Age at onset, childhood psychopathology, and 2-year outcome in psychotic bipolar disorder

OBJECTIVE: The relationships of age at onset and childhood psychopathology to 2-year clinical and functional outcomes in first-admission patients with bipolar I disorder were examined. METHOD: Patients with bipolar I disorder (N=123) presenting with psychotic symptoms were followed over a 2-year period. Age at onset was stratified into <19 and >or=19 years. Childhood psychopathology was categorized as behavior problems, other psychopathology, and none. Functional and clinical outcomes were rated with standard measures. RESULTS: Childhood psychopathology and age at onset were independently related to poorer functional and clinical outcome. In the multivariate models that included psychopathology, age at onset, sex, and education, early age at onset was related to incomplete remission, and childhood psychopathology was related to functional outcome. CONCLUSIONS: Childhood psychopathology and age at onset contribute independently to outcomes of bipolar disorder. Childhood psychopathology is a much stronger predictor of functioning than age at onset.     

Predictive value of the ocular globe compression in meningeal syndromes

Meningeal syndromes are evaluated in clinical practice by classic semiological signs all of them showing important sensibility and specificity but with some limitations. Thus, we propose a clinical method in order to diagnose meningeal syndromes capable of being easily executed and without risks for patients: to evaluate the pain by ocular globe compression as a semiological sign in meningeal syndromes. We studied 160 patients both gender, assorted age, distributed into two groups of patients, group I with meningeal syndrome and group II without meningeal syndrome. Results: in group I (n=80), at least one of the classic signal in meningeal syndrome was present in 71 patients (88.75%), while pain by ocular globe compression was positive in 78 patients (98.7%) with meningeal syndrome. In group I, this sign reached important sensibility (97.5%), specificity (98.8%) in meningeal syndromes. In conclusion, pain by ocular globe compression seems to be an important semiological sign and would be better investigated.     

Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence.

Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas.     

The use of low molecular weight heparin in pediatric patients: a prospective cohort study

OBJECTIVE: Low molecular weight heparins (LMWHs) offer several advantages over standard anticoagulant therapy (unfractionated heparin/warfarin) including predictable pharmacokinetics, minimal monitoring, and subcutaneous administration. Our objective was to determine the safety and efficacy of LMWHs in children. METHODS: A prospective cohort of children treated with the LMWH enoxaparin (Rhone Poulenc Rorer) was monitored at the Hospital for Sick Children, Toronto, Canada, from March 1994 until July 1997. RESULTS: There were 146 courses of LMWH administered for treatment and 31 courses for prophylaxis of thromboembolic events (TEs). Clinical resolution of TEs occurred in 94% of children receiving therapeutic doses of LMWH, and 96% of children receiving prophylactic doses of LMWH had no symptoms of recurrent or new TEs. Major bleeding occurred in 5% of children receiving therapeutic doses. Recurrent or new TEs occurred in 1% and 3% of children receiving therapeutic and prophylactic doses of LMWH, respectively. CONCLUSION: LMWH appears to be efficacious and safe for both management and prophylaxis of TEs. The results of this cohort study justify a randomized controlled trial comparing LMWH with standard therapy for the management of TEs in children.     

Does intervention by the dietitian and diabetes educator of a More Allied Health Services program improve glycosylated haemoglobin levels for those with type 2 diabetes? Implications for rural dietetic practice

