Importancia de la historia familiar en el cáncer de mama y ovario

Objetivo: Presentar el caso de una paciente, quien acudió para evaluación ginecológica. La misma resultó clínicamente sana pero en su grupo familiar destaca la alta frecuencia de cáncer de mama y de ovario, lo cual indujo a sospechar alto riesgo para el cáncer de mama hereditario (CaMH); a propósito del mismo se revisa esta patología y se resalta la importancia de la historia familiar. Caso clínico: Mujer de 25 años de edad, que acude a la consulta para realizar control ginecológico. Diagnóstico: paciente clínicamente sana, pero con antecedentes familiares, de alta frecuencia de cáncer de mama (CaM) y cáncer de ovario, razón por la cual se procede a investigar al grupo familiar. Se revisan las historias clínicas del archivo del IAHULA y se entrevistan los familiares. Familia no consanguínea, padres sanos, mayores de 70 años sin cáncer, 3 hermanos y 7 hermanas. Cuatro hermanas fallecieron en un periodo de 9 años, en edades comprendidas entre 24 y 35 años: 3 por CaM y 1 por Ca de ovario, tía materna con CaM y abuela paterna con probable Ca de ovario (síndrome ascítico no ictérico) ambas fallecidas en el medio rural. Antecedentes personales de las 4 hermanas fallecidas: menarquia en promedio de 12.3 años, paridad y lactancia 2/4, nulípara 2/4, ninguna obesa, ni hábitos alcohólicos. Al momento del diagnóstico todas en estadios avanzados de cáncer. Tipo histopatológico del CaM: ductal infiltrante poco diferenciado (2/3), lobulillar y medular (2/3); bilateral (1/3); sin determinar receptores de estrógeno, progesterona o andrógenos. Metástasis a cerebro y pulmón (2/3) durante tratamiento. En ovario: cistoadenoma mucinoso, estadio IV, recidiva al año a pesar del tratamiento. Sobrevida de 3 meses a 3 años. A la paciente se le recomendó realizar el estudio genético para poder precisar el riesgo de padecer cáncer de Mama y ovario Hereditario (CaMH) y establecer las medidas de vigilancia. Conclusiones: Se recomienda que ante una paciente con antecedentes familiares de CaM, se investigue a fondo su historia familiar, la cual aún en ausencia de marcadores genéticos, permite sospechar la presencia de un CaMH el cual requiere de un protocolo de prevención y vigilancia diferente al CaM esporádico.

Objective: To present the case of a patient, who went for a gynecological assessment. She was healthy but in his family group stressed a high frequency of breast and ovarian cancer, which led to suspect high risk for hereditary breast cancer (HBCa). This condition is reviewed, highlighting the importance of family history. Case report: A 25 year old woman who consults for a gynecological examination. Healthy patient with a high frequency of breast cancer (BCa) in her family. Not consanguineous family. Healthy parents, 3 brothers and 6 sisters. Four sisters died within a period of 9 years, aged between 24 and 35 years old: 3 from BCa and 1 from ovarian cancer. Maternal aunt with BCa and paternal grandmother with ovarian cancer. Personal history of the 4 deceased sisters: average age of menarche 12.3 years, parity and lactation 2/4, nulliparous 2/4, no obesity, nonalcoholic habits. Initial diagnosis in advanced stages of cancer. Histopathological type of BCa: poorly differentiated (2/3), lobular and medullary (2/3); bilateral 1/3; lung and brain metastases during treatment (2/3). In ovarian: mucinous cystadenoma stage IV, recurrence in one year despite treatment. Survival between 3 months and 3 years. The patient is recommended to perform the genetic study in order to clarify the risk of suffering BCa and surveillance measures. Conclusions: It is recommended in a patient with a family history of BCa, to carry out a thorough investigation of family history, which, even in the absence of genetic markers, allows to suspect the presence of hereditary breast cancer.

Relationship between BMI, total testosterone, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men.

