Chronic Cadmium Exposure Accelerates the Development of Atherosclerosis and Induces Vascular Dysfunction in the Aorta of ApoE-/- Mice.

Cadmium exposure is related to cardiovascular diseases, including hypertension, atherosclerosis, increased oxidative stress, endothelial dysfunction, and specific biochemical changes induced by this metal. Thus, we aimed to investigate whether cadmium exposure induces endothelial dysfunction, accelerates atherosclerotic plaque formation in the aorta, and enhances oxidative stress in apolipoprotein E knockout (ApoE-/-) mice. Experiments were performed in 14-week-old male wild-type and ApoE-/- mice. ApoE-/- mice received cadmium (CdCl2 100 mg/L in drinking water for 28 days) or vehicle (distilled water). After treatment, vascular reactivity to phenylephrine, acetylcholine, and sodium nitroprusside was analyzed using isolated aorta. Bone marrow cells were isolated to assess the production of nitric oxide and reactive oxygen and nitrogen species. ApoE-/- cadmium-treated mice had higher cholesterol levels than non-exposed mice. Cadmium exposure decreased the vasodilatation response to acetylcholine in aortic ring of ApoE-/- mice, though no changes in phenylephrine or sodium nitroprusside responses were observed. L-NAME reduced vasodilator responses to acetylcholine; this effect was lower in ApoE-/- cadmium-treated mice, suggesting reduction in nitric oxide (NO) bioavailability. Moreover, in bone marrow cells, cadmium decreased cytoplasmic levels of NO and increased superoxide anions, hydrogen peroxide, and peroxynitrite in ApoE-/- mice. Morphological analysis showed that cadmium exposure increased plaque deposition in the aorta by approximately 3-fold. Our results suggest that cadmium exposure induces endothelial dysfunction in ApoE-/- mice. Moreover, cadmium increased total cholesterol levels, which may promote the early development of atherosclerosis in the aorta of ApoE-/- mice. Our findings support the hypothesis that cadmium exposure might increase the risk of atherosclerosis.

[Measurement of lens density with a Scheimpflug camera in diabetic patients]. / Medida de la densidad del cristalino con cámara de Scheimpflug en pacientes diabéticos tipo II.

OBJECTIVE: To assess if diabetes, in patients without cataracts or diabetic retinopathy, alters the densitometric values of the lens and to what degree this occurs. METHODS: A total of 93 patients, divided into two groups, were studied: the diabetic patients had a visual acuity equal to or greater than 0.8 and normal eye funduscopy, and the control group consisted of healthy patients of a similar age. Measurements in all patients were made with the Scheimpflug camera and the lens density of the anterior capsule, anterior cortex and nucleus was defined. The values obtained in the two groups were compared by analysis of variance (ANOVA). RESULTS: All densitometric values were greater in the diabetic patients than in the normal controls. The greatest difference was seen in the values of the anterior capsule, followed by the nucleus and cortex. The differences approached statistical significance (P=0.07) only in the case of the anterior capsule. CONCLUSIONS: Diabetes increases densitometric values of the anterior capsule and to a lesser degree of the anterior cortex. However, further studies are necessary to verify if this alteration is of significance.

[Have patients who go to the emergency department changed? Evolutive study for the years 1997 and 2005]. / ¿Han cambiado los pacientes oftalmológicos que acuden a urgencias? Estudio evolutivo entre los años 1997 y 2005.

OBJECTIVE: To study the change in number and profile of patients who came to the Emergency Department of a level 2 hospital with ophthalmic emergencies in the years 1997 and 2005. METHOD: Two groups of randomly selected patients who came to the Emergency Service on the same day in the years 1997 and 2005 were studied. The study focused on the following variables: number of visits per day, gender, age, time period, number of examinations done, diagnoses and type of treatment prescribed. Comparison of proportions was carried out with a confidence interval study and Chi Square Test. RESULTS: The statistically significant changes (p<0.05) were as follows: increase in number of patients seen; increase in the diagnosis of corneal foreign body (25%); decrease in the diagnosis of conjunctivitis (12%); increase in cases in which only one examination was done (19%); increase in frequency of visits between 6 p.m. and 9 p.m. and decrease between 9 a.m. and 12 p.m; reduced attendance of those of female gender (13%) and increase in the male gender (13%); increase in patients between the age of 31 and 40 years (9%); decrease in the use of treatments such as occlusion and epithelializing ointment (7% and 6% respectively); increase in use of analgesics (5%), artificial tears (5%) and NSAIDs (8%); increase in referral of patients to their primary care physician (17%) and decrease in ophthalmology check ups (34%). CONCLUSIONS: The number of ophthalmological emergencies has increased in the last eight years, especially in young male patients, with work-related disease, who came in the evening. Treatments such as the use of artificial tears have increased, and patients are sent to the primary care physician more often.

