Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion- associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one- way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA- GVHD.     

Use of B cell-bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen

Recent studies have detected Wilms tumor antigen (WT1)-specific cytotoxic T lymphocytes (CTLs) in patients with acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) and demonstrated that most of these CTLs were low avidity. Although HLA-mismatched donors can mount high-avidity CTLs against HLA-A2-presented peptides of WT1, a dominant anti-alloimmune response usually obscures detection of peptide-specific CTLs. Here we explored the feasibility of using recombinant HLA-A2 monomers containing single peptide epitopes as immunogens to generate peptide-specific CTLs from allogeneic donors. We demonstrate that the coating of HLA-A2(-) B lymphocytes with A2/peptide monomers provides a strong stimulus for autologous peptide-specific CTLs. After 3 to 5 rounds of stimulation a population of CD8(+) T cells binding A2/peptide tetramers is easily detectable by fluorescence-activated cell sorting analysis. Furthermore, sorted A2/WT1 tetramer-positive CTLs display strong cytotoxic activity against leukemia cells expressing WT1 endogenously but not against WT1(-) human tumor cells. Thus, HLA/peptide monomers may be useful to isolate peptide-specific donor lymphocytes for treatment of patients with leukemia after HLA-mismatched transplantation.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Cytopathological and chemico‐physical analyses of smears of mucosa surrounding oral piercing

Oral Diseases (2010) 16 , 160–166 Objective: The aim of this comparative study was to analyze cytopathologically and chemico‐physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back‐scattered) scanning electron microscope (SEM) and X‐ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X‐ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.     

Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome

PURPOSE: The incidence of kidney stones in adults has increased in the last 30 years. This retrospective, single site review was done to test the hypotheses that the incidence of urolithiasis in pediatric patients increased from 1994 to 2005, and that metabolic abnormalities were more common in patients with renal stones in the final 3 years of the study period. MATERIALS AND METHODS: Charts from 2 time periods were reviewed, 1994 to 1996 (period 1) and 2003 to 2005 (period 2). Clinical and laboratory data, including demographics, presenting complaints, laboratory assessment, treatment and outcome, were tabulated in patients with confirmed urolithiasis. RESULTS: The number of patients with urolithiasis increased from 7 in period 1 to 61 in period 2. When expressed as cases per 100 new patients the incidence increased 4.6 times (p = 0.014). Focusing on period 2, 28% of patients were younger than 10 years. While blood tests were generally normal, 76% of patients had at least 1 abnormality in the 24-hour urine collection. Hypocitraturia, which was the most common metabolic abnormality, was noted in 52% of patients. The small number of patients in period 1 precluded determination as to whether metabolic abnormalities were more common in period 2. Surgery and/or lithotripsy was required in 12 children. Stone disease recurred in 39% of the patients. CONCLUSIONS: The incidence of urolithiasis in the pediatric population increased nearly 5-fold at our institution during the last decade. We recommend that the primary diagnostic test be a 24-hour urine collection. The most common metabolic abnormality was hypocitraturia, followed by hypercalciuria. Recurrence of stones is common (approximately 40% rate) and followup is advised.     

Tailoring oxygen needs of extremely low birth weight infants in the delivery room

Fetal to neonatal transition poses an extraordinary challenge for the extremely low birth weight (ELBW) neonate. Indeed a significant number of ELBW neonates will need proactive resuscitation to achieve postnatal stabilization. Positive pressure ventilation and oxygenation are the most relevant interventions in the delivery room (DR). Oxygen needs during resuscitation still represent a conundrum for neonatologists. While hyperoxemia favors oxidative stress and subsequent organ injury, hypoxemia is associated with long-term neurodevelopmental impairment. It has been shown that ELBW neonates can be successfully resuscitated with lower concentrations of oxygen as had been done traditionally. Moreover, reducing oxygen load has resulted in achievement of arterial partial pressures of oxygen at admission closer to the physiologic range, less oxidative stress and less inflammation. The availability of reference ranges for arterial oxygen saturation (SpO(2)) for ELBW neonates in the first 10 min after birth has been an extraordinary step forward in our ability to individually titrate oxygen needs thus avoiding the risks of both hypo- and hyperoxemia. The optimal fraction of inspired oxygen (FiO(2)) to initiate resuscitation and the safest SpO(2) percentiles for ELBW neonates during the first minutes of life are still unknown and will need further research in the future. Until then, optimal ventilation at birth and individually tailoring FiO(2) according to the nomogram seem to be the most reasonable and safe approach.     

Metaplastic carcinoma of the breast,an unusual disease with worse prognosis: the experience of the European Institute of Oncology and review of the literature

The contribution of BRCA1 and BRCA2 to breast cancer incidence in Brazil has not yet been explored. In order to estimate the proportion of breast cancers due to BRCA1 and BRCA2 mutations in Brazil, we conducted a study of unselected breast cancer patients from Rio de Janeiro, Brazil. We enrolled 402 women with breast cancer from a large public hospital and two private medical clinics in the city. A detailed family history was obtained from each patient and a blood sample was obtained for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques, but all mutations were confirmed by direct sequencing. Overall, nine mutations were identified (six in BRCA1 and three in BRCA2) representing 2.3% of the total. The most common mutation, 5382insC in BRCA1, was seen five times and accounted for 56% of all identified mutations. A second mutation, in BRCA2 (6633del5) was seen in two unrelated women. In summary, BRCA1 and BRCA2 mutations are not uncommon in Brazilian women with breast cancer. It appears that a small number of founder mutations may be predominant. Moreover, a small number of founder mutations may be prevalent in Brazil, raising the possibility that a rapid and inexpensive genetic test may be developed to screen for inherited susceptibility to breast cancer in Brazil. All studies listed in this paper are in accordance with the ethical standards of the regional hospitals in the listed study area.     

Nasal polyposis: clinical course during 20 years.

BACKGROUND: The etiology of nasal polyposis is mainly unknown although it has been connected with many clinical conditions. The long-term clinical course of nasal polyposis is largely unknown, because long-term followup studies on the recurrence of nasal polyposis have rarely been reported. OBJECTIVE: The aim of the study was to find out the clinical course of nasal polyposis over a long period of time. PATIENTS AND METHODS: Our report describes a 20-year follow-up study of 41 patients with nasal polyps. These patients had surgery for nasal polyp disease 20 years previously and they were initially grouped according to occurrence of (1) acetylsalicylic acid (ASA) intolerance, (2) atopic allergy (AT), and (3) intrinsic allergy-like disease (INTR). Patients were now re-examined, sinus computed tomography (CT) scanning was made, and a biopsy from polyp or from mucosa of the middle turbinate was taken. RESULTS: Anterior rhinoscopy revealed polyps in 35 of 41 patients. Thus nasal polyposis was still active in 85% of patients after 20 years. Mucosal changes in paranasal sinuses were found in every patient. Anosmia or hyposmia was found in 61% (25/41) of the patients. Eight patients had had 11 or more surgical operations during the 20-year period. Of these, 88% (7/8) belonged to the ASA group. Bronchial asthma was found in all ASA intolerance patients (11/11), and in 36% (4/11) of AT and in 16% (3/19) of INTR patients, respectively. CONCLUSION: Because of the high recurrence tendency and insidious symptoms of nasal polyposis, patients will require followup for the rest of their lives.