Diagnóstico na infância: quais as implicações possíveis? / Diagnosis of childhood: what are the possible implications?

Este artigo objetivou abordar as especificidades do processo diagnóstico nas psicopatologias na infância apartir de uma revisão da literatura. Num primeiro momento, realizou-se uma fundamentação teóricaacerca de como a psicanálise concebe o diagnóstico, contrapondo com a perspectiva médica.Posteriormente, refletiu-se sobre como pensar esse processo na infância, considerando suasparticularidades. Por fim, discutiram-se as repercussões do ato diagnóstico nesse período tão peculiar,tendo como inspiração recortes da prática em psicologia clínica e escolar, articulando-os com os achadosteóricos. Enfim, discutiu-se sobre a excessiva prescrição medicamentosa percebida na atualidade, comotambém sobre os efeitos possíveis que podem surgir nos espaços por onde a criança circula: seu meiofamiliar, escolar e social(AU)

Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure.

BACKGROUND: Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V(1A) (vascular and myocardial effects) and V(2) receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. METHODS AND RESULTS: A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V(1a)/V(2) vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6+/-0.7, -5.4+/-0.7, and -4.6+/-0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0+/-0.4, -3.7+/-0.4, and -3.5+/-0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11+/-17, 68+/-17, 152+/-19, and 176+/-18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. CONCLUSIONS: In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.

The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients with type 2 diabetes mellitus poorly controlled with sulfonylurea and metformin. A multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The thiazolidinediones are a new class of antidiabetes medication that enhances the actions of insulin in muscle, liver, and adipose tissue. Data have been lacking on their use in combination with both sulfonylurea and metformin among patients for whom insulin is the usual therapeutic alternative for improved glycemic control. OBJECTIVE: To determine the effects of troglitazone on hemoglobin A(1c) level in patients treated with maximum tolerated doses of sulfonylurea and metformin who have hemoglobin A(1c) levels of at least 0.085 (8.5%). This trial was completed before troglitazone was taken off the U.S. market. DESIGN: Randomized, double-blind, placebo-controlled trial, followed by an open-label extension during which all patients received troglitazone. SETTING: 16 outpatient clinics in Canada. PATIENTS: 200 patients (mean age, 59 years) with type 2 diabetes mellitus and hemoglobin A(1c) levels at least 0.085 (8.5%) (mean hemoglobin A(1c) level, 0.097 [9.7%] and mean fasting plasma glucose level, 12.9 mmol/L [233 mg/dL]) while receiving maximum doses of sulfonylurea and metformin. MEASUREMENTS: Levels of hemoglobin A(1c), fasting plasma glucose, total insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. RESULTS: Troglitazone, 400 mg/d, when added to sulfonylurea and metformin, significantly decreased hemoglobin A(1c) level by 0.014 +/- 0.002 (95% CI, 0.0167 to 0.0109; P < 0.001) (1.4% +/- 0.2% [CI, 1.67% to 1.09%]) and insulin by 19 +/- 4 pmol/L (CI, 30 to 10 pmol/L; P < 0.001). At 6 months, 43% of troglitazone-treated patients achieved hemoglobin A(1c) levels of 0.08 (8%) or lower compared with 6% of placebo recipients. Efficacy was maintained at 12 months. CONCLUSIONS: The thiazolidinedione troglitazone, at a dosage of 400 mg/d, is effective when used in combination with sulfonylurea and metformin. Thiazolidinediones may therefore offer an effective alternative to insulin for patients treated with sulfonylurea and metformin who do not achieve adequate glycemic control.

Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial.

We hypothesized that the administration of troglitazone, an insulin-sensitizing agent of the thiazolidinedione class, would improve the ovulatory dysfunction, hirsutism, hyperandrogenemia, and hyperinsulinemia of polycystic ovary syndrome (PCOS) patients. Four hundred and ten premenopausal women with PCOS in a multicenter, double blind trial were randomly assigned to 44 weeks of treatment with placebo (PBO) or troglitazone [150 mg/day (TGZ-150), 300 mg/day (TGZ-300), or 600 mg/day (TGZ-600)]. We compared changes in ovulatory function (by monitoring the urinary level of pregnanediol-3-glucuronide daily), hirsutism (by a modified Ferriman-Gallwey scoring method), hormonal levels (total and free testosterone, androstenedione, sex hormone-binding globulin, LH, FSH, and the LH/FSH ratio), and measures of glycemic parameters (fasting levels of glucose, insulin, hemoglobin A(1c), and the glucose and insulin areas under the curve during an oral glucose challenge) among study groups. Of the 410 patients recruited, 305 (74.4%) met evaluability criteria and were included in the analyses. The patients' baseline characteristics were similar across all treatment arms. Ovulatory rates were significantly greater for patients receiving TGZ-300 and TGZ-600 than for those receiving PBO (0.42 and 0.58 vs. 0.32; P < 0.05 and 0.0001, respectively). Of PCOS patients treated with TGZ-600, 57% ovulated over 50% of the time compared with 12% of placebo-treated patients. There was a significant decrease in the Ferriman-Gallwey score with TGZ-600 compared with PBO (0.22 +/- 0.53 vs. -2.21 +/- 0.49; P < 0.05, respectively). Free testosterone decreased and sex hormone-binding globulin increased in a dose-related fashion with troglitazone treatment, and all three troglitazone treatment groups were significantly different from placebo. Nearly all glycemic parameters showed dose-related decreases with troglitazone treatment. The total number and severity of adverse events (including elevations in liver enzymes) and the proportion of patients withdrawn from the study due to the development of adverse effects were similar between treatment groups. Troglitazone improves the ovulatory dysfunction, hirsutism, hyperandrogenemia, and insulin resistance of PCOS in a dose-related fashion, with a minimum of adverse effects.