Synergism between two growth regulatory pathways: cooperative transformation of NIH3T3 cells by G alpha 12 and c-raf-1.

The alpha-subunit of the heterotrimeric G-protein, G12, has been shown to induce cellular transformation when overexpressed or oncogenically activated in rodent fibroblasts. To investigate the interaction between Galpha12 transforming pathway and the Ras-Raf-MAPK pathway, we examined the ability of mitogenic signaling molecules in cooperating with Galpha12 in transforming NIH3T3 fibroblasts. We observed a striking cooperative effect on focus-forming ability when Galpha12 and c-raf-1 cDNAs were co-transfected into NIH3T3 cells. NIH3T3 cells coexpressing both Galpha12 and c-raf-1 resulted in the constitutive activation of the mitogenic-activated protein kinase (MAPK). In addition, the levels of GTP-bound Ras were elevated in Galpha12 transformed NIH3T3 cells. Our results provide a model for studying the effects of simultaneous activation of two distinct growth regulatory pathways in cellular transformation.

Modulation by dexamethasone of insulin binding and insulin receptor mRNA levels in U-937 human promonocytic cells.

Treatment with 5 x 10(-6) M dexamethasone stimulated insulin binding in human promonocytic U-937 cells. When curvilinear Scatchard plots were examined according to the one-site model, only changes in affinity, but not in receptor numbers, were observed. However, when the two-site model was applied, an increase in both the affinity and the number of the high affinity-low capacity sites was observed, with maximum values at 15 h. By contrast, the low affinity-high capacity sites did not undergo significant alterations. Northern blot assays revealed two insulin receptor-related mRNAs of approximately 11 and 7 kb in size. Dexamethasone increased the levels of these RNAs, following similar kinetics to those of high affinity receptor expression. This suggests that the 11 and 7 kb species carry information for high affinity insulin receptors, and that in U-937 cells the expression of this receptor subclass is primarily regulated at the mRNA level.

[False positive with Tl-201 in the study of Ewing's sarcoma of the astragalus caused by reflex sympathetic dystrophy]. / Falso positivo con T1201 en el estudio de un sarcoma de Ewing de astrágalo causado por una distrofia simpático-refleja.

We describe a 14 year old male, diagnosed of Ewing sarcoma in left astragalus. We performed two 201-Thallium scan for evaluating the response to chemotherapy (before and after the treatment). The scan performed after chemotherapy showed patchy uptake in astragalus, calcaneus and some joints of the foot. The following radiology and scintigraphy diagnosed a reflex sympathetic dystrophy in the left foot due to disuse of the limb. The 201-Thallium overestimated viability of the tumour for this reason. We must discard the presence of this kind of associated pathology in order that they could be cause of false positives.

[Extraosseous accumulation of 99mTc-HMDP in knees with synovial effusion]. / Acúmulo extraóseo de 99mTc-HMDP en rodillas con derrame sinovial.

In the presence of extraosseous activity seen in the late phase of the bone scintigraphy (BS) localized in the distal femur of patients prior to radiation synovectomy, we decided to review the frequency of this finding in 20 patients (24 joints) and its relationship with scintigraphic and clinical parameters. Mild soft tissue accumulation was seen in the late phase of the BS in 14 out of 24 joints, without association between this finding and knee uptake in vascular blood pool and late phases of the BS. However, a significant association with synovial effusion was found, and patients with higher degree of effusion presented extraosseous activity more frequently. In conclusion, we think that soft tissue accumulation in the late phase of the BS is a sign of synovial effusion.

Parir después de los 50 años. Estudio piloto observacional / Birth over 50: A pilot observational study

