Migraine and frequent tension-type headache are not associated with multiple sclerosis in a Norwegian case-control study.

BACKGROUND: Inconsistent results have been obtained with regard to headache comorbidity in multiple sclerosis (MS). OBJECTIVE: Investigate the one-year prevalence of migraine and tension-type headache (TTH) in Norwegian MS patients and relate this to clinical parameters. METHODS: A questionnaire concerning headache was administered to 756 MS patients and 1090 controls and used to determine the one-year prevalence of migraine and frequent TTH. RESULTS: No significant differences were seen between patients and controls or between patients with different disease course. Less migraine was observed in patients with Expanded Disability Status Scale score (EDSS) ≥4.0. CONCLUSIONS: This case-control study does not support an association between migraine or TTH and MS.

Distinct calcium signals in developing cortical interneurons persist despite disorganization of cortex by Tbr1 KO.

Cortical development involves the structuring of network features by genetically programmed molecular signaling pathways. Additionally, spontaneous ion channel activity refines neuronal connections. We examine Ca(2+) fluctuations in the first postnatal week of normal mouse neocortex and that expressing knockout of the transcription factor T-brain-1 (Tbr1): a signaling molecule in cortical patterning and differentiation of excitatory neurons. In cortex, glutamatergic neurons express Tbr1 just before the onset of population electrical activity that is accompanied by intracellular Ca(2+) increases. It is known that glutamatergic cells are disordered with Tbr1 KO such that normal laying of the cortex, with newer born cells residing in superficial layers, does not occur. However, the fate of cortical interneurons is not well studied, nor is the ability of Tbr1 deficient cortex to express normal physiological activity. Using fluorescent proteins targeted to interneurons, we find that cortical interneurons are also disordered in the Tbr1 knockout. Using Ca(2+) imaging we find that population activity in mutant cortex occurs at normal frequencies with similar sensitivity to GABAA receptor blockade as in nonmutant cortex. Finally, using multichannel fluorescence imaging of Ca(2+) indicator dye and interneurons labeled with red fluorescent protein, we identify an additional Ca(2+) signal in interneurons distinct from population activity and with different pharmacological sensitivities. Our results show the population activity described here is a robust property of the developing network that continues in the absence of an important signaling molecule, Tbr1, and that cortical interneurons generate distinct forms of activity that may serve different developmental functions. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 705-720, 2016.

No association between multiple sclerosis and periodontitis after adjusting for smoking habits.

BACKGROUND AND PURPOSE: Periodontitis has been reported to be associated with several systemic disorders, and recently a possible relationship with multiple sclerosis (MS) was suggested. The aim of the present study was to investigate the association between periodontitis and MS in a Norwegian cohort. METHODS: A case-control study in 756 MS patients and 1090 controls was conducted, and logistic regression analysis, adjusting for age, gender, place of residence, mononucleosis and smoking, was performed to investigate the association between MS and periodontitis. RESULTS: In the unadjusted analysis a higher prevalence of periodontitis was seen in MS patients, but this difference was not statistically significant after adjusting for the covariates. CONCLUSIONS: The previously suggested association between MS and periodontitis is not supported in this study. Our results underline the importance of adjusting for relevant covariates in epidemiological research.

Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin.

Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8-809) compared with healthy controls (median 110 pg/ml, range 8-359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma.

High prevalence and no latitude gradient of multiple sclerosis in Norway.

The prevalence of multiple sclerosis (MS) is increasing, and the presence of a latitude gradient for MS risk is still discussed. We present the first nationwide prevalence estimates for Norway, spanning the latitudes from 58-71 degrees North, in order to identify a possible latitude gradient. Information from the Oslo MS Registry and the Norwegian MS Registry and Biobank was combined with data from the Norwegian Patient Registry, the Norwegian Prescription Database and Statistics Norway. We estimated a crude prevalence of 203/100,000 on 1 January 2012. The prevalence in the Northern and Southern regions were not significantly different. MS prevalence in Norway is among the highest reported worldwide. We found no evidence of a latitude gradient.

Intrathecal levels of vitamin D and IgG in multiple sclerosis.

