Hypertension in a cohort of obese Caucasian children and adolescents and its association with glycometabolic indices: A proposed screening tool.

BACKGROUND AND AIM: Hypertension (HTN) is common among obese children and adolescents and increases their cardiovascular risk later in adulthood. The aim of the study was to evaluate the prevalence of HTN identified by office blood pressure (BP) measurement and ambulatory BP monitoring (ABPM) in a cohort of obese children and adolescents and its association with anthropometric and glycometabolic indices. METHODS AND RESULTS: Seventy consecutive obese Caucasian children and adolescents aged 7-16 years were enrolled. Patients underwent ABPM, echocardiogram and carotid ultrasonography. Sex- and age-adjusted logistic multivariable analysis models were used to assess the association between HOMA-IR, HOMA-ß, QUICKI with HTN at ABPM. Receiver Operation Curve (ROC) analysis with Youden J statistics was used to identify the optimal HOMA-IR, HOMA-ß and QUICKI cut-off to predict HTN at ABPM. Hypertensive office BP was found in 25.7% of obese patients. ABPM diagnosed HTN in 34.9% of patients: 20.6% of obese patients had masked HTN (MHTN), and 12.7% had white coat HTN (WCH). Hypertensive obese patients (according to ABPM) had higher HOMA-IR and HOMA-ß, and a lower QUICKI than normotensive subjects. HOMA-IR, HOMA-ß and QUICKI predicted HTN at ABPM in obese patients in age- and sex-adjusted logistic multivariable models. Optimal cut-offs to predict HTN at ABPM in obese patients were: HOMA-IR ≥ 3.30, HOMA-ß ≥ 226.7 and QUICKI <0.33, with high sensitivity. CONCLUSIONS: A sequential testing strategy applying office BP and glycometabolic indices can identify hypertensive obese pediatric patients with high diagnostic accuracy and potentially reducing costs. This strategy needs validation in an external and larger cohort.

The epilepsy specialist nurse: A mixed-methods case study on the role and activities.

PURPOSE: To describe the role and activities of epilepsy specialist nurses (ESNs) operating as a team in the setting of a hospital specialising in the diagnosis and management of seizure disorders. METHODS: We conducted a descriptive mixed-methods embedded single case study. We recruited 9 ESNs, 14 of their professional colleagues and 9 'key informants' to analyse their perceptions of the role and activities of ESNs. We collected data through interviews, questionnaires, observations, and documentation. The study was conducted at the Filadelfia Epilepsy Hospital, Denmark. RESULTS: The team of ESNs offers holistic care to patients and their caregivers regarding the clinical, social, and emotional aspects of epilepsy. The ESNs are integrated in a multidisciplinary team and promote collaboration among the team members. ESNs also contribute to organisational aspects and perform research activities. CONCLUSION: A structured group of ESNs can operate effectively and extensively in a specialised hospital setting. Our findings contribute to clarifying the description of the ESN's role, and provide an example of how ESNs can be incorporated into a hospital's organisational structure.

Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID-hu Thy/Liv mice.

Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that may act as a cofactor in the progression of AIDS. Here, we describe the first small animal model of HHV-6 infection. HHV-6 subgroup A, strain GS, efficiently infected the human thymic tissue implanted in SCID-hu Thy/Liv mice, leading to the destruction of the graft. Viral DNA was detected in Thy/Liv implants by quantitative polymerase chain reaction (PCR) as early as 4 d after inoculation and peaked at day 14. The productive nature of the infection was confirmed by electron microscopy and immunohistochemical staining. Atypical thymocytes with prominent nuclear inclusions were detected by histopathology. HHV-6 replication was associated with severe, progressive thymocyte depletion involving all major cellular subsets. However, intrathymic T progenitor cells (ITTPs) appeared to be more severely depleted than the other subpopulations, and a preferred tropism of HHV-6 for ITTPs was demonstrated by quantitative PCR on purified thymocyte subsets. These findings suggest that thymocyte depletion by HHV-6 may be due to infection and destruction of these immature T cell precursors. Similar results were obtained with strain PL-1, a primary isolate belonging to subgroup B. The severity of the lesions observed in this animal model underscores the possibility that HHV-6 may indeed be immunosuppressive in humans.

