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Differential activation of trigeminal C or Adelta nociceptors by infrared diode laser in rats: behavioral evidence.

Radiant heat is often used for studying thermal nociception, although inherent characteristics such as the broad spectrum of applied wavelengths of typical light sources limit control over and repeatability of stimuli. To overcome these problems, we used a diode infrared laser-based stimulator (wavelength: 980 nm) for selectively stimulating trigeminal Adelta or C thermonociceptors in rats. To provide indirect evidence for nociceptor-selective stimulation, we tested the effects of capsaicin, dimethylsulfoxide (DMSO), and morphine on withdrawal latencies for long pulses with a low current (hypothesized to selectively stimulate C nociceptors) and for threshold currents of short pulses with high current (hypothesized to selectively stimulate Adelta nociceptors) in lightly anesthetized rats. Nonmem analysis was used to perform pharmacodynamic modeling. The measured baseline withdrawal latency for long pulses was 12.5 +/- 0.3 s which was changed significantly to 6.7 +/- 0.4 s after applying topical capsaicin which selectively sensitizes C nociceptors and to 16.5 +/- 1.3 s after 1.0 mg/kg morphine which preferentially attenuates C fiber nociception. Topical DMSO which appears to selectively sensitize Adelta afferents did not significantly alter withdrawal latencies to the long pulses. Fitted threshold currents for short pulses after DMSO were however significantly lower (974 +/- 53 mA vs. 1113 +/- 12 mA for baseline) indicating Adelta sensitization. Capsaicin and morphine did not significantly change threshold currents. Best Nonmem fits for the long pulse were obtained using a model assuming no DMSO effect, but a different inter-individual variability after applying this substance. For the short pulse, a model assuming no capsaicin or morphine effect, but again allowing different inter-individual variabilities after applying these drugs, best described the data. We conclude that different settings of the stimulator used in this study were capable of selectively activating trigeminal Adelta or C thermonociceptors.

Analgesics, Opioid↗

Clinical predictors of ongoing infection in secondary peritonitis: systematic review.

INTRODUCTION: The decision to perform a relaparotomy in patients with secondary peritonitis is based on "clinical judgment" with inherent variability among surgeons. Our objective was to review the literature on prognostic variables for ongoing abdominal infection. Predictive variables for positive findings at relaparotomy can generate more objective criteria to support the decision whether to perform a relaparotomy in patients with secondary peritonitis. METHODS: Multiple databases were searched for studies assessing the prognostic value of clinical variables predicting outcome of relaparotomy or general outcome in patients with secondary peritonitis. Data on the methodologic quality of the study as well as statistical strength of predictors and validity of individual variables were extracted and scored. A cumulative score was calculated from these three scores, and the variables were ranked. RESULTS: A total of 37 of 197 retrieved articles were included for final assessment. The median score for methodologic quality of individual articles was 36 (range 19-54). After calculation of the combined scores, 76 individual variables (patient, peritonitis, surgery, clinical, and laboratory variables) were identified from which the top 10 were eventually selected. These variables were age, concomitant disease, upper gastrointestinal source of peritonitis, generalized peritonitis, elimination of the focus, bilirubin, creatinine, lactate, PaO2/FiO2 ratio, and albumin. This set of variables proved to be moderately predictive for positive findings during relaparotomy in a retrospective cohort of 219 patients operated on for secondary peritonitis (receiver operator curve 0.75, with 95% confidence interval 0.68-0.82). CONCLUSIONS: This review generated a hierarchy (weighted ranking) of published variables that could play a role in the decision to perform a relaparotomy in patients with secondary peritonitis. The top sixtile of ranked variables (10 variables) showed promising results in the discrimination between patients having a positive and negative relaparotomy when tested on a peritonitis patient database. This ranking of variables provides evidence for potential inclusion of variables in future predictive scores, although improvement in overall predictive strength of a set of variables in such a score is needed.

Humans↗

[The effect of similar speed's walking and functional classification of foot contact on variability of the vertical ground reaction force].

