Gender,race and socioeconomic influence on diagnosis and treatment of thyroid disorders in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Thyroid diseases are common, and use of levothyroxine is increasing worldwide. We investigated the influence of gender, race and socioeconomic status on the diagnosis and treatment of thyroid disorders using data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of civil servants (35-74 years of age) from six Brazilian cities. Diagnosis of thyroid dysfunction was by thyrotropin (TSH), and free thyroxine (FT4) if TSH was altered, and the use of specific medications. Multivariate logistic regression models were constructed using overt hyperthyroidism/hypothyroidism and levothyroxine use as dependent variables and sociodemographic characteristics as independent variables. The frequencies of overt hyper- and hypothyroidism were 0.7 and 7.4%, respectively. Using whites as the reference ethnicity, brown, and black race were protective for overt hypothyroidism (OR=0.76, 95%CI=0.64-0.89, and OR=0.53, 95%CI=0.43-0.67, respectively, and black race was associated with overt hyperthyroidism (OR=1.82, 95%CI=1.06-3.11). Frequency of hypothyroidism treatment was higher in women, browns, highly educated participants and those with high net family incomes. After multivariate adjustment, levothyroxine use was associated with female gender (OR=6.06, 95%CI=3.19-11.49) and high net family income (OR=3.23, 95%CI=1.02-10.23). Frequency of hyperthyroidism treatment was higher in older than in younger individuals. Sociodemographic factors strongly influenced the diagnosis and treatment of thyroid disorders, including the use of levothyroxine.     

I-123 MIBG and serial radionuclide angiocardiography in doxorubicin-related cardiotoxicity.

In six patients with doxorubicin-related cardiotoxicity, the severity of decrease in left ventricle ejection fraction (LVEF) was associated with faster myocardial I-123 MIBG washout rates. In four patients with severely decreased LVEF (range 19% to 28%), the 4-hour washout rate varied from 43% to 56%. In two patients with moderate cardiotoxicity (LVEF 42% and 43%), the washout rates were 37% and 35%, respectively. In contrast, in another patient thought to have initial left ventricular dysfunction (LVEF dropped from 66% to 54%), the myocardial I-123 MIBG retention rate was not reduced (6% washout). Subsequent continuation of chemotherapy in this patient was without complication. Reduced I-123 MIBG uptake in the left ventricle generally correlated with areas with abnormal Fourier amplitude values, but in one of the patients with moderate cardiotoxicity, the I-123 MIBG uptake was not reduced in a region with loss of amplitude, indicating dysfunction but probably no myocardial denervation. Analysis of the regional myocardial retention in patients with cardiotoxicity showed no significant difference in the I-123 MIBG washout rates of both segments with or without loss of amplitude. These data suggest that in spite of a localized loss of ventricular function demonstrated by radionuclide angiocardiography, doxorubicin-related cardiotoxicity appears to be based on a global process of myocardial adrenergic derangement.     

Technetium-99m dimercaptosuccinic acid and ifosfamide tubular dysfunction in children with cancer

Quantitative ^99mTc-dimercaptosuccinic acid (^99mTc-DMSA) renal scintigraphy was used to asses ifosfamide-induced changes in renal function in 11 children who received chemotherapy for various malignancies. Serial measurements of absolute ^99mTc-DMSA renal uptake, calculated on conjugated views, were performed during and after chemotherapy. Data of 37 studies obtained before and at different cumulative dose levels of ifosfamide were analysed in relation to clinical and biochemical parameters. A highly significant relationship between ^99mTc-DMSA uptake and cumulative ifosfamide dose was found (P<0.001). The most frequently observed abnormal pattern on scintigraphic images was decreased kidney uptake together with increased accumulation in bladder. ^99mTc-DMSA uptake was more consistent than ₂-microglobulin values in urine and more sensitive than quantitative hyperaminoaciduria and tubular resorption of phosphate for the detection of ifosfamide-induced tubular dysfunction. ^99mTc-DMSA uptake was decreased in both patients with and patients without clinical toxicity. Persistently reduced ^99mTc-DMSA uptake was observed in four patients during follow-up; in one of them, who was asymptomatic after ifosfamide therapy, sudden onset of Fanconi syndrome was observed when he was retreated with carboplatin 1 year later. It is concluded that ^99mTc-DMSA renal scintigraphy is a suitable method to assess progressive ifosfamide-induced tubular injury whereas scintigraphic imaging is helpful for interpreting renal uptake changes. The test is able to detect subclinical injury and may potentially predict high risk at retreatment.     

Pharmacological and molecular discrimination of brain I2-imidazoline receptor subtypes

I₂-imidazoline receptors labelled with [³H]-idazoxan in the rabbit and rat brains displayed high and low affinity, respectively, for the guanidide amiloride; reinforcing the previous definition of I_2A-imidazoline receptors expressed in the rabbit brain and Its-imidazoline receptors expressed in the rat brain. Other drugs tested displayed biphasic curves in competition experiments, indicating the existence of high and low affinity sites for both subtypes of I₂-imidazoline receptors. Among the drugs studied, bromoxidine, moxonidine, (+)- and (-)-medetomidine and clorgyline were more potent on the high and/or low affinity sites of 1_2B- than on their corresponding of I_2A-imida-zoline receptors (K _iH ratios 20 to 65). No correlation was found for the potencies of the drugs tested at the low affinity sites of both I₂-imidazoline receptor subtypes. Preincubation (30 min at 25°°C) with 10^-6 M clorgyline reduced by 60% the B _max of [³H]-idazoxan binding to I₂ B-imidazoline receptors in the rat brain, but it did not affect the binding parameters of the radioligand saturation curves to I_2A-imidazoline receptors in the rabbit brain. These results indicated that I_2A- and I_2B-imidazoline receptor subtypes differ in the pharmacological profiles of their high and low affinity sites and in the ability to irreversibly bind clorgyline. In rat cortical membranes western blot detection of immunoreactive imidazoline receptor proteins revealed a double band of 29/30 kDa and two less intense bands of 45 and 66 kDa. In rabbit cortical membranes the antibody used detected proteins of 30, 57 and 66 kDa. It is suggested that different imidazoline receptor proteins (45 vs 57 kDa) may account for the different pharmacological profiles of I2-imidazoline receptor subtypes.     