Anti-asthmatic drug prescriptions to an Italian paedriatic population.

To estimate the prevalence and evaluate the appropriateness of anti-asthmatic drug prescriptions in an Italian paediatric population, drug prescriptions involving 24,407 children <18 years old, dispensed during 2003 by the retail pharmacies of the local health unit in Lecco, Italy, were analysed. Children > or = 6 years old receiving anti-asthmatics were categorized into three subgroups based on the number of boxes prescribed: occasional (one box), low (two and three boxes) and high (> or = four boxes) users. A logistic regression analysis was performed to estimate the relationship between the drug use patterns and formulations, antibiotic co-prescriptions, systemic steroid prescriptions and rate of hospitalization. Anti-asthmatic drugs were prescribed to 6594 (12%) children and adolescents; 58% of whom received only one box of the drug. Prevalence varied according to age, with the highest values at 1 and 4 years (24% and 21% respectively), and decreased to 6% in 17-year-old adolescents. Inhaled steroids were the most prescribed drugs (83%). The most common of these was beclomethasone. Occasional, low and high users represented 58%, 29%, and 13%, respectively, of the treated population > or = 6 years old. High users were found to be at increased risk of systemic steroid prescriptions (OR 8.6) and hospital admission for asthma (OR 6.8). This study confirms that in Italy the prevalence of anti-asthmatic prescription is much higher than prevalence of disease, indicating that anti-asthmatics are over-prescribed. Moreover, steroids, especially nebulized, are mainly prescribed only once in a year, supporting the idea that are prescribed not for asthma, which as chronic disease requires a chronic therapy. The approach to create subgroups on the basis of number of boxes prescribed seems to be effective in estimating asthma severity and appropriateness of the therapies.

Potentially severe drug interactions in elderly outpatients: results of an observational study of an administrative prescription database.

PURPOSE: To estimate the prevalence of potentially severe drug-drug interactions (DDIs) and their relationship with age, sex and number of prescribed drugs. METHODS: We analysed all prescriptions dispensed from 1 January 2003 to 31 December 2003 to individuals aged 65 or more registered under the Local Health Authority of Lecco, a northern Italian province with a population of almost 330 000 persons. Elderly who received at least two co-administered prescriptions were selected to assess the presence of DDIs. RESULTS: The prevalence of potentially severe DDIs was 16%, and rose with increasing patient's age and number of drugs prescribed. At multivariate analysis, the adjusted odds ratios rose from 1.07 (95% CI 1.03-1.11) in patients aged 70-74 to 1.52 (95% CI 1.46-1.60) in those aged 85 or older. Elderly taking more than five drugs on a chronic basis had a statistically significant higher risk of sever DDIs than those receiving less than 3 or 3-5 such drugs. CONCLUSIONS: The elderly constitutes a population at high risk of DDIs. As physicians still have some difficulty in managing this problem, it is essential to highlight for them, which factors raise the risk of DDIs.

Heterotopic rectal gastric mucosa: a rare cause of lower gastrointestinal bleeding in children. Case report and review of pediatric literature.

The authors report a very unusual case of intermittent and painful rectal bleeding occurring in a two-year-old female. At proctosigmoidoscopy, a bluish mucosal fold was found in the rectal ampulla. Histological examination showed the presence of heterotopic gastric mucosa islands intermingled with normal rectal mucosa. Surgical transanal excision of the lesion was undertaken due to the persistence of rectal bleeding with anemia, notwithstanding a three-month course of pharmacological therapy with a proton pump inhibitor. At a one-year follow-up, the child is well and symptom-free. The international pediatric literature was reviewed.

Basilar Artery Changes in Fabry Disease.