Troglitazone in combination with sulfonylurea restores glycemic control in patients with type 2 diabetes. The Troglitazone Study Group.

OBJECTIVE: To determine if the combination of troglitazone (a peroxisome proliferator-activated receptor-gamma activator) and sulfonylurea will provide efficacy not attainable by either medication alone. RESEARCH DESIGN AND METHODS: There were 552 patients inadequately controlled on maximum doses of sulfonylurea who participated in a 52-week randomized active-controlled multicenter study. Patients were randomized to micronized glyburide 12 mg q.d. (G12); troglitazone monotherapy 200, 400, or 600 mg q.d. (T200, T400, T600); or combined troglitazone and glyburide q.d. (T200/G12, T400/G12, T600/G12). Efficacy measures included HbA1c, fasting serum glucose (FSG), insulin, and C-peptide. Effects on lipids and safety were also assessed. RESULTS: Patients on T600/G12 had significantly lower mean (+/- SEM) FSG (9.3 +/- 0.4 mmol/l; 167.4 +/- 6.6 mg/dl) compared with control subjects (13.7 +/- 0.4 mmol/l; 246.5 +/- 6.8 mg/dl; P < 0.0001) and significantly lower mean HbA1c (7.79 +/- 0.2 vs. 10.58 +/- 0.18%, P < 0.0001). Significant dose-related decreases were also seen with T200/G12 and T400/G12. Among patients on T600/G12, 60% achieved HbA1c < or =8%, 42% achieved HbA1c < or =7%, and 40% achieved FSG < or =7.8 mmol/l (140 mg/dl). Fasting insulin and C-peptide decreased with all treatments. Overall, triglycerides and free fatty acids decreased, whereas HDL cholesterol increased. LDL cholesterol increased slightly, with no change in apolipoprotein B. Adverse events were similar across treatments. Hypoglycemia occurred in 3% of T600/G 12 patients compared with <1% on G12 or troglitazone monotherapy CONCLUSIONS: Patients with type 2 diabetes inadequately controlled on sulfonylurea can be effectively managed with a combination of troglitazone and sulfonylurea that is safe, well tolerated, and represents a new approach to achieving the glycemic targets recommended by the American Diabetes Association.

Troglitazone monotherapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled study. The Troglitazone Study Group.

To assess the effects of troglitazone monotherapy on glycemic control in patients with type 2 diabetes mellitus, we carried out a 6-month, randomized, double-blind, placebo-controlled study in 24 hospital and outpatient clinics in the United States and Canada. Troglitazone 100, 200, 400, or 600 mg or placebo once daily with breakfast was administered to 402 patients with type 2 diabetes with fasting serum glucose (FSG) > 140 mg/dL, glycosylated hemoglobin (HbA1c) > 6.5%, and fasting C-peptide > or = 1.5 ng/mL. Prior oral hypoglycemic therapy was withdrawn in patients who received it before the study. FSG, HbA1c, C-peptide, and serum insulin were evaluated at baseline and the end of the study. Analysis was performed on two subsets of patients based on prestudy therapy: Patients treated with diet and exercise only before the study (22% of patients), and those who had been receiving sulfonylurea therapy (78% of patients). Patients treated with 400 and 600 mg troglitazone had significant decreases from baseline in mean FSG and HbA1c at month 6 compared with placebo-treated patients (FSG: -51 and -60 mg/dL, respectively; HbA1c: -0.7 and -1.1%, respectively). In the diet-only subset, 600 mg troglitazone therapy resulted in a significant (P < 0.05) reduction in HbA1c (-1.35%) and a significant reduction in FSG (-42 mg/dL) compared with placebo. Patients previously treated with sulfonylurea therapy had significant (P < 0.05) decreases in mean FSG with 200-600 mg troglitazone therapy compared with placebo (-48, -61, and -66 mg/dL, respectively). Significant (P < 0.05) decreases in mean HbA1c occurred with 400 and 600 mg troglitazone therapy at month 6 (-0.8 and -1.2%, respectively) compared with placebo in this same subset. Significant (P < 0.05) decreases in triglycerides and free fatty acids occurred with troglitazone 400 and 600 mg, and increased high-density lipoprotein occurred with 600 mg troglitazone. We conclude that troglitazone monotherapy significantly improves HbA1c and fasting serum glucose, while lowering insulin and C-peptide in patients with type 2 diabetes. Troglitazone 600 mg monotherapy is efficacious for patients who are newly diagnosed and have never received pharmacological intervention for diabetes.

Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep.

Continuous withdrawal of hypophyseal portal blood from unrestrained sheep has permitted detailed assessments of the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the sensory dynamics of pituitary hormones, patterns of luteinizing hormone (LH) in the hypophyseal portal blood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood were collected every 5 min from six ovariectomized ewes over 6-12 h. Hypophyseal portal blood contained GnRH-associated, sharply defined LH pulses that were much larger than in the periphery. Pulses of secreted LH (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an average of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated baselines. The interpulse baseline concentrations of secreted LH (99.6 ng/mL) in hypophyseal portal blood were 31-fold higher than those for jugular LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must represent newly secreted LH. The non-Gaussian profiles of this secreted LH were substantially more complex than the inputs predicted from jugular LH measurements by deconvolution. Furthermore, regardless of the analytical approach, estimations of the mass of secreted LH in each pulse did not correlate well with inputs predicted by deconvolution or Kushler-Brown pulsefit analysis of corresponding pulses in jugular blood (r2 ranging 0.40-0.48). Among alternative explanations is the possibility of heterogeneity in concentrations of GnRH in the portal vessels and variable distribution within the hypophysis. In summary, assay of hypophyseal portal blood obtained directly from the pituitary provides a method for direct assessment of secretory responses to hypothalamic peptides, and thereby serves as an unmatched method for studying the dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more sharply defined that those in the periphery, include non-GnRH-dependent, secretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.

Cardiac and glycemic benefits of troglitazone treatment in NIDDM. The Troglitazone Study Group.

Troglitazone is a thiazolidinedione under development for the treatment of NIDDM and potentially other insulin-resistant disease states. Treatment with troglitazone is associated with an improvement in hyperglycemia, hyperinsulinemia, and insulin-mediated glucose disposal. No significant side effects have been observed in humans. Because of reported cardiac changes in animals treated with drugs of this class, this multicenter 48-week study was conducted to evaluate whether NIDDM patients treated with troglitazone develop any cardiac mass increase or functional impairment. A total of 154 NIDDM patients were randomized to receive troglitazone 800 mg q.d. or glyburide titrated to achieve glycemic control (< or =20 mg b.i.d. or q.d.). Two-dimensional echocardiography and pulsed Doppler were used to measure left ventricular mass index (LVMI), cardiac index (CI), and stroke volume index (SVI). All echocardiograms were performed at each center (baseline, 12, 24, 36, and 48 weeks), recorded on videotape, and forwarded to a blinded central echocardiographic interpreter for analysis. The results showed that LVMI of patients treated with troglitazone was not statistically or clinically different from baseline after 24 or 48 weeks. Statistically significant increases in SVI and CI and a statistically significant decrease in diastolic pressure and estimated peripheral resistance were observed in troglitazone-treated patients. These results were not sex-specific. Glycemic benefits of troglitazone treatment were observed as evidenced by long-term improvement of HbA1c and C-peptide levels. Furthermore, triglycerides were significantly lower, and HDL was significantly higher at weeks 24 and 48. In conclusion, NIDDM patients treated with troglitazone do not show any cardiac mass increase or cardiac function impairment. Conversely, patients on troglitazone benefited from enhanced cardiac output and stroke volume, possibly as a result of decreased peripheral resistance. Treatment with troglitazone appears to have a favorable impact on known cardiovascular risk factors and could potentially lower cardiovascular morbidity in NIDDM patients.

Continuous on-line hydrogen ion monitoring to study flow dynamics of perifusion systems and cellular metabolism.

Time-dependent concentration profiles of input signals and feedback of metabolic products can strongly influence cellular responsiveness. To study these parameters, we developed a perifusion system that can deliver biological signals to cells with minimal dispersion, monitor real time responses, and remove waste products continuously. By monitoring pH with miniature hydrogen ion-selective electrodes at intervals of 1 s, effects of dispersion, flow rate, pumping system, and changes in cellular metabolism were demonstrated. Dynamic responses of a human cell line to a series of 10-min pulses of the metabolic uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) were monitored. A rapid 1-min increase in acid release occurred on exposure to CCCP, followed by a decrease in acidification and then a gradual return to a baseline slightly more acidic than before administration of CCCP. These observations demonstrate that this perifusion system can reveal small changes in pH (+/- 0.0005 units) induced by metabolic perturbations and has the potential to reveal the dynamics of cellular responsiveness to a wide range of hormonal, metabolic, and other chemical signals.