The objective of this work was to evaluate the relationship between sex steroid hormones, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Anthropometrical indexes, total testosterone (Tt), free testosterone (fT), estradiol (E), sex hormone-binding-globulin (SHBG), glucemia, insulin and leptin were measured in 77 men, with ages between 20 and 60 years. According to their body mass index (BMI), subjects were grouped into three categories: normal body weight (< 24.9 kg/m2), overweight (25-29.9 kg/m2) and obese group (> 30 kg/m2). Insulin resistance index was obtained by the homeostasis assessment model for insulin resistance (HOMA-IR). Total testosterone and SHBG concentrations were lower in the obese group compared with normal and overweight subjects (p < 0.05). The mean insulin concentration was significantly higher in the obese group compared with the other groups (p < 0.05). T was negatively correlated with the BMI (r = -0.447; p < .01), WC (r = -0.464); p < .01, leptin (r = -0.382; p < .01), insulin (r = -0.391; p < 0.01) and also with the HOMA-IR (r = -0.416; p < 0.01). The SHBG negatively and significantly correlated with BMI (r = -0.334; p < 0.01) and WC index (= -0.322; p < 0.01), as well with insulin levels (r = -0.313; p < 0.01) and insulin resistance (= -0.266; p < 0.05). Our results shows that in a sample of men, Tt and SHBG concentrations proportionally diminished with both the increase of BMI and insulin resistance index.

[Atherogenic lipid profile in children with subclinical hypothyroidism]. / Perfil lipídico aterogénico en niños con hipotiroidismo subclínico.

OBJECTIVE: To evaluate lipid profile in children with subclinical hypothyroidism. PATIENTS AND METHODS: Forty-six children of both sexes aged between 2 and 9 years old, 17 with subclinical hypothyroidism (study group) and 23 healthy children (control group), were studied. Subclinical hypothyroidism was diagnosed when levels of thyroid-stimulating hormone (TSH) were greater than 4.65 .U/mL and those of free thyroxin (fT4) were normal. Children with subclinical hypothyroidism were observed for 4 months with no interventions and TSH and fT4 were again determined to confirm the diagnosis. A complete medical history was taken and a blood sample was extracted for lipid determinations including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Anti-thyroglobulin antibodies (ATGA) and antithyroid peroxidase (anti-TPO) antibodies were also determined. RESULTS: Of the 17 children who initially presented elevated serum TSH levels, seven (41.2 %) had normal levels at 4 months and were consequently excluded. No significant differences were found in age, weight, height or body mass index between the study and the control groups. No differences were found between the two groups in levels of anti-TPO antibodies and ATGA. The mean plasma HDL-C level was significantly lower in children with subclinical hypothyroidism than in controls (p < 0.05) and a statistically significant association (p < 0.013) was found between the presence of subclinical hypothyroidism and a greater frequency of low HDL-C levels. CONCLUSION: Subclinical hypothyroidism may be transitory in a considerable percentage of children. Children with subclinical hypothyroidism had significantly lower HDL-C levels, suggesting an atherogenic lipid profile in this entity.

Surgical vs. untreated cryptorchidism: effects on fertility.

Forty-four patients with history of cryptorchidism were studied: 15 untreated (group A); 14 treated by orchiopexy at age 4.5 +/- 1.4 years (group B), and 15 with unilateral orchiectomy of undescended testis at 8.4 +/- 1.6 years (group C). Testicular volume, semen analysis, and LH and FSH were measured. Normal sperm counts were noted in 53%, 36% and 47% of patients in groups A, B and C, respectively. FSH and LH serum levels showed no differences between the groups. Testicular volume of the normal descended testes showed no differences between the three groups. Positive correlation was obtained between testicular volume/sperm concentration and negative correlation between gonadotropins/sperm concentration. The remaining testicular volume and gonadotropin serum values from adults with history of chryptorchidism who underwent orchiectomy were not different from those orchiopexied treated nor with untreated patients. The percentage of men with sperm count greater than 20 millions/mL was lower in the orchiopexied men compared to A and C groups. There seems to be different etiologic factors in our patients.

GnRH and hCG tests in healthy adolescents and adults.