BACKGROUND AND PURPOSE: Dolichoectasia of the basilar artery is a characteristic finding of Fabry disease. However, its prevalence, severity, and course have been poorly studied. This study quantitatively evaluated, by MRA, a panel of basilar artery parameters in a large cohort of patients with Fabry disease. MATERIALS AND METHODS: Basilar artery mean diameter, curved length, "origin-to-end" linear distance (linear length), and tortuosity index ([curved length ÷ linear length] - 1) were retrospectively measured on 1.5T MRA studies of 110 patients with Fabry disease (mean age, 39.4 ± 18.6 years; 40 males) and 108 control patients (mean age, 42.0 ± 18.2 years; 40 males). RESULTS: Patients with Fabry disease had increased basilar artery mean diameter (P < .001) and basilar artery linear length (P = .02) compared with control patients. Basilar artery curved length and tortuosity index correlated with age in both groups (P < .001), whereas basilar artery linear length correlated with age only in patients with Fabry disease (P = .002). Patients with Fabry disease showed a basilar artery curved length mean increase of 4.2% (9.7% in male patients with Fabry disease versus male control patients), whereas the basilar artery mean diameter had a mean increase of 12.4% (14.3% in male patients with Fabry disease versus male control patients). Male patients with Fabry disease had increased basilar artery mean diameter, curved length, and tortuosity index compared with female patients with Fabry disease (P = .04, P = .02, and P < .001, respectively) and male control patients (P < .001, P = .01, and P = .006, respectively). Female patients with Fabry disease demonstrated an age-dependent increase of basilar artery mean diameter that became significant (P < .001) compared with female control patients above the age of 45 years. CONCLUSIONS: The basilar artery of patients with FD is subjected to major remodeling that differs according to age and sex, thus providing interesting clues about the pathophysiology of cerebral vessels in Fabry disease.

Development of a novel Italian speech-in-noise test using a roving-level adaptive method: adult population-based normative data.

In recent years the increasing development of hearing devices has led to a critical analysis of the standard methods employed to evaluate hearing function. Being too far from reality, conventional investigation of hearing loss based on pure-tone threshold audiometry and on mono/disyllabic word lists, presented in quiet conditions, has been shown to be inadequate. A speech-in-noise test using a roving-level adaptive method employs target and competing signals varying in level in order to reproduce everyday life speaking conditions and explore a more complete sound range. Up to now, only few roving-level adaptive tests have been published in the literature. We conducted a rovinglevel adaptive test in healthy Italian adults to produce new normative data on a language of Latin origin.

Hepatitis C virus NS3 NTPase/helicase: different stereoselectivity in nucleoside triphosphate utilisation suggests that NTPase and helicase activities are coupled by a nucleotide-dependent rate limiting step.

Hepatitis C virus (HCV) NS3 protein is a multifunctional enzyme, possessing protease, NTPase and helicase activities within a single polypeptide of 625 amino acid residues. These activities are essential for the virus life cycle and are considered attractive targets for anti-HCV chemotherapy. Beside ATP, the NS3 protein has the ability to utilise deoxynucleoside triphosphates (dNTPs) as the energy source for nucleic acid unwinding. We have performed an extensive analysis of the substrate specificities of both NS3 NTPase and helicase activities with respect to all four dNTPs as well as with dideoxynucleoside triphoshate (ddNTP) analogs, including both d-(beta) and l-(beta)-deoxy and dideoxy-nucleoside triphosphates. Our results show that almost all dNTPs and ddNTPs tested were able to inhibit hydrolysis of ATP by the NTPase activity, albeit with different efficiencies. Moreover, this activity showed almost no stereoselectivity, being able to recognise both d-(beta), l-(beta)-deoxy and ddNTPs. On the contrary, the helicase activity had more strict substrate selectivity, since, among d-(beta)-nucleotides, only ddTTP and its analog 2',3'-didehydro-thymidine triphosphate could be used as substrates with an efficiency comparable to ATP, whereas among l-(beta)-nucleotides, only l-(beta)-dATP was utilised. Comparison of the steady-state kinetic parameters for both reactions, suggested that dATP, l-(beta)-dCTP and l-(beta)-dTTP, specifically reduced a rate limiting step present in the helicase, but not in the NTPase, reaction pathway. These results suggest that NS3-associated NTPase and helicase activities have different sensitivities towards different classes of deoxy and dideoxy-nucleoside analogs, depending on a specific step in the reaction, as well as show different enantioselectivity for the d-(beta) and l-(beta)-conformations of the sugar ring. These observations provide an essential mechanistic background for the development of specific nucleotide analogs targeting either activity as potential anti-HCV agents.

