Range Of Normal Responses Research Articles

Aging-Related Structural and Functional Changes in Cerebral Arteries: Caloric Restriction (CR) Intervention

Cerebral arteries play a crucial role in the regulation of blood flow to the brain to satisfy the demand of oxygen and glucose for proper function of the organ. Physiological cerebral blood flow (CBF) is maintained within a normal range in response to changes in blood pressure a mechanism named Cerebral Blood Flow Auto Regulation (CBFAR). Structure and function of cerebral arteries have an important impact on CBFAR. Several studies in human and animals have showed significant morphological and functional changes in cerebral vessels of aged brain associated with a reduced CBF which is also impaired in cerebrovascular pathology linked to brain diseases. Interestingly, one new emergent aspect is the lifelong Calorie Restriction (CR) as a potential intervention to prevent age-related cerebral artery changes and preserve the health of aging brain. This review summarizes the recent literature on the effects of aging on cerebral artery structure and function and the potential of CR as opportunities for prevention and treatment

Somatosensory corticospinal tract axons sprout within the cervical cord following a dorsal root/dorsal column spinal injury in the rat.

The corticospinal tract (CST) is the major descending pathway controlling voluntary hand function in primates, and though less dominant, it mediates voluntary paw movements in rats. As with primates, the CST in rats originates from multiple (albeit fewer) cortical sites, and functionally different motor and somatosensory subcomponents terminate in different regions of the spinal gray matter. We recently reported in monkeys that following a combined cervical dorsal root/dorsal column lesion (DRL/DCL), both motor and S1 CSTs sprout well beyond their normal terminal range. The S1 CST sprouting response is particularly dramatic, indicating an important, if poorly understood, somatosensory role in the recovery process. As rats are used extensively to model spinal cord injury, we asked if the S1 CST response is conserved in rodents. Rats were divided into sham controls, and two groups surviving post-lesion for ~6 and 10 weeks. A DRL/DCL was made to partially deafferent one paw. Behavioral testing showed a post-lesion deficit and recovery over several weeks. Three weeks prior to ending the experiment, S1 cortex was mapped electrophysiologically, for tracer injection placement to determine S1 CST termination patterns within the cord. Synaptogenesis was also assessed for labeled S1 CST terminals within the dorsal horn. Our findings show that the affected S1 CST sprouts well beyond its normal range in response to a DRL/DCL, much as it does in macaque monkeys. This, along with evidence for increased synaptogenesis post-lesion, indicates that CST terminal sprouting following a central sensory lesion, is a robust and conserved response.

Response to pneumococcal polysaccharide vaccine in children with asthma, and children with recurrent respiratory infections, and healthy children

BackgroundTo analyse specific immune response to the 23-valent pneumococcal polysaccharide vaccine by measuring pneumococcal antibodies in children with asthma and with respiratory recurrent infection (RRI) as compared to healthy children. MethodsThe study included 60 children, divided into three groups: 20 with asthma, 20 with RRI, and 20 healthy controls. Post-vaccination specific IgG antibodies against 10 pneumococcal serotypes (S1, S3, S4, S5, S6B, S9V, S14, S18C, S19F, and S23F) contained in the 23-valent pneumococcal polysaccharide vaccine (PPV) were measured. A specific IgG concentration ≥1.3μg/mL was considered a protective response to the vaccine. For statistical analysis, levels of specific IgG antibodies against each of the 10 pneumococcal serotypes were compared across the three groups of children using the x2 test. ResultsAll of the children showed antipneumococcal antibody levels >1.3μg/mL for over 70% of the serotypes, considered within the normal range of response. Average IgG antibody levels and percentages of children protected were statistically comparable among the three groups studied. ConclusionThe asthmatic children without RRI had pneumococcal antibody levels and percentages of serotype-specific protection to PPV comparable to those of healthy children. Asthmatic children with recurrent infections should be evaluated for specific antibody deficiency (SAD). Because asthma patients are at high risk for invasive pneumococcal infections, it would be worthwhile to explore systematic administration of PPV in children over the age of two years who have not received a pneumococcal conjugate vaccine, considering the positive response to PPV reported here.