With the aim of obtaining reference values of GnRH test and of hCG test in a Venezuelan population, the authors evaluated the response of the pituitary LH and FSH to the GnRH action in 48 adolescents and 43 adults. Also, in 22 adolescents and in 22 adults from the same sample they evaluated the hCG effect on the gonadal steroids secretion. The maximum LH increment was obtained 30 min after GnRH stimulation, independently from the patients' age and their sexual development. FSH maximum increment was obtained 60 min after GnRH in the adults; meanwhile, the FSH maximum increment was obtained 30 min after GnRH stimulation in the Tanner stage 4 adolescents, and 90 min post-GnRH in the Tanner 5 adolescents. The gonadal steroid secretion 2, 24, 48, and 72 h post-hCG was significantly lower in the Tanner 4 adolescents. The gonadal steroid response post-hGC stimulation in the Tanner 5 adolescent group was similar to the one obtained in the adults. In late puberty the LH response to GnRH stimulus is not related either to age or to sexual development, contrary to the FSH response obtained after GnRH and the gonadal steroid response after hCG stimulus, both of which are related to age and patients' sexual development.

[Concentration of thyrotropic hormone and free thyroxin in children with Down's syndrome]. / Concentraciones de hormona tirotropa y tiroxina libre en niños con síndrome de Down.

The incidence of hypothyroidism is higher among children with Down syndrome than among children in the general population. The frequency of hypothyroidism is higher in the areas of endemic goiter than in other areas. The aim of this paper was to study the concentrations of TSH and FT4 in children with Down syndrome residents of Mérida, a region of Venezuelan Andes. At the Centro de Estudio y Prevención del Retardo Mental y Alteraciones en el Desarrollo (CEPREMAD), the thyroid function was studied in 48 children (1 month to 6 years old), who had Down syndrome, and in 123 healthy children of similar ages. All the children were referred to the Center for thyroid function evaluation. Two (4.2%) of the 48 children with Down syndrome had congenital hypothyroidism and 22 (45.8%) had subclinical hypothyroidism (high concentration of thyrotropin-TSH). Among the control children, only 14% had elevated levels of TSH. There were no differences in relation to the gender. In conclusion in children with Down syndrome, the frequency of high concentrations of TSH was three times higher than the frequency among the healthy children. The frequency of hypothyroidism was similar to that found in areas without endemic goiter.

[Influence of age and gender on plasma norepinephrine changes produced by orthostatic stress]. / Influencia de la edad y el sexo sobre los cambios de norepinefrina plasmática producidos por el stress ortostático.

The aim of this work was to determine the effect of aging and gender on plasma norepinephrine (NE) response to orthostatic stress. Fifty-six men and sixty women non-smokers, sedentary, non-obese, were studied at supine and standing positions. On the basis of the age of the subjects, they were divided into three groups of either men or women. Group A, young, range 17-34 years, Group B, middle-age, range 40-60 years, and Group C: senescent, range 61-91 years. Senescent subjects had the highest absolute supine values of NE and significant differences between women and men were found in groups B Men: 298 +/- 15 pg/mL; Women: 348 +/- 14 pg/mL), and C (M: 386 +/- 29 pg/mL; W: 473 +/- 19 pg/mL), but not between young (M: 246 +/- 21 pg/mL; W: 261 +/- 18 pg/mL). NE increased markedly in response to the orthostatic stress but the relative (percentage) increases were smaller in the older subjects perhaps related to their elevated baseline levels. The highest percent positive variation was observed in group A (M: 85%; W: 82%). The oldest group (C), had the lowest variation (M: 23%; W: 21%). The relative increases in NE responses were not different in men and women. The orthostatic-induced variation in NE was negatively related to aging in both men and women (M: r = -0.654; p < 0.0001; W: r = -0.557; p < 0.0001). It is concluded that orthostatic stress induced rise of blood NE is attenuated by age but does not appear to be dependent on gender.

Nonsperm cells in human semen and their relationship with semen parameters.

