Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients

In 10 untreated epileptic patients, we evaluated the functional integrity of the hypothalamic-pituitary axis before and during chronic treatment with sodium valproate, a gamma-aminobutyric acid-mimetic compound. The GH response to L-dopa (250-500 mg po) was absent in 3 and severely impaired in 2 of the 10 patients though being, on the average, only slightly lower in the epileptic subjects than in normal controls. Conversely, the GH rise following GHRH (0.5 micrograms/kg body weight, iv) was normal in 9 of the patients. A significant blunting of the GH response to L-dopa occurred in the 7 patients initially responsive after 6 month of sodium valproate (P less than 0.05). The GH response to GHRH also underwent an evident though not significant attenuation. The ACTH and the ACTH/cortisol elevations elicited by metyrapone (35 mg/kg body weight infused over 4 h), and by CRH (1 microgram/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P less than 0.05, less than 0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH (200 micrograms iv) remained normal over the whole study period. Growth arrest ensued in 1 patient after 6 months of sodium valproate and disappeared after drug withdrawal. These observations point to a defective hypothalamic control of GH secretion in some epileptic patients. They also indicate that chronic administration of sodium valproate, hence activation of central gamma-aminobutyric acid system, results in a blunting of the stimulated GH and ACTH secretion. Occasionally, a reversible arrest of skeletal growth may also ensue.     

Effect of an antiserotoninergic drug, metergoline, on the ACTH and cortisol response to insulin hypoglycemia and lysine-vasopressin in man.

The effect of metergoline, a specific antiserotoninergic drug, on ACTH secretion was investigated in 29 normal volunteers and in 4 patients with increased ACTH production (3 with Addison's disease, 1 with Cushing's disease). In 15 normal subjects, a 4-day treatment with 10 mg daily of metergoline significantly blunted the ACTH response to insulin hypoglycemia. Mean peak ACTH values before and after treatment were, respectively, 333 +/- 39.2 (SE) and 235 +/- 38.8 pg/ml (P less than 0.05). The corresponding values of plasma cortisol were 29.6 +/- 2.96 and 20.5 +/- 2.67 mug/100 ml (P less than 0.05). In contrast, metergoline failed to affect the ACTH response to lysine-vasopressin (LVP) administered iv (8 subjects studied) and im (6 subjects studied). In 3 patients suffering from Addison's disease, an appreciable although not statistically significant lowering of the plasma ACTH levels was noted during metergoline administration. The mean pre- and post-treatment values of plasma ACTH in these patients were, respectively, 1116 +/- 192.2 and 666 +/- 100.8 pg/ml, 4240 +/- 50.0 and 3398 +/- 368.0 pg/ml, and 431 +/- 44.0 and 352 +/- 23.9 pg/ml. In one patient with Cushing's disease caused by a pituitary adenoma, metergoline did not appreciably modify plasma ACTH levels. Taken together, these results lend support to the concept of a physiological stimulating effect of serotonin on ACTH secretion. Moreover, they are compatible with the view that serotonin exerts its action chiefly at the hypothalamic level while LVP promotes ACTH release by a primary action on the pituitary.     

Ras activation in myelodysplastic syndromes: clinical and molecular study of the chronic phase of the disease

We studied N-ras and Ki-ras point mutations respectively at codons 12-13 and 12 in 15 patients with myelodysplastic syndromes (MDS) using the polymerase chain reaction (PCR) method for DNA amplification, and slot blot hybridization to allele specific oligonucleotide (ASO) probes. We analysed peripheral blood and bone marrow samples collected at diagnosis and repeatedly during the chronic phase of the disease to define when the activation occurred and in which haemopoietic cell populations, in order to establish possible relationships between clinical and molecular features. In three cases the N-ras oncogene was mutated at codon 12 in every cell population, both at diagnosis and throughout the chronic phase. Point mutations were not seen at the 12 codon of the Ki-ras oncogene. In patients lacking activated ras oncogene at diagnosis, mutations were not discovered during the entire period of observation. Therefore in our cases disease progression and leukaemic transformation did not correlate with the presence of the activated N-ras. Our data suggest that ras activation occurs early in the pathogenesis of MDS and involves a haemopoietic progenitor with multiple differentiative capacity, without however conferring an apparent proliferative advantage on its progeny.     

Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation.

OBJECTIVES: The goal of this study was to investigate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with permanent atrial fibrillation (AF) and the role of atrioventricular junction (AVJ) ablation. BACKGROUND: Cardiac resynchronization therapy has been proven effective in heart failure patients with sinus rhythm (SR). However, little is known about the effects of CRT in heart failure patients with permanent AF. METHODS: Efficacy of CRT on ventricular function, exercise performance, and reversal of maladaptive remodeling process was prospectively compared in 48 patients with permanent AF in whom ventricular rate was controlled by drugs, thus resulting in apparently adequate delivery of biventricular pacing (>85% of pacing time), and in 114 permanent AF patients, who had undergone AVJ ablation (100% of resynchronization therapy delivery). The clinical and echocardiographic long-term outcomes of both groups were compared with those of 511 SR patients treated with CRT. RESULTS: Both SR and AF groups showed significant and sustained improvements of all assessed parameters (model p < 0.001 for all parameters). However, within the AF group, only patients who underwent ablation showed a significant increase of ejection fraction (p < 0.001), reverse remodeling effect (p < 0.001), and improved exercise tolerance (p < 0.001); no improvements were observed in AF patients who did not undergo ablation. CONCLUSIONS: Heart failure patients with ventricular conduction disturbance and permanent AF treated with CRT showed large and sustained long-term (up to 4 year) improvements of left ventricular function and functional capacity, similar to patients in SR, only if AVJ ablation was performed.     

