The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.

Contemporary analysis of the influence of acute kidney injury after reduced intensity conditioning haematopoietic cell transplantation on long-term survival.

We evaluated retrospectively the incidence of acute kidney injury (AKI), defined by risk, injury, failure, loss and end-stage kidney disease (RIFLE) and its influence on long-term survival, in 82 patients aged 18-60 years who underwent a reduced intensity conditioning (RIC) haematopoietic cell transplantation (HCT). Patients (53.6%) developed AKI after HCT: 25% were on risk, 45.5% on injury and 29.5% on failure. In all, 64 patients survived after 100 days of post transplant and were available for long-term survival analysis. At follow-up, 43.7% of patients died. A 5-year overall survival of AKI patients was 41.6% as compared with 67.1% for those who did not develop AKI (P=0.028), and decreased according to AKI severity (risk, 55.6%; injury plus failure, 33.3%; P=0.045). After adjusting for age, history of cardiovascular disease, high-risk disease and chronic GVHD, AKI predicted 5-year overall mortality (AKI: adjusted hazards ratio (AHR), 2.36, 95% CI: 1.03-5.37; P=0.041). Moreover, moderate and severe AKI (injury plus failure) was also associated with an increased 5-year overall mortality (injury plus failure: AHR, 1.64, 95% CI: 1.06-2.54; P=0.024). According to RIFLE, 53.6% of patients had AKI after RIC HCT. Such patients have poor long-term survival, particularly in moderate or severe AKI.

Influence of cardiopulmonary reflex on the sympathetic activity during myocardial infarction.

The time-course of changes in renal sympathetic nerve activity (RSNA), arterial and cardiopulmonary baroreflexes sensitivities was evaluated in conscious rats eight hours (8 h) and ten days (10 day) after myocardial infarction (MI), induced by coronary artery ligation. RSNA was recorded by a platinum electrode implanted in left renal nerve. Arterial and cardiopulmonary baroreflexes sensitivities were evaluated by changes in blood pressure and serotonin administration, respectively. Both 8 h and 10 day groups presented hypotension (103+/-4 vs. 102+/-2 vs. 115+/-4 mm Hg), but only 8 h showed tachycardia (422+/-22 vs. 378+/-11 vs. 384+/-9 bpm) when compared to Control rats. RSNA was depressed 8 h after MI and increased in 10 day group (12+/-2 vs. 39+/-8 vs. 22+/-2 mV/cycle). Although arterial baroreflex control of heart rate was similar in all groups, the arterial baroreflex control of RSNA in 8 h group was impaired during reductions (-0.35+/-0.10 vs. -1.66+/-0.23 vs. -0.09+/-0.14 mV/cycle/mm Hg) or increases (-0.77+/-0.17 vs. -1.63+/-0.58 vs. -1.66+/-0.17 mV/cycle/mm Hg) in blood pressure when compared to Control animals. Moreover, cardiopulmonary baroreflex bradycardic response was increased in 8 h rats and normalized in 10 day group. The results suggest that the increased cardiopulmonary baroreflex sensitivity in 8 h may contribute to the reduction in the tonic level of RSNA as well as in the impairment of the baroreflex control of RSNA in the presence of hypotension.

Allogeneic stem cell transplantation in patients with myelodysplastic syndrome: outcome analysis according to the International Prognostic Scoring System.

We determined the outcome of patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after allogeneic stem cell transplantation according to their international prognostic scoring system (IPSS) risk categories at diagnosis. A total of 11 females and 7 males, with a median age of 45 years, were transplanted. With a median follow-up of 60 months, the 6-year actuarial event-free survival (EFS) for Less Advanced (Low and Intermediate-1 risk IPSS) and Advanced (Intermediate-2 and High risk IPSS) MDS was 71.4% and 43.6%, respectively (p=0.002). We did not observe a difference in EFS depending on cytogenetics at diagnosis (good risk 53.8% Vs intermediate and high risk 53.3%, p=ns), neither on the type of conditioning regimen used (myeloablative 50% Vs reduced intensity 52.2%, p=ns). Our results support that IPSS score at diagnosis may be used to predict EFS in patients with MDS undergoing allogeneic SCT.

Invasive aspergillosis of the central nervous system after allogeneic stem cell transplantation.

Central nervous system aspergillosis is a rare infectious complication in patients submitted to allogeneic stem cell transplantation. When it arises, this infection appears early post-transplant and most patients present with multiple central nervous system lesions. We report the clinical case of a 52 year old woman with IgGk multiple myeloma in relapse after a matched related allogeneic bone marrow transplant, who presented with a single large central nervous system Aspergillus lesion 11 months post-transplant in the setting of acute graft vs. host disease developing after the infusion of donor leucocytes. Although liposomal amphotericin B was promptly instituted, the patient died 1 week after the diagnosis.

Dental erosion in 12-year-old schoolchildren: a cross-sectional study in Southern Brazil.