Lack of correlation between cerebrospinal fluid thyrotropin-releasing hormone (TRH) and TRH-stimulated thyroid-stimulating hormone in patients with depression.

BACKGROUND: It has been proposed that elevated central thyrotropin-releasing hormone (TRH) is associated with the blunted thyroid-stimulating hormone (TSH) response to TRH in patients with depression. Few studies have directly evaluated this relationship between central nervous system and peripheral endocrine systems in the same patient population. METHODS: 15 depressed patients (4 male, 11 female, 12 bipolar, and 3 unipolar) during a double-blind, medication-free period of at least 2 weeks duration, underwent a baseline lumbar puncture followed by a TRH stimulation test. Cerebrospinal fluid (CSF) TRH and serial serum TSH, free thyroxine, triiodothyronine, prolactin, and cortisol were measured. A blunted response to TRH was defined as a delta TSH less than 7 microU/mL. RESULTS: There was no significant difference in mean CSF TRH between "blunters" (2.82 +/- 1.36 pg/mL) and "non-blunters" (3.97 +/- 0.62 pg/mL, p = .40). There was no evidence of an inverse relationship between CSF TRH and baseline or delta TSH. There was no correlation between CSF TRH and the severity of depression or any other endocrine measure. CONCLUSIONS: These data are not consistent with the prediction of hypothalamic TRH hypersecretion and subsequent pituitary down-regulation in depression; however, CSF TRH may be from a nonparaventricular nucleus-hypothalamic source (i.e., limbic area, suprachiasmatic nucleus, brain stem-dorsal raphe) and thus, not necessarily related to peripheral neuroendocrine indices.

HIV-1 reverse transcriptase inhibitors: current issues and future perspectives.

One of the major advances in the recent history of the treatment of HIV infections has been the development of different classes of effective antiretroviral drugs. In particular, the reverse transcriptase (RT) inhibitors still represent the majority of the clinically used anti-HIV drugs and constitute the main backbone of currently employed combinatorial regimens. Highly active antiretroviral combination chemotherapy (HAART), combining RT and protease inhibitors, has proven the most effective approach to treat HIV disease, since it has been shown to markedly suppress viral replication and appearance of drug resistance for a relatively long period. These therapies, however, do not constitute a definitive cure, since they are not able to completely eradicate the virus from the infected individual. Beside drug toxicity problems, the emergence of drug resistance associated with the particular regimen employed further complicates the situation. This review will summarise the most recent achievements, as well as the future directions in the development of novel anti-RT compounds.

Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients.

The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD). These response fluctuations appear when intrasynaptic dopamine concentrations begin to reflect the swings in levodopa availability that attend standard dosing regimens. Drugs that prolong the biologic half-life of levodopa and dopamine should thus prove beneficial. We administered levodopa/carbidopa in combination with single oral doses of tolcapone (Ro 40-7592), an inhibitor of catechol-O-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone prolonged the antiparkinson response to levodopa/carbidopa by about 67% at several doses ranging from 50 to 400 mg (p < 0.05). There was no significant change in the peak levodopa effect on parkinsonian signs or in the severity of dyskinesias. No dose-limiting adverse effects occurred. Multiple daily dosing with tolcapone would thus be expected to safely reduce the wearing-off phenomenon associated with levodopa/carbidopa therapy.

Altered cortical excitability in obsessive-compulsive disorder.

