Intrarenal Angiotensin ii is associated with inflammation, renal damage and dysfunction in dahl salt-sensitive hypertension.

BACKGROUND: The goal of this study was to test the hypothesis that intrarenal Ang II has a proinflammatory effect leading to renal damage and dysfunction in Dahl S rats on high Na intake. METHODS: Forty-six 7-to 8-week old Dahl S or R/Rapp strain rats were maintained for 5 weeks on high sodium (8%) with or without candesartan cilexetil in daily doses of 10-15 mg/kg/day. Arterial catheters were implanted at day 28. RESULTS: By day 35 in the high Na S + candesartan rats, renal tissue Ang II concentration, renal monocytes/macrophages, TNFalpha, and MCP-1 significantly decreased. Plasma Ang II remained at very low levels in all groups. Reduced renal damage in candesartan-treated Dahl S rats was demonstrated by marked decreases in urinary protein excretion and renal glomerular and interstitial damage. After 5 weeks of high Na, compared to high Na Dahl S rats, arterial pressure was unchanged in candesartan S rats, but creatinine clearance was increased. CONCLUSIONS: Therefore, candesartan reduced renal tissue Ang II, renal damage, infiltration of immune cells, cytokines, chemokines, and improved renal hemodynamics. These data suggest that intrarenal Ang II plays an important role in causing renal inflammation which leads to renal cortical damage, proteinuria, and decreases in renal hemodynamics.

The relation of ultraviolet radiation and multiple sclerosis in Newfoundland.

BACKGROUND: It has been thought that the occurrence of multiple sclerosis (MS) could be associated with daily ultraviolet exposure. In this study we investigated the geospatial association between average daily ultraviolet B (UVB) irradiance and MS prevalence in Newfoundland and Labrador (NL), Canada. METHODS: A complete list of patients diagnosed with MS in the province of NL was constructed. Places of habitation from birth to diagnosis were ascertained by mailout survey. RESULTS: A 74% rate of return on the survey results was obtained. A plot of the average daily erythemal UV over the available five years (1998-2002) shows that the distribution of MS follow a north-south gradient. Average daily UVB measurements are lower in the higher latitudes. A statistically significant negative correlation of MS incidence with erythemal UVB was found that is stronger than the correlation using latitude. This correlation appears to be strongest in the first year of life and declines when subsequent years are examined up to age ten. No significant correlation was found for the subjects' locale of habitation at the time of their first MS attack. CONCLUSIONS: This study suggests that UVB radiation may contribute to the pathogenesis of MS.

The relation between menarche and the age of first symptoms in a multiple sclerosis cohort.

BACKGROUND: Previously, multiple sclerosis (MS) has been thought to be associated with changes in hormone levels. This study investigates the association between the age of menarche and the age of onset of the first symptoms of MS. METHODS: A complete list of patients diagnosed with MS in the province of Newfoundland and Labrador was constructed. The age of menarche for our entire relapsing remitting female MS (RRMS) population was requested by mailout survey. Age of symptom onset was ascertained by chart review. RESULTS: A 74% rate of return on the survey results was obtained (150 RRMS patients). A linear regression model demonstrated that the age of first symptoms increased by 1.16 years as the age of menarche increased by one year (R2 = 0.69, P = 0.04). Another analysis showed that the average age of first symptoms for women with reported menarche from 10 to 12 years was 28.96 years compared with 31.83 years for a reported menarche from 13 to 15 years, a significant difference (P = 0.047, t-test). CONCLUSIONS: This study suggests that menarche may be related to the pathogenesis of MS.

Incidence and prevalence of multiple sclerosis in Newfoundland and Labrador.