Combining agreement and frequency rating scales to optimize psychometrics in measuring behavioral health functioning

ObjectiveThe goal of this article was to investigate optimal functioning of using frequency vs. agreement rating scales in two subdomains of the newly developed Work Disability Functional Assessment Battery: the Mood & Emotions and Behavioral Control scales. Study Design and SettingA psychometric study comparing rating scale performance embedded in a cross-sectional survey used for developing a new instrument to measure behavioral health functioning among adults applying for disability benefits in the United States was performed. ResultsWithin the sample of 1,017 respondents, the range of response category endorsement was similar for both frequency and agreement item types for both scales. There were fewer missing values in the frequency items than the agreement items. Both frequency and agreement items showed acceptable reliability. The frequency items demonstrated optimal effectiveness around the mean ± 1–2 standard deviation score range; the agreement items performed better at the extreme score ranges. ConclusionFindings suggest an optimal response format requires a mix of both agreement-based and frequency-based items. Frequency items perform better in the normal range of responses, capturing specific behaviors, reactions, or situations that may elicit a specific response. Agreement items do better for those whose scores are more extreme and capture subjective content related to general attitudes, behaviors, or feelings of work-related behavioral health functioning.

What’s Next for Somatic Symptom Disorder?

What’s Next for Somatic Symptom Disorder?

Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation

Since the inaugural description in 1959 by Prinzmetal,1 coronary artery spasm and abnormal coronary artery vasomotion have been extensively studied both clinically and scientifically. There is no doubt that abnormal...

Augmented Ocular Vestibular Evoked Myogenic Potentials to Air-Conducted Sound in Large Vestibular Aqueduct Syndrome

To demonstrate the value of recording air-conducted ocular Vestibular Evoked Myogenic Potentials (oVEMP) in a patient with bilaterally enlarged vestibular aqueducts. Cervical VEMP and oVEMP were recorded from a patient presenting with bilateral hearing loss and imbalance, attributable to large vestibular aqueduct syndrome. The stimuli were air-conducted tone bursts at octave frequencies from 250 to 2000 Hz. Amplitudes and thresholds were measured and compared with the normal response range of 32 healthy control subjects. oVEMP reflexes demonstrated pathologically increased amplitudes and reduced thresholds for low-frequency tone bursts. Cervical VEMP amplitudes and thresholds were within normal limits for both ears across all frequencies of stimulation. This study is the first to describe the augmentation of AC oVEMPs in an adult with large vestibular aqueduct syndrome.

Characterization of currently marketed heparin products: Adverse event relevant bioassays

The polyanion oversulfated chondroitin sulfate (OSCS) was identified as a contaminant in heparin products and was associated with severe hypotensive responses and other symptoms in patients receiving the drug. The OSCS associated adverse reactions were attributed to activation of the contact system via the plasma mediator, activated factor XII (FXIIa), which triggers kallikrein (KK) activity. Unlike heparin alone, OSCS, is able to activate FXII in plasma and stably bind to FXIIa enhancing plasma KK activity and the induction of vasoactive mediators such as bradykinin (BK), C3a and C5a. Similarly OSCS can interfere with heparin neutralization by the polycationic drug protamine. Here, we assess heparin (heparin sodium, dalteparin, tinzaparin or enoxaparin)-protamine complex formation and plasma based bioassays of KK, BK and C5a in a 96-well plate format. We establish the normal range of variation in the optimized bioassays across multiple lots from 9 manufacturers. In addition, because other oversulfated (OS) glycosaminoglycans (GAGs) besides OSCS could also serve as possible economically motivated adulterants (EMAs) to heparin, we characterize OS-dermatan sulfate (OSDS), OS-heparan sulfate (OSHS) and their native forms in the same assays. For the protamine test, OS-GAGs could be distinguished from heparin. For the KK assay, OSCS and OSDS were most potent followed by OSHS, and all had similar efficacies. Finally, OSDS had a greater efficacy in the C5a and BK assays followed by OSCS then OSHS. These data established the normal range of response of heparin products in these assays and the alteration in the responses in the presence of possible EMAs.

