The relative biological effectiveness of photon radiation from encapsulated iodine-125, assessed in cells of human origin: I. Normal diploid fibroblasts

The relative biological effectiveness (RBE) of photon radiation from encapsulated Iodine-125 "seed" sources has not previously been investigated in human cells. The RBE of 125I photons relative to 137Cs gamma rays was examined in normal diploid human fibroblasts derived from lung and skin. The cells were irradiated in plateau phase using a specially designed incubator-irradiator which permitted simultaneous 125I and 137Cs irradiation. The cells were irradiated at various dose rates ranging from 7 to 70 cGy/hr. Dosimetry was performed using Monte Carlo computer calculations to simulate the 125I irradiations and the exposure-standardization measurements made by the U.S. National Bureau of Standards which are the basis for the specified strengths of 125I seeds. Simulation of the exposure standardization measurements revealed systematic errors due to the unrecognized presence of low-energy fluorescence X rays. The specified activity of the type of seeds used for this study (high-activity, no radiographic marker) was found to be too high by more than 10%. The RBE of 125I assessed with both lung fibroblast lines was found to be 1.2 and was 1.3 for the skin fibroblasts. The RBE did not change over the range of dose rates tested. In fact, for both 125I and 137Cs, the dose response curves did not change with dose rate over the range tested, implying full repair of sublethal damage at dose rates below 70 cGy/hr in these non-dividing cells.     

Dynamics of the reactivity to MBP in multiple sclerosis

Though many lines of evidence support the importance of myelin basic protein (MBP) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), its role in multiple sclerosis (MS) is still debated as well as the significance of epitope spreading in disease progression. We characterised the response to MBP in eight MS subjects and three of these were followed over time. In one case, the follow up lasted over a 6-year period. Clonal expansion, clonal persistence and epitope spreading against other MBP determinants was detected irrespective of disease course. In one patient we identified a novel T-cell receptor variable gene (BV28S2) which may be involved in the selection of MBP determinants, as suggested by experiments performed in the presence of mismatched antigen presenting cells (APC) between two subjects compatible for HLA-DR2 subtype but differing for the epitope recognised. Our findings do not sustain a role for the response to MBP effecting on clinical course and suggest that a novel TCR gene may be involved in the recognition of unusual self antigens.     

Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients.

PURPOSE: Imatinib (Glivec) is a potent inhibitor of bcr/abl, an oncogenic fusion protein that causes chronic myelogenous leukemia (CML). alpha1 acid glycoprotein (AGP) binds to imatinib with high affinity and inhibits imatinib activity in vitro and in vivo in an animal model. A pharmacokinetics analysis of imatinib was undertaken in CML patients. EXPERIMENTAL DESIGN: Imatinib plasma concentrations were measured in 19 CML patients treated with imatinib (400 or 600 mg/day). Five patients received a concomitant short-term course of clindamycin (CLI). RESULTS: A positive correlation between AGP and imatinib plasma levels was observed. CLI administration decreased imatinib plasma concentrations, evaluated as area under the curve (AUC) and peak concentrations (C(max)). The effects of a bolus of CLI was studied in three patients on imatinib 23 h after the last imatinib dose. Within 5-10 min in three of three cases, CLI caused a decrease in imatinib plasma concentrations of 2.6-, 2.7-, and 4.7-fold, respectively. In vitro experiments using fresh blasts from CML patients showed that AGP, at concentrations observed in the patients, decreased imatinib intracellular concentrations up to 10 times and blocked imatinib activity. The incubation with CLI restored imatinib intracellular concentrations and biological activity. CONCLUSION: AGP exerts significant effects of the pharmacokinetics, plasma concentrations, and intracellular distribution of imatinib in CML patients; these data indicate that plasma imatinib levels represent unreliable indicators of the cellular concentrations of this molecule.     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Collision nodal metastasis of bladder cancer and melanoma: The first reported case and literature review

Collision metastasis is a rare phenomenon of concomitant localization of 2 or more different tumors in the same lymph node. In most cases, primary malignancies are synchronous carcinomas arising in the same organ or area of the body. A 82-year-old man presented with hematuria and acute renal failure; he had undergone dermatological consultation ten months ago because of a large deep brown skin lesion in his dorso-lumbar region, which was not excised upon patient’s request. He underwent radical cystectomy with extended pelvic lymphadenectomy due to nonpapillary high-grade urothelial carcinoma, with focal squamous features, infiltrating the bladder wall and prostate gland. In one left iliac lymph node, small foci of metastatic urothelial carcinoma (positive for P63 and CK34betaE12) were close to melanoma cells (positive for HMB45). The patient refused further treatment and died of metastatic disease 12 months after cystectomy. There is no specific clinical feature for nodal collision metastasis. A polymorphic histologic appearance poses the suspect, but immunohistochemical stains are needed to define the primary tumors. Collision metastases are thought to carry a poor prognosis. Their clinical relevance is linked to the fact that the patient faces 2 different metastatic tumors that may require specific multidisciplinary approach once diagnosed as metastatic. We present, to the best of our knowledge, the first case of collision nodal metastasis from bladder cancer and melanoma, and describe its clinical and histopathological characteristics to raise awareness on this rare occurrence, which portends a poorer prognosis than each single tumor.     

Comparison of the human electro-oculographic response to green and near-ultraviolet stimuli

We recorded the electro-oculogram from 27 normal subjects by means of green and near-ultraviolet (UVA) stimulation. After a 40-minute dark-adaptation period, baseline responses were recorded. In response to the green stimulus, the electro-oculogram increased from this level by an average (± standard error of the mean) of 49.5% ±4.0%. Although the predicted scotopic effectiveness of the ultraviolet stimulus was more than 3 log units below that of the green stimulus, the near-ultraviolet-induced electro-oculogram increased to an average of 21.9% ±3.0% above baseline. This response cannot be due to lens fluorescence to the near-ultraviolet stimulus, since two aphakic subjects had electro-oculographic responses of 32% and 76% above baseline to near-ultraviolet stimuli. Neither the green nor the ultraviolet electro-oculogram changed significantly with age. These large responses to near-ultraviolet stimulation demonstrate the need for standardizing light sources for electro-oculographic testing because the degree of near-ultraviolet irradiance varies considerably according to their design characteristics.     

ASSOCIATION BETWEEN SMOKING,CRACK COCAINE ABUSE AND THE DISCONTINUATION OF COMBINATION ANTIRETROVIRAL THERAPY IN RECIFE,PERNAMBUCO, BRAZIL

Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.