Objetivos: Evaluar si existe una mayor tasa de resultados obstétricos adversos, incontinencia urinaria posparto y problemas sexuales entre las mujeres que dan a luz después de los 50 años.Material y métodos: Estudio observacional ambispectivo de un solo centro. Se registraron la tasa de parto por cesárea, la diabetes gestacional, la preeclampsia, la restricción del crecimiento intrauterino (RCIU), la prematuridad, la incontinencia urinaria (Cuestionario de incontinencia en formato corto [ICIQ-SF]) y la disfunción sexual (índice de función sexual femenina [FSFI-6]). Resultados: Veinticinco (0,06%) de 38.510 nacimientos ocurrieron en mujeres mayores de 50 años durante el período de estudio en nuestro centro. Hubo 16 (64%) partos por cesárea. Siete (28%) mujeres padecieron diabetes gestacional. Se diagnosticó preeclampsia en 3 (12%) mujeres. Hubo 5 (20%) casos de RCIU. Hubo 5 (20%) partos prematuros. Las diferencias en la tasa de parto por cesárea, diabetes gestacional y RCIU entre el grupo de estudio y la población total fueron estadísticamente significativas. Los resultados de los cuestionarios ICIQ-SF y FSFI-6 se obtuvieron de 17 mujeres. Se encontró algún grado de incontinencia urinaria en 7 (41,1%) y disfunción sexual en 9 (52,9%) mujeres. Conclusiones: Los embarazos en mujeres mayores de 50 años parecen estar asociados con una mayor tasa de diabetes gestacional, RCIU y preeclampsia. Hay una alta prevalencia de incontinencia urinaria y problemas sexuales entre estas mujeres.(AU)

Objectives: To assess whether there is a higher rate of adverse obstetric outcomes, postpartum urinary incontinence, and sexual problems among women who give birth over 50. Material and methods: A single-center ambispective observational study. Rate of cesarean birth, gestational diabetes, preeclampsia, intrauterine growth restriction (IUGR), prematurity, urinary incontinence (Incontinence Questionnaire Short Form [ICIQ-SF]), and sexual dysfunction (Female Sexual Function Index [FSFI-6]) were recorded. Results: Twenty-five (0.06%) of 38,510 births occurred in women over 50 during the study period. There were 16 (64%) cesarean births. Seven (28%) women had gestational diabetes. Preeclampsia was diagnosed in 3 (12%) women. There were 5 (20%) cases of IUGR. There were 5 (20%) preterm births. The differences in the rate of cesarean birth, gestational diabetes, and IUGR between the study group and the total population were statistically significant. The results of the ICIQ-SF and FSFI-6 questionnaires were obtained from 17 women. Some degree of urinary incontinence was found in 7 (41.1%) and sexual dysfunction in 9 (52.9%) women. Conclusions: Pregnancies in women over 50 may be associated with a higher rate of gestational diabetes, IUGR, and preeclampsia. There is a high prevalence of urinary incontinence and sexual problems among these women.(AU)

[Appropriateness of treating glaucoma suspects. Concordancy study with the RAND study group]. / Idoneidad de tratamiento en sospechosos de glaucoma. Estudio de concordancia con el grupo de estudio RAND.

OBJECTIVE: The Appropriateness of Treating Glaucoma Suspects Study Group proposes to identify which patients suspected of glaucoma are suitable for treatment. Our objective is to analyse the concordance between our clinical decisions and this Study Group. METHODS: Retrospective study of 77 patients (39 suspects, 38 ocular hypertensives). Variables such as age, family history, intraocular pressure, disc size, cup-to-disc ratio, central corneal thickness and life expectancy were collected.They were scored following the Appropriateness of Treating Glaucoma Suspects Scale. Whether there was a consensus to treat or not depended on this value. The kappa index was used to measured the concordancy. RESULTS: The kappa index was 0.082 (95% confidence interval between -0.11 and 0.27). Total concordancy was obtained in 41 patients (63,08%). We decided to treat 25 patients (22 of which were not treated by the experts) and not to treat 40 patients (2 of which were treated by the experts). In 12 patients there was noconsensus by the experts to treat, but we decided to treat 8 of them. CONCLUSIONS: [corrected] The concordancy index was low. Others variables such as visual fields and Heidelberg Retina Tomography (HRT III) parameters were not collected by the experts but were important in our decisions. There are no clinical guidelines on suspects. Individualised decisions are still necessary.

Idoneidad de tratamiento en sospechosos de glaucoma. Estudio de concordancia con el grupo de estudio RAND / Appropriateness of treating glaucoma suspects. Concordancy study with the RAND study group