BACKGROUND: Intrathecal synthesis of IgG is a hallmark of multiple sclerosis (MS). Vitamin D may modulate B-cell function and dampen the synthesis of IgG. OBJECTIVE: To investigate the relation between vitamin D levels in cerebrospinal fluid and serum and intrathecal synthesis of IgG. METHODS: 25-hydroxyvitamin D (25(OH)D) and IgG were assessed in cerebrospinal fluid and serum in 40 patients with MS. RESULTS: There was no significant correlation between the IgG index and 25(OH)D levels in cerebrospinal fluid or serum. The levels of 25(OH)D in cerebrospinal fluid and serum did not differ between patients with and without intrathecal synthesis of IgG. There was a non-significant trend towards a positive correlation between the concentrations of 25(OH)D and IgG in the cerebrospinal fluid, but not in serum. CONCLUSION: Physiological variation in vitamin D does not exert a major impact on intrathecal synthesis of IgG in MS.

Low bone mass in newly diagnosed multiple sclerosis and clinically isolated syndrome.

OBJECTIVE: Osteoporosis is common in patients with multiple sclerosis (MS) with long-standing disease. Hypovitaminosis D is a candidate risk factor for MS, and vitamin D also mediates bone mineralization. If vitamin D exerts a major effect on MS risk, skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS. In order to test this hypothesis, we assessed bone mineral density (BMD) at early stages of disease in patients with no or minor disability. METHODS: A population-based case-control study was conducted on 99 consecutive and newly diagnosed patients with clinically isolated syndrome or MS, and on 159 age-, sex-, and ethnicity-matched controls. BMD was measured by dual-energy x-ray absorptiometry of the femoral neck, total hip, anterior-posterior lumbar spine, total body, and nondominant ultradistal radius. RESULTS: A total of 50.5% of the patients exhibited either osteopenia (-2.5 < T score < -1.0) or osteoporosis (T score ≤-2.5) in at least one skeletal site, compared to 37.1% of controls (p = 0.034). After adjusting for possible confounders, left femoral total hip T score and lumbar spine BMD and T score were significantly lower in patients than in controls (p = 0.023, 0.039, and 0.026, respectively). CONCLUSIONS: Low bone mass appears to occur early in MS. This is compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS.

Fractures and falls in patients with newly diagnosed clinically isolated syndrome and multiple sclerosis.

BACKGROUND: Increased risk of falls and reduced bone strength may both contribute to enhanced fracture risk in patients with multiple sclerosis (MS). Fall tendency and fractures have not been investigated in newly diagnosed patients. OBJECTIVES: The aim was to compare the fall tendency and fracture risk in a cohort of newly diagnosed clinically isolated syndrome (CIS) and MS patients with that in the general population. METHODS: We performed a population-based case-control study in Oslo of self-reported fall tendency and fracture history in consecutive patients diagnosed with either a CIS suggestive of demyelinating disease or MS between January 2005 and January 2008. Two age-, sex-, and ethnicity-matched control groups were included; one group from the population registry and one group recruited by the patients. RESULTS: Ninety-nine patients (mean time since the first symptom 1.6 ± 1.3 years, mean expanded disability status scale [EDSS] score 1.4 ± 1.1) and 159 controls were included. Whereas no difference in the number of fractures was reported, 20% of the patients and 3% of the controls reported a tendency to fall (P<0.001). Fall tendency was associated with degree of disability (mean EDSS score among patients with and without self-reported fall tendency was 2.4 ± 1.4 and 1.1 ± 0.9, respectively; P=0.001). Fall tendency was also reported in two of 22 patients with EDSS 0. CONCLUSIONS: Fall tendency may occur early in the disease course of MS, before impairment of locomotion and balance becomes evident on clinical examination.

Assessing vitamin D in the central nervous system.

Epidemiological and experimental evidence suggest that vitamin D deficiency is a risk factor for multiple sclerosis and other autoimmune diseases. The activated form of vitamin D exerts several immunomodulating properties in vitro and in vivo, that could contribute to explain the association with multiple sclerosis. Hypovitaminosis D is also associated with several other neurological diseases that is less likely mediated by dysregulated immune responses, including Parkinson's disease and Alzheimer's disease, schizophrenia and affective disorders, suggesting a more diverse role for vitamin D in the maintenance of brain health. Accordingly, both the vitamin D receptor and the enzymes necessary to synthesize bioactive 1,25-dihydroxyvitamin D are expressed in the brain, and hypovitaminosis D is associated with abnormal development and function of the brain. We here review current knowledge on the intrathecal vitamin D homeostasis in heath and disease, highlighting the need to assess vitamin D in the intrathecal compartment.

Toll-like receptors mediate proliferation and survival of multiple myeloma cells.