OBJECTIVE: To assess cortical inhibitory and excitatory mechanisms in obsessive-compulsive disorder (OCD). BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found decreased neuronal inhibition and a reduced cortical silent period in the primary motor area in Tourette's syndrome, focal dystonia, and other disorders believed to involve dysfunction of subcortical structures, including the basal ganglia. Dysfunction of the basal ganglia and linked regions also has been implicated in OCD, which has significant clinical and familial overlap with tic disorders. METHODS: We applied the TMS techniques previously used in Tourette's syndrome to a group of 16 OCD patients (seven unmedicated) and 11 age-matched healthy volunteers extensively screened for psychopathology. Measures of motor cortex excitability included resting and active motor threshold, cortical silent period duration, and intracortical inhibition and facilitation using a paired-pulse TMS technique with a subthreshold conditioning stimulus. RESULTS: Similar to recent findings in Tourette's syndrome and focal dystonia, this study reports significantly decreased intracortical inhibition (ICI) relative to the volunteers at interstimulus intervals from 2 to 5 msec. We also found decreased active and resting motor evoked potential threshold in the OCD patients, another indication of increased cortical excitability. Neither abnormality appeared medication related. The decreases in ICI and motor threshold were greatest in OCD patients with comorbid tics, but remained significant in patients without tics. CONCLUSIONS: The data suggest abnormal cortical excitability in obsessive-compulsive disorder. These findings are congruent with the hypothesis that Tourette's syndrome and obsessive-compulsive disorder (OCD) are analogous disorders with overlapping dysfunction in corticobasal circuits. Patients with tic-related OCD may have more abnormal motor cortex excitability than OCD patients without tics.

Sequential monitoring of urine-soluble interleukin 2 receptor and interleukin 6 predicts acute rejection of human renal allografts before clinical or laboratory signs of renal dysfunction.

BACKGROUND: The significance of noninvasive techniques to the early diagnosis of acute rejection in kidney transplants remains elusive. In this study, we examined whether an early posttransplant increase in serum- and urine-soluble interleukin (IL) 2 receptor (sIL-2R) and IL-6 levels predicted acute rejection. METHODS: Sequential determinations of serum and urine sIL-2R and IL-6 were performed in the first 30 postoperative days in 40 renal transplant patients. Changes during the posttransplant period observed in 26 patients who had one or more episodes of acute rejection (group A) were compared with those recorded in 14 patients who did not experience acute rejection of their graft (group B). RESULTS: Serum sIL-2R was higher than normal in patients of groups A and B without statistical differences between the two groups. In the first 3 days after transplantation, urinary sIL-2R was higher than normal in group A but not in group B. Urinary sIL-2R at days 2 and 3 was significantly higher (P<0.05) in group A than in group B. In the first 5 days after transplantation, urinary IL-6 was persistently higher than normal in group A, whereas it progressively decreased to normal value on day 4 in group B. Sudden increases (doubling within 24 hr) in urine IL-6 preceded clinical diagnosis of acute rejection by a mean period of 2 days, with an 87% sensitivity and a 64% specificity, and also predicted recurrent rejection episodes. CONCLUSIONS: Sequential monitoring of urinary sIL-2R and IL-6 levels does allow very early diagnosis of rejection without invasive procedures. Specifically, high urinary sIL-2R in the first 5 posttransplant days identifies the subgroup of patients at risk. In the subsequent days, a sudden increase in urinary IL-6 occurs in those of the above patients who will indeed reject their graft.

The Senning operation for transposition of the great arteries.

The original Senning technique of interatrial transposition of venous return was selectively employed for physiological correction in 24 patients with transposition of the great arteries (TGA) ranging in age from 74 days to 26 months (median 7 months). Twenty-three had intact ventricular septum and one had a large ventricular septal defect and diaphragmatic subpulmonary stenosis. There were no hospital or late deaths, and at follow-up examination 1.5 to 12 months postoperatively, each patient was asymptomatic, in normal sinus rhythm, and had no clinical evidence of caval or pulmonary venous obstruction. Nine patients underwent cardiac catheterization and angiocardiographic studies between 1.3 and 9 months postoperatively which demonstrated widely patent venous pathways and effective "left" and "right" atrial contraction. This experience lends support to the continued use of the Senning technique for interatrial transposition of venous return.

Repair of tetralogy of Fallot after Waterston anastomosis.