Aim:  The present study aimed to investigate the effect of the number and intensity of visits to the More Allied Health Services (MAHS) clinics and a change in glycosylated haemoglobin (HbA₁c) levels in people with type 2 diabetes.
Methods:  Data on subjects accessing diabetes clinics in rural southern New South Wales were analysed retrospectively. Data included age at the end of the data collection period, sex, number and dates of visits to the MAHS dietitian and diabetes educator, weights and heights, HbA₁c and cholesterol levels.
Results:  Sixty-four patient records were analysed. The median period of clinic attendance was 32.5 months; median number of combined visits to MAHS dietitian and diabetes educator was three. Older subjects were significantly more likely to show a reduction in HbA₁c than younger subjects. Subjects visiting the MAHS program more regularly than once every eight months were significantly more likely to achieve a reduction in HbA₁c than those who were seen by MAHS staff once every eight months or more. Sixty per cent of those subjects with four or more visits to the MAHS program showed a reduction in HbA₁c, while 38% of those with fewer than four visits showed a reduction in HbA₁c, but this association did not reach significance.
Conclusions:  Older subjects and those attending the MAHS diabetes clinics more intensively were significantly more likely to show a reduction in HbA₁c than younger subjects and those attending the clinic once every eight months or more. Future, larger studies using additional outcome measures will allow for an improved evaluation of interventions by dietitians and diabetes educators for those with type 2 diabetes.     

Study of subcellular localization of membrane‐bound choline acetyltransferase in Drosophila central nervous system and its association with membranes

Choline acetyltransferase (ChAT), the enzyme which catalyses the biosynthesis of the neurotransmitter acetylcholine, exists in a soluble and membrane-bound form in cholinergic nerve terminals of different animal species. This study was performed on the enzyme present in Drosophila central nervous system. We show that the two forms of the enzyme have the same apparent molecular weight (75 kDa) when analysed by immunoblotting using an antibody we raised against the recombinant enzyme. According to different authors, membrane-bound enzyme might be associated with synaptic vesicles or plasma membrane. Subfractionation of Drosophila head homogenates in linear glycerol gradients showed that ChAT does not associate with synaptic vesicles. Analysis of ChAT activity and immunoreactivity showed that two peaks of ChAT were produced. One peak was present in fractions containing soluble components and the other was associated with rapidly sedimenting membranes containing plasma membranes. ChAT in the first peak was mainly hydrophilic. A large proportion of ChAT associated with rapidly sedimenting membranes was amphiphilic. Further fractionation of these membranes by flotation in sucrose gradients showed that membrane-associated ChAT sedimented in fractions containing plasma membrane marker. Membrane-bound ChAT was neither solubilized nor converted to hydrophilic enzyme after membrane treatment with 1 m hydroxylamine, suggesting that the enzyme is not palmitoylated and therefore not anchored to membrane through thioester-linked long chain fatty acid. Partial solubilization of ChAT present on membranes with urea and carbonate suggests that this form of ChAT is a peripheral membrane protein. Carbonate solubilization of membrane-bound ChAT converted the enzyme from hydrophobic to hydrophilic protein.     

PK11195 potently sensitizes to apoptosis induction independently from the peripheral benzodiazepin receptor

1-(2-Chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195) is a prototypic ligand of the peripheral benzodiazepine receptor (PBR), a mitochondrial outer membrane protein. PK11195 can be used to chemosensitize tumor cells to a variety of chemotherapeutic agents, both in vitro and in vivo. PK11195 has been suggested to exert this effect via inhibition of the multiple drug resistance (MDR) pump and by direct mitochondrial effects which could be mediated by the PBR. Here, we established a model system in which PK11195 and another PBR ligand, 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (Ro5-4864), sensitize to nutrient depletion-induced cell death. In this MDR-independent model, PK11195 and Ro5-4864 are fully active even when the PBR is knocked down by small interfering RNA. Cells that lack PBR possess low-affinity binding sites for PK11195 and Ro5-4864. The starvation-sensitizing effects of PK11195 are not due to a modulation of the adaptive response of starved cells, namely autophagy and NF-kappaB activation. Rather, it appears that the combination of PK11195 with autophagy or NF-kappaB inhibitors has a potent synergistic death-inducing effect. Starved cells treated with PK11195 exhibit characteristics of apoptosis, including loss of the mitochondrial transmembrane potential, mitochondrial cytochrome c release, caspase activation and chromatin condensation. Accordingly, stabilization of mitochondria by overexpression of Bcl-2 or expression of the viral mitochondrial inhibitor (vMIA) from cytomegalovirus inhibits cell death induced by PK11195 plus starvation. Thus, PK11195 potently sensitizes to apoptosis via a pathway that involves mitochondria, yet does not involve the PBR.     

