher than normal.