Efficacy of combination therapy for systolic blood pressure in patients with severe systolic hypertension: the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study

Systolic hypertension is predominant among patients over 50 years of age, is a more important cardiovascular risk factor than diastolic blood pressure, and is more difficult to control than diastolic blood pressure. Consequently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends combination therapy as first-line treatment for patients with stage 2 hypertension. In the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study, 24-hour ambulatory blood pressure monitoring was used to identify patients with systolic hypertension and to determine the impact of 8 weeks of treatment with either amlodipine besylate/benazepril HCl 5/20 mg combination therapy (n=149), amlodipine besylate 5 mg (n=146), or benazepril HCl 20 mg (n=148). Combination therapy was significantly more effective in reducing systolic blood pressure and pulse pressure than either monotherapy (p<0.0001). Significantly greater percentages of patients in the combination group compared with either monotherapy achieved blood pressure control (p<0.0001). Adverse events were low in all three treatment arms, with less peripheral edema in the combination group than in the amlodipine-treated group. The combination of amlodipine besylate/benazepril HCl given to patients with stage 2 systolic hypertension resulted in significantly greater reductions in blood pressure and pulse pressure than those seen with monotherapy and was at least as well tolerated as the separate components. This data supports the recommendation of the JNC 7 for the use of combination therapy in patients with stage 2 hypertension.     

Improving survival of patients with candidaemia: analysis of prognostic factors from a long-term, nationwide study in Iceland

A population-based epidemiological and clinical study of candidaemia in Iceland was conducted during a 20-y period, 1980-1999. As previously reported, the incidence of candidaemia increased 3.5-fold during the study period, without major changes in species distribution or antifungal resistance (Asmundsdottir et al., J Clin Microbiol 2002;40:3489-92). In this study detailed clinical information was collected and registered on all candidaemic patients (n=165, episodes n=172) in Iceland during 1980-1999. Clinical characteristics were compared between adults and children. Univariate and multivariate analyses were used to determine predictors of 30-d mortality. In comparison with adults, young children with candidaemia more often presented with respiratory distress, without fever p<0.001. Adult patients were more likely to have underlying malignancies (p=0.009) and to have undergone surgical operations (p=0.002). During the study a steady decrease in 30-d case fatality ratio was noted, from 58.8% in 1980-1984, to 26.7% in 1995-1999 (p=0.02). At the same time a more aggressive approach to candidaemia management was documented. In multivariate analysis, prompt removal of central venous catheters (odds ratio for death, 0.22, p=0.004), and septic shock (odds ratio for death, 8.01, p=0.001) were the strongest independent predictors of outcome. Our results underline the strong association between prompt removal of vascular catheters and favourable outcome, suggesting that mortality may be reduced by more aggressive management.     

Transumbilical approach for shunt insertion in the pediatric population: an improvement in cosmetic results

Objective In spite of the recent interest in endoscopic third ventriculostomy, ventriculoperitoneal (VP) shunt is still the gold standard in treating non-obstructive hydrocephalus in children. The peritoneal cavity remains the optimal site for cerebrospinal fluid (CSF) diversion. Shunt insertion and re-interventions carry a high risk of inaesthetic abdominal scars and long-term morbidity. We report a technique of transumbilical shunt insertion, which provides better cosmetic results and without many more complications. This approach has been performed for a long period in a wide variety of intra-abdominal conditions by pediatric surgeons.Methods Between March and October 2003, we inserted 12 VP shunts in children. For eight consecutively treated children the follow-up is more than 3 months. All the shunts were inserted through the umbilicus. These eight children are the subjects of this study. Indications for shunting were: communicating hydrocephalus (6 cases), subdural hematoma (1 case), and hygroma associated with an arachnoid cyst (1 case). The population consisted of 7 boys and 1 girl, ranging in age between 6 weeks and 47 months (mean age: 15 months), and their body weights varied between 2,110 g and 18,000 g (mean weight: 8,470 g). All children were examined twice a day for 3 days, and wounds were examined daily to check for the absence of sepsis or dehiscence. Clinical controls were performed 1 month after discharge. The operating surgeon was invited to comment on any difficulties encountered in making or closing this incision afterwards.Results The average length of clinical follow-up was 6 months (range 4–7 months). One infection of the VP shunt occurred. It was treated with external drainage and antibiotics. After 1 week, a second VP shunt was inserted using the same technique without particular difficulty and with a nice cosmetic result. Concerning the seven other children, the cosmetic results were optimal, with no puckered abdominal scars or wound dehiscence, and with no perioperative or long-term complications related to the umbilical approach.Conclusion At this early follow-up, umbilical incision for shunt insertion is a safe and easy technique. It provides an optimal cosmetic result, even in cases of re-intervention. This minimally invasive surgery does not require long specialized training. We have not shown an increase in complications associated with a learning curve. Longer follow-up is needed to evaluate the risk of infection.     