The prevalence and clinical significance of leukocytes (WBC) and immature germ cells in semen is currently a matter of controversy. The aim of this work was to assess the prevalence of leukocytospermia in semen samples from Venezuelan men and its possible effects on sperm parameters. The concentration of WBC and round cells (RC) was evaluated in 118 semen samples from 19 fertile subjects (group 1), 62 infertile patients (group II), and 37 men with varicocele (group III). Semen WBC concentration was assessed by peroxidase assay. Twenty-six (22%) of the total samples had more than 10 WBC/mL semen. Twenty of the infertile men had leukocytospermia (32%) compared with 16% in the fertile group and 8% in the varicocele group. Semen RC concentration was lower than 5 x 10(6)/mL in all groups but, in groups II and III was significantly higher compared with group I. Infertile men had the highest WBC concentration. WBC concentration was negatively correlated with progressive motility, percentage of morphologically normal sperm, and hypoosmotic swelling test in infertile men but not in the varicocele group. In this group a negative correlation was obtained between immature germ cells and normal sperm morphology. The data show that leukcytospermia occurs frequently in infertile patients and is associated with poor semen quality parameters. In contrast, in men with varicocele, the increased number of immature germ cells might play a pivotal role in the pathogenesis of abnormal spermatozoa.

Postprandial triglyceride response in patients with polycystic ovary syndrome: relationship with waist-to-hip ratio and insulin.

OBJECTIVE: To examine the postprandial triglyceride response to a high-fat meal in women with polycystic ovary syndrome (PCOS) compared with a matched control group. DESIGN: Controlled clinical study. SETTING: Department of Endocrinology and Pathophysiology, School of Medicine, Universidad de Los Andes. PATIENT(S): 18 Hispanic women with PCOS (nine overweight and nine nonobese) and 9 healthy control women. INTERVENTION(S): Biometric measures and blood sample collection. MAIN OUTCOME MEASURE(S): Insulin and glucose levels during a standard oral glucose tolerance test. Plasma triglyceride, cholesterol, and high-density lipoprotein cholesterol levels were measured at baseline and at 4, 5, and 6 h after a high-fat meal. RESULT(S): Both obese and nonobese PCOS women had higher waist-to-hip ratios than controls. PCOS women had higher levels of fasting and postglucose insulin and fasting triglyceride and postprandial triglyceride response and had lower levels of postprandial high-density lipoprotein cholesterol response, but no significant differences within PCOS groups were observed. CONCLUSION(S): An expanded postprandial hypertriglyceridemia in PCOS women is related to a higher waist-to-hip ratio and insulin resistance, regardless of obesity, and contributes to increase the risk for coronary artery disease.

[Effect of budesonide on bone density and metabolism in asthmatic children]. / Efecto de budesonida sobre la densidad y el metabolismo óseo en niños asmáticos.

OBJECTIVE: To assess the effect of inhaled budesonide on the mineral density, content and bone metabolism in children with asthma. MATERIAL AND METHODS: From September 1996 to July 1997, a cross-sectional study was conducted in 38 prepubertal children aged 6 to 11 years, selected from the pediatric chest outpatient clinic of the Instituto Autónomo Hospital Universitario de Los Andes, Mérida, Venezuela. Three study groups were assembled: 9 asthmatic children treated with inhaled budesonide (300 micrograms/day) for over 6 months (Group A); 14 asthmatic children not treated with inhaled corticosteroids (Group B); and 15 non-asthmatic children (Group C). All of them underwent testing of bone formation and resorption markers, and measurement of bone mineral density (DMO) and content (CMO). Statistical analysis consisted of central tendency and dispersion measures, analysis of variance, and Fisher and Scheffe tests for comparison of means. RESULTS: In the groups studied (A, B, and C) calcium serum levels were 9.1 +/- 0.3; 9.6 +/- 0.4; 9.3 +/- 0.6 mg/ml, respectively; osteocalcin levels were 14.8 +/- 4.6; 13.0 +/- 2.5; 11.9 +/- 3.4 ng/dl; the type I collagen carboxyterminal telopeptide (ICTP) levels were 19.6 +/- 16.5; 14.2 +/- 15.4; 13.0 +/- 18.3 micrograms/l; the DMO levels were 0.67 +/- 0.06; 0.68 +/- 0.06; 0.69 +/- 0.06 g/cm2; and the CMO levels were 1,158.8 +/- 217.4; 1,106.4 +/- 256.1; 1,176.5 +/- 240.5 g, respectively. No statistically significant differences were observed between the groups. CONCLUSIONS: The administration of 100-400 micrograms/day of inhaled budesonide for a period of six months, did not change the bone mineral density and metabolism of asthmatic children.

