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Understanding psychological stress, its biological processes, and impact on primary headache.

Psychological stress is generally acknowledged to be a central contributor to primary headache. Stress results from any challenge or threat, either real or perceived, to normal functioning. The stress response is the body's activation of physiological systems, namely the hypothalamic-pituitary-adrenal axis, to protect and restore functioning. Chronic activation of the stress response can lead to wear and tear that eventually can predispose an individual to disease. There are multiple ways that stress and headache are closely related. Stress can (a) be a predisposing factor that contributes to headache disorder onset, (b) accelerate the progression of the headache disorder into a chronic condition, and (c) precipitate and exacerbate individual headache episodes. How stress impacts headache is not often understood. However, stress is assumed to affect primary headache by directly impacting pain production and modulation processes at both the peripheral and central levels. Stress can also independently worsen headache-related disability and quality of life. Finally, the headache experience itself can serve as a stressor that compromises an individual's health and well-being. With the prominent role that stress plays in headache, there are implications for the evaluation of stress and the use of stress reduction strategies at the various stages of headache disorder onset and progression. Future directions can help to develop a better empirical understanding of the pattern of the stress and headache connections and the mechanisms that explain the connections. Further research can also examine the interactive effects of stress and other factors that impact headache disorder onset, course, and adjustment.

Analgesics↗

Cysteine-rich region of X-Serrate-1 is required for activation of Notch signaling in Xenopus primary neurogenesis.

The Notch family genes encode single-pass transmembrane proteins which function in a variety of cell fate specifications in invertebrates and vertebrates. In Xenopus primary neurogenesis, the Notch ligands, X-Delta-1 and X-Serrate-1, mediate Notch signaling and regulate cell differentiation. In the present study, we examined the role of the Serrate-specific cysteine-rich (CR) region in the primary neurogenesis of Xenopus embryos. The ligand constructs containing the DSL (Delta/Serrate/Lag-2) domain in the extracellular region caused a reduction in primary neurons, whereas the DSL-deleted form of X-Delta-1 resulted in the overproduction of primary neurons. However, the DSL-deleted form of X-Serrate-1 or the construct containing only the CR region in the extracellular domain (SerCR) reduced the number of primary neurons. In contrast, the CR-deleted form of X-Serrate-1 (SerACR) lost activity as a Notch ligand, regardless of the presence of the DSL domain within the extracellular domain. Overexpression of X-Delta-1 and X-Serrate-1 strongly induced the expression of Xenopus ESR-1 (XESR-1), a gene related to Drosophila Enhancer of split. SerCR alone also moderately induced the expression of XESR-1, but the SerACR form did not induce this expression. Co-injection of X-Notch-1deltaICD, which deletes the intracellular domain (ICD), with SerCR suppressed a neurogenic phenotype, although co-injection of X-Su(H)1DBM with SerCR did not, indicating that SerCR affects primary neurogenesis through the Notch/Su(H) pathway. These results suggestthatthe CR region of Xenopus Serrate is required for the activation of Notch signaling and cell fate specification in primary neurogenesis.

Animals↗

[Hyperbaric oxygenation in neurotraumatology].

The use of hyperbaric oxygenation (HBO) as a therapeutic measure has a favorable effect, in the postoperative period also, on traumatic affections of different levels of the nervous system (the brain, spinal cord, peripheral nerve trunks and plexuses. It allows the severity of the neurologic deficit and the degree of the patient's disability to be reduced and in some cases it prevents the growth of vital disorders. At the same time, the effect may exert a certain load on the adaptation mechanisms which are very limited in many neurosurgical patients. In view of this, the tolerance of the patient's organism to this load must be taken into account in choosing the HBO schedules. The tolerance is decisively determined by the intactness of the integral function of the central nervous system and diminishes markedly as the impairment of the consciousness of patients with primary affection of the brain gradually becomes deeper and longer in duration.

Brain Injuries↗

Single-incision, minimally invasive total hip arthroplasty: length doesn't matter.