INTRODUCTION: The variability of the normal ground reaction force (F(z)) is a restrictive factor for the clinical analyse of kinetics parameters recorded during walking. OBJECTIVE: The aim of this study is the decrease of the inter-individual variability of the normal ground reaction force: F(z). MATERIAL AND METHOD: The method tested consists in imposing a similar speed to the subjects during walking tests, then to class foot according to their function: loading or propulsive foot. A group of seven young adults walk at spontaneous speed (VSpon) for the first walking test then at similar speed (Vsim = N(Fr) x square root of (g x li); where N(Fr) is the Froud's number, g is the gravitational acceleration and li is the length of the lower limb) for the second walking test. Two forces platforms register the F(z) of two consecutive steps. The normal ground reaction force and the mean coefficient of variability are retained to test for speed (VSim and VSpon) and functional classification effects. RESULTS: The CoV of F(z) decreases from 13% to 8% when the subjects walk at similar speed rather than at spontaneously chosen speed. The variability decreases by 1-1.5% when the data are classified according to functional criterion. The inter-individual variability of the F(z) significantly reduces when the tests are performed at similar speed and when the loading or propulsive factors are used for functional classification. CONCLUSION: The coupling of the methods described must permit to the clinician to constitute a data base which, tainted of less variability, should make easier the detection of pathology affecting the ground reaction force.

Adult↗

A fully automated system for the evaluation of masseter silent periods.

Exteroceptive suppression of masseter muscle activity, 'masseter inhibitory reflex', comprises one or 2 silent periods (SP1 and SP2) interrupting the voluntary activation. The main problem when evaluating exteroceptive suppression is the lack of an objective and precise measure for the onset and end of the silent period which so far has not been overcome by various automated systems. We describe a new fully automated system for determining the onset and end of the masseter silent period. The decision approach is essentially based upon deterministic properties of median filters which are used to partition the local variances of the EMG traces into constant segments and edges between them. The system was tested in 13 healthy volunteers with 2 subjects tested serially 10 times each to get estimates of the inter- and intra-individual variability. The performance of the system compared favourably to that of a simpler approach and to earlier results from our laboratory. The inter-individual variability of the SP1 onset was 17 times smaller than when based on a subjective decision process.

Adolescent↗

N-glucuronidation of carcinogenic aromatic amines catalyzed by rat hepatic microsomal preparations and purified rat liver uridine 5'-diphosphate-glucuronosyltransferases.

The N-glucuronidation of three carcinogenic aromatic amines (4-aminobiphenyl, alpha-naphthylamine, and beta-naphthylamine) was investigated in hepatic microsomal preparations from two rat strains. In preparations from Wistar rats, individual variability was observed for the glucuronidation of the arylamines. This variability correlated with high and low levels of 3 alpha-hydroxysteroid UDP-glucuronosyltransferase (UDPGT) in hepatic microsomal preparations from Wistar rats. This individual variability was not observed in Sprague-Dawley rat hepatic microsomal preparations because hepatic 3 alpha-hydroxysteroid UDPGT levels do not vary in this strain of rats. Five highly purified rat liver UDPGTs were investigated for their ability to catalyze the conjugation of the aromatic amines. Of the purified enzymes investigated, only 3 alpha-hydroxysteroid UDPGT catalyzed the glucuronidation of 4-aminobiphenyl. alpha-Naphthylamine and beta-naphthylamine conjugations were catalyzed by 3 alpha-hydroxysteroid, 17 beta-hydroxysteroid, and 3-methylcholanthrene-inducible p-nitrophenol UDPGTs. The three aromatic amines did not serve as substrates for purified digitoxigenin monodigitoxoside or phenobarbital-inducible morphine UDPGTs. The results show that N-glucuronide formation can be catalyzed by UDPGT isoforms which also catalyze the formation of O-glucuronides. In addition, variable levels of 3 alpha-hydroxysteroid UDPGT in Wistar rat liver may have toxicological significance for substrates of this isoenzyme.