Heart rate responses to a muscarinic agonist in rats with experimentally induced acute and subacute chagasic myocarditis.

We administered arecoline to rats, with experimentally induced chagasic myocarditis, in order to study the sinus node sensitivity to a muscarinic agonist. Sixteen month old rats were inoculated with 200,000 T. cruzi parasites ("Y" strain). Between days 18 and 21 (acute stage), 8 infected rats and 8 age-matched controls received intravenous arecoline as a bolus injection at the following doses: 5. 0, 10.0, 20.0, 40.0, and 80.0 microg/kg. Heart rate was recorded before, during and after each dose of arecoline. The remaining 8 infected animals and 8 controls were subjected to the same experimental procedure during the subacute stage, i.e., days 60 to 70 after inoculation. The baseline heart rate, of the animals studied during the acute stage (349 +/- 68 bpm, mean +/- SD), was higher than that of the controls (250 +/- 50 bpm, p < 0.005). The heart rate changes were expressed as percentage changes over baseline values. A dose-response curve was constructed for each group of animals. Log scales were used to plot the systematically doubled doses of arecoline and the induced-heart rate changes. The slope of the regression line for the acutely infected animals (r = - 0.99, b =1.78) was not different from that for the control animals (r = - 0.97, b = 1.61). The infected animals studied during the subacute stage (r = - 0.99, b = 1.81) were also not different from the age-matched controls (r = - 0.99, b = 1.26, NS). Consequently, our results show no pharmacological evidence of postjunctional hypersensitivity to the muscarinic agonist arecoline. Therefore, these results indirectly suggest that the postganglionic parasympathetic innervation, of the sinus node of rats with autopsy proved chagasic myocarditis, is not irreversibly damaged by Trypanosoma cruzi.

Cardiac afferents and neurohormonal activation in congestive heart failure.

Cardiac chambers have afferent connections to the brainstem and to the spinal cord. Vagal afferents mediate depressor responses and become activated by volume expansion, increased myocardial contractility and atrial natriuretic factor. Sympathetic afferents, on the contrary, are activated by metabolic mediators, myocardial ischemia and cardiac enlargement. These opposite behaviors may lead to activation or suppression of the sympathetic nervous system and of the renin-angiotensin-aldosterone system. As cardiac diseases progress, the heart dilates, plasma norepinephrine increases, atrial natriuretic factor is released and the renin-angiotensin-aldosterone system is suppressed to maintain water and sodium excretion. This dissociation of the neurohormonal profile of cardiac patients, may be explained by coactivation of sympathetic afferents, by cardiac dilatation, and of vagal afferents by atrial natriuretic factor. In more advanced stages, atrial natriuretic factor suppression of the renin-angiotensin-aldosterone system is overridden by overt sympathetic activation and sodium and water retention ensues. Digitalis, angiotensin-converting enzyme inhibitors and beta-blockers selectively decrease cardiac adrenergic drive. A common mechanism of action, to all three groups of drugs, would be attenuation of sympathetic afferents and partial normalization of vagal afferents. Consequently, heart size and cardiac afferents emerge as the key factors to understand the pathophysiology and treatment of the syndrome of congestive heart failure.

[Adrenal function and lipid metabolism in asthmatic children treated with budesonide]. / Función adrenal y metabolismo lipídico en niños asmáticos tratados con budesonida.

