Long-term risk of first recurrent stroke in the Perth Community Stroke Study

Background and Purpose-Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke. This study aimed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population-based series of people with first-ever stroke in Perth, Western Australia. Methods-Between February 1989 and August 1990, all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. Results-Three hundred seventy patients with a first-ever stroke were registered, of whom 351 survived >2 days. Data were available for 98% of the cohort at 5 years, by which time 199 patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12 (23%) of which were fatal within 28 days. The 5-year cumulative risk of first recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8% (95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard ratio [HR], 2.6; 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1; 95% CL, 0.98, 4.4), and diabetes mellitus (HR, 2.1; 95% CL, 0.95, 4.4). Conclusions-Approximately 1 in 6 survivors (15%) of a first-ever stroke experience a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days. The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88% of cases. The predictors of first recurrent stroke in this study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but numbers of recurrent events were modest. Because the risk of recurrent stroke is highest (8.8%) in the first 6 months after stroke, strategies for secondary prevention should be initiated as soon as possible after the index event.

The currency of case management: benefits and costs

Case management models evolved as the mental health care system shifted hospital to community settings. The research evidence underscores the efficacy of certain case management models under 'ideal' conditions; what is less clear, is how these models perform in day to day clinical practice. Moreover, the economic perspective adopted by most studies is relatively narrow thus limiting a proper understanding of the costs and benefits of such models. This paper reviews recent work in the field and highlights gaps in both method and application as a focus for future work. Curr Opin Psychiatry 12:195-199, (C) 1999 Lippincott Williams & Wilkins.

The influence of Lys68 in decapeptide agonists of C5a on C5a receptor binding, activation and selectivity

The potent, conformationally biased C5a agonist peptide YSFKPMPLaR (C5a(65-74), Y65, F67, P69, P71, D-Ala73) was used as a template to gain insight into the nature and importance of lysine at position 68 in the peptide-receptor interaction. A panel of YSFKPMPLaR analogs with systematic substitutions for Lys68 was evaluated for C5a receptor (C5aR) binding affinity and activation in two well-characterized assay systems: human polymorphonuclear leukocytes (PMNs) and human fetal artery. In addition, we determined the activity of these new analogs in transfected rat basophilic leukemia (RBL) cells in which the Glu at position 199 of the C5aR (wtGlu199) was replaced by a Gin (C5aR-Gln199) or a Lys (C5aR-Lys199). Our results indicated that Lys68 in YSFKPMPLaR plays an important role in binding the C5aR expressed on PMNs and RBL cells. Furthermore, the data indicated that Lys68 interacted with Glu199 of the C5aR in PMNs and RBL cells. In human fetal artery, however, Lys68 substitutions had little or no effect on activity, which suggested that the receptor conformation may be different in this tissue. Thus, the interaction between Lys68 of the decapeptide agonist and Glu199 of the C5aR may be cell type-specific and may form the molecular basis for tissue-specific responses to C5a agonists.

