Ytterbium-DTPA. A potential intravascular contrast agent

Ytterbium-DTPA was evaluated as a potential intravascular contrast agent. Ytterbium-DTPA was synthesized from ytterbium oxide and diethylene triamine penta-acetic acid (DTPA). CT scans of increasing concentrations of ytterbium and iodine showed that at 125 kVp, ytterbium was denser than an equal concentration of iodine. The LD50 of intravenous ytterbium-DTPA was 10 mM/kg (1.73 g ytterbium/kg) in rats. In enhanced CT scans and pulmonary angiography in dogs, ytterbium was visibly denser than iodine, and CT Hounsfield units showed greater enhancement of the aorta and inferior vena cava with ytterbium. The animals showed no sign of acute or delayed toxicity. Ytterbium-DTPA deserves further evaluation as a contrast agent for high kVp techniques.     

Changes in immunologic response in tonsillectomized children. I. Immunosuppression in recurrent tonsillitis.

The possible immunoregulatory role of the tonsils was studied by determining immunoglobulins IgG, A, M, E and factors C'3, C'4 and PFB of the complement system before and after tonsillectomy. The synthesis in vitro of IgG and IgM by lymphocytes stimulated with pokeweed mitogen was also measured. There were statistically significant differences between pre and post-operative levels of serum IgG, IgA and IgM, which decreased after surgery. Practically no change in the mean values of IgE and no significant differences in the levels of serum C'3, C'4, and PFB, were found. The in-vitro synthesis of both immunoglobulins (IgG, IgM) by lymphocytes increased significantly after tonsillectomy. Our results suggest that not only does tonsillectomy have no counterproductive effect on the immune system, but that, on the contrary, it seems to improve the immune response, since it appears to unblock the suppression to which the immune system was subject.     

Myopic keratomileusis: short-term results

The first 97 eyes operated with keratomileusis by two surgeons starting to use this technique are evaluated. The 30- and 90-day postoperative results of this initial experience are reported. Average preoperative myopia was -10.53 D spherical equivalent (range -5.25 to -22.25 D); average refractive correction at 90 days was -10.20 D. Preoperative visual acuities without correction were between 0.01 and 0.15 Snellen scale (20/2000 to 20/133), and 90 days postoperatively they varied between 0.02 and 0.60 Snellen scale (20/1000 to 20/33) with an average of 0.29 (20/69). Average preoperative visual acuity with correction was 0.70 Snellen scale (20/29), and 90 days afterward it was 0.60 Snellen scale (20/33). Preoperative average refractive cylinder was 1.33 D and postoperative was 1.86 D, showing that significant amounts of astigmatism were not induced.     

Induction of Donor-Specific Allograft Tolerance by Short-Term Treatment with LF15-0195 After Transplantation. Evidence for a Direct Effect on T-Cell Differentiation

A 20-day treatment with LF15-0195, a deoxyspergualine analog, induced long-term heart allograft survival in the rat without signs of chronic rejection. LF15-0195-treated recipients did not develop an anti-donor alloantibody response. Analysis of graft-infiltrating cells, IL10, TNFalpha, IFNgamma mRNA and iNOS protein expression in allografts, 5 days after transplantation, showed that they were markedly decreased in allografts from LF15-0195-treated recipients compared with allografts from untreated recipients. Surprisingly, spleen T cells from LF15-0195 recipients, 5days after grafting, were able to proliferate strongly in vitro, when stimulated with donor cells, but had reduced mRNA expression for IFNy compared with spleen T cells from untreated graft recipients. Furthermore, when T cells from naive animals were stimulated in vitro, using anti-CD3 and anti-CD28, LF15-0195 also increased T-cell proliferation in a dose-dependent fashion: however, these cells expressed less of the Th1 -related cytokines, IFNgamma and IL2, compared with untreated cells, suggesting that LF15-0195 could act on T-cell differentiation. In conclusion, we show here that a short-term treatment with LF15-0195 induced long-term allograft tolerance, decreasing the in situ anti-donor response, and we illustrate evidence for the development of regulatory mechanisms.     

Ictal chronology and interictal spikes predict perfusion patterns in temporal lobe epilepsy: a multivariate study.

Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive variables for the occurrence of TPP and APP. Fifty-one TLE patients were submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and multivariate (MVA) analysis were performed upon clinical data, distribution of interictal spikes, and ictal chronology of seizures. From MVA, a final predictive model (FPM) was determined to better predict TPP and APP. Forty patients showed TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P = 0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the electrographic seizure occurring after completion of tracer injection, and longer clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic-clonic seizures did not result in more APP. We concluded that analysis of ictal SPECT in TLE requires the knowledge of TPP and APP, the distribution of interictal spikes on temporal lobes and the ictal chronology of seizures. BIS showed that beyond a more complex epileptogenicity and seizure propagation, they may also lead to APP.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Functional signatures of protective antiviral T-cell immunity in human virus infections

Summary: The most common human viruses have different abilities to establish persistent chronic infection. Virus‐specific T‐cell responses are critical in the control of virus replication and in the prevention of disease in chronic infection. A large number of phenotypic markers and a series of functions have been used to characterize virus‐specific CD4⁺ and CD8⁺ T‐cell responses, and these studies have shown great phenotypic and functional heterogeneity of the T‐cell responses against different viruses. The heterogeneity of the T‐cell response has been proposed to be specific to each virus. However, over the past 2 years, several studies have provided evidence that the phenotypic and functional heterogeneity of CD4⁺ and CD8⁺ T‐cell responses is predominantly regulated by the levels of antigen load. The levels of antigen load modulate the phenotypic and functional patterns of the T‐cell response within the same virus infection. Furthermore, the functional characterization of virus‐specific CD4⁺ and CD8⁺ T‐cell responses has identified signatures of protective antiviral immunity. Polyfunctional, i.e. interleukin‐2 and interferon‐γ (IFN‐γ) secretion and proliferation, and not monofunctional, i.e. IFN‐γ secretion, CD4⁺ and CD8⁺ T‐cell responses represent correlates of protective antiviral immunity in chronic virus infections.     

Risk factors for asthma in adolescents in a large urban region of Brazil.

BACKGROUND: Identify risk factors for asthma in adolescents from S?o Paulo, Brazil. METHODS: total of 528 adolescents (141 asthmatics, 387 control subjects) from the ISAAC study (phase III) were submitted to a complementary questionnaire to evaluate risk factors, through response to questions regarding personal history, environment, and diet and an agreement to undergo the skin prick test (SPT) for aeroallergens. RESULTS: Positive SPT to at least one allergen occurred in 49.4% adolescents. The risk factors for asthma were: prematurity (OR: 3.84, 95% CI: 1.54-9.64), rhinitis (OR: 3.18, 95% CI: 1.71-5.91), positivity in the SPT (OR: 2.81, 95% CI: 1.48-5.32), eczema in characteristic skin-folds (OR: 2.86, 95% CI: 1.13-7.26), and an allergic mother (OR: 2.01, 95% CI: 1.02-3.93). The consumption of cooked vegetables was a protective factor for asthma (OR: 0.37, 95% CI: 0.18-0.79) CONCLUSIONS: Asthma is a multifatorial disease. An allergic mother, aeroallergen sensitization, rhinitis, eczema and prematurity were considered risk factors and the consumption of cooked vegetables was considered a protective factor for asthma in this population.     

Reduction of Blood Pressure Retards the Progression of Chronic Renal Failure in Man

The effect of blood pressure reduction on the progression rateof chronic renal failure (CRF) was studied in 28 patients withCRF of diverse aetiology entering a prospective study (observationtime 7–24 months, mean 16 months). Endogenous creatinineclearance was 12–66 ml/mm (mean 30±3 ml/mm). Weaimed to keep the blood pressure below 160/90 mmlHg. Dietaryprotein was not restricted. The progression rate of CRF wasassessed from the regression coefficients of the regressionsof creatinine clearance and the inverse of s-creatinine, respectively,on time. Progression rate and the means of all recordings ofmean arterial blood pressure (MAP) and urinary protein excretion,respectively, in each patient during the prospective phase werecompared with retro spective data from the proceeding period(observation time 4–25 months, mean 19 months). The patientsreceived various combinations of antihypertensive drugs includingdiuretics, beta-blockers and vasodilatory drugs. In 19 patientsMAP decreased from 109±2 to 102±2 mmHg (groupI), whereas MAP increased from 105±2 to l08±2mmHgin nine patients (group II). In group I proteinuria was significantlylower (P<0.05) and the progression of CRF was approximately50% slower (P.<0.01) in the prospective phase than in theretrospective phase; no changes were observed in group II. Calculatedfor all patients, significant correlations were observed betweenthe change in MAP and the change in progression rate and proteinexcretion, respectively. These results indicate that loweringof blood pressure results in decreased proteinuria and retardationof the progression of CRF irrespective of the aetiology.