Cognitive functioning in siblings discordant for schizophrenia

OBJECTIVE: The objective of this study was to investigate neuropsychological impairment as a genetically mediated risk indicator for schizophrenia while accounting for prevalence of schizotypy signs/symptoms in siblings. METHOD: Cognitive functioning in 25 individuals with schizophrenia, 25 unaffected siblings and 25 unrelated healthy controls, was assessed using neuropsychological tests of sustained attention, memory and learning, executive function, visual-spatial ability and psychomotor performance. RESULTS: Unaffected siblings demonstrated better performance than patients on some measures of memory and learning and executive function. Patients and siblings demonstrated impaired Full Scale IQ and verbal fluency, otherwise siblings performed similarly to healthy controls. Controlling for differences in IQ, the shared deficit in verbal fluency disappeared. CONCLUSION: Patients with schizophrenia and unaffected siblings (without schizotypy personality disorder) shared a neuropsychological deficit in verbal fluency. This deficit appeared to be mediated by IQ. Deficits, which differentiated patients from controls, may not be inherited and perhaps are related to the manifestation or treatment of schizophrenia.     

Attention deficits in children with 22q.11 deletion syndrome

This study examined attention abilities of children with 22q.11 deletion syndrome. Thirty children (14 males, 16 females; age range 7 to 13y) were given comprehensive neuropsychological and neuropsychiatric assessments. Learning disability was found in 13 children. Superiority in verbal over performance IQ was very common. Attention-deficit-hyperactivity disorder (mainly of inattentive subtype) was diagnosed in 13 children. There appeared to be a relation between low IQ and presence of autism spectrum problems. The presence of attention deficits was clearly supported by the scores on the Child Behavior Checklist and the Conners Questionnaire. On the Becker attention tests the reaction times were significantly longer in the two visual and auditory tests, indicating that the ability to sustain attention is critically impaired in this group. A tendency of inferiority on auditory compared with visual tests was noted but there were no specific problems with the focus-execute aspect of attention.     

Kinetics of tyrosine transport and cognitive functioning in schizophrenia

BACKGROUND: Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (Vmax) across the cell membrane and an increased affinity (Km) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction--a core feature of schizophrenia. METHODS: Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters Vmax and Km were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. RESULTS: Patients with low Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. CONCLUSIONS: Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low Km and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons.     

The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India

The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as 'gold standard' for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety of immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, these impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed to indicate more severe neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk of those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment.     

Axonal development in the cerebral white matter of the human fetus and infant

After completion of neuronal migration to form the cerebral cortex, axons undergo rapid elongation to their intra- and subcortical targets, from midgestation through infancy. We define axonal development in the human parietal white matter in this critical period. Immunocytochemistry and Western blot analysis were performed on 46 normative cases from 20-183 postconceptional (PC) weeks. Anti-SMI 312, a pan-marker of neurofilaments, stained axons as early as 23 weeks. Anti-SMI 32, a marker for nonphosphorylated neurofilament high molecular weight (NFH), primarily stained neuronal cell bodies (cortical, subcortical, and Cajal-Retzius). Anti-SMI 31, which stains phosphorylated NFH, was used as a marker of axonal maturity, and showed relatively low levels of staining (approximately one-fourth of adult levels) from 24-34 PC weeks. GAP-43, a marker of axonal growth and elongation, showed high levels of expression in the white matter from 21-64 PC weeks and lower, adult-like levels beyond 17 postnatal months. The onset of myelination, as seen by myelin basic protein expression, was approximately 54 weeks, with progression to "adult-like" staining by 72-92 PC weeks. This study provides major insight into axonal maturation during a critical period of growth, over an age range not previously examined and one coinciding with the peak period of periventricular leukomalacia (PVL), the major disorder underlying cerebral palsy in premature infants. These data suggest that immature axons are susceptible to damage in PVL and that the timing of axonal maturation must be considered toward establishing its pathology relative to the oligodendrocyte/myelin/axonal unit.