A pilot cohort study of 60 primary total hip arthroplasties (THAs) was undertaken to evaluate the technical aspects and possible clinical advantages of performing THA through a single-incision, minimally invasive, 10-cm-length, direct lateral approach compared with the same approach performed through a standard-length skin incision. We could not show any significant difference with regard to operative time; in-hospital equianalgesic opioid consumption; postoperative blood loss; complications; hospital length of stay; or flexion, Harris Hip and Oxford Scores at 6 weeks' postoperatively. Restricting the length of skin incision for THA performed through a direct lateral approach does not appear to afford any clinical advantage to the patient in the short term. The mini-exposure creates technical challenges that have the potential to adversely affect primary THA outcome.

Aged↗

Histological features of axial structures during embryonic and fetal stages of human craniorachischisis.

Histological characteristics of developing axial structures in human conceptuses with craniorachischisis were investigated during the embryonic and fetal periods and compared with normal samples. The morphological relationship of the notochord to the axial skeleton and neural tube was analyzed along cervical and thoracic vertebral segments using serial paraffin sections. The embryonic stage of malformed conceptuses disclosed a correlated affection of the notochord and vertebral column, as well as the overlying central nervous system. The degree of histological changes within the spinal cord depended on the level of the vertebral axis examined: completely unorganized nervous tissue was overlying cervical and upper thoracic vertebrae, while more caudally it resembled a normal spinal cord. During the fetal period the histological disturbances of all axial structures were more pronounced. Extensive notochordal branching was associated with the malformed formation and ossification of the vertebral column. At this stage we found no correlation of histological changes between the spinal cord and the mesodermally derived structures (notochord, vertebral column) along the cranio-caudal body extent, as neural tissue had completely transformed into area cerebrovasculosa. We speculate that our histological observations could be the result of primary affection of mesodermal structures during very early stages of development. Divergence in histological findings within axial structures between the embryonic and fetal periods support recent mutational investigations on animals.

Brain↗

Patterns of DST positivity in remitted affective disorders.

BACKGROUND: While the Dexamethasone Suppression Test (DST) has been extensively used in cross-sectional observations of patients with major affective disorders, studies have tended to ignore the longitudinal application of the DST in patients stabilized on long-term prophylactic medication. METHODS: Monthly DST's were performed on 19 patients, 16 with bipolar disorder and 3 with recurrent major depression. All cases had an excellent response to lithium treatment, and family history positive for bipolar disorder. The average duration of observation was 4 years. RESULTS: All patients remained clinically stable throughout the period of observation. Eleven patients showed intermittent DST positivity ranging from 10% to 60% of tests, and 2 patients exhibited no positivity. Six patients had fewer than 10% positive DST's. Females showed significantly higher positivity than males. The frequency of positivity did not correlate with current age, age of illness onset, duration of illness, duration of lithium treatment, or season. The risk of primary affective disorders in first-degree relatives was also unrelated to the frequency of positivity. CONCLUSIONS: While the highly selected and small sample population limits generalizability, our observations suggest that clinically sufficient lithium prophylaxis does not automatically prevent intermittent HPA dysregulation. We hope that a better understanding of this phenomenon will offer new approaches to the long-term management of mood disorders.

Adult↗

Compliance with outpatient lithium therapy.

This study was conducted to identify factors that influence compliance in patients being treated with lithium carbonate and regularly scheduled supportive clinic appointments for major affective disorders. The researcher examined the predictive value of elements of the Health Belief Model relative to patient compliance, the demographic characteristics of patients, and the effects of patient mood and type of treatment on patient compliance. Patient compliance was operationally defined as serum lithium level within a recommended therapeutic range and attendance at 75 percent or more of regularly scheduled clinic appointments for six months prior to the study. Fifty patients (67%) were compliant with both indices specified by the research, and only three patients (4%) were noncompliant with both indices. Lithium compliance was significantly greater among married patients and patients with higher levels of education. Appointment-keeping compliance was positively associated with individual therapy and increased patients' perceptions of continuity, and negatively correlated with patients' perceptions of increased costs of treatment. The study demonstrates the complexity of the issue of patient compliance with the long-term treatment of primary affective disorders and supports the need for additional research. While some findings suggest interventions to improve patient adherence, scrutiny and testing of these strategies to promote compliance is necessary to determine their effectiveness.