Calcium accretion in girls and boys during puberty: A longitudinal analysis

The primary purpose of this study was to estimate the magnitude and variability of peak calcium accretion rates in the skeletons of healthy white adolescents. Total-body bone mineral content (BMC) was measured annually on six occasions by dual-energy X-ray absorptiometry (DXA; Hologic 2000, array mode), a BMC velocity curve was generated for each child by a cubic spline fit, and peak accretion rates were determined. Anthropometric measures were collected every 6 months and a 24-h dietary recall was recorded two to three times per year. Of the 113 boys and 115 girls initially enrolled in the study, 60 boys and 53 girls who had peak height velocity (PHV) and peak BMC velocity values were used in this longitudinal analysis. When the individual BR IC velocity curves were aligned on the age of peak bone mineral velocity, the resulting mean peak bone mineral accrual rate was 407 g/year for boys (SD, 92 g/year; range, 226-651 g/year) and 322 g/year for girls (SD, 66 g/year; range, 194-520 g/year). Using 32.2% as the fraction of calcium in bone mineral, as determined by neutron activation analysis (Ellis et al., J Bone Miner Res 1996;11:843-848), these corresponded to peak calcium accretion rates of 359 mg/day for boys (81 mg/day; 199-574 mg/day) and 284 mg/day for girls (58 mg/day; 171-459 mg/day). These longitudinal results are 27-34% higher than our previous cross-sectional analysis in which we reported mean values of 282 mg/day for boys and 212 mg/day for girls (Martin et al., Am J Clin Nutr 1997;66:611-615). Mean age of peak calcium accretion was 14.0 years for the boys (1.0 years; 12.0-15.9 years), and 12.5 years for the girls (0.9 years; 10.5-14.6 years). Dietary calcium intake, determined as the mean of all assessments up to the age of peak accretion was 1140 mg/day (SD, 392 mg/day) for boys and 1113 mg/day (SD, 378 mg/day) for girls. We estimate that 26% of adult calcium is laid down during the 2 adolescent years of peak skeletal growth. This period of rapid growth requires high accretion rates of calcium, achieved in part by increased retention efficiency of dietary calcium.

Rewarded associative and instrumental conditioning after neonatal ventral hippocampus lesions in rats

Sprague Dawley rats were submitted to bilateral ventral hippocampus lesions 7 days after birth. This corresponds to the Lipska and Weinberger`s procedure for modeling schizophrenia. The aim of the present work was to test the learning capacity of such rats with an associative Pavlovian and an instrumental learning paradigm, both methods using reward outcome (food, sucrose or polycose). The associative paradigm comprised also a second learning test with reversed learning contingencies. The instrumental conditioning comprised an extinction test under outcome devaluation conditions. Neonatally lesioned rats, once adults (over 60 days of age), showed a conditioning deficit in the associative paradigm but not in the instrumental one. Lesioned rats remained able to adapt as readily as controls to the reversed learning contingency and were as sensitive as controls to the devaluation of outcome. Such observations indicate that the active access (instrumental learning) to a reward could have compensated for the deficit observed under the ""passive"" stimulus-reward associative learning condition. This feature is compared to the memory management impairments observed in clinical patients. (c) 2008 Elsevier B.V. All rights reserved.

Glucose and Fructose Fermentation by Wine Yeasts in Media Containing Structurally Complex Nitrogen Sources

Glucose and fructose fermentations by industrial yeasts strains are strongly affected by both the structural complexity of the nitrogen Source and the availability of oxygen. In this Study two Saccharomyces cerevisiae industrial wine strains were grown, under shaken and static conditions, in a media containing either a) 20% (w/v) glucose, or b) 10% (w/v) fructose and 10% (w/v) glucose or c) 20% (w/v) fructose, all supplemented with nitrogen Sources varying from a single ammonium salt (ammonium Sulfate) to free amino acids (casamino acids) and peptides (peptone). Data Suggest that 1 complex Structured nitrogen source is not submitted to the same control mechanisms as those involved in the utilization of simpler structured nitrogen Sources, and mutual interaction between carbon and nitrogen Sources, including the mechanisms involved ill the regulation of aerobic/anaerobic metabolism, may play in important role in defining yeast fermentation performance and the differing response to the structural complexity of the nitrogen Source, with a strong impact oil fermentation performance.

Depression in women living with HIV: clinical and psychosocial correlates

The number of Brazilian women living with HIV has increased significantly in past years, rendering studies of their particular care demands including psychiatric issues. This study measures the prevalence of major depression, using the Structured Clinical Interview for DSM-IV Axis I Disorders, in a sample of 120 women living with HIV in treatment at a reference centre in So Paulo. Socio-demographic variables, HIV-related clinical and laboratory data, including CD4+ cell counts and HIV plasma viral loads, as well as psychosocial features (intimate relationships, disclosure of HIV serostatus, partner`s serostatus and patient`s emotional and financial support) were investigated as factors potentially associated with depression. The prevalence of major depression at the time of evaluation was 25.8% (95% CI 18.2-33.4%). Clinical status (p = 0.002), lack of emotional support (p = 0.02), use of antidepressants (p = 0.028) and length of time since HIV diagnosis (p = 0.05) were associated with major depression in univariate analysis. In multivariate multiple-regression model, HIV clinical status, lack of emotional support and higher plasma viral loads were associated with depression. Sixty per cent of the women have a major depression diagnosis during lifetime. We conclude that major depression is highly prevalent among women living with HIV, but it is still underdiagnosed and undertreated.