Cowden disease: report of 8 cases in 2 families (author's transl)]

These 8 cases of multiple hamartoma syndrome are the first reported in Switzerland. Two men aged respectively of 65 and 28 years presented a cobblestone appearance of the gingiva and of the tongue ("pebbly tongue"), which suggested Cowden disease. This diagnosis was confirmed by the discovery of numberous skin lesions, a thyroid goiter, gastrointestinal polyposis, and a mild skelettal dysmorphosis. The older patient had a grade one carcinoma of the bladder; his son and his daughter presented the syndrome, which was also discovered in the family of the second patient (his father, his brother, his sister and one of her daughters). The ultrastructural study of two skin biopsies demonstrated anomalies of the fibroblasts and collagen fibers.     

In vivo imaging of apoptosis by 99mTc-Annexin V scintigraphy: visual analysis in relation to treatment response.

BACKGROUND AND PURPOSE: Anticancer therapy induces apoptosis in a dose- and time-dependent fashion. (99m)Tc-Hynic-rh-Annexin V scintigraphy (TAVS) enables non-invasive in vivo imaging of treatment-induced apoptosis. We identified the visual patterns of (99m)Tc-Hynic-rh-Annexin V tumour uptake and related these to treatment response. PATIENTS AND METHODS: Thirty-three patients with malignant lymphoma (n=26), leukaemia (n=1) NSCLC (n=5), H&NSCC (n=1), scheduled for radiotherapy (n=27), platinum-based chemotherapy (n=5) or concurrent chemoradiation (n=1), underwent TAVS before and early after the start of treatment. Planar and SPECT images were visually examined to assess changes in tumour (99m)Tc-Hynic-rh-Annexin V uptake. Twenty-nine patients were eligible for further analysis. Annexin V uptake before (U(baseline)) and early after (U(post)) the start of treatment was graded using a four-step scale: 0, absent; 1, weak; 2, moderate and 3, intense. The difference between these values (Delta U) was calculated and correlated to tumour response after therapy (Spearman rank correlation test). RESULTS: Weak to moderate U(baseline) was detected in 13/15 patients with a complete response and U(post) was markedly increased in all these cases (Delta U range 1-3). Partial response (n=7) was associated with weak to moderate U(baseline) and a moderately increased U(post) (Delta U range 1-2). In patients with stable disease (n=5), U(baseline) was predominantly weak, without considerable changes in uptake after the start of treatment (Delta U range 0-1). Finally, in case of progressive disease (n=2), either no tumour uptake or a decrease in U(post) was detected (Delta U=-1). A statistically significant correlation was found between changes in (99m)Tc-Hynic-rh-Annexin V tumour uptake and clinical response (correlation coefficient=0.62; P<0.001). CONCLUSIONS: Complete or partial tumour response was associated with a marked increase of (99m)Tc Hynic-rh-Annexin V accumulation early during treatment compared to baseline values. In case of stable or progressive disease, pretreatment scans demonstrated predominantly low (99m)Tc Hynic-rh-Annexin V tumour uptake and no significant increase early after treatment. These results indicate that TAVS might be useful as a predictive test for treatment response.     

Efficacy of a single dose of urapidil for preventing arterial hypertension during the pre-bypass period in coronary surgery

OBJECTIVES: To assess the effect of a single prophylactic dose of urapidil for arterial hypertension during the period before start of extracorporeal circulation. PATIENTS AND METHODS: Forty-four patients with good ventricular function (ejection fraction < 40%) scheduled for coronary surgery were enrolled for prospective study. The patients were randomly assigned to receive 0.5 mg/kg of urapidil (group U, n = 22) or nothing (group N, n = 22) 3 min before skin incision. If hypertension developed sodium nitroprusside was administered, starting with a dose of 0.5 microgram/kg/min. Monitoring of arterial pressure, heart rate and ST segment (DII and V5) was continuous. The study ended with cannulation of the aorta. RESULTS: The demographic features, cardiovascular history, medication and duration of surgery were comparable in the two groups. Six patients in group U (27%) and 19 in group N (86%) developed arterial hypertension (p < 0.001), the duration of which was 2.23 +/- 4.49 min in group U and 9.64 +/- 9.7 min in group N (p < 0.05). Arterial hypotension was observed in 13 group U patients and 7 group N patients (NS). No significant differences in duration of tachycardia, bradycardia or myocardial ischemia were found. CONCLUSIONS: The administration of a single dose of urapidil prevents arterial hypertension during the phase before extracorporeal circulation for coronary surgery and reduces the need for nitroprusside. No clinically relevant side effects are evident.     

Natural infection in Pampas fox (Lycalopex gymnocercus) by Lagochilascaris major Leiper, 1910 (Nematoda: Ascarididae) in Buenos Aires,Argentina

Parasitology Research - Lagochilascariosis is an emerging parasitic disease limited to the American continent, caused by nematodes of the genus Lagochilascaris. Its life cycle is heteroxenous,...