OBJECTIVE: To assess the effect of low doses of inhaled budesonide on the adrenal function and lipid metabolism of asthmatic children. MATERIAL AND METHODS: The study included 10 asthmatic children (mean age, 8.8 years) treated with inhaled budesonide (200-300 micrograms/day) for a period longer than 3 months (group A); 15 asthmatic children (mean age, 7.8 years) without steroid treatment (group B) and 10 non-asthmatic children (group C). Basal cortisol levels, as well as postACTH, adrenal androgens, lipids and urinary cortisol were determined. RESULTS: No significant differences were detected between groups A and B in the studied variables. In asthmatic children, urinary cortisol was significantly higher than in non-asthmatic children. Triglycerides, total cholesterol, low density lipoprotein cholesterol and atherogenic index levels were higher in asthmatic children with and without budesonide treatment, compared with non-asthmatic children. CONCLUSIONS: Treatment of asthmatic children with low doses of inhaled budesonide did not modify the adrenal axis function nor lipid metabolism. Asthmatic patients showed an atherogenic lipid profile which could increase the risk of cardiovascular disease.

[Estimation of cardiac vagal reserve by dynamic exercise in patients with recent myocardial infarction]. / Estimacícon de la reserva cardiaca vagal mediante el ejercicio dinámico en pacientes con infarto miocárdico reciente.

In patients with coronary artery disease, the risk of sudden death is related to the degree of left ventricular dysfunction and to cardiac parasympathetic activity. The relation between these two consequences of myocardial infarction is still the matter of intense controversy. In this investigation, we have estimated the resting cardiac parasympathetic tone and assessed the left ventricular systolic function of 25 patients who had suffered an acute myocardial infarction. The absolute increase in heart rate recorded in the first 10 seconds of a programmed dynamic exercise, was considered as the resting cardiac parasympathetic tone or cardiac parasympathetic reserve. Twenty five age and sex-matched normal sedentary subjects were used as controls. Patients showed a significantly smaller increase in their heart rate (16 +/- 4 lats/min, M +/- DS) than the controls 32 +/- 5 P < 0.0001), during the first 10 seconds of exercise. Moreover, the absolute increase in heart rate was inversely related to the degree of left ventricular dilatation ( r = - 0.71, P < 0.0001) and directly related to the left ventricular ejection fraction (r = 0.84, P < 0.0001). In other words, those patients with larger left ventricles and depressed ventricular function had a more prominent reduction of their resting cardiac parasympathetic tone. These results indirectly suggest that, left ventricular size and function are indeed related to cardiac parasympathetic activity.

[Effects of dehydroepiandrosterone on blood cells of the rat]. / Effectos de la dehidroepiandrosterona sobre las células sanguíneas de la rata.

The effects of dehydroepiandrosterone (DHEA) on haemoglobin, hematocrit and white cell counts values were studied in male and female rats, castrated rats and pregnant rats. After 5 continuous days of DHEA administrated subcutaneously (80 mg/kg/d; body w.) haemoglobin and hematocrit values were similar those values obtained before the treatment. White cell counts were reduced (40%) in female no castrated rats due to a significantly lymphopenia. The white cell counts were increased in castrated rats and with DHEA administration there were reduced to the initial values. Estradiol treatment had the same effect as DHEA on castrated rats. These data suggest that DHEA administrated to castrated or sexually active male and female rats affects the white cells without important effects on red blood cells.

Cryptorchidism: treatment with human chorionic gonadotropin--a Venezuelan experience.

The study comprised 323 cryptorchidic boys, between 6 months and 14 years of age (mean age 5.68 years) with 440 maldescended testes. Testicular position was graded as inguinal low or prescrotal (I), inguinal middle (II), inguinal high (III), and abdominal testes (IV). Boys before 4 years of age received human chorionic gonadotropin (hCG) as intramuscular injections (I.M.), 500 IU twice a week for 5 weeks; and boys 4 or more years of age received hCG (IM), 1000 IU twice a week for 5 weeks. The objectives of this study were to evaluate the response of maldescended testes to treatment with hCG, and to investigate possible associations between the patients' ages and position of the testes with the response to hCG. Out of the 440 maldescended testes, 329 were in an inguinal location (75%) and 111 were abdominally located (25%). The overall response to hCG was 40%, and the inguinal testes response was 49%, with the highest success rates (72%) for the prescrotal testes. A positive correlation was found (p < .0001) between the rate of success and the testicular position. There was no association between the hCG response and the age at which treatment was initiated.

