Renal functional reserve: its significance in normal and salt depletion conditions.

The aim of this study was the evaluation, in healthy subjects, of the renal functional reserve (RFR), that is, the GFR increase induced by a combined infusion of amino acids (AA) and dopamine (D), in conditions of extracellular volume depletion caused by diuretic administration. In particular, this study was undertaken: a) to evaluate whether and to which extent, AA + D can reverse the functional GFR impairment induced by salt depletion, without volume restoration; b) to study whether any relationship may be found between the GFR in normal condition (the so-called "resting" GFR), and/or the renal functional reserve and the GFR impairment induced by salt depletion, in order to understand the role of both "resting" GFR and RFR in the degree of renal dysfunction induced by salt depletion. In control conditions the i.v. infusion of AA + D significantly increased RPF (+ 41% vs. baseline period) with a mean absolute increase of 211 ml/min. A similar pattern was observed in GFR behavior (+31.5% with 34 ml/min of mean absolute increase). A significant inverse exponential relationship was observed between GFR before AA + D i.v. infusion ("resting" GFR) and renal functional reserve (P less than 0.05), suggesting that, in normal conditions, these inversely related parameters may widely vary according to the tone of the glomerular arterioles. Following salt depletion, we observed a variable degree of GFR impairment. Both GFR and RPF were significantly decreased (-25.9%, P less than 0.05 and -29%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal visual event-related potentials in obsessive-compulsive disorder without panic disorder or depression comorbidity

Visual event-related potentials and spline map topography during a discriminative response task (DRT) were studied in 8 obsessive-compulsive disorder (OCD) patients without comorbidity for panic disorder or depression and in 12 age-matched controls. In the DRT task (like in a go/no-go task) the subject had to press a button when the target stimuli appeared and had to retain the response when the non-target stimulus appeared (vertical bars were intermixed with an equal probability of horizontals). OC patients had greater N1 latency than controls and their N1 and P3 amplitude was larger for the target stimuli, but not for non-target stimuli. In the normals, non-target stimuli (no-go task) produced a larger activation than target stimuli (go task). In the OCD patients the target stimuli produced the same large activation as the non-target. These findings are consistent with theories that consider OCD to be an attentional disorder deriving from a misallocating of cognitive resources. Moreover, spline map topography confirmed that P3 hyperactivation is localised principally on the frontal lobes.     

Relations Between Coercive Strategies and MMPI-2 Scale Elevations Among Women Survivors of Childhood Sexual Abuse

The relationship between coercion strategies used by perpetrators of childhood sexual abuse (CSA) and elevations of CSA survivors on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) was investigated. Participants were 151 women survivors of CSA in outpatient treatment at a university-based community mental health center. Scores on the MMPI-2 clinical scales and the Keane posttraumatic stress disorder (PTSD) scale were examined. Main effects were found for promised or received rewards on several clinical scales and the PTSD scale of the MMPI-2, independent of the presence of force. Specifically, the presence of such rewards was associated with significantly higher levels of symptomatology on Paranoia (Pa), Psychasthenia (Pt), Schizophrenia (Sc), and PTSD (Pk). There were no main or interaction effects noted for the presence of actual or threatened force on any of the scales.     

Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients.

PURPOSE: Imatinib (Glivec) is a potent inhibitor of bcr/abl, an oncogenic fusion protein that causes chronic myelogenous leukemia (CML). alpha1 acid glycoprotein (AGP) binds to imatinib with high affinity and inhibits imatinib activity in vitro and in vivo in an animal model. A pharmacokinetics analysis of imatinib was undertaken in CML patients. EXPERIMENTAL DESIGN: Imatinib plasma concentrations were measured in 19 CML patients treated with imatinib (400 or 600 mg/day). Five patients received a concomitant short-term course of clindamycin (CLI). RESULTS: A positive correlation between AGP and imatinib plasma levels was observed. CLI administration decreased imatinib plasma concentrations, evaluated as area under the curve (AUC) and peak concentrations (C(max)). The effects of a bolus of CLI was studied in three patients on imatinib 23 h after the last imatinib dose. Within 5-10 min in three of three cases, CLI caused a decrease in imatinib plasma concentrations of 2.6-, 2.7-, and 4.7-fold, respectively. In vitro experiments using fresh blasts from CML patients showed that AGP, at concentrations observed in the patients, decreased imatinib intracellular concentrations up to 10 times and blocked imatinib activity. The incubation with CLI restored imatinib intracellular concentrations and biological activity. CONCLUSION: AGP exerts significant effects of the pharmacokinetics, plasma concentrations, and intracellular distribution of imatinib in CML patients; these data indicate that plasma imatinib levels represent unreliable indicators of the cellular concentrations of this molecule.     

Magnetic resonance imaging compared with echocardiography in the evaluation of pulmonary artery abnormalities in children with tetralogy of Fallot following palliative and corrective surgery

Background. Abnormalities of the pulmonary arteries following palliative or corrective surgery for tetralogy of Fallot (TOF) are common. Our purpose was to compare the usefulness of magnetic resonance imaging (MRI) and echocardiography in the post- operative evaluation of the pulmonary arteries in children with TOF. Objective. Our hypothesis was that MRI is more sensitive than echocardiography in the detection of branch pulmonary artery abnormalities in children with TOF. Materials and methods. Pulmonary artery MRI and echocardiography were performed in 20 children following palliative and/or corrective surgery for TOF. MRI and echocardiography were compared in their ability to detect abnormalities of the pulmonary arteries. Angiographic or surgical correlation was available in 15 children. A perfusion scan for confirmation of pulmonary artery patency was available in one additional child. Results. Abnormalities of the branch pulmonary arteries identified by MRI included: absence or occlusion (2), focal stenosis (15), hypoplasia (2), aneurysm (1), and non-confluence (1). Echocardiography could not adequately visualize the right and left branch pulmonary arteries in eight and ten children, respectively. Echocardiography missed stenosis in 13 branch pulmonary arteries, patency of hypoplastic pulmonary arteries in two children, non-confluence of the pulmonary arteries in one child, and a left pulmonary artery aneurysm in one child. Abnormalities identified by MRI were confirmed in 16 children by angiography, surgery or perfusion scan. Conclusion. MRI is more sensitive than echocardiography for the evaluation of branch pulmonary artery abnormalities in children following surgery for TOF. Received: 13 January 1997 Accepted: 31 July 1997     