Objetivo: El grupo de estudio Appropriateness of Treating Glaucoma Suspects propone identificar qué pacientes sospechosos de glaucoma son apropiados o no para tratamiento. Nuestro objetivo es analizar la concordancia entre las decisiones clínicas de nuestra unidad de glaucoma y la del panel de expertos. Métodos: Estudio retrospectivo de 77 pacientes (39 sospechosos, 38 hipertensos oculares). Se recogen datos de edad, antecedentes familiares, tamaño de disco óptico, cociente excavación/papila, presión intraocular, paquimetría y esperanza de vida. Se asignó una puntuación, a partir del esquema propuesto por el grupo de trabajo Appropriateness of Treating Glaucoma Suspects, según la cual se decide si es idóneo tratar o no hay consenso. Para analizar la concordancia se calculó el índice kappa. Resultados: El valor de índice kappa fue 0,082 (intervalo de confianza al 95% entre -0,11 y 0,27). Se obtuvo una concordancia completa en 41 de los sujetos (63,08%). Nuestra decisión clínica fue tratar a 25 sujetos (22 no tratados según el comité de expertos) y no tratar a 40 (dos tratados por el comité de expertos). De los 12 individuos en los que el comité no encontraba consenso, en 8 nuestra actitud fue tratar. Conclusiones: El índice de concordancia entre nuestra actitud y la del comité de expertos es bajo. Otras variables no recogidas por los expertos (campo visual y parámetros del láser confocal de barrido [Heidelberg Retina Tomography, HRT III]) fueron importantes en nuestras decisiones. No se han elaborado aún guías clínicas precisas en casos de sospecha por lo que es necesario individualizar el tratamiento(AU)

Objective: The Appropriateness of Treating Glaucoma Suspects Study Group proposes to identify which patients suspected of glaucoma are suitable for treatment. Our objective is to analyse the concordance between our clinical decisions and this Study Group. Methods: Retrospective study of 77 patients (39 suspects, 38 ocular hypertensives). Variables such as age, family history, intraocular pressure, disc size, cup-to-disc ratio, central corneal thickness and life expectancy were collected. They were scored following the Appropriateness of Treating Glaucoma Suspects Scale. Whether there was a consensus to treat or not depended on this value. The kappa index was used to measured the concordancy. Results: The kappa index was 0.082 (95% confidence interval between -0.11 and 0.27). Total concordancy was obtained in 41 patients (63,08%). We decided to treat 25 patients (22 of which were not treated by the experts) and not to treat 40 patients (2 of which were treated by the experts). In 12 patients there was noconsensus by the experts to treat, but we decided to treat 8 of them. Conclussions: The concordancy index was low. Others variables such as visual fields and Heidelberg Retina Tomography (HRT III) parameters were not collected by the experts but were important in our decisions. There are no clinical guidelines on suspects. Individualised decisions are still necessary(AU)

Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial.

OBJECTIVE: To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis. DESIGN: Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses. SETTING: Los Angeles County-University of Southern California Medical Center. PATIENTS: Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis. RESULTS: Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27). CONCLUSION: Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.

[Detection of young female carriers of Duchenne muscular dystrophy]. / Detección de portadoras jóvenes de distrofia muscular de Duchenne.

36 females aged through 1 to 16 years were studied. They were sisters or close kin, on the maternal side, of patients with Duchenne's Muscular Dystrophy (DMD). 23 healthy controls were also studied so as to evaluate the usefulness of determining serum creatine phosphokinase (CPK) as means for detecting young carriers of DMD. 18 of 36 girls (50%) who were the daughters of the affected families, showed CPK seric values more than twice the standard deviation of the mean of the witness group (21 +/- 7.9 U/L). The Bayesian analysis performed on the problem group showed a good correspondence. These findings imply a high range of detection in possible carriers under 16 years of age. We believe that the absence of symptomatology in some of these girls does not eliminate the possibility of being a carrier.

Effect of dexamethasone on insulin receptor mRNA levels, RNA stability and isotype RNA pattern in U-937 human promonocytic cells.

The administration of 5 x 10(-6) mol/l dexamethasone transiently increased insulin receptor (IR) mRNA levels in U-937 human promonocytic cells, which reached the maximum level at 15 h of treatment. Dexamethasone treatment did not affect the IR mRNA half-life (approximately 4 h), suggesting that the increase is regulated at the transcriptional level. The stimulatory action of dexamethasone was not prevented by the simultaneous presence of the protein synthesis inhibitor cycloheximide, indicating that the induction of IR gene transcription occurs as a direct response to the action of the synthetic glucocorticoid. Finally, the A isoform (lacking exon 11) was found to be the only IR isoform present in both untreated and dexamethasone treated-U-937 cells.

The effect of 1,25-dihydroxyvitamin D3 on insulin binding, insulin receptor mRNA levels, and isotype RNA pattern in U-937 human promonocytic cells.