Adult↗

Cytomegalovirus aggravates intimal hyperplasia in rats by stimulating smooth muscle cell proliferation.

Epidemiological and animal studies suggest a role for cytomegalovirus (CMV) in restenosis. Previously, we demonstrated that proliferating smooth muscle cells (SMCs) in the injured arterial wall are particularly susceptible to CMV-induced effects. Therefore, we hypothesised that, depending on the time point of infection after vascular injury, CMV infection may affect cell proliferation either in the media or in the neointima, thereby aggravating the process of restenosis. In the present study, we focused on the individual layers of the arterial wall by evaluating, besides the neointima-to-media ratio, the medial and neointimal area and cellularity in the rat femoral artery. Vascular injury was photochemically induced in rat femoral arteries. Immediately or 14 days thereafter, rats were infected with rat CMV (RCMV) or mock infected. The presence of RCMV in the vascular wall was determined at 3, 5, 14 and 35 days after infection by quantitative real-time PCR. When rats were infected immediately after injury, a significant increase was seen only in the medial but not in the neointimal cross-sectional area. On the other hand, when rats were infected 14 days after the initial injury, a significant increase was only seen in the neointimal area, thereby confirming our hypothesis that RCMV infection primary affects proliferating SMCs. As the mean number of SMCs per microm2 in both cell layers was unchanged despite an increase in cross-sectional area, this implies that RCMV stimulated SMC proliferation. Furthermore, these vascular effects were observed without the virus being abundantly present in the vascular wall, suggesting that inflammatory and immune-mediated responses to RCMV infection are more important in aggravating the response to vascular injury than the virus itself.

Animals↗

Effect of blood transfusions on immune function. Part VI. Effect on immunologic response to tumor.

Transfusions are reported to increase the incidence of tumor metastasis in clinical studies and primary tumor growth in animal studies. We evaluated the effect of transfusions on immunologic response to primary and metastatic tumors in multiple rat models. One half of the animals were administered lactated Ringer's solution and one half ACI rat blood at the time of tumor challenge. In 80 rats a slow-growing colon tumor was implanted subcutaneously. At 4 months there were no significant differences in tumor size or leukocyte infiltration of the tumor. Similar results were obtained with a rapidly growing colon cancer. Analysis of T-lymphocyte subpopulations in both groups showed no differences. Rats transfused at the time of intravenous challenge with a suspension of 1 x 10(6) tumor cells had a mean survival time of 38.3 +/- 0.8 days and the control group had a mean survival time of 41.1 +/- 0.8 days (p = 0.016). One week after transfusion, natural killer cell lysis of tumor cells at a 100:1 effector/target cell ratio was 18.0% +/- 1.8% in the transfusion group and 23.0% +/- 1.3% in the control group (p = 0.034). In conclusion, transfusions in multiple rat cancer models did not affect primary tumor growth or the host's immunologic response to it but did significantly impair natural killer cell function and survival with tumor metastases.

Adenocarcinoma↗

Effects of acetylsalicylic acid and dietary intervention on primary hemostasis.

There is evidence that pathological aggregation of platelets in atherosclerotic arteries is initiated by hemorrhage through fissures in atheromatous plaques. Bleeding time determination reflects in vivo the physiologic function of platelets in their aggregation in injured vessels and can be used as a relevant model for primary hemostasis in investigations with antithrombotic aims. Acetylsalicylic acid is known to cause prolongation of bleeding time by inhibiting prostaglandin biosynthesis. Recent experiments have shown that dietary supplementation with omega-3 polyunsaturated fatty acids results in prolongation of bleeding time and decreased platelet aggregability. This paper is mainly concerned with the effect of different doses of aspirin (3.5 mg/kg, 5 mg/kg, and 10 mg/kg), and fish diets rich in omega-3 polyunsaturated fatty acids, on bleeding time and platelet aggregation. The effects of aspirin separately, as well as aspirin administration during dietary intervention, will be described. Administration of all three dose levels of aspirin prolonged bleeding time significantly (p less than 0.001). The effect of aspirin on bleeding time was dose-dependent and an optimum interval was found. A fish diet, rich in omega-3 polyunsaturated fatty acids, causes bleeding time prolongation and decreased platelet aggregability similar to those caused by aspirin. Aspirin taken during this diet prolonged bleeding time by more than the sum of the increases in bleeding time caused by aspirin and the diet with omega-3 polyunsaturated fatty acids, separately, but the synergism was not significantly more than additive. These observations suggest that fish diets affect primary hemostasis by mechanisms different from those of aspirin. Dietary intervention may therefore enhance the antithrombotic effects of aspirin.