Treatment and prevention of cerebrovascular disorders in children

Opinion statement Cerebrovascular disorders are an important cause of mortality and chronic morbidity in children. Ischemic stroke is more common than cerebral venous thrombosis and hemorrhagic stroke in children. Several medical disorders have been associated with stroke in children, and a thorough evaluation of underlying causes is needed to determine the best treatment and prevention strategy. The treatment and prevention of stroke in children is not well studied, and current recommendations are based on adult studies, nonrandomized trials, or expert opinion. Children with stroke require immediate, special attention and if possible should be stabilized and transferred to an institution that can offer pediatric neurovascular expertise and care. All children with stroke should be referred to or have their care managed by a pediatric neurologist. The treatment of stroke in adults is well studied, and when applicable this evidence should be considered in the treatment of children with stroke. Data from animal and adult stroke studies have demonstrated a benefit for the aggressive treatment of infection, fever, blood pressure, hypo/hyperglycemia, intracranial pressure, and seizures, and should be applied to children with stroke. The use of thrombolytic, antithrombotic, and antiplatelet therapies is based on adult studies, cohort studies, and/or expert opinion. Two consensus guidelines regarding the treatment of arterial ischemic stroke and cerebral venous thrombosis were recently published and recommend the use of anticoagulants or antiplatelet agents in the acute setting, depending on the underlying cause of stroke. The evidence for the primary prevention of stroke in children is restricted to sickle cell disease (SCD) and derived from the Stroke Prevention in Sickle Cell Study Project studies. Long-term chronic transfusion therapy to maintain hemoglobin S levels below 30% is indicated in children with SCD and intracranial stenosis. It has also been recently determined that chronic transfusion therapy should not be stopped in children with SCD and an increased risk for stroke. The recurrence rate of arterial ischemic stroke (AIS) in children ranges from 6% to 30% and is highest among children with recurrent transient ischemic attack, cardiac disease, arteriopathies, and metabolic and coagulation abnormalities. Recommendations for secondary prevention are based on adult studies and the underlying pathophysiology of the stroke. Antiplatelet therapy (aspirin 1–5 mg/ kg/day) is recommended in most children with a history of AIS. Although there is minimal evidence to support its use in children, anticoagulation may be indicated in AIS associated with extracranial arterial dissection, prothrombotic disorders, cardiac disease, severe intracranial stenosis, and recurrent AIS while on antiplatelet therapy.     

The effect of whey acidic protein fractions on bone loss in the ovariectomised rat

Bovine milk has been shown to contain bioactive components with bone-protective properties. Earlier studies on bovine milk whey protein showed that it suppressed bone resorption in the female ovariectomised rat. A new osteotropic component was subsequently identified in the whey basic protein fraction, but bone bioactivity may also be associated with other whey fractions. In the present study, we investigated whether acidic protein fractions isolated from bovine milk whey could prevent bone loss in mature ovariectomised female rats. Six-month-old female rats were ovariectomised (OVX) or left intact (sham). The OVX rats were randomised into four groups. One group remained the control (OVX), whereas three groups were fed various whey acidic protein fractions from milk whey as 3 g/kg diet for 4 months. Outcomes were bone mineral density, bone biomechanics and markers of bone turnover. Bone mineral density of the femurs indicated that one of the whey AF over time caused a recovery of bone lost from OVX. Plasma C-telopeptide of type I collagen decreased significantly in all groups except OVX control over time, indicating an anti-resorptive effect of whey acidic protein. Biomechanical data showed that the AF may affect bone architecture as elasticity was increased by one of the whey AF. The femurs of AF-supplemented rats all showed an increase in organic matter. This is the first report of an acidic whey protein fraction isolated from milk whey that may support the recovery of bone loss in vivo.