OBJECTIVE: The aim of this study was to assess the prevalence and severity of dental erosion among 12-year-old schoolchildren in Joaçaba, southern Brazil, and to compare prevalence between boys and girls, and between public and private school students. METHODS: A cross-sectional study was carried out involving all of the municipality's 499, 12-year-old schoolchildren. The dental erosion index proposed by O'Sullivan was used for the four maxillary incisors. Data analysis included descriptive statistics, location, distribution, and extension of affected area and severity of dental erosion. RESULTS: The prevalence of dental erosion was 13.0% (95% confidence interval = 9.0-17.0). There was no statistically significant difference in prevalence between boys and girls, but prevalence was higher in private schools (21.1%) than in public schools (9.7%) (P < 0.001). Labial surfaces were less often affected than palatal surfaces. Enamel loss was the most prevalent type of dental erosion (4.86 of 100 incisors). Sixty-three per cent of affected teeth showed more than a half of their surface affected. CONCLUSION: The prevalence of dental erosion in 12-year-old schoolchildren living in a small city in southern Brazil appears to be lower than that seen in most of epidemiological studies carried out in different parts of the world. Further longitudinal studies should be conducted in Brazil in order to measure the incidence of dental erosion and its impact on children's quality of life.

Autologous stem cell transplantation in acute myeloid leukemia. Factors influencing outcome. A 13 year single institution experience.

We report our results of autologous stem cell transplantation (SCT) in patients with AML during the last 13 years. Between August 1990 and December 2003, 42 patients with acute myeloid leukemia (AML) received an autologous SCT. Patients were classified as standard risk if first complete remission (CR) was induced after one or two chemotherapy regimens and the white blood cell count at presentation was below 50,000/mL (n=12), while patients requiring more than two induction regimens to attain first CR and with CR2 ou more advanced disease and/or had a higher white blood cell count at presentation were defined as high risk (n=30). Twenty one patients were transplanted in first CR. The median patient age was 24 years (range, 2-56 years), and the median time interval from diagnosis to autologous SCT was 9 months (range 3-87 months). The conditioning regimen for SCT consisted of busulfan (BU) 16 mg/kg and melfalan (MEL) 180 mg/m2 (BUMEL) in 17 (40%) patients and busulfan 16 mg/kg and VP-16 60 mg/kg (BUVP16) in 22 (52%) patients. Three patients received a different conditioning regimen with BCNU 300 mg/m2, VP16 2 g/m2 and melphalan 160 mg/m2 (BEM). Twenty five (60%) patients received bone marrow (BM), 11 (26%) patients received peripheral blood stem cells (PBSC) and 6 patients (14%) received BM plus PBSC. With a median follow-up of 7 years, the 13 year overall survival (OS) and diseasefree survival (DFS) of all patients is 52% and 40%, respectively. In univariate analysis, males had a significantly superior DFS than females (55% vs 22%, p=0.003), and patients younger than 15 years of age had significantly superior OS and DFS than older patients (50% vs 35%, p=0.05; and 50% vs 28%, p=0.03, respectively). Patients with FAB M3 subtype also had a superior OS than the other FAB subtypes (100% vs 44%, p=0.05). There was a strong statistical correlation between risk group and survival. In fact, the patients with standard risk had a superior OS and DFS than those with high risk disease (67% vs 23%, p=0.0004; and 50% vs 27%, p=0.01, respectively). When patients with FAB M3 disease were excluded from the analysis, the group with standard risk continue to have a superior OS and DFS (67% vs 13%, p=0.008; and 50% vs 14%, p=0.02, respectively). We conclude that autologous SCT is an effective treatment in AML with the possibility of long survivorship, particularly in patients with standard risk disease.

Efeito da trinitroglicerina na fase prodrômica da laminite equina experimental

O artigo não apresenta resumo.

Haploidentical stem cell transplantation with purified CD34 cells after a chemotherapy-alone conditioning regimen.

We investigated whether a novel chemotherapy-alone conditioning regimen would permit durable engraftment of standard doses of CD34+ purified stem cell grafts from full-haplotype mismatched related donors. We also examined the role of infusing limited doses of donor leukocytes for prevention of leukemia relapse. Our conditioning regimen consisted of thiotepa, fludarabine, rabbit antithymocyte globulin, melphalan, cyclosporin, and prednisolone. Since October 1998, 14 patients with high-risk leukemia were treated; 13 donor-patient pairs shared 3 of 6 HLA antigens, and 1 pair shared 5 of 6 HLA antigens. A median of 5.4 x 10(6) CD34+ cells per kilogram, 1.62 x 10(4) CD3+ cells per kilogram, and 9.32 x 10(4) CD19+ cells per kilogram were infused. T-cell depletion was the only graft-versus-host disease (GVHD) prophylaxis. All patients had prompt engraftment, and no late graft rejections were observed. All surviving patients received at least 1 infusion of donor whole blood containing 5, 7, 10, 25, or 50 x 10(3) CD3+ cells per kilogram between days 25 and 95 after transplantation, after which 8 developed acute GVHD (3 grade I, 2 grade II, 2 grade III, and 1 grade IV) and 2 developed a bronchiolitis obliterans-like syndrome. After attaining complete remission, 5 patients relapsed and died with active leukemia. The estimated relapse-related mortality at 4 years is 38.1%. As of June 15, 2003, 6 of 14 patients have survived a median of 43.5 months after transplantation with 100% donor cells. All 6 surviving patients developed acute GVHD and had a natural killer cell mismatch with their donors in the direction of graft versus host. The estimated overall survival and event-free survival for the 14 patients at 4 years is 41.7% +/- 13.5%.