Animals↗

Platelets and soluble fibrin promote plasminogen activation causing downregulation of platelet glycoprotein Ib/IX complexes: protection by aprotinin.

Blood loss during and after open-heart surgery with cardiopulmonary bypass (CPB) is largely caused by platelet dysfunction. Previous studies indicate that plasmin can induce platelet dysfunction and affect primary hemostasis by proteolytic degradation and/or redistribution of essential platelet membrane glycoprotein complexes such as the glycoprotein Ib/IX complex. In this study, we present a model for plasmin generation localized on the platelet surface. Platelets treated with soluble fibrin or platelets in a mixture with soluble fibrin, t-PA, and plasminogen caused a significantly increased plasmin generation (p<0.01), dependent on t-PA, soluble fibrin, and platelet concentration. The plasmin generation resulted in a downregulation of platelet membrane glycoprotein Ib/IX glycoprotein complexes. Finally, we demonstrated that inhibitors of fibrinolysis, such as %2-antiplasmin, tranexamic acid, and aprotinin, can inhibit plasmin activity in the fluid phase. The downregulation of platelet glycoprotein Ib/IX complexes, however, was only prevented by aprotinin and not by alpha2-antiplasmin and tranexamic acid. These in vitro observations suggest a platelet localized activation of plasminogen, dependent on t-PA, enhanced by the presence of soluble fibrin. Since high concentrations of soluble fibrin and elevated levels of t-PA during CPB are observed, plasmin activity on the platelet surface during this period is anticipated. This plasmin activity reduces platelet metabolic functions and can be directed towards membrane glycoproteins such as glycoprotein Ib/IX complexes, thereby affecting hemostasis during and after CPB.

Antibodies, Monoclonal↗

[Functional thyroid pathology in the elderly].

OBJECTIVE: To describe the prevalence of functional thyroid pathology (FTP) and pathologies associated with it in an elderly population. DESIGN: Descriptive, cross-sectional study. SETTING: Urban primary care centre. PATIENTS: Representative sample of the entire population attended that was 60 years old or over. MAIN MEASUREMENTS: Demographic variables, clinical history of thyroid pathology and pathology associated with it, Body Mass Index, small tests for diagnosing depression and anxiety, the mini-mental test, electrocardiogram, determination of total cholesterol and LDL cholesterol, and of free thyrotrophin and thyroxin if it is disturbed. RESULTS: 192 people were studied, 56% women, 53% between 60 and 69 and 12% over 79 years old. 10% had a history of previous FTP. Prevalence of active FTP was 13% (10.41% sub-clinical hypothyroidism, 0.52% clinical hypothyroidism, 1.56% sub-clinical hyperthyroidism, and 0.52% clinical hyperthyroidism). Prevalence of new diagnoses of FTP was 4.1% (7 with hypothyroidism and 1 with hyperthyroidism, all sub-clinical). During the study the following pathology was detected in hypothyroidism sufferers: 43% anxiety disorder, 38% depressive syndrome, 28.5% cognitive deterioration, 9.5% dementia, 26% electrocardiographic disturbances, 47.6% obesity, and 28.5% with total cholesterol > or =250 mg/dL. In hyperthyroidism, 50% with depressive syndrome, 25% with cognitive deterioration, 25% with electrocardiographic disturbances, and 50% with obesity were detected. CONCLUSIONS: FTP is more prevalent among the elderly than in the population as a whole, with predominance of hypothyroidism, subclinical pathology and among women. In terms of pathology traditionally linked to thyroid malfunction, few differences were found between the population affected with FTP and those not affected. Primary care doctors are important in reducing under-diagnosis.