Logarithmic decrease of serum alpha-fetoprotein or human chorionic gonadotropin in response to chemotherapy can distinguish a subgroup with better prognosis among highly malignant intracranial non-germinomatous germ cell tumors

Intracranial non-germinomatous germ cell tumors (NGGCTs) are a heterogeneous group of tumors. Although alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are considered reliable markers for making diagnosis, the relationship between serum concentration of them and prognosis remains unclear. The present study investigated the decrease of serum tumor markers AFP and HCG as prognostic factors for patients with highly malignant NGGCTs. Eight consecutive patients with AFP>1000ng/ml or HCG>2000mIU/ml at initial treatments after January 2004 were retrospectively reviewed. Serum AFP or HCG concentration and tumor volume were sequentially measured during the therapeutic period. Six patients were treated by neoadjuvant chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by salvage surgery and/or radiation therapy. A 14-year-old boy with choriocarcinoma and a 2-year-old boy with yolk sac tumor underwent radical resection because of acute hydrocephalus and mass effect on the brain stem, followed by chemotherapy and radiation therapy. Five patients showed complete response and survived at follow-up periods of 9, 26, 41, 63, and 75months, and the other three showed partial response but subsequent recurrence, finally died. Patients with complete response showed logarithmic decrease of serum AFP to the normal range in response to chemotherapy, but the others did not. Logarithmic decrease and normalization of serum AFP and HCG levels during neoadjuvant chemotherapy can distinguish a subgroup with better prognosis within highly malignant NGGCTs. To determine it, sequential measurement of serum tumor marker level was efficient. Outcomes were still dismal for slow responding patients, but this simple method may indicate more aggressive therapy.

Squamous Cell Carcinoma of the Uterine Cervix Producing Granulocyte Colony-Stimulating Factor

Granulocyte colony-stimulating factor (G-CSF)-producing malignant tumor has been reported to occur in various organs, and most of which has been associated with poor clinical outcome. However, because of the rarity of the reported cases, information regarding the G-CSF-producing gynecological malignancies is limited. We report 4 cases of G-CSF-producing cervical cancers. At initial diagnosis, all of the 4 patients exhibited marked leukocytosis without an obvious sign of infection. Of the 4 patients, 3 had their disease initially treated with definitive radiotherapy, and one was treated with radical surgery. Despite the aggressive treatments, all of these patients experienced recurrences within 6 months. In all cases, the white blood cell count returned to the normal range in response to the initial treatment and then increased again with recurrences. Based on the facts that the tumor cells were positive for G-CSF, the serum level of G-CSF was elevated, and their clinical course correlated well with the white blood cell count, we concluded that these tumors were G-CSF-producing cancers. All patients died from disease progression in less than 15 months. These cases strongly indicate the aggressive nature of the G-CSF-producing cervical cancer.

The Near Mallett Unit Foveal Suppression Test: a cross‐sectional study to establish test norms and relationship with other optometric tests

When the binocular system comes under prolonged stress in decompensated heterophoria, a small suppression area can develop at the fovea. This foveal suppression (FS) may be an adaptation to eliminate symptoms. The near Mallett unit (NMU) is a hand-held instrument that contains a binocular status test for detecting and quantifying FS. We measured FS in a cross-sectional study of 131 patients to investigate the normal range of responses. A ratio scoring method was devised which considers the number of letters read with dichoptic viewing when binocularly fused (b) and under monocular (m) conditions, using the formula 100 x (m - b)/m. The 95th percentile value of the FS ratios was calculated as the limit of the normal range and this gave a value for the right eye (RE; 33%), left eye (LE; 43%) and total (38%). This result shows that statistically significant FS occurs when a patient can read approximately one line further in the test monocularly, compared to under fused dichoptic conditions. A statistically significant correlation was found between absolute values of horizontal aligning prism (associated heterophoria on the NMU) and FS ratio. Some limitations of the FS test and unexpected results became apparent during our research and an abnormal result on the test does not always indicate a binocular vision anomaly. Nonetheless, we feel that the test can provide useful information when the results are taken in the context of other clinical tests. Our results are used to develop recommendations and clinical guidelines for using the FS test, and to make suggestions for improvements in future designs of the test.