Multiple myeloma (MM) is an incurable B-cell malignancy characterized by accumulation of malignant plasma cells in bone marrow (BM) and recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections and today 10 human TLRs (TLR1-TLR10) and one TLR-homolog (RP105) have been characterized. B cells express several TLRs (mainly TLR1, 6, 7, 9, 10 and RP105) and TLR-initiated responses in B cells include proliferation, anti-apoptosis effect and plasma cell (PC) differentiation. The present study was designed to analyze the role of TLRs in MM. We show that frequent expressions of TLRs were detected in cell lines from MM patients (minimum six TLRs in each). In comparison, only few TLRs (mainly TLR1 and or RP105) were found expressed in PCs from BM of healthy donors. In addition, TLR-specific ligands induce increased proliferation and survival of the MM cell lines, partially due to an autocrine interleukin-6 production. Importantly, we demonstrate that also PC from MM patients proliferates in response to TLR-specific ligands. In conclusion, TLR-ligands may contribute to increased growth and survival of MM cells in MM patients.

Severe poisoning with sotalol and verapamil. Recovery after 4 h of normothermic CPR followed by extra corporeal heart lung assist.

In acute poisoning with beta-blocking drugs and calcium-channel blockers patients may present with serious symptoms. We present a case of life-threatening sotalol and verapamil intoxication in a 29-year-old female suffering from depression. She was admitted to our hospital a few hours after she had taken 3.6 g verapamil and 4.8 g sotalol. On being found the patient was breathing and had a palpable pulse. On admission the patient experienced a cardiovascular collapse and CPR was started. Echocardiography confirmed cardiac standstill. After 4 h of normothermic CPR, extra corporeal heart lung assist (ECHLA) was established. Vasoactive drugs could be stopped after 2 days with ECHLA, and after 5 days the patient was extubated. The patient experienced several complications (intestinal bleeding, transient nerve paralysis, and renal failure due to rhabdomyolysis) but made a complete recovery and started working 6 months after the poisoning. She was no longer depressed.

The frequency of nutritional rickets among hospitalized infants and its relation to respiratory diseases.

This case control study was conducted to determine the frequency of nutritional rickets among hospitalized infants and to assess their relation to respiratory diseases. All infants between the age of 3 months and 2 years admitted to the pediatric ward of Queen Alia Military Hospital during the period February-October 2001 were examined and investigated to rule out nutritional rickets. Children admitted for the first time to hospital for acute illnesses were only included in the study. A special data collection sheet was designed for this study which includes information on the age, sex, causes of admission, family size, the rank of the child in the family, family monthly income, outdoor clothing habit of the mother, and the mode of feeding. Data were collected from the infant charts and/or by interviewing the child's mother or guardian. Clinical signs of rickets were also recorded, including rosary beads, craniotabes, wide anterior fontanel, delayed dentition, widening of epiphysis, bowing of the legs, and double malulous. Blood sample was collected for calcium, phosphorus, alkaline phosphatase, and hemoglobin level. Those infants with any clinical sign of rickets and/or abnormal chemical results had a wrist X-ray to confirm the diagnosis of rickets. The rachitic group (cases) was compared for statistical significance with the remaining non-rachitic infants (controls) for the data collected. Rachitic infants received intramuscular 600,000 IU of vitamin D; a follow-up wrist X-ray and blood sample for calcium, phosphorus and alkaline phosphatase was arranged 3 weeks later. Forty-seven infants (10.6 per cent) out of the 443 included in the study were found to have nutritional rickets. Forty (85.1 per cent) of the rachitic infants were admitted due to lower respiratory tract diseases compared with 30 per cent of the control group and the difference was statistically significant (p < 0.01). Duration of hospital stay in the rachitic infants was also significantly more prolonged than the non-rachitic control group (9.5 days vs. 7.4 days, p = 0.002). Rachitic infants were breastfed in 82.9 per cent, ranked second or more in the family in 87.2 per cent, and had mothers who wore head cover outdoors in 80.8 per cent compared with 60.8, 40.1, and 60.3 per cent, respectively, in the non-rachitic group (p < 0.01). High alkaline phosphatase, hypocalcemia, hypophosphatemia, and anemia was found in 100, 19, 50, and 78.7 per cent, respectively, in the rachitic group compared with 9.8, 2, 1.2, and 43.7 per cent, respectively, in the control group (p < 0.001). Nutritional rickets seems to be a common problem among infants in Jordan. Further studies at national level are needed to determine the prevalence of rickets in Jordan. Rachitic infants are commonly hospitalized due to lower respiratory tract infections, thus there is a high index of suspicion for rickets among hospitalized infants with lower respiratory tract diseases.

Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.