Aged↗

Immunological and hematological effects observed in B6C3F1 mice exposed to JP-8 jet fuel for 14 days.

JP-8 is the primary jet fuel used by the U.S. Air Force and NATO allies. Exposure is likely to be widespread and to include both military and aviation industry personnel as well as residents living near fuel contaminated sites. This study examines the effects of JP-8 on humoral and cell-mediated and hematological parameters. A suite of immunotoxicological endpoints was evaluated in adult female B6C3F1 mice gavaged with JP-8 (in an olive oil carrier) ranging from 250-2500 mg/kg/d for 14 d. One day following the last exposure, significant increases in liver mass were detected beginning at exposure levels of 1000 mg/kg/d, while thymic mass was decreased at exposure levels of 1500 mg/kg/d and above. Decreases in thymic cellularity, however, were only observed at exposure levels of 2000 mg/kg/d and above. Mean corpuscular volume was increased (1500-2500 mg/kg/d), while the hematocrit, hemoglobin concentration, and red blood cell count were decreased only at the 2500 mg/kg/d exposure level. Natural killer cell (NK) activity and T- and B-cell proliferation were not altered. Decreases in the plaque-forming cell (PFC) response were dose responsive at levels of 500 mg/kg/d and greater, while unexpectedly, serum levels of anti-SRBC immunoglobulin M (IgM) were not altered. Alterations were detected in thymic and splenic CD4/8 subpopulations, and proliferative responses of bone marrow progenitor cells were enhanced in mice exposed to 2000 mg/kg/d of JP-8. This study establishes that humoral immune function is impaired with lower exposure levels of JP-8 than are required to affect primary and secondary immune organ weights and cellularities, CD4/8 subpopulations, and hematological endpoints.

Animals↗

Competition modifies effects of enhanced ozone/carbon dioxide concentrations on carbohydrate and biomass accumulation in juvenile Norway spruce and European beech.

Elevated concentrations of carbon dioxide ([CO2]) and ozone ([O3]) affect primary metabolism of trees in opposite ways. We studied their potential interactions on carbohydrate concentrations and contents. Two hypotheses currently under debate were tested. (1) Stimulation of primary metabolism by prolonged exposure to elevated [CO2] does not compensate for the adverse effects of O3 on carbohydrate accumulation and biomass partitioning to the root. (2) Growth in a mixed-species planting will repress plant responses to elevated [O3] and [CO2] relative to conditions in a monoculture. To this end, European beech (Fagus sylvatica L.) and Norway spruce (Picea abies (L.) Karst.) saplings grown under conditions of intra- and interspecific competition were pre-acclimated for 1 year to ambient or elevated [CO2]. In the following 2-year phytotron study, trees were exposed to factorial combinations of ambient and elevated [O3] and [CO2]. The total carbohydrate content (sugar and starch) of spruce was greater in plants exposed to elevated [CO2] than in plants exposed to ambient [CO2]. In beech, the opposite response was observed, especially when this species was grown in combination with spruce. Overall, the data did not support Hypothesis 1, because the adverse effects of O3 were counteracted by elevated [CO2]. Support for Hypothesis 2 was species-dependent. In beech saplings, reduction of carbohydrates by elevated [O3] and stimulation by elevated [CO2] were repressed by competitive interaction with spruce. In contrast, in spruce, stimulation of carbohydrates by elevated [CO2] was similar in mono- and mixed cultures. Thus Hypothesis 2 was supported for beech but not spruce. We conclude that, in juvenile beech and spruce, a 3-year exposure to elevated [CO2] counteracts the adverse effects of O3 on carbohydrate concentrations and contents. For beech, sensitivity to elevated [CO2] and [O3] was high in monoculture but was largely repressed by interspecific competition with spruce. In contrast, the response of spruce to perturbations of atmospheric chemistry was not significantly affected by either intra- or interspecific competition.

Biomass↗

Colorectal carcinoma metastases to the liver. Does primary tumor location affect its lobar distribution?