Proteomics in cardiovascular surgery

Proteomics describes, analogous to the term genomics, the study of the complete set of proteins present in a cell, organ, or organism at a given time. The genome tells us what could theoretically happen, whereas the proteome tells us what does happen. Therefore, a genomic-centered view of biologic processes is incomplete and does not describe what happens at the protein level. Proteomics is a relatively new methodology and is rapidly changing because of extensive advances in the underlying techniques. The core technologies of proteomics are 2-dimensional gel electrophoresis, liquid chromatography, and mass spectrometry. Proteomic approaches might help to close the gap between traditional pathophysiologic and more recent genomic studies, assisting our basic understanding of cardiovascular disease. The application of proteomics in cardiovascular medicine holds great promise. The analysis of tissue and plasma/serum specimens has the potential to provide unique information on the patient. Proteomics might therefore influence daily clinical practice, providing tools for diagnosis, defining the disease state, assessing of individual risk profiles, examining and/or screening of healthy relatives of patients, monitoring the course of the disease, determining the outcome, and setting up individual therapeutic strategies. Currently available clinical applications of proteomics are limited and focus mainly on cardiovascular biomarkers of chronic heart failure and myocardial ischemia. Larger clinical studies are required to test whether proteomics may have promising applications for clinical medicine. Cardiovascular surgeons should be aware of this increasingly pertinent and challenging field of science.

The investigation of biomarkers in cardiovascular disease: time for a coordinated, international effort

This editorial refers to ‘Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome. An ENTIRE-TIMI 23 substudy’† by K.K. Ray et al ., on page 440 Biomarkers may be defined as measurable cells, proteins, and/or metabolic by-products that represent, either directly or indirectly, one or more biological or pathological processes active within a defined system or disease state. In a majority of cases, biomarkers delineate variances from normal biology and either appear for the first time (newly expressed) or, more commonly according to traditional thinking, elevate beyond a normal range in response to one or more stimuli or pathologic events [e.g. cardiac specific troponin in acute myocardial infarction (MI)], rendering a clinical diagnosis; however, biomarkers may themselves participate actively in the subsequent evolution and expression of disease (e.g. C-reactive protein in atherothrombosis). Thus, biomarkers, considered collectively and functionally, serve as diagnostic aids (type I), prognostic indicators (type II) and, perhaps more often than previously realized, fundamental contributors to the pathobiological basis of disease (type III) (types I–III are examples of a biomarker classification or categorization scale). In the article by Ray et al. ,1 von Willebrand factor (vWF) is considered as a biomarker of the type II and III categories.1 The ENTIRE-TIMI 23 Investigators1 evaluated enoxaparin, a … *Corresponding author. E-mail address : becke021{at}mc.duke.edu

O, p'-DDDの漸増投与を適用した犬の副腎皮質機能充進症4症例

Four dogs with spontaneous hyperadrenocorticism were treated with incremental administrations of o, p'-DDD. The initial dosage was 5mg/kg. Subsequent doses were administered at intervals of 3 to 5 days with a stepwise increase of 5mg/kg. After the dosage level reached 25 mg/kg, doses were raised at 2 to 3mg/kg increments. When such clinical signs as polyposia and polyuria had improved, the adrenocorticotropic hormone (ACTH) stimulation test confirmed the effectiveness of the therapy. The goal of treatment with o, p'-DDD was to achieve an ACTH stimulation result suggesting a normal range of responses. Possibly gradual o, p'-DDD dosage increases made it possible to achieve optimum individual dosages that resulted in high efficacy.