BACKGROUND: The incidence and prevalence of multiple sclerosis (MS) in Newfoundland and Labrador (NL) had been reported in 1984 and was considered to be relatively low at that time. This study revisits the incidence and prevalence of MS in NL for the year 2001. METHODS: Case searches through patient files of neurologists in NL were conducted. A complete list of patients billed for MS in NL between 1996 and 2003 was obtained and all cases were confirmed via chart review. RESULTS: There were 493 living MS patients yielding a prevalence of 94.4/100,000 which is significantly higher than previously reported. Of the living patients, 330 had relapsing remitting (RRMS), 94 had secondary progressive, 66 had primary progressive (PPMS) and three had unspecified MS. The total female to male ratio was 2.7:1. There was no difference between the female to male ratios for RRMS vs PPMS. Patients with PPMS had a later onset compared to RRMS (p<0.00001). Yearly incidences were relatively constant from 1994 to 2001 (5.6/100,000). Significant delays between first symptoms and final diagnosis were common and the delay time has not changed over the past 15 years. A prevalence of 88.9/100,000 was estimated from survival and incidence trends and was not significantly different than the measured prevalence (p=0.38). CONCLUSIONS: The increase in incidence and prevalence are accounted for through both better access to diagnostic facilities and more practicing neurologists. The revised prevalence and incidence are more in keeping with recently reported values throughout Canada.

Multiple sclerosis in Newfoundland and Labrador--a model for disease prevalence.

BACKGROUND: Newfoundland and Labrador, Canada, have been almost exclusively populated by immigrants from southwest England and southeast Ireland. The province's population grew largely by natural increase from 20,000 people in 1835 to half a million at present. Very little interregional migration occurred within the province. This uniquely-populated region and its subsequent founder effect provide the basis to develop models of disease prevalence. OBJECTIVES: To develop a model for the regional prevalence of multiple sclerosis (MS), accounting for settlement patterns and geographic location (latitude). METHODS: All living MS patients with confirmed addresses (438 patients) in the province were mailed a survey requesting their place of birth. Regional prevalences were calculated from a 75% rate of return of the survey. Theoretical regional prevalences were proportionally calculated from the source prevalences of southwest England, southeast Ireland, Scotland and the Channel Islands based on settlement patterns. These theoretical regional prevalences were corrected for geographical variations of latitude based on observations in the United Kingdom. Theoretical and actual regional prevalences were compared. RESULTS: When actual regional prevalences were compared with theoretical prevalences, very little variation was noted, especially after correcting for variation in latitude. CONCLUSION: A regional variation in MS prevalence is noted in the island portion of Newfoundland and Labrador. This regional variation can be modeled by using both migration patterns and latitudinal position. This model demonstrates that the prevalence of MS is influenced by both genetic and environmental contributions.

Guidelines for the nonpharmacologic management of migraine in clinical practice. Canadian Headache Society.

OBJECTIVE: To provide physicians and allied health care professionals with guidelines for the nonpharmacologic management of migraine in clinical practice. OPTIONS: The full range and quality of nonpharmacologic therapies available for the management of migraine. OUTCOMES: Improvement in the nonpharmacologic management of migraine. EVIDENCE AND VALUES: The creation of the guidelines followed a needs assessment by members of the Canadian Headache Society and included a statement of objectives; development of guidelines by multidisciplinary working groups using information from literature reviews and other resources; comparison of alternative clinical pathways and description of how published data were analysed; definition of the level of evidence for data in each case; evaluation and revision of the guidelines at a consensus conference held in Ottawa on Oct. 27-29, 1995; redrafting and insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all conference participants. BENEFITS, HARMS AND COSTS: Augmentation of the use of nonpharmacologic therapies for the acute and prophylactic management of migraine is likely to lead to substantial benefits in both human and economic terms. RECOMMENDATIONS: Both the avoidance of migraine trigger factors and the use of nonpharmacologic therapies have a part to play in overall migraine management. VALIDATION: The guidelines are based on consensus of Canadian experts in neurology, emergency medicine, psychiatry, psychology and family medicine, and consumers. Previous guidelines did not exist. Field testing of the guidelines is in progress.

Guidelines for the diagnosis and management of migraine in clinical practice. Canadian Headache Society.