BACKGROUND: There is considerable evidence that blood returning from different abdominal organs does not mix completely but maintains streamline flow in the portal vein. This study tested the hypothesis that the location of primary colorectal carcinoma affects the intrahepatic distribution of liver metastases according to streamline flow in the portal vein. METHODS: Eighty-five patients with histologically verified liver metastases from colorectal carcinoma underwent potentially curative hepatectomy. Primary tumor location was the right-sided colon in 18 patients and the left-sided colon in 67. The liver was divided into two lobes by Cantlie's line. RESULTS: A total of 195 metastatic deposits were resected: 135 in the right lobe and 60 in the left. In the right-sided colon carcinoma group, 29 deposits were in the right lobe and 3 in the left. In the left-sided colon carcinoma group, 106 deposits were in the right lobe and 57 in the left. The pattern of lobar distribution was significantly different in the two groups (P = 0.003). CONCLUSIONS: Right-sided colon cancers selectively involve the right lobe, while left-sided tumors involve the entire liver, considering the ratio of weights of the right to left lobe is 2:1. This difference suggests that primary tumor location affects the pattern of lobar distribution of colorectal carcinoma liver metastases according to streamline flow in the portal vein.

Carcinoma↗

A content analysis of news coverage of skin cancer prevention and detection, 1979 to 2003.

OBJECTIVE: To analyze newspaper coverage between 1979 and 2003 to understand how print coverage may affect primary and secondary skin cancer prevention in the US population. DESIGN: Content analysis of 921 skin cancer articles released by the Associated Press during the study period. MAIN OUTCOME MEASURES: Amount of attention given to primary and secondary prevention practices and to risk communication. RESULTS: Media attention to skin cancer has not increased since 1986. Neither prevention (31.8% of all stories) nor detection (24.4% of all stories) received as much attention as treatment (47.0% of all stories). Specific sun protection practices were mentioned infrequently. Dermatologic detection (6.6%) or self-detection (5.5%) of skin cancer was rarely discussed. Risk communication about skin cancer was suboptimal: articles rarely presented absolute and relative risk. CONCLUSIONS: The media pay little attention to skin cancer, and, in general, stories do not contain important educational information. Strategies for generating increased media attention are discussed.

Female↗

Cerebral metabolism and depression in patients with complex partial seizures.

Twenty-three patients with complex partial seizures were evaluated with 18F-2-deoxyglucose positron emission tomography and with the Beck Depression Inventory. Five of 10 patients with left and zero of eight with right temporal electroencephalographic foci had depressive symptoms; one of five patients with poorly localized electroencephalographic foci also scored in the depressed range. Temporal, frontal, caudate, and thalamic normalized glucose metabolic rates among five patients with depressive symptoms and well-localized left temporal epileptogenic regions were compared with five patients without depressive symptoms but with similar electroencephalographic characteristics. Multifactorial analysis of variance yielded a significant nonlateralized mood by region interaction. Of nine individual regions compared, only inferior frontal cortex showed a significant difference in normalized regional metabolic rate between depressed and nondepressed patients. Metabolism in this region also distinguished patients with depressive symptoms from normal control subjects. Depressive symptoms in patients with complex partial seizures are associated with a bilateral reduction in inferior frontal glucose metabolism, compared with patients without depressive symptoms and normal control subjects. The frontal lobe hypometabolism observed in patients with depressions associated with epilepsy, Parkinson's disease, and primary affective disorder suggests that similar frontal lobe metabolic disturbances could underlie these conditions.

Adolescent↗

Rapid eye movement sleep density. An objective indicator in severe medical-depressive syndromes.

The electroencephalographic sleep patterns of 12 patients with a final diagnosis of primary depression and those of 12 patients admitted to the Clinical Research Unit with this diagnosis, but subsequently also found to be suffering from severe medical disease, were compared. Patients with depression concurrent with severe medical disease have significantly less phasic conjugate rapid eye movement (REM) activity during REM sleep than subjects with the diagnosis of a primary depression. These findings suggest that quantification of REM density may be used clinically to distinguish between medical-depressive syndromes and primary affective disorders.

Adolescent↗