Sensitization studies in chemically intolerant individuals: implications for individual difference research.

Chemical intolerance (CI) is an individual difference trait in which persons report feeling ill in multiple physiological systems from low levels of a wide range of chemically unrelated environmental substances. This paper discusses the neural sensitization model for progressive host amplification of polysymptomatic responses elicited by chemical exposures following an initiating event. The sensitization model accommodates hypotheses for initiating and eliciting CI in human populations that involve both environmental chemicals and physical or psychological stressors. Recent studies in this laboratory have demonstrated sensitization in individuals with CI over repeated sessions for dependent variables such as electroencephalographic (EEG) activity and diastolic blood pressure. Psychological distress variables alone do not explain these findings. Individuals with CI and/or vulnerability to sensitization share specific characteristics, for example, female gender, certain genetic background (offspring of alcohol-preferring parents), and personal preference for high sugar/ carbohydrate intake. Overall, the data suggest that the 15-30% of the general population who report heightened CI are highly sensitizable. Sensitizability may serve an adaptive, sentinel function in threatening environments with poor signal-to-noise ratios. However, as sensitization gradually shifts operating set points of physiological systems out of the normal range in response to allostatic load, this process may contribute to the development of chronic, polysymptomatic health conditions such as multiple chemical sensitivity and/or fibromyalgia. Individual response specificity and stereotypy rather than toxicant properties may determine which types of central, autonomic, and/or peripheral nervous system dysfunctions manifest at subclinical and clinical levels.

A survey of chiropractors’ use of nutrition in private practice

ABSTRACT Objective To survey the private practice use of nutrition by chiropractors with emphasis on recommendations and education. Design A 3-page mail survey was sent to chiropractors practicing in the United States. Results The response rate was within the normal response range, 34% (74 of 217). Of those that responded, 77% were male; the mean number of years since graduation from chiropractic college was 13, with a range from 1-39 years. The average practice time spent on nutrition was 19%. Fifty-three percent of responders felt that their chiropractic college provided them with an adequate understanding in nutrition. Eightyone percent incorporated nutritional counseling, handed out nutritional literature or recommended nutritional supplements. Forty-two percent felt that chiropractors are able to address all nutritional concerns and 21% feel that the services of a nutritional specialist should only be used for second opinion interpretations. Discussion Nutrition is an important factor in the pursuit of optimal health. Most chiropractors in our sample incorporated nutritional services in their practice. The results of this study suggest that a significant amount of practice time is spent on services other than chiropractic adjustments. Approximately half of the chiropractors felt that their chiropractic college provided an adequate understanding in nutrition.

Orthostatic intolerance in the chronic fatigue syndrome

This study aims to investigate the prevalence and pathophysiology of orthostatic intolerance (OI) and its potential contribution to symptoms of a group of unselected patients with chronic fatigue syndrome (CFS). Seventy five patients (65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical suspicion as to the likelihood of observing laboratory evidence of OI was assigned. Laboratory investigation consisted of beat-to-beat recordings of heart rate, blood pressure (Finapres), and stroke volume (impedance cardiograph) while supine and during 80° head-up tilt (HUT), during rhythmic deep breathing (6 breaths/min) and during the Valsalva maneuver. The responses of 48 age-matched healthy controls who had no history of OI were used to define the range of normal responses to these three maneuvers. Forty percent of patients with CFS had OI during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven tachycardia (>35 bpm averaged over the whole of the head-up tilt) and six a mixture of tachycardia and syncope. Eight of 48 controls exhibited neurally-mediated syncope. The responses to the Valsalva maneuver and to deep breathing were similar in controls and patients. On average, the duration of disease and patient age were significantly less and the onset of symptoms was more often subacute in patients with OI than in those without OI. We conclude that there exists a clinically identifiable subgroup of patients with CFS and OI that differs from control subjects and from those with CFS without OI for whom treatment specifically aimed at improving orthostatic tolerance may be indicated.