OBJECTIVE: To provide physicians and allied health care professionals with guidelines for the diagnosis and management of migraine in clinical practice. OPTIONS: The full range and quality of diagnostic and therapeutic methods available for the management of migraine. OUTCOMES: Improvement in the diagnosis and treatment of migraine, which will lead to a reduction in suffering, increased productivity and decreased economic burden. EVIDENCE AND VALUES: The creation of the guidelines followed a needs assessment by members of the Canadian Headache Society and included a statement of objectives; development of guidelines by multidisciplinary working groups using information from literature reviews and other resources; comparison of alternative clinical pathways and description of how published data were analysed; definition of the level of evidence for data in each case; evaluation and revision of the guidelines at a consensus conference held in Ottawa on Oct. 27-29, 1995; redrafting and insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all conference participants. BENEFITS, HARMS AND COSTS: Accuracy in diagnosis is a major factor in improving therapeutic effectiveness. Improvement in the precise diagnosis of migraine, coupled with a rational plan for the treatment of acute attacks and for prophylactic therapy, is likely to lead to substantial benefits in both human and economic terms. RECOMMENDATIONS: The diagnosis of migraine can be improved by using modified criteria of the International Headache Society as well as a semistructured patient interview technique. Appropriate treatment of symptoms should take into account the severity of the migraine attack, since most patients will have attacks of differing severity and can learn to use medication appropriate for each attack. When headaches are frequent or particularly severe, prophylactic therapy should be considered. Both the avoidance of migraine trigger factors and the application of nonpharmacological therapies play important roles in overall migraine management and will be addressed at a later date. VALIDATION: The guidelines are based on consensus of Canadian experts in neurology, emergency medicine, psychiatry, psychology, family medicine and pharmacology, and consumers. Previous guidelines did not exist. Field testing of the guidelines is in progress.

Neuroradiologic MR applications with multiparametric color composite display.

The purpose of this article is to demonstrate the application of a PC-based multiparameter full color composite display technique of MR images of 14 selected patients with neuropathology while assessing the ability of this technique to display clinically important neuroanatomic and neuropathologic tissues. Using a PC with a 386 microprocessor and full color 24-bit graphics display capabilities, custom and commercially available image-processing softwares were applied to spatially aligned multiparameter proton density, T1-weighted (with and/or without gadolinium-DTPA) and T2-weighted MR image sets obtained from 14 patients with known neuropathology to generate intensity-based color composites. Quantitative color channel applications were used to assess the ability of this technique to differentiate anatomically and pathologically confirmed tissue types into unique color regions within the full color spectrum display in each patient case. Based on the results of pathologic correlation and quantitative color imaging analysis, the application of full color composite generation techniques to multiple MR images of selected neuropathology cases represents a viable technique for displaying diagnostically relevant tissue contrast information in one color image. With this technique, it is possible to generate composites that simultaneously display uniquely color-coded neuroanatomic and neuropathologic tissue information within the context of partially natural-appearing images.

Sudden death in multiple sclerosis associated with sun exposure: a report of two cases.

BACKGROUND: Two cases of sudden unexpected deaths in patients with multiple sclerosis were investigated by the Office of The Chief Forensic Pathologist. METHOD: Case studies. RESULTS: Marked similarities of the deaths, including circumstances, scene examination, and autopsy findings including a complete drug screen were recorded. CONCLUSIONS: Exposure to high ambient temperature may pose a danger to patients with multiple sclerosis. Mechanisms of death and the potential dangers to patients with clinically widespread disease are discussed.

Automatic magnetic resonance tissue characterization for three-dimensional magnetic resonance imaging of the brain.

Computer-assisted diagnostic systems enhance the information available from magnetic resonance imaging. Segmentations are the basis on which three-dimensional volume renderings are made. The application of a raw data-based, operator-independent (automatic), magnetic resonance segmentation technique for tissue differentiation is demonstrated. Segmentation images of vasogenic edema with gross and histopathological correlation are presented for demonstration of the technique. A pixel was classified into a tissue class based on a feature vector using unsupervised fuzzy clustering techniques as the pattern recognition method. Correlation of fuzzy segmentations and gross and histopathology were successfully performed. Based on the results of neuropathological correlation, the application of fuzzy magnetic resonance image segmentation to a patient with a brain tumor and extensive edema represents a viable technique for automatically displaying clinically important tissue differentiation. With this pattern recognition technique, it is possible to generate automatic segmentation images that display diagnostically relevant neuroanatomical and neuropathological tissue contrast information from raw magnetic resonance data for use in three-dimensional volume reconstructions.

Lumbosacral spinal intradural extramedullary paciniomyolipoma: magnetic resonance imaging, computed tomography, and pathology findings.

This report describes a paciniomyolipoma as an intradural tumor of the lumbar spinal cord composed of adipose tissue, striated skeletal muscle, and pacinian corpuscles. Simple lipomas, myolipomas, and other variant lipomas of the spinal cord have been described in the literature; to the authors' knowledge, however, this is the first report of this unusual and unique lipoma.