Bile duct ligation in neonatal rats: Is it a valid experimental model for biliary atresia studies?

BA is the most important disease requiring liver transplantation in children. Common BDL in rats is a classic experimental model to study biliary obstruction. The response of the neonatal animal to BDL has yet to be completely understood and few reports have focused on the behavioral differences of the liver between neonatal and adult animals. Ninety newborn Wistar rats aged six days, weighing 8.0-13.9 g, and 90 adult Wistar rats weighing 199.7-357.0 g, were submitted to BDL. After surgery, they were randomly divided and killed on the 3rd, 5th, 7th, 14th, 21st and 28th day post-BDL. Hepatic biopsies were obtained and the following were measured: (i) semiquantification of the bile ductule proliferation and inflammatory infiltrate by HE stain, (ii) quanti. cation of portal and periportal fibrosis with the Sirius-red stain. Although the initial response of ductule proliferation and inflammatory infiltrate were less intense in the newborn animal, the portal and periportal fibrosis were higher when compared with adult animals (p < 0.0491). These findings may contribute to the understanding of the pathophysiology of BA.

Heterozygosity for the S180L Variant of MAL/TIRAP, a Gene Expressing an Adaptor Protein in the Toll-Like Receptor Pathway, Is Associated with Lower Risk of Developing Chronic Chagas Cardiomyopathy

Background. Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. Among T. cruzi-infected individuals, only a subgroup develops severe chronic Chagas cardiomyopathy (CCC); the majority remain asymptomatic. T. cruzi displays numerous ligands for the Toll-like receptors (TLRs), which are an important component of innate immunity that lead to the transcription of proinflammatory cytokines by nuclear factor-kappa B. Because proinflammatory cytokines play an important role in CCC, we hypothesized that single-nucleotide polymorphisms (SNPs) in the genes that encode proteins in the TLR pathway could explain differential susceptibility to CCC among T. cruzi-infected individuals. Methods. For 169 patients with CCC and 76 T. cruzi-infected, asymptomatic individuals, we analyzed SNPs by use of polymerase chain reaction-restriction fragment length polymorphism analysis for the genes TLR1, TLR2, TLR4, TLR5, TLR9, and MAL/TIRAP, which encodes an adaptor protein. Results. Heterozygous carriers of the MAL/TIRAP variant S180L were more prevalent in the asymptomatic group (24 [32%] of 76 subjects) than in the CCC group (21 [12%] of 169) (chi(2) = 12.6; P = .0004 [adjusted P (P(c)) = .0084]; odds ratio [OR], 0.31 [95% confidence interval {CI}, 0.16-0.60]). Subgroup analysis showed a stronger association when asymptomatic patients were compared with patients who had severe CCC (i.e., patients with left-ventricular ejection fraction <= 40%) (chi(2) = 11.3; P = .0008 [P(c) = .017]; OR, 0.22 [95% CI, 0.09-0.56]) than when asymptomatic patients were compared with patients who had mild CCC (i.e., patients with left-ventricular ejection fraction >40%) (chi(2) = 7.7; P = .005 [P(c) = .11]; OR, 0.33 [95% CI, 0.15-0.73]). Conclusion. T. cruzi-infected individuals who are heterozygous for the MAL/TIRAP S180L variant that leads to a decrease in signal transduction upon ligation of TLR2 or TLR4 to their respective ligand may have a lower risk of developing CCC.