1-Naphthylamine↗

Low-dose endotoxin elicits variability in the inflammatory response in healthy volunteers.

Endotoxin has been implicated as a cause of sepsis, inflammation and organ dysfunction after surgery. Patients differ in their response to endotoxin, and this may account for differences in outcome. The traditional human model of endotoxin challenge (2-4 ng/kg) is not associated with significant inter-individual variability in systemic inflammation and may not be suitable for studying variability in the inflammatory response. We examined whether low-dose regimens of endotoxin cause significant variability in inflammation. Volunteers (n = 30) were randomised in a double-blinded ('double-dummy') study to one of 6 dosing regimens: saline (placebo) or Escherichia coli O:113 endotoxin as a 4 ng/kg bolus (positive control), 0.25 ng/kg (bolus), 0.25 ng/kg (30 min infusion), 0.75 ng/kg (bolus) or 0.75 ng/kg (30 min infusion). Temperature, white cell count, platelet count, C-reactive protein and cytokine changes from baseline were measured. In contrast to subjects receiving placebo, those randomised to 4 ng/kg endotoxin exhibited significant systemic inflammation during the 10-h observation period. The four low-dose regimens elicited variability in most markers of inflammation. We conclude that low-dose endotoxin elicits inter-individual variability in inflammation and could be used to test factors that may affect the human response to endotoxin.

Adolescent↗

Measuring CDR3 length variability in individuals during ontogeny.

The portion of the antibody sequence that contributes most to the conformation of the antigen-combining site is the third complementarity-determining region (CDR3). The CDR3 in antibody heavy chains are somatically produced by the rearrangement of three different immunoglobulin (Ig) gene segments, VH, D and JH, and are therefore highly variable in sequence and length. We have devised a technique for rapid analysis of CDR3 length variability from a large number of cDNA samples. This technique allows comparative evaluation of IgH heterogeneity in individuals without recourse to DNA cloning and sequencing. We also present data on Ig sequences from different stages of development in the amphibian, Xenopus laevis. Most of the larval and post-metamorphic Ig samples contained CDR3 of 3-10 codons, two codons shorter than those of the adult CDR3, which were 5-12 codons. Antibodies may by immunized tadpoles have been shown to be much less diverse than those produced by adults to the same antigen. The shorter tadpole CDR3 perhaps generates a more limited spectrum of antigen-combining site structures and, in this way, makes for a more restricted antibody repertoire.

Animals↗

Daily variation in energy expenditure during weight-training versus continuous arm cranking and cycling.

To quantify day-to-day variability in energy expenditure (EE) during weight-training, 10 male subjects completed 6 training sessions that consisted of a warming-up and cooling-down phase (10 min; arm cranking or cycling) and a computer-paced weight-training phase using standard weights (42 min; 10 exercises, 3 x 15 repetitions, work to rest ratio = 1:1). The first 2 sessions were used to accommodate. During sessions 3-6 (labelled session A, B, C and D) cardiorespiratory response was continuously measured. Gas-exchange was converted to EE using the Weir formula. In the last two sessions training weights were raised by +/- 50% and the initial warming-up and cooling-down exercise being arm-cranking was replaced by cycling. Mean EE was calculated for last five minutes of the warming-up (WU5) and cooling-down (CD5) and the complete weight-training phase (WT). Mean EE during WT for session A to D was 20.0 +/- 2.7, 19.1 +/- 2.5, 22.2 +/- 2.2 and 21.9 +/- 2.4 kj.min-1, respectively. Daily variation was tested by comparing test-retest phases (A vs B and C vs D). Intra-individual variability in EE during respectively the lower (session A vs B) and higher (session C vs D) weight-training intensity was expressed as: absolute test-retest difference (0.9 +/- 0.5 and 0.7 +/- 0.6 kj.min-1), difference relative to the mean of the test-retest measurements (2.3 +/- 1.4 and 1.6 +/- 1.4%) and as the mean coefficient of variation (3.3 and 2.2%). There were no differences in variability between both WT-intensities nor exercise modes, irrespective of the way variability was expressed. In conclusion, intra-individual variability in EE during weight-training does not differ from variability during arm cranking or cycling.