Critical illness neuromuscular disease in children manifested as ventilatory dependence.

Four children with prolonged dependency on a ventilator were found to have reversible quadriparesis, muscle wasting, and hyporeflexia after 8 to 20 days of assisted ventilation for life-threatening sepsis or respiratory failure. Critical illness neuromuscular disease, which was recently recognized as a distinct clinical syndrome in adults, may also be manifested in children by prolonged ventilatory dependency.

Application of fuzzy c-means segmentation technique for tissue differentiation in MR images of a hemorrhagic glioblastoma multiforme.

The application of a raw data-based, operator-independent MR segmentation technique to differentiate boundaries of tumor from edema or hemorrhage is demonstrated. A case of a glioblastoma multiforme with gross and histopathologic correlation is presented. The MR image data set was segmented into tissue classes based on three different MR weighted image parameters (T1-, proton density-, and T2-weighted) using unsupervised fuzzy c-means (FCM) clustering algorithm technique for pattern recognition. A radiological examination of the MR images and correlation with fuzzy clustering segmentations was performed. Results were confirmed by gross and histopathology which, to the best of our knowledge, reports the first application of this demanding approach. Based on the results of neuropathologic correlation, the application of FCM MR image segmentation to several MR images of a glioblastoma multiforme represents a viable technique for displaying diagnostically relevant tissue contrast information used in 3D volume reconstruction. With this technique, it is possible to generate segmentation images that display clinically important neuroanatomic and neuropathologic tissue contrast information from raw MR image data.

Ruptured intracranial dermoid tumor secondary to closed head trauma. Computed tomography and magnetic resonance imaging.

A patient with an intracranial dermoid tumor that ruptured secondary to closed head trauma is described. Intracranial dermoid tumors (cysts) have been reported to rupture spontaneously during or following surgery. To the authors' knowledge, rupture of a dermoid cyst following closed head trauma has not been reported.

Immunological associations in familial and non-familial Alzheimer patients and their families.

A number of autoimmune diseases and immune-related conditions were investigated in a series of 100 Alzheimer patients and their families. The group was divided into those who had familial dementia of the Alzheimer type and non-familial dementia of the Alzheimer type. HLA DR3 was associated with the familial dementia of the Alzheimer type patients. Adult exposure to tuberculosis appeared to be a risk factor for familial dementia of the Alzheimer type patients. Autoimmune diseases clustered among the non-familial dementia of the Alzheimer type patients, and also among their relatives. Asthma and infertility were also significantly increased among non-familial dementia of the Alzheimer type relatives. The analysis showed that (1) autoimmunity may be important in the sporadic form of Alzheimer disease; (2) it may be possible to confer a decreased risk for Alzheimer disease among relatives when many autoimmune diseases occur in the family; (3) it may be important to assess environmental risk factors for Alzheimer disease separately in patients with familial and sporadic disease; and (4) the efficacy of drug therapies may be dependent on whether the patients have a familial or sporadic form of Alzheimer disease.

Recognition of the aberrant right subclavian artery on cervical spine MR.

Neuroradiologists performing cervical spine MR scans are reminded that an aberrant right subclavian artery is detectable on sagittal cervical spine views. This review of 335 consecutive patients revealed two such anomalies for a prevalence of 0.6%, which compares favorably with the published range of occurrences in the literature (0.5 to 2%).

The focal encephalopathies associated with mycoplasma pneumoniae.

Five patients with evidence of focal encephalopathy are reported. In each case, evidence of mycoplasma pneumoniae infection was detected. No patient improved with conventional antibiotic therapy, but in three subjects, rapid and complete recovery did occur contemporaneously with the administration of high dose steroid therapy. It is suggested that focal as well as diffuse cerebral or cerebellar lesions may occur as manifestations of auto-immune disease complicating mycoplasmal infections in young people and that this illness may be designated as acute mycoplasma-associated encephalopathy.

Use of serial casting in the management of knee joint contractures in an adolescent with cerebral palsy.

Treatment of adolescents with cerebral palsy often presents clinical problems that differ from those encountered when treating younger children with cerebral palsy. Muscle contractures, which may not yield to traditional therapeutic exercise, may be a problem. The purpose of this case report is to describe the use of serial casting in the treatment of knee joint flexion contractures in an adolescent with cerebral palsy.