BACKGROUND: Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis. OBJECTIVE: The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infarction (MI) on subsequent cardiac events and serum lipids. DESIGN: Three hundred patients with acute MI were randomly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil, administered in a double-blind manner over 12-24 mo. Median follow-up time was 1.5 y. Clinical follow-up, including the drawing of blood samples, was performed after 6 wk of treatment and later at 0.5-year intervals. RESULTS: Forty-two (28%) patients in the n-3 group and 36 (24%) in the corn oil group experienced at least one cardiac event (cardiac death, resuscitation, recurrent MI, or unstable angina). No significant difference in prognosis was observed between groups for single or combined cardiac events. Total cholesterol concentrations decreased in both groups, with no significant intergroup differences. On average, the monthly increase in HDL cholesterol was 1.11% in the n-3 group and 0.55% in the corn oil group (P = 0.0016). Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group, whereas they increased by 0.35%/mo in the corn oil group (P < 0.0001). CONCLUSION: No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids.

Assessment of aspiration in patients with tracheostomies: comparison of the bedside colored dye assessment with videofluoroscopic examination.

BACKGROUND: Aspiration is a serious clinical concern in patients with long-term artificial airways. The purpose of this study was to determine the reliability of a bedside colored dye assessment of aspiration in tracheostomized patients and to determine its comparability to a more sophisticated videofluoroscopic study. METHODS: This was a prospective, blinded comparison study conducted in a large, urban, university teaching hospital. We studied 20 consecutive patients who underwent tracheostomy for bronchial hygiene needs and who were referred for videofluorographic evaluation for suspected oropharyngeal dysphagia and possible aspiration. Excluded were patients unable to follow verbal commands and those requiring mechanical ventilatory support. All patients were brought to the videofluorography suite for colored dye assessment for aspiration and videofluorographic assessment of oropharyngeal swallow. A nurse, blinded to the results of videofluorographic swallow study, performed colored dye assessments for aspiration. Speech-language pathologists, blinded to the results of the colored dye assessments, interpreted simultaneous (preliminary) and subsequent complete (final) videofluorographic evaluations of swallow. RESULTS: The colored dye aspiration assessments and the videofluoroscopic studies were compared for the frequency of aspiration detection. Sensitivity and specificity were determined using standard methods. Seven patients showed no aspiration on either the colored dye test or videofluoroscopic examination. Eight patients were judged to aspirate by videofluorography but not by the colored dye test. Five patients were judged to aspirate by both the colored dye test and videofluorography. The data indicate that the colored dye test for aspiration carries a low sensitivity of 38% (95% confidence interval = +/- 7%), but a high specificity of 100%. The videofluoroscopic study detected a significantly greater frequency of aspiration than did the colored dye test (p < 0.01). CONCLUSIONS: The colored dye test for aspiration can provide useful information when positive, but because there is a significant false negative rate, decisions made on the basis of a negative test must be made with caution.

Lumbar bone mineral density in adolescent female runners.

BACKGROUND: The purpose of this study was to determine if there were significant differences in lumbar bone mineral density (L2-L4, g/cm2) or several hormones among 3 groups of adolescent females: 10 amenorrheic runners, 10 eumenorrheic runners, and 10 eumenorrheic controls. EXPERIMENTAL DESIGN: comparative. SETTING: Cooper Clinic, Aerobics Center, Dallas, Texas. PATIENTS OR PARTICIPANTS: The subjects were white, non-smokers, aged 15.1-18.8 years, who were not taking birth control pills. All amenorrheic runners had less than 5 menstrual period in the past year, averaging 2,4 periods. The runners averaged approximately 36 miles/week (58.1 km) during the last 9 months of their training season and had been running for 1-5 years. INTERVENTIONS: None. MEASURES: Lumbar bone mineral density (BMD), 10 hormones, percentage of body fat, and dietary intake were measured. RESULTS: Mean lumbar BMD (g/cm2) did not differ significantly among groups (amenorrheic runners = 1.134, eumenorrheic runners = 1.165, controls = 1.148). However, expected trends were observed. Compared to the controls, the amenorrheic runners tended to have lower lumbar BMD and the eumenorrheic runners, higher. Although there were significant differences in concentrations of five serum hormones measured, all mean hormonal values were within normal ranges. Calcium intakes were low for all groups. CONCLUSIONS: In this study, with its small number of subjects and great variability within each group, it was concluded that there is no significant difference among amenorrheic runners, eumenorrheic runners, and controls in lumbar BMD. However, a longer period of amenorrhea might result in significantly lower BMD for the amenorrheic runners.

Evaluation of an on-demand, ex vivo bedside blood gas monitor on pulmonary artery blood gas determinations.