Adult↗

Effects of body weight-supported treadmill training on heart rate variability and blood pressure variability in individuals with spinal cord injury.

Individuals with spinal cord injury are prone to cardiovascular dysfunction and an increased risk of cardiovascular disease. Body weight-supported treadmill training (BWSTT) may enhance ambulation in individuals with incomplete spinal cord injury; however, its effects on cardiovascular regulation have not been investigated. The purpose of this study was to examine the effects of 6-mo of BWSTT on the autonomic regulation of heart rate (HR) and blood pressure (BP) in individuals with incomplete tetraplegia. Eight individuals [age 27.6 yr (SD 5.2)] with spinal cord injury [C4-C5; American Spinal Injury Association B-C; 9.6 yr (SD 7.5) postinjury] participated. Ten-minute HR and finger arterial pressure (Finapres) recordings were collected during 1) supine rest and 2) an orthostatic stress (60 degrees head-up tilt) before and after 6 mo of BWSTT. Frequency domain measures of HR variability [low-frequency (LF) power, high-frequency (HF) power, and LF-to-HF ratio] and BP variability (systolic and diastolic LF power) were used as clinically valuable indexes of neurocardiac and neurovascular control, respectively. There was a significant reduction in HR [61.9 (SD 6.9) vs. 55.7 beats/min (SD 7.7); P=0.05] and LF-to-HF ratio [1.23 (SD 0.47) vs. 0.99 (SD 0.40); P < 0.05] after BWSTT. There was a significant reduction in LF systolic BP [183.1 (SD 46.8) vs. 158.4 mmHg2 (SD 45.2); P < 0.01] but no change in BP. There were no significant effects of training on HR variability or BP variability during 60 degrees head-up tilt. In conclusion, individuals with incomplete tetraplegia retain the ability to make positive changes in cardiovascular autonomic regulation with BWSTT without worsening orthostatic intolerance.

Adult↗

The role of busulfan in bone marrow transplantation.

High-dose busulfan is an important component in many conditioning protocols for hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) in both adults and children. During the past 12y several studies have reported the wide inter-individual variability in busulfan disposition. Age, disease status, hepatic function, circadian rhythmicity, drug interactions and bioavailability, were identified as factors contributing to the high inter-individual variability found in busulfan disposition. Traditionally, a standard busulfan dose of 4mg/kg/d for four days is used in most BMT/HSCT protocols. Many investigations have pointed out the pharmacodynamic relationship between a high busulfan systemic exposure and the occurrence of BMT related toxicity including hepatic veno-occlusive disease (VOD), interstitial pneumonia and alopecia in adult patients. However, studies in young patients have shown a high rate of graft failure and subsequently relapse which most probably is due to the low systemic exposure despite the standard dose schedule. In children and infants VOD was not observed with the standard doses. Increasing interest for the drug and new modification strategies for children led to higher rate of VOD and CNS toxicity when busulfan was administered according to the body surface area. More pharmacodynamic studies are required to establish the relation between the systemic exposure to busulfan and the therapeutic efficacy, especially in young children undergoing BMT or HSCT. In the present time an accurate and effective busulfan plasma level monitoring combined with dose adjustment based on the known pharmacological parameters may improve the clinical outcome for patients undergoing BMT.

Adult↗

Temporal decline in sirolimus elimination immediately after pancreatic islet transplantation.

