Patients who undergo transplantation with haploidentical “three-loci” mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony- stimulating factor-mobilized peripheral blood progenitor cells from HLA- haploidentical “three-loci” incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E- rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.

A 12-month EET intervention may reduce the progression of age-related cognitive decline in healthy older adults.

Abstract-Chronic periodontitis has been associated with an increased risk for cardiovascular disease. Left ventricular mass is an established independent predictor of cardiovascular disease. In the present cross-sectional study, we tested the association between periodontitis and left ventricular mass in subjects with essential hypertension. One hundred four untreated subjects with essential hypertension underwent clinical examinations, including echocardiographic study, laboratory tests, and assessment of periodontal status according to the community periodontal index of treatment needs (CPITN eriodontium is a complex and highly specialized pressure-sensing system consisting of 4 tissues (cementum, periodontal ligament, alveolar bone, and junctional and sulcular epithelia) supporting the teeth. Of these structures, periodontal ligament is a dynamic tissue with a high rate of remodeling and turnover, which connects the teeth to the alveolar bone. 1 Prevalence of periodontal disease approaches 14% over a wide age span, including younger and elderly people. 1 Periodontitis begins with a loss of alveolar bone and subsequent formation of a pocked around the tooth, the final stage being tooth mobility and loss. 2 Periodontal pocket can be detected with a periodontal probe and estimated through measurement of distance from gingival margin to the base of the periodontal pocket. 3 In a healthy periodontium, there is no loss of epithelial attachment or pocket formation, and the gingival crevice is Ͻ2 mm deep. 3 Established risk factors for periodontal disease are dental plaque, calculus, age, genetics, smoking, and diabetes. 4 At least 9 cohort studies 5-13 examined the association between periodontal disease and coronary heart disease (CHD), with conflicting results. An overview of these studies 14 showed a 15% excess risk of CHD in association with periodontal disease, with 95% confidence intervals ranging from 8% to 122%. To define the underlying mechanisms of such association, several studies, reviewed in depth by Armitage, 15 examined the potential link between periodontal disease and cardiovascular risk factors, including diabetes, smoking, hyperlipidemia, and hypertension. Surprisingly, despite the high prevalence of hypertension in the general population and its leading prognostic importance, few data are available on the relation between elevated blood pressure (BP), hypertensive organ damage, and periodontal disease. Castelli et al 16 found a proliferation of the intima and elastic layers with lumen reduction of vessels feeding the periodontal membrane in hypertensive subjects. 16 In another study, tooth position and movements were affected by the force of BP transmitted through periodontal vessels. 17 Interestingly, periodontal pulsation reflected changes in pulse pressure rather than in mean BP. 17 Left ventricular (LV) mass is abnormally increased in about one third of people with hypertension, 18 and LV hypertrophy is associated with an excess risk of cardiovascular complications independently of BP and oth...

Background: The levels of B-type natriuretic peptide (BNP), a marker of heart failure, are higher in women and anaemic subjects, and tend to be lower in obese people. These relationships are still largely unexplained and it is unclear whether they also apply to the N-terminal portion of BNP precursor (NT-proBNP). Aims: This cross-sectional study was performed to assess general and abdominal obesity, sex and other variables as possible extra-cardiac determinants of NT-proBNP. Methods and results: A random sample of 713 subjects aged 65 -74 years resident of Pianoro (Northern Italy) underwent assessment of NTproBNP, several haemato-chemical variables, body mass index (BMI), body fat estimation (through skinfold measurement), waist circumference, intra-abdominal thickness and possible presence of hepatic steatosis (by ultrasound examination). An echocardiogram was performed in a subset of 125 subjects. In multivariable analysis NT-proBNP was inversely associated with haematocrit (r = 0.22, P < 0.0001) and hepatic steatosis (r = 0.13, P = 0.0001), while no association was found with BMI and body fat estimation. NT-proBNP was higher in women, but this relationship disappeared when haematocrit was included in the multivariable model. The associations with haematocrit and hepatic steatosis were independent from echocardiographic measurements. Conclusion: NT-proBNP is increased in subjects with low haematocrit, which explains the higher values in women. Although NT-proBNP is not affected by general adiposity, low levels of NT-proBNP are associated with hepatic steatosis.

We studied peripheral blood and apheresis samples from 39 consecutive normal donors who were parents or siblings of patients who received matched or mismatched bone marrow transplants using a combination of rhG-CSF-mobilized peripheral blood stem cells (PBSCs) and bone marrow (BM). BM was harvested from donors 1-7 days before starting rhG-CSF treatment: 12 micrograms/kg/day rhG-CSF was administered by continuous s.c. infusion for 4-7 days. Peripheral blood progenitor cells were harvested by leukapheresis using an automated continuous-flow blood cell separator, beginning on day 4 of rhG/CSF, for 1-4 consecutive days. Peak peripheral blood CD34+ cell and CFU-GM levels were reached simultaneously on day 5 or 6 of rhG-CSF administration. Median peak levels were 1.65% for CD34+ cells (range 0.34%-4.7%) and 142 CFU-GM/10(5) plated cells (range 16-700). The greatest numbers of CD34+ cells and CFU-GM, expressed per liter of blood volume processed, were harvested during the second and third leukapheresis: CD34+ cells 37.77 +/- 25.48 x 10(6) and CFU-GM 3.32 +/- 2.51 x 10(6) during the second leukapheresis, and CD34+ cells 37.01 +/- 16.33 x 10(6) and CFU-GM 3.82 +/- 4.36 x 10(6) during the third. The number of CD34+ cells and CFU-GM did not correlate with the sex, age, or body weight of the donors. This study indicates that this protocol for administration of rhG-CSF mobilizes large numbers of hematopoietic progenitor cells into the peripheral blood and that bone marrow harvesting before G-CSF administration does not impair stem cell mobilization.