Critically ill patients often have cardiopulmonary perturbations that require rapid and frequent assessment for optimal care, including cardiac output determinations, measurement of cardiac filling pressures, and arterial and mixed venous blood gas determinations. We evaluated the performance of a rapid, on-demand bedside blood gas monitor to determine arterial and mixed venous blood gas values. The blood gas monitor uses fluorescent optode technology to directly measure Po2, Pco2, and pH. This measurement is accomplished by aspirating blood from the artery or vein into a sampling chamber where it interfaces with the fluorescent optode. After approximately 90 s of equilibration, the blood gas values are reported. Since the blood is drawn into the sampling chamber, it can be returned to the patient, thus eliminating the need for phlebotomy. We studied 15 critically ill patients requiring systemic and pulmonary arterial catheterization. Conventional blood gas analysis was performed simultaneously. The results obtained from the blood gas monitor were compared with those obtained via traditional blood gas analysis using Bland-Altman plots and examination of bias and precision. The results were well within the expected clinical variance. During the study period, there was no interference with patient care or adverse events related to the use of the monitoring system. In conclusion, the blood gas monitor can provide rapid, accurate determinations of arterial and mixed venous blood gases allowing optimal therapeutic interventions in critically ill patients.

Microbial contamination of blood conservation devices during routine use in the critical care setting: results of a prospective, randomized trial.

OBJECTIVES: To compare microbial contamination of two different blood conservation devices; to determine if there was an association between contamination of the blood conservation devices and clinical infections; to determine if there was a significant user preference for either of the two devices. DESIGN: Prospective, randomized trial. SETTING: Medical, neurosurgical, and spinal cord intensive care units of an urban, university hospital. PATIENTS: Forty patients who required clinically indicated intrafierial catheters placed at new sites. INTERVENTIONS: The two most widely available blood conservation devices at the time of the study (Venous Arterial blood Management Protection system [VAMP], Baxter Edwards Critical-Care, Irvine, CA; and Safe Draw, Ohmeda, Madison, WI) were chosen for comparison. After the normal 48 to 72 hrs of device use, the blood conservation systems were removed and semi-quantitative and quantitative cultures were taken from comparable sites of the two devices. Positive cultures from the patients were recorded and correlated with cultures obtained from the devices. In order to assess preference for either device, a survey tool was administered to the nursing staff who participated in the study. MEASUREMENTS AND MAIN RESULTS: Quantitative cultures from all sites cultured in both groups demonstrated mean colony counts of < 10(3) colony-forming units (cfu)/mL. There were no statistically significant differences in the colony counts at any of the sites compared between the two groups. There were no statistically significant relationships between positive cultures and patient age, gender, duration of device utilization, frequency of device entry, or the intensive care unit in which the study was conducted. In no circumstance did positive cultures from any of the blood conservation devices correlate with positive culture results from any sites of clinical infection. The clinical survey demonstrated a statistically significant preference for the VAMP system, which persisted despite increased experience with the Safe Draw system. CONCLUSIONS: The levels of microbial contamination noted in these devices were not consistent with clinical infection (defined as 10(3) cfu/mL on quantitative cultures). There was no significant difference in degree or pattern of contamination between the two devices. When utilized and changed according to the Centers for Disease Control guidelines, blood conservation devices are not harbors of infection in the critical care setting. Blood conservation devices can be used as part of a comprehensive blood conservation program in the critical care setting without undue concern for exacerbating infectious processes.

Right and left proximal femur analyses: is there a need to do both?

The purpose of this study was to determine if differences existed between right and left proximal femur bone mineral density (BMD) in a group of women. Participants for the study were 198 women ranging in age from 16 to 73 years. Bone mineral densities of both proximal femurs (femoral neck, Ward's area, and trochanter) were assessed using dual energy X-ray absorptiometry (Lunar DPX). Mean (+/-SD) age, height, and weight of the participants were 32.9 +/- 18 years, 164 +/- 7.4 cm, and 64.9 +/- 12.1 kg, respectively. Significant differences between right and left femoral BMDs were found only in the trochanter. Overall, mean differences in BMD were low (neck = 0. 7%, Ward's = 0.2%, and trochanter = 1.9%) but individual variations were as high as 22%. Based on BMD z-scores of <-1.0, 84 women were classified as "at risk" for osteoporosis. When right and left z-scores were compared, misclassifications of at risk women were 4, 15, and 11 for neck, Ward's area, and trochanter, respectively. In conclusion, analyses of both right and left proximal femurs may not be necessary for either the researcher or the clinician.