Pancreatic islet transplantation is a curable treatment for type 1 diabetes and has been put into practice in various countries. In this study, we analyzed the pharmacokinetic characteristics of sirolimus and tacrolimus in six Japanese patients with pancreatic islet transplants immediately after surgery, and monitored efficacy and toxicity. The patients were treated with immunosuppressive therapy based on the Edmonton protocol, that is, sirolimus and low-dose tacrolimus. Pharmacokinetic analyses were performed using the nonlinear mixed-effects modeling program NONMEM. Large inter- and intra-individual variability was observed in the pharmacokinetics of sirolimus and tacrolimus. A model with increased apparent clearance in the postoperative period explained well the intra-individual variability in the pharmacokinetics of both drugs. The most frequent drug-induced toxicity was a decrease in the white blood cell count, and two of six patients required the administration of granulocyte colony-stimulating factor. Clinical laboratory tests immediately before the transplantation and cytochrome P450 3A5 genotype were not related to the high blood concentrations of sirolimus after the loading dose. From these results, the apparent clearance of sirolimus and tacrolimus might temporally decline immediately after pancreatic islet transplantation. A high trough concentration of sirolimus might increase the risk of hematological toxicy, and adjustment of the dosage for immunosuppressive treatment will be necessary in Japanese patients.

Adult↗

[Utilization of health care services in Brazil: gender, family characteristics, and social status].

OBJECTIVE: To investigate the pattern of utilization of health care services by men and by women in Brazil. METHODS: We used data from the Brazilian National Household Sample Survey (Pesquisa Nacional por Amostra de Domicílios) carried out in 1998. Logistic regression models were developed to analyze information concerning men and women who had and who did not have restrictions in their routine activities due to health problems during the 15 days before the survey. The individual variables considered were: labor market position (type of employment), amount of schooling completed, and race. Also analyzed were family-related variables: per capita family income, size of the family, and, for the head of the family, the amount of schooling and labor market position. The two-level models (with family and individual variables) showed an effect from family characteristics, but the variables analyzed did not explain that effect. RESULTS: Women used health services more often than did men, even after controlling for restrictions in routine activities due to health reasons. The use of health services by men and women was dependent on family income and on the social status of the individual, indicating a pattern of social inequality. In both the group with restrictions in their activities and in the group without such restrictions, the men and women differed from each other in their utilization of health care services. Family variables were more important in explaining the utilization of health services among people without restrictions in their activities. CONCLUSIONS: Policies aimed at reducing inequalities in access to health care services must take into consideration the differences between women and men as well as the importance of family characteristics. It is also important to stress the need to include the dimensions of gender and family in the design of health service utilization models.

Adolescent↗

[Normal and abnormal daily variability of urinary excretion of albumin].

Urinary albumin excretion (UAE) is very variable from day to day. We analyzed day-to-day UAE in 207 elderly (60-75 years) inpatients (134 with and 73 without diabetes mellitus) attending the department of internal medicine of the Angers University hospital. Twenty-four-hour urine was collected 3 times during a 5-10 day hospitalization period. One-hundred-fifty-one patients (73%) displayed normoalbuminuria (UAE < 30 mg/24 h in 2 or 3 measures) while 56 patients (27%) had microalbuminuria (UAE within 30-300 mg/24 h in 2 or 3 measures). As the raw data of UAE was not normally distributed, we transformed UAE into the variable z = log(log(k+ UAE)) where k is an integer. We found that z has a gaussian distribution for k = 2. Mean value and coefficient of variation of z in the 3 measurements were used to define the level and the temporal intra-individual variability of UAE. Expressed in term of z, the day-to-day intra-individual variability of UAE showed a potent change (from large variability to small variability) at the particular level z = 1.25, corresponding to UAE = 30.8 mg/24 h, which is precisely the level currently used to define microalbuminuria in diabetic subjects.

Aged↗

Relationships among salinity, egg size, embryonic development, and larval biomass in the estuarine crab Chasmagnathus granulata Dana, 1851.

