Evaluation of the epidemiologic utility of secondary typing methods for differentiation of Mycobacterium tuberculosis isolates

Spoligotyping and mycobacterial interspersed repetitive unit-variable-number tandem repeat analysis (MIRU-VNTR) were evaluated for the ability to differentiate 64 Mycobacterium tuberculosis isolates from 10 IS6110-defined clusters. MIRU-VNTR performed slightly better than spoligotyping in reducing the number of clustered isolates and the sizes of the clusters. All epidemiologically related isolates remained clustered by MIRU-VNTR but not by spoligotyping.     

Pharmacological characterization of mouse hind paw oedema induced by Bothrops insularis (jararaca ilhoa) snake venom.

Bothrops snake venoms produce marked local effects, including oedema, haemorrhage and necrosis. The ability of Bothrops insularis venom to induce oedema in mice was investigated. Venom was injected into hind paws and the change in volume over time was measured by plethysmometry. B. insularis venom (0.01-2.5 microg/paw) induced paw oedema which, at high doses (>/=0.5 microg/paw), was accompanied by haemorrhage. The peak oedematogenic response occurred 3 h after venom injection with all doses and decreased gradually thereafter, but was still elevated with high doses after 24 h. Pretreating the mice with cyproheptadine (histamine H(1) and serotonin 5-HT(2) receptor antagonist), mepyramine (histamine H(1) receptor antagonist), L-NAME (inhibitor of nitric oxide synthase), indomethacin and rofecoxib (inhibitors of cyclooxygenases), and dexamethasone (indirect inhibitor of PLA(2)) significantly attenuated venom-induced oedema, whereas methysergide, a serotonin 5-HT(1)/5-HT(2) receptor antagonist, had no effect. The administration of antivenom 30 min before or immediately after venom injection also significantly inhibited venom-induced oedema. These results show that B. insularis venom causes oedema in the mouse hind paw and that this response is mediated by histamine, nitric oxide, and arachidonic acid metabolites formed by cyclooxygenases 1 and 2. The neutralization by commercial antivenom indicates that the venom components responsible for oedema are recognized by the antivenom and share immunological identity with their counterparts in the venoms of mainland Bothrops species.     

A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. This study is registered at www.clinicaltrials.gov as NCT00429143.     

Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068

Thirty-four subjects with symptomatic HIV-1 infection, p24 antigenaemia, and CD4 cell counts > 200/mm3 were randomly assigned to receive treatment with either zidovudine (ZDV) orally, interferon-alpha (IFN-alpha) subcutaneously, or both at respective low (200 mg ZDV/ 2 million international units IFN-alpha (MIU)), middle (400 mg/4 MIU) or high (600 mg/6 MIU) daily dose levels for 12 weeks. Thereafter, all patients received combination therapy at the initially assigned dose level to a total of 96 weeks. This design permitted analysis by the combination index (CI) method, which demonstrated antiretroviral synergy between ZDV and IFN-alpha with respect to p24 antigen suppression. Over the first 12 weeks, combination therapy was acceptably tolerated, more so than IFN-alpha monotherapy, and it was significantly more active in suppressing antigenaemia than either of the monotherapies. Similarly, the high-dose combination was the most active dose level over weeks 12 to 96. Combination ZDV/IFN-alpha at the optimal dose level defined by this trial merits further study. In addition, the CI design strategy employed here may be useful for the investigation of new antiretroviral combinations.     

Age-related variations of serum CK and CK MB response in females.

The objective was to determine whether serum creatine kinase (CK) and serum CK MB activity following exercise-induced muscle damage activity differs among females of varying menarchial status and to determine whether there is a relationship between serum estradiol (E2) concentration, CK, and CK MB activity. Fifteen menarchial (M), 15 premenarchial (P), and 10 postmenopausal (PM) females participated in the study. Exercise consisted of eccentric hamstring contractions. Estradiol concentrations were significantly higher in M women (p =.0001; M, 125.0 +/- 20.8 pg/mL, P, 54.6 +/- 38.6 pg/mL, PM, 46.2 +/- 34.6 pg/mL). Menarchial women had lower resting CK and CK MB activity and responded with a higher efflux of CK and CK MB post exercise (p =.0001). An inverse relationship was found between E2 concentration and baseline CK (p =.02) and CK MB activity (p =. 006). No relationship existed between post exercise efflux of CK and CK MB and E2 concentration. At rest, E2 influenced CK and CK MB activity across menarchial levels. However, E2 did not significantly reduce the level of CK and CK MB activity following this intense bout of eccentric exercise.     

n-3 Fatty acid supplementation in burned paediatric patients

Aim:  To determine the effect of dietary supplementation with n-3 fatty acids (FA) in paediatric burned patients who had less than 20% of total body surface affected.
Methods:  Burned patients were randomly assigned into two groups, one of them received a supplement of n-3 FA during 5 weeks; the other group was considered as not n-3 supplemented burned group. A third group of no burned patients was selected as control. Blood samples were collected at admission and in burned groups at the final of the study. Plasma and erythrocyte phospholipid FA composition and some biochemical parameters related to the clinical evolution: total plasma proteins and C3 and C4 complement proteins were determined.
Results:  In the early post-burn patients, there is an increase in saturated and monounsaturated FAs in plasma phospholipids, and a decrease in polyunsaturated FAs compared with control. These alterations are in favour of proinflammatory response to burn injury. In n-3 FA supplemented group, these changes were further reverted, and a favourable response in the amount of total plasma proteins and in C3 and C4 proteins of the complement system was demonstrated.
Conclusion:  Dietary n-3 FA supplementation might be beneficial for patients suffering thermal injury.     

Incidental discovery of duplicated inferior vena cava in a septuagenarian: the radiologist's viewpoint

Duplication of the inferior vena cava is a rare malformation, normally without clinical impact, explained by abnormal development and regression of certain segments of the venous system during embryonic life. However, its presence and type should be systematically reported in the radiological report because of its potential implications for diagnostic and interventional procedures. This observation describes the case of a 77-year-old man with a complete asymmetric duplication of the inferior vena cava (type III IVC according to Natsis) that was incidentally discovered on CT-scan.