Osmoregulation in clinical disorders of thirst appreciation

Thirst and drinking are essential components of normal osmoregulation in healthy man. Abnormalities of thirst appreciation, in particular hypodipsia, have profound implications for water homeostasis. The combination of cranial diabetes insipidus and hypodipsia can have particularly serious consequences, with the potential for life-threatening hyponatraemia. Although the tools for measuring thirst are subjective and lack true specificity, their use in clinical research has contributed greatly to our understanding of the physiology of thirst appreciation and the abnormal control of thirst in osmoregulatory disorders. The precise neural control of thirst appreciation remains unknown, and perhaps as a result of this, satisfactory therapies for the treatment of disorders of thirst have not yet been developed; behavioural modification and retraining of drinking habits remain the rather limited cornerstones of management.

Modeling for Risk Assessment of Neurotoxic Effects

The regulation of noncancer toxicants, including neurotoxicants, has usually been based upon a reference dose (allowable daily intake). A reference dose is obtained by dividing a no-observed-effect level by uncertainty (safety) factors to account for intraspecies and interspecies sensitivities to a chemical. It is assumed that the risk at the reference dose is negligible, but no attempt generally is made to estimate the risk at the reference dose. A procedure is outlined that provides estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect and the dose of a chemical. Knowledge of biological mechanisms and/or pharmacokinetics can assist in the choice of plausible mathematical models. The mathematical model provides estimates of average responses as a function of dose. Secondly, estimates of risk require selection of a distribution of individual responses about the average response given by the mathematical model. In the case of a normal or lognormal distribution, only an estimate of the standard deviation is needed. The third step is to define an adverse level for a response so that the probability (risk) of exceeding that level can be estimated as a function of dose. Because a firm response level often cannot be established at which adverse biological effects occur, it may be necessary to at least establish an abnormal response level that only a small proportion of individuals would exceed in an unexposed group. That is, if a normal range of responses can be established, then the probability (risk) of abnormal responses can be estimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal values and ranges for ventilation and breathing pattern at maximal exercise

Assessment of the breathing pattern at maximal exercise in patients is limited because the range of ventilatory responses (minute ventilation; tidal volume; respiratory rate) at maximal exercise in humans is unknown. We studied 231 subjects (120 women; 111 men) equally distributed according to age from 20 to 80 years. Each subject performed a progressive incremental cycle ergometer exercise test to their symptom-limited maximum. Mean ventilation at the end of exercise (Vemax) was significantly higher in men (mean +/- SD, 97 +/- 25 L/min) than in women (69 +/- 22 L/min) (p less than 0.001). Minute ventilation at the end of exercise as a fraction of predicted maximal voluntary ventilation (Vemax/MVV) for all subjects was 0.61 +/- 0.14 (range, 0.28 to 1.02). There was no difference in Vemax/MVV between men (0.62 +/- 0.14) and women (0.59 +/- 0.14). Tidal volume at the end of exercise (Vtmax) was higher in men (2.70 +/- 0.48 L) than in women (1.92 +/- 0.41 L) (p less than 0.001). Any differences in Vtmax between men and women disappeared when Vtmax was corrected for baseline FVC. Respiratory rate at the end of exercise (RRmax) was 36.1 +/- 9.2 breaths per minute for all subjects. There was no difference in RRmax between men and women. The Vemax correlated best with carbon dioxide output at the end of exercise (r = 0.91; p less than 0.001) and with maximal oxygen uptake (r = 0.90; p less than 0.001) for all subjects. This study of a large group of subjects has demonstrated the wide range of possible breathing patterns which are adopted during exercise and has provided a wide range of normal responses which must be taken into consideration when maximal ventilatory data from exercise tests are analyzed.