Incidence, Risk Factors, and Outcome of Herpes Zoster in Systemic Lupus Erythematosus

Background: The incidence and outcome of Herpes zoster (HZ) in systemic lupus erythematosus (SLE) are not completely defined as well as the relevance to HZ of disease and therapy factors. Objective: To determine HZ features in SLE. Patients and Methods: SLE patients ( 1997 update of the American College of Rheumatology classification criteria) with definitive HZ infection were identified from our Lupus Clinic computerized database of 1145 patients. Results: HZ was diagnosed in 51 SLE patients (4.45%) with an annual incidence rate of 6.4 events/1000 patient-years. At HZ diagnosis, mean disease duration was 9.78 +/- 8.37 years, median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 1, and only 17.6% had SLEDAI >= 8. Frequency of manifestations and immunosuppressor use were similar between patients with and without HZ. Forty-two patients (82.5%) with HZ were under prednisone with concomitant immunosuppressive therapy in 66.7%. Thirty-five patients (68.6%) were using immunosuppressors: azathioprine (39.2%), cyclophosphamide (9.8%), and mycophenolate mofetil ( 9.8%). The mean lymphocyte count was 1219 +/- 803/mm(3) (43.1% < 1000/mm(3) and 17.6% < 500/mm(3)). Only patients using azathioprine and cyclophosphamide had lymphocyte counts < 500/mm(3) (15% and 40%). All patients received acyclovir, 19.6% had postherpetic neuralgia, and recurrence occurred in only 7.8%. Thoracic nerves were the most involved site (56.8%) followed by lumbar (23.5%). Bacterial suprainfection occurred in 11.7% but was not associated with therapy, lymphocyte count, or SLEDAI scores ( P > 0.05). Conclusion: This is the largest cohort to determine that HZ is a late SLE complication with some peculiar features, such as good prognosis and typical dermatomal distribution. In addition, we have identified that the major trigger factor for this viral infection in SLE is therapy, particularly the concomitant use of corticosteroid and immunosuppressors, and not active disease.

The effects of plantar fasciitis and pain on plantar pressure distribution of recreational runners

Background: Plantar fasciitis is the third most frequent injury in runners. Despite its high prevalence, its pathogenesis remains inconclusive. The literature reports overload as the basic mechanism for its development. However, the way that these plantar loads are distributed on the foot surface of runners with plantar fasciitis and the effects of pain on this mechanical factor has not yet been investigated. Therefore, the aim of this study was to evaluate and compare the plantar pressure distributions during running in runners with symptom or history of plantar fasciitis and runners without the disease. Methods: Forty-five recreational runners with plantar fasciitis (30 symptomatic and 15 with previous history of the disease) and 60 runners without plantar fasciitis (control group) were evaluated. Pain was assessed by a visual analogue scale. All runners were evaluated by means of the Pedar system insoles during running forty meters at a speed of 12(5%) km/h, using standard sport footwear. Two-way ANOVAS were employed to investigate the main and interaction effects between groups and plantar areas. Findings: No interaction effects were found for any of the investigated variables: peak pressure (P=0.61), contact area (P=0.38), contact time (P=0.91), and the pressure-time integral (P=0.50). Interpretation: These findings indicated that the patterns of plantar pressure distribution were not affected in recreational runners with plantar fasciitis when compared to control runners. Pain also did not interfere with the dynamic patterns of the plantar pressure distributions. (C) 2010 Elsevier Ltd. All rights reserved.

Estimation of the pore size of the large-conductance mechanosensitive ion channel of Escherichia coli