We have studied the effect of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on insulin binding, insulin receptor gene expression, and isotype mRNA pattern in U-937 human promonocytic cells. Binding assays indicated that 1,25-(OH)2D3 increased total receptor number without altering receptor affinity, while the dissociation rate of the hormone bound to its receptor remained unchanged. RNA blot assays indicated that 1,25-(OH)2D3 increased the levels of the two major insulin receptor mRNAs (11 and 8.5 kb) present in these cells. Experiments with the RNA synthesis inhibitor actinomycin D suggested that 1,25-(OH)2D3 did not alter the stability of total insulin receptor mRNA. Experiments with the protein synthesis inhibitor cycloheximide indicated that the increase in the amounts of this mRNA occurs as a direct response to the action of the hormone. Finally, polymerase chain reaction assays revealed that the insulin receptor mRNA isotype lacking the exon 11 (A isotype) was the only one present in both untreated and 1,25-(OH)2D3-treated U-937 cells. This indicates that 1,25-(OH)2D3 does not alter the splicing of the primary insulin receptor transcript in this cell line.

Tissue-specific modulation of insulin receptor mRNA levels in a patient with a phaeochromocytoma.

We have observed that the expression of the insulin-receptor gene is regulated in a tissue-specific manner in a patient with a phaeochromocytoma. Our results indicate that insulin receptor mRNA levels are decreased in adipose tissue and increased in both liver and skeletal muscle as compared with the corresponding values in the same tissues of a control patient. These findings provide the first evidence that insulin receptor mRNA levels may be modulated in vivo by high levels of catecholamines.

Tissue-specific changes in insulin receptor mRNA concentrations in dexamethasone-treated and adrenalectomized rats.

The relative concentrations of total insulin receptor (IR) mRNA were measured in the epididymal adipose tissue and liver of intact untreated rats, dexamethasone-treated rats, adrenalectomized rats and adrenalectomized rats treated with dexamethasone, using RNA blot assays and a specific IR cDNA probe. Northern blot assays revealed two IR mRNA species of approximately 9.5 and 7.5 kb, in both tissues. Dot-Blot assays followed by densitometry indicated that dexamethasone induced an approximately three-fold increase in IR mRNA in liver, but not in epididymal adipose tissue. By contrast, neither adrenalectomy alone nor the combination of adrenalectomy plus dexamethasone treatment altered the IR mRNA concentrations in liver nor in adipose tissue, which indicates that adrenalectomy was able to prevent the stimulation of IR gene expression caused by dexamethasone in rat liver. These results provide evidence for an "in vivo" tissue-specific regulation of IR gene expression, at the mRNA level, in rats under experimental conditions of an excess or insufficiency of glucocorticoids.

[The rodent. Akodon arviculoides, Wagner, 1842 (Cricetidae)--importance in plague foci in Brazil]. / Estudo do roedor Akodon arviculoides, Wagner, 1842 (Cricetidae)--importância nos focos pestosos do Brasil.

The occurrence of the rodent Akodon arviculoides Wagner, 1842 in the plague focus of the "Agreste" region of the State of Pernambuco and a report on its ability for survival, reproduction and development in captivity, its susceptibility to Yersinia pestis infection and the role of this rodent species in Brazilian plague foci are reported.

Persistent Cryptococcus neoformans infection of the prostate after successful treatment of meningitis. California Collaborative Treatment Group.

STUDY OBJECTIVE: To assess the frequency of persistent Cryptococcus neoformans infection in patients with the acquired immunodeficiency syndrome (AIDS) after receiving apparently adequate treatment for meningitis. DESIGN: Blood, urine, and cerebrospinal fluid were cultured at the conclusion of primary therapy to assess the adequacy of treatment. SETTING: Outpatient clinics at three medical centers. PATIENTS: Patients had C. neoformans grown in culture from cerebrospinal fluid. Primary therapy consisted of either 2.0 g of amphotericin B alone; 6 weeks of combination therapy with flucytosine; or, if flucytosine was poorly tolerated, an adjusted minimum total amphotericin B dose. To meet criteria for adequate treatment of meningitis all patients had two sequential cerebrospinal fluid samples which were culture negative. MEASUREMENTS AND MAIN RESULTS: Nine of forty-one patients grew C. neoformans from urine after completion of primary treatment, but none had urinary symptoms. Fungi were visualized in expressed prostatic secretions in 4 of these patients. One patient refused further treatment and developed cryptococcemia within 5 weeks. Three patients received additional amphotericin B; all had persistent funguria without systemic relapse. Six patients received fluconazole; 4 became urine culture negative, and 2 had systemic relapse. CONCLUSION: The persistence of urinary C. neoformans after adequate therapy for meningitis suggests that the urinary tract (probably the prostate) is a sequestered reservoir of infection from which systemic relapse may occur.