Incidence of apnoea and bradycardia in preterm infants following DTPw and Hib immunization: A prospective study

Objective: To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors.
Methodology: A prospective study of 98 preterm infants, of gestational age 24–31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTP_w) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization.
Results: Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation <90%). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTP_w were less likely to have apnoea and/or bradycardia than those given DTP_w alone.
Conclusion: When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization.     

Prevention of albuminuria by aminoguanidine or ramipril in streptozotocin-induced diabetic rats is associated with the normalization of glomerular protein kinase C

This study examined whether the prevention of diabetes-related albuminuria by aminoguanidine (AG) or ramipril (RAM) may be mediated by a common post-glomerular basement membrane renal intracellular mechanism involving protein kinase C (PKC). The renal handling of albumin was examined over 24 weeks in control and streptozotocin (STZ)-induced diabetic rats. A radioimmunoassay (RIA) that measures intact albumin, and intravenously injected tritium-labeled rat serum albumin, was used to assess the proportion of intact albumin and albumin fragments in urine. Diabetes was induced in male Sprague-Dawley rats by the intravenous administration of STZ at a dose of 50 mg/kg. Age-matched control rats received buffer alone. Diabetes was characterized by an increase in blood glucose (>15 mmol/l), an increase in GHb (means at 24 weeks 29.3+/-1.1%; control 6.1+/-0.1%, P<0.005), an increase in glomerular filtration rate (GFR) (4.13+/-0.15 ml/min; control 3.54+/-0.19 ml/min, P<0.005), an increase in intact albumin excretion rate (expressed as geometric mean 11.64 times/divided by 2.11 mg/24 h; control 0.74 times/divided by 1.57 mg/24 h, P<0.005) as measured by RIA, and an increase in glomerular PKC activity (26.83+/-2.38 pmol x mg(-1) x min(-1); control 14.6+/-2.99 pmol x mg(-1) x min(-1), P<0.005). Treatment of diabetic rats with either AG or RAM prevented the rise in intact albuminuria and glomerular PKC activity. Renal lysosomal cathepsin activity decreased in diabetic rats and this was not prevented by AG or RAM. Neither drug affected glycemic control or GFR, but RAM reduced systolic blood pressure (BP), whereas AG did not. These data indicate that urinary excretion of intact albumin and albumin-derived fragments in diabetes may be modulated independently of glycemic control (AG and RAM) and systolic BP (RAM). While both drugs are known for their different mechanisms of action, the fact that both prevent diabetes-related increases in glomerular PKC activity and albuminuria supports the hypothesis that PKC plays a central role in the development of diabetic nephropathy.     

Perioperative complications in acoustic neuroma (vestibular schwannoma) surgery.

OBJECTIVE: Retrospective study and review of the complications other than those related to the facial nerve and hearing, encountered in acoustic neuroma surgery. Also, an evaluation of hospital stay and its relation with various factors. STUDY DESIGN: Retrospective case review. SETTING: Tertiary neurotologic and skull base referral center. PATIENTS: A series of 707 patients who underwent surgical removal of acoustic neuroma from April 1987 to December 2001. INTERVENTIONS: The surgical approaches used were the enlarged translabyrinthine approach, the enlarged middle fossa approach, and the retrosigmoid approach. In a small number of cases, the operations were performed through other approaches. MAIN OUTCOME MEASURES: The duration of hospital stay and appearance of complications in the perioperative period along with their management. Results related to the facial nerve and hearing were not considered in this study. RESULTS: The most frequent complication was abdominal subcutaneous hematoma (site of fat harvest), which occurred in 23 patients (3.2%). Cerebrospinal fluid leak was present in 20 patients (2.8%), 15 of whom needed revision surgery. Other complications included VIth cranial nerve dysfunction in 12 cases (1.68%), subdural hematoma in 3 cases (0.4%), cerebellopontine angle hematoma in 4 cases (0.6%), cerebellar edema in 2 cases (0.28%), brainstem hematoma in 1 case (0.14%), transitory aphasia in 1 case (0.14%), and lower cranial nerve dysfunction in 1 case (0.14%). Mortality occurred in only one case (0.14%). Medical complications seldom occurred. The postoperative hospital stay ranged from 2 to 36 days, with an average of 6.4 days. The overall hospital stay diminished over time from 10.2 days in 1987 to 1990, to 4.9 days in 2001. There was a significant relation between hospital stay and tumor size, approach used, and presence/absence of complications. CONCLUSIONS: Perioperative complications in acoustic neuroma surgery do exist, but this study demonstrated how low the incidence is. The authors believe that the low percentage of complications is mainly attributable to the majority of operations being carried out in specialized clinics, where they are considered routine operations. They believe that following individualized approaches, depending on tumor size and on the preoperative function of the cranial nerves, is the proper way to reach a significant reduction in complications while maintaining a high percentage of total tumor removal. The results of this study, considered as a basis of comparison with other studies, will certainly be useful in preoperative patient counseling.