Cardiovascular responses to microinjections of GABA or anesthetics into the rostral ventrolateral medulla of conscious and anesthetized rats

The rostral ventrolateral medulla (RVLM) contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA) and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv) anesthetized Wistar rats (300-350 g). In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl) induced a small but significant decrease in blood pressure (from 130 ± 3.6 to 110 ± 5.6 mmHg, N = 7). A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl). However, in the same animals, the fall in blood pressure induced by GABA (from 121 ± 8.9 to 76 ± 8.8 mmHg, N = 7) or pentobarbital (from 118 ± 4.5 to 57 ± 11.3 mmHg, N = 6) was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 ± 4.1 to 92 ± 5.9 mmHg, N = 7) and anesthetized rats (from 123 ± 6.9 to 87 ± 8.7 mmHg, N = 7) when lidocaine (34 nmol/200 nl) was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition

Cardiovascular responses to microinjections of GABA or anesthetics into the rostral ventrolateral medulla of conscious and anesthetized rats.

The rostral ventrolateral medulla (RVLM) contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA) and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv) anesthetized Wistar rats (300-350 g). In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl) induced a small but significant decrease in blood pressure (from 130 +/- 3.6 to 110 +/- 5.6 mmHg, N = 7). A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl). However, in the same animals, the fall in blood pressure induced by GABA (from 121 +/- 8.9 to 76 +/- 8.8 mmHg, N = 7) or pentobarbital (from 118 +/- 4.5 to 57 +/- 11.3 mmHg, N = 6) was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 +/- 4.1 to 92 +/- 5.9 mmHg, N = 7) and anesthetized rats (from 123 +/- 6.9 to 87 +/- 8.7 mmHg, N = 7) when lidocaine (34 nmol/200 nl) was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition.

Oral myiasis by screwworm Cochliomyia hominivorax.

We report a rare case of periodontal myiasis by New World screwworm Cochliomyia hominivorax, an obligatory larval parasite, in a 66-year-old woman. The myiasis occurred in the anterior upper jaw associated with a pre-existent generalised periodontitis. About 40 larvae were removed from the lesion. One week later the periodontal tissues were healing normally and the patient was referred to a periodontist. As all of the larvae were in the last stage, they were probably deposited 5-7 days before.

Follow-up of anti-Aspergillus IgG and IgA antibodies in bone marrow transplanted patients with invasive aspergillosis.

A total of 89 patients at risk for, or with invasive aspergillosis (IA) were recruited from bone marrow transplantation (BMT) units in two Lisbon hospitals, and followed for 2(1/2) years to monitor their immune response. Of these patients, six developed probable IA, from which five died. The presence of serum IgG or IgA antibodies against seven Aspergillus recombinant antigens was assessed in patients with IA, using an enzyme-linked immunosorbent assay (ELISA). In parallel, the serum levels of galactomannan (GM) were also monitored, using the Platelia Aspergillus kit (Sanofi Pasteur, Marnes-la-Coquette, France). Superoxide dismutase (Sod) and 94 kDa were the most immunogenic antigens for IgA, while the IgG pattern of recognition changed from patient to patient. From our results we conclude that although follow-up of antibodies against these antigens should not be used as a diagnostic method, patients with IA do produce an immune response that may influence disease outcome.

Parenteral nutrition and cyclosporine: do lipids make a difference? A prospective randomized crossover trial.

AIMS: This prospective, controlled, randomized crossover trial was conducted to assess the effects of parenteral nutrition, with or without lipids, in cyclosporine (CyA) pharmacokinetics. METHODS: 10 adult patients were randomized on the day of allogeneic bone marrow transplantation to receive isocaloric and isonitrogenous parenteral nutrition admixtures without (regimen A) or with lipids (regimen B). Admixtures were started on average by day + 7.4; 5 patients received regimen A followed by B, 5 in reverse order. Blood samples were collected at day 4 after transplantation, under oral diet, and 4 days after the initiation of each regimen as the sole nutrition support. At each time point, 8 whole blood samples were analysed for CyA to evaluate: area under the curve (AUC), trough concentration and systemic clearance. Clinical/laboratory events were recorded until 31 months of follow-up. RESULTS: There was no evidence of a period or treatment-by period interaction, thus results were combined for further analysis. There were no statistically significant differences between regimens in any CyA pharmacokinetic parameters; there were no significant differences from baseline values, except for a higher systemic clearance of CyA with regimen A (0.40+/-0.09 vs 0.29+/-0.06 L/Kg/h, p=0.03). CONCLUSIONS: The provision of 0.8 g/Kg/d of a 50:50 mixture of medium and long chain triglycerides did not affect CyA parameters, which were closer to baseline. In the short or long term there were no attributable side effects.