The open channel diameter of Escherichia coli recombinant large-conductance mechanosensitive ion channels (MscL) was estimated using the model of Hille (Hille, B. 1968. Pharmacological modifications of the sodium channels of frog nerve. J. Gen. Physiol. 51:199-219)that relates the pore size to conductance. Based on the MscL conductance of 3.8 nS, and assumed pore lengths, a channel diameter of 34 to 46 Angstrom was calculated. To estimate the pore size experimentally, the effect of large organic ions on the conductance of MscL was examined. Poly-L-lysines (PLLs) with a diameter of 37 Angstrom or larger significantly reduced channel conductance, whereas spermine (similar to 15 Angstrom), PLL19 (similar to 25 Angstrom) and 1,1'-bis-(3-(1'-methyl-(4,4'-bipyridinium)-1-yl)-propyl)-4,4'-bipyridinium (similar to 30 Angstrom) had no effect. The smaller organic ions putrescine, cadaverine, spermine, and succinate all permeated the channel. We conclude that the open pore diameter of the MscL is similar to 40 Angstrom, indicating that the MscL has one of the largest channel pores yet described. This channel diameter is consistent with the proposed homohexameric model of the MscL.

Sphenoid sinus symmetry and differences between sexes

Objectives: To evaluate the anatomic variations of neurovascular structures adjacent to the sphenoid sinus and their agreement between right and left sides as well as differences between sexes. Methods: Forty-five cadavers were dissected (24 men, and differences between sexes and agreement of anatomic variations of the sphenoid sinus between sides were analyzed. Results: The mean distance from the sphenoid sinus ostium to the anterior nasal spine was greater in males than in females by an average of 3.0 mm (p = 0.001) while the mean difference of distances between the right and left side was -1.1 +/- 3.1 mm. Female cadavers had a greater frequency of optic-carotid recess (p = 0.04) and dehiscence over the maxillary nerve (p = 0.02), as well as greater relative risk of optic nerve protrusion (p < 0.001), and dehiscence over the internal carotid artery (ICA) (p = 0.002). In male cadavers the intersinus septum was inserted on the course of the ICA 3.5 times more often than in female (p = 0.02). Agreement of anatomic variations between sides ranged from moderate to almost perfect depending on the structures evaluated. Conclusions: There are anatomic differences of the sphenoid sinus between sexes and between right and left sides, and these differences should be taken into consideration during surgery.

Case Series: Sensory Intolerance as a Primary Symptom of Pediatric OCD

Introduction. Marked intolerance or intrusive re-experiencing of ordinary sensory stimuli that in turn drive functionally impairing compulsive behaviors are occasionally seen in voting children with OCD. Methods. We describe a number of children with DSM-IV OCD ascertained from of family genetic study of pediatric OCD, whose intolerance: of ordinary sensory stimuli created significant subjective distress and time-consuming ritualistic behavior that was clinically impairing. Results. In each case these sensory symptoms were the primary presenting symptoms and were experienced in the absence of intrusive thoughts, images, or ideas associated with ""conventional"" OCD symptoms. Conclusions. These symptoms suggest abnormalities in sensory processing and integration in at least a subset of OCD patients. Recognition of these sensory symptoms and sensory-driven behaviors as part of the broad phenotypic Variation in children with OCD could help clinicians more easily identify OCD patients and,facilitate treatment.

Hyaluronidase shortens levobupivacaine lumbosacral epidural anaesthesia in dogs

Methods: Six adult mixed breed dogs (two males and four females) weighing 7 to 14 kg (10 center dot 5 +/- 1 center dot 5 kg) and aged two to five years were used. Each dog received both treatments in random order: levobupivacaine alone (LBA; n=6) or levobupivacaine plus hyaluronidase (LBH; n=6) administered in the lumbosacral epidural space. Systemic effects, spread and duration of anaesthesia and motor block were determined before treatment and at predetermined intervals. Results: The duration of local anaesthesia was 90 +/- 10 minutes (P=0 center dot 001) for LBH treatment and 150 +/- 15 minutes for LBA treatment. In the LBH treatment, anaesthesia reached the T12 to T13 dermatome and in the LBA treatment it reached the T11 to T12 dermatome in all animals in 5 and 15 minutes, respectively. Complete motor blockade was 75 +/- 12 minutes (P=0 center dot 01) and 120 +/- 15 minutes for LBH and LBA treatments, respectively. Clinical Significance: Hyaluronidase added to levobupivacaine significantly shortens the duration of epidural anaesthesia with the same dermatome spread into the epidural space in dogs.