Heart rate changes during the Valsalva maneuver in patients with isolated aortic insufficiency

To determine the possible relationship between left ventricular dilatation and heart rate changes provoked by the Valsalva maneuver (Valsava ratio), we studied 9 patients with isolated chronic aortic insufficiency. Left ventricular systolic function was assessed by two dimensional echocardiography and cardiac catheterization. All patients were asymptomatic (functional class I of the New York Heart Association). The left ventricular internal diameters and volumes were significantly increased in all patients. The asymptomatic patients had either normal or slightly depressed ejection fraction (EF>0.40). The Valsalva ratio of these asymptomatic patients showed no significant correlation with the left ventricular volumes or with the left ventricular ejection fraction. In other words, parasympathetic heart rate control, as expressed by the Valsalva ratio, was normal in the asymptomatic patients with left ventricular dilatation and preserved left ventricular ejection fraction. Therefore, left ventricular dilatation may not be the major mechanism responsible for the abnormal parasympathetic heart rate control of patients with acquired heart disease.

Heart rate changes during the Valsalva maneuver in patients with isolated aortic insufficiency.

To determine the possible relationship between left ventricular dilatation and heart rate changes provoked by the Valsalva maneuver (Valsalva ratio), we studied 9 patients with isolated chronic aortic insufficiency. Left ventricular systolic function was assessed by two-dimensional echocardiography and cardiac catheterization. All patients were asymptomatic (functional class I of the New York Heart Association). The left ventricular internal diameters and volumes were significantly increased in all patients. The asymptomatic patients had either normal or slightly depressed ejection fraction (EF > 0.40). The Valsalva ratio of these asymptomatic patients showed no significant correlation with the left ventricular volumes or with the left ventricular ejection fraction. In other words, parasympathetic heart rate control, as expressed by the Valsalva ratio, was normal in the asymptomatic patients with left ventricular dilatation and preserved left ventricular ejection fraction. Therefore, left ventricular dilatation may not be the major mechanism responsible for the abnormal parasympathetic heart rate control of patients with acquired heart disease.

Acute effects of digitalis and enalapril on the neurohormonal profile of chagasic patients with severe congestive heart failure.

Chagasic patients with congestive heart failure are usually treated with digitalis and converting enzyme inhibitors. According to the neurogenic and dysautonomic theories, chagasic patients would not benefit from these drugs. To clarify this controversial issue, we have studied patients with congestive heart failure and suspected Chagas' heart disease. All patients received intravenous methyl-digoxin for 24 h and oral enalapril for 96 h. Blood samples for plasma norepinephrine, aldosterone and renin were taken at baseline, after acute digitalization and following enalapril. Based on the serology for Chagas' disease, the patients were divided into non-chagasic and chagasic patients. In the chagasic group three patients were in functional class III and 3 were in functional class IV. In the non-chagasic group five patients were in functional class III and 2 were in functional class IV. Both groups had a marked and quantitatively similar degree of neurohormonal activation. All patients improved at least one functional class and lost more than 5 kg of body weight with treatment. The chagasic patients had a statistically significant reduction in plasma norepinephrine (2262 +/- 1407 to 865 +/- 390, P < 0.008, pg/ml, M +/- S.D.), plasma aldosterone (330 +/- 168 to 155 +/- 75, P < 0.01, pg/ml, M +/- S.D.) and plasma renin activity (14 +/- 13 to 2 +/- 1.6 ng/ml per h, M +/- S.D., P < 0.05), with digitalis. Following enalapril, norepinephrine and aldosterone there was a further but non-significant reduction, when compared to postdigitalis values. These results indicated that chagasic patients do benefit from digitalis and enalapril. Furthermore, the prominent and significant reduction in all three neurohormones suggest that the parasympathetic and sympathetic systems of these chagasic and non-chagasic patients, are responding to the neuromodulatory effects of digitalis and enalapril.