High prevalence rate of Entamoeba histolytica asymptomatic infection in a rural Mexican community

The frequency of Entamoeba histolytica and Entamoeba dispar infection was analyzed in a rural community in the state of Morelos, Mexico, using polymerase chain reaction (PCR). Sociodemographic variables as risk factors for the infection were assessed. Results highlighted the number of individuals with intestinal parasites (43.1%) in the community, indicating extensive fecalism. A high frequency of E. histolytica asymptomatic infection, higher than E. dispar infection (13.8% versus 9.6%), was detected by PCR. Anti-amebic antibody levels (IgG) in serum and saliva (IgA) samples were not associated with E. histolytica intestinal infection. These findings suggest a predominant distribution of E. histolytica strains of low invasive potential in this community.     

Can the left ventricular early diastolic tissue-to-blood time interval be used to identify a normal pulmonary capillary wedge pressure?

The pulsed Doppler early diastolic left ventricular (LV) tissue (e)-blood (E) onset temporal relationship (e-E) is suggested to predict pulmonary capillary wedge pressure (PCWP), through the formulas: tau = 32 + 0.7(e-E) and PCWP = LV end-systolic pressure x e(-IVRT/tau). Small changes/errors in E could influence the quotient IVRT/tau by oppositely affecting IVRT and e-E. At rest in 50 healthy individuals we noted: e-E: 2 +/- 14 ms; IVRT: 89 +/- 17 ms; calculated tau: 33 +/- 10 ms; and PCWP: 9 +/- 9 mmHg (> 12 mmHg in 28%). Non-pharmacological preload alterations in 14 individuals rendered an intraindividual 'PCWP'-fluctuation of up to 40 mmHg. This application may therefore not be clinically robust.     

Pathogenic molds (including Aspergillus species) in hospital water distribution systems: a 3-year prospective study and clinical implications for patients with hematologic malignancies

The incidence of mold infections in patients with hematologic malignancies continues to increase despite the widespread use of air filtration systems, suggesting the presence of other hospital sources for these molds. Water sources are known to harbor pathogenic molds. We examined samples from water, water surfaces, air, and other environment sources from a bone marrow transplantation unit with optimal air precautions. Molds (Aspergillus species, others) were recovered in 70% of 398 water samples, in 22% of 1311 swabs from plumbing structures and environmental surfaces, and in 83% of 274 indoor air samples. Microscopic examination of the water plumbing lines revealed hyphal forms compatible with molds. Four findings suggest that indoor airborne molds were aerosolized from the water: (1) higher mean airborne concentrations of molds in bathrooms (16.1 colony-forming units [CFU]/m(3)) than in patient rooms (7 CFU/m(3)) and hallways (8.6 CFU/m(3); P =.00005); (2) a strong type and rank correlation between molds isolated from hospital water and those recovered from indoor hospital; (3) lack of seasonal correlation between the airborne mold concentration in outdoor and indoor air; and (4) molecular relatedness between a clinical strain and a water-related strain (previously reported). Hospital water distribution systems may serve as a potential indoor reservoir of Aspergillus and other molds leading to aerosolization of fungal spores and potential exposure for patients.     

Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system

OBJECTIVES: This study examined the characteristics of continuously measured right ventricular (RV) hemodynamic information derived from an implantable hemodynamic monitor (IHM) in heart failure patients. BACKGROUND: Hemodynamic monitoring might improve the day-to-day management of patients with chronic heart failure (CHF). Little is known about the characteristics of long-term hemodynamic information in patients with CHF or how such information relates to meaningful clinical events. METHODS: Thirty-two patients with CHF received a permanent RV IHM system similar to a single-lead pacemaker. Right ventricular systolic and diastolic pressures, heart rate, and pressure derivatives were continuously measured for nine months without using the data for clinical decision-making or management of patients. Data were then made available to clinical providers, and the patients were followed up for 17 months. Pressure characteristics during optimal volume, clinically determined volume-overload exacerbations, and volume depletion events were examined. The effect of IHM on hospitalizations was examined using the patients' historical controls. RESULTS: Long-term RV pressure measurements had either marked variability or minimal time-related changes. During 36 volume-overload events, RV systolic pressures increased by 25 +/- 4% (p < 0.05) and heart rate increased by 11 +/- 2% (p < 0.05). Pressure increases occurred in 9 of 12 events 4 +/- 2 days before the exacerbations requiring hospitalization. Hospitalizations before using IHM data for clinical management averaged 1.08 per patient year and decreased to 0.47 per patient-year (57% reduction, p < 0.01) after hemodynamic data were used. CONCLUSIONS: Long-term ambulatory pressure measurements from an IHM may be helpful in guiding day-to-day clinical management, with a potentially favorable impact on CHF hospitalizations.