We studied interrelationships between initial egg size and biomass, duration of embryogenesis at different salinities, and initial larval biomass in an estuarine crab, Chasmagnathus granulata. Ovigerous females were maintained at three different salinities (15 per thousand, 20 per thousand and 32 per thousand); initial egg size (mean diameter), biomass (dry weight, carbon and nitrogen) as well as changes in egg size, embryonic development duration, and initial larval biomass were measured.Initial egg size varied significantly among broods from different females maintained under identical environmental conditions. Eggs from females maintained at 15 per thousand had on average higher biomass and larger diameter. We hypothesise that this is a plastic response to salinity, which may have an adaptive value, i.e. it may increase the survivorship during postembryonic development. The degree of change in egg diameter during the embryonic development depended on salinity: eggs in a late developmental stage were at 15 per thousand significantly larger and had smaller increment than those incubated at higher salinities. Development duration was longer at 15 per thousand, but this was significant only for the intermediate embryonic stages. Initial larval biomass depended on initial egg size and on biomass loss during embryogenesis. Larvae with high initial biomass originated either from those eggs that had, already from egg laying, a high initial biomass (reflecting individual variability under identical conditions), or from those developing at a high salinity (32 per thousand), where embryonic biomass losses were generally minimum. Our results show that both individual variability in the provisioning of eggs with yolk and the salinity prevailing during the embryonic development are important factors causing variability in the initial larval biomass of C. granulata, and thus, in early larval survival and growth.

Journal Article↗

Meridional variations in orientation discrimination in normal and amblyopic vision.

Orientation discrimination for single long lines presented in a frameless environment was measured with a method of constant stimuli in 18 normal subjects and in both eyes of 9 amblyopes. Orientation discrimination was tested at four meridians (horizontal, vertical, left, and right oblique). Although the normal subjects showed considerable individual variability in their just noticeable differences in orientation, each subject showed a consistent oblique effect. In amblyopic subjects, the interocular differences were strongly meridian-dependent and individually variable. Across amblyopic subjects, a two-fold increase in just noticeable differences ( JNDs ) was observed for the principal meridians, while the impairments were not significant for the oblique meridians. These small impairments in orientation discrimination strongly contrast with the high losses in acuity for the same subjects, which suggests that different mechanisms underly acuity and orientation discrimination.

Adolescent↗

Variability in cardiovascular and plasma norepinephrine responses to head-up tilt in healthy human subjects.

Eight healthy, young adult males underwent three separate, 10-min 70 degrees head-up tilts (HUT) over a period of nine days, in order to assess the intra- and inter-individual variability of cardiovascular and plasma norepinephrine (NE) responses to the manoeuvre. Cardiovascular parameters and plasma NE were measured in the basal state and at 2-min intervals during the HUT. The results indicate that: (1) the intra-individual variability is a smaller component of the total variability of both cardiovascular and plasma NE responses to HUT; (2) the variability in cardiovascular parameters is smaller than that in plasma NE levels, both basal and in response to postural stress; (3) there does not appear to be any difference in variability when expressed either as the maximal or the mean response to HUT; and (4) there does not appear to be an increase in the variability of the measured parameters over the duration of the HUT.

Adult↗

Hemispheric specialization for language.

Hemispheric specialization for language is one of the most robust findings of cognitive neuroscience. In this review, we first present the main hypotheses about the origins of this important aspect of brain organization. These theories are based in part on the main approaches to hemispheric specialization: studies of aphasia, anatomical asymmetries and, nowadays, neuroimaging. All these approaches uncovered a large inter-individual variability which became the bulk of research on hemispheric specialization. This is why, in a second part of the review, we present the main facts about inter-individual variability, trying to relate findings to the theories presented in the first part. This review focuses on neuroimaging as it has recently given important results, thanks to investigations of both anatomical and functional asymmetries in healthy subjects. Such investigations have confirmed that left-handers, especially "familial left-handers", are more likely to have an atypical pattern of hemispheric specialization for language. Differences between men and women seem less evident although a less marked hemispheric specialization for language was depicted in women. As for the supposed relationship between anatomical and functional asymmetries, it has been shown that the size of the left (not the right) planum temporale could explain part of the variability of left hemispheric specialization for language comprehension. Taken as a whole, findings seem to vary with language tasks and brain regions, therefore showing that hemispheric specialization for language is multi-dimensional. This is not accounted for in the existing models of hemispheric specialization.

Animals↗