Sixty-three corrective operations have been performed in patients with Tetralogy of Fallot and a previously constructed Waterston shunt. The patients were from 1.4 to 8 years of age (median 4.3 years), and the mean interval between the Waterston shunt and the repair was 39.3 +/- 16.05 months. Three patients developed pulmonary atresia and six required a second anastomosis prior to intracardiac repair. Kinking and stenosis of the right pulmonary artery at the site of the Waterston anastomosis occurred in 12 (19 percent; 70 percent confidence limits 14 to 26 percent) patients who required patch enlargement of the right pulmonary artery at repair. Seven (11 percent; 70 percent confidence limits 7 to 17 percent) patients died in the hospital and three (5 percent; 70 percent confidence limits 2 to 11 percent) during the period of late follow-up. None of the early or late deaths was specifically related to the presence of the previously performed Waterston anastomosis.

Waterston anastomosis for initial palliation of tetralogy of Fallot.

Two hundred twenty-seven patients (median age 5.4 months) in whom a Waterston anastomosis was done for initial palliation of tetralogy of Fallot between 1966 and 1979 were studied. Twelve patients died in the hospital (5.3%; 70% confidence limits, 3.8% to 7.3%). Young age, low weight, and poor clinical condition did not appear to be incremental risk factors, whereas a too large or a too small shunt was largely responsible for the hospital mortality and morbidity. Follow-up information was available in all the 215 patients discharged from the hospital. At the last follow-up visit, before any further surgical procedure, 74% of the patients were clinically in good condition. By actuarial methods, 97.7% of hospital survivors were alive and 95.8% were event-free at and beyond 3 years postoperatively. Eighty-six patients have been catheterized in preparation for secondary repair (mean interval between Waterston shunt and catheterization, 2.9 +/- 1.38 years). One patient developed pulmonary vascular disease, four acquired pulmonary atresia, and 14 had a severe kinking of the right pulmonary artery at the site of the anastomosis.

Erythrocyte antioxidant activity, serum ceruloplasmin, and trace element levels in subjects with alcoholic liver disease.

Erythrocyte antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and reduced glutathione, serum ceruloplasmin, and serum trace elements (copper, zinc, iron, and selenium) related to antioxidant enzymes were assayed in subjects with alcoholic liver disease of different degrees of severity. The erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis had an unbalanced antioxidant system (normal superoxide dismutase, low catalase and glutathione peroxidase activities, and low glutathione content). Serum ceruloplasmin levels were in the normal range. Levels of the serum trace elements zinc and selenium were significantly low in subjects with moderate and severe cirrhosis, whose red cell half-life was also significantly short, as measured by radioactive chromium. These data suggest that the erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis are less protected against oxidant stress. The particular erythrocyte antioxidant system and serum trace element pattern may play a role in the genesis of hemolytic disorders and of alcoholic hepatic damage.

Clozapine in bipolar disorder: treatment implications for other atypical antipsychotics.

Traditional neuroleptics are often utilized clinically for the management of bipolar disorder. Although effective as antimanic agents, their mood stabilizing properties are less clear. Additionally, their acute clinical side effect profile and long term risk of tardive dyskinesia, particularly in mood disorder patients, portend significant liability. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder focusing on clozapine as the prototypical agent. Although, preclinical research and clinical experience suggest that the atypical antipsychotics are distinctly different from typical antipsychotics, they themselves are heterogeneous in profiles of neuropharmacology, clinical efficacy, and tolerability. The early clinical experience of clozapine as a potential mood stabilizer suggests greater antimanic than antidepressant properties. Conversely, very preliminary clinical experience with risperidone suggests greater antidepressant than antimanic properties and some liability for triggering or exacerbating mania. Olanzapine and sertindole are under investigation in psychotic mood disorders. The foregoing agents and future drugs with atypical neuroleptic properties should come to play an increasingly important role, compared to the older classical neuroleptics, in the acute and long term management of bipolar disorder.

Open heart surgery in the first six months of life.

Intracardiac repair of a variety of cardiac anomalies was performed in 104 infants aged 10 days to 6 mo, presenting with severe hypoxia and/or intractable heart failure. Thirty-eight patients (33 less than three mo of age) did not survive the operation or died during the first postoperative month. Above 6 mo of age, correction of heart defects is often carried out on an elective basis, and results are more favorable. A more convenient choice between corrective and palliative procedures is suggested to achieve better results in the difficult group of patients who require surgery within the first 6 mo of life.