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PubMed1998

CD34+ cell dose and CD33- subsets: collection and engraftment kinetics in autologous peripheral blood stem cells transplantation.

BACKGROUND AND OBJECTIVE: We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC) collected for transplant in order to establish a minimum threshold for rapid hematopoietic recovery. DESIGN AND METHODS: From January 1995 to November 1996, a consecutive series of 67 patients, with hematologic and solid tumors underwent autologous PBSC transplantation. Collection of PBSC was performed after mobilization with granulocyte-colony stimulating factor (G-CSF) or with chemotherapy (CT) plus G-CSF. We calculated the factors that influenced PBSC collection, the kinetics of granulocyte and platelet recovery and the threshold value of CD34+ cells for a rapid recovery. The data were analyzed by means of multivariate Cox regression model and the receiver operating characteristic (ROC) methodology. RESULTS: Our results showed that mobilization with chemotherapy plus G-CSF was associated with a higher yield of PBSC in comparison with mobilization with G-CSF alone. Disease status, fewer cycles of conventional prior chemotherapy and absence of prior radiation therapy also influenced the yield of PBSC. The number of CD34+ cells, CD34+CD33- cell subsets, the mobilization schedule, and the conditioning regimen correlated significantly with time to hematopoietic recovery. In the multivariate analysis only the CD34+CD33- cell content and the total number of CD34+ were related with rapid neutrophil and platelet recovery, respectively. Use of G-CSF after transplant significantly shortened the neutrophil recovery time only in patients transplanted with suboptimal dose of PBSC. INTERPRETATION AND CONCLUSIONS: These data suggest the utility of quantitation of CD34+ cells subsets to predict quick engraftment.

Adolescent↗
PubMed1994

[Cardiopulmonary exercise evaluation: value and influence of the use of a ramp protocol versus triangular protocol].

The aim of the study was to evaluate a ramp bicycle ergometer exercise protocol consisting of a very small but rapid increase in load (2 watts/12 seconds) for direct measurement of the VO2 max. Eighteen sedentary healthy subjects were in Group I (16 men, mean age 29 +/- 6 years) and 10 men with chronic stable cardiac failure in Group II (mean age: 51 +/- 16 years). All subjects performed two exercise tests within a period of 8 days, one with a ramp protocol (protocol R) and the other with a standard triangular exercise protocol (protocol T) of 30 watts/3 minutes for Group I and 20 watts/2 minutes for Group II. All procedures were performed until the subjects were exhausted. Direct measurement of VO2 max was performed by rapid response analysers enabling a cycle to cycle study. The parameters were measured and compared by a paired Student t test at each stage of the test: at rest, at submaximal exercise (third level), at anaerobic threshold and at maximal exercise. There was no significant difference between VO2 max and VO2 at the threshold of ventilation between the two populations. An increase in carbon dioxide production at different stages was observed with the ramp protocol. Furthermore, the highest maximal respiratory quotient and anaerobic threshold appeared earlier in Group II with the ramp protocol. Therefore, with respect to the standard triangular protocol, the ramp protocol provides comparable VO2 values. Its potential value, reported in the literature, is a better correlation between the observed and theoretical VO2 values. However, an increase in CO2 production should be underlined, probably related to greater recruitment of anaerobic metabolism in the absence of a steady state. This may be the reason for attaining the anaerobic threshold earlier.

Adolescent↗
PubMed1992

Menstrual migraine without aura: cortical excitability to magnetic stimulation.

The purpose of the present study was the evaluation of the excitability threshold and the central motor conduction time (CCT) studied by means of electromagnetic cortical stimulation in ten subjects affected by menstrual migraine without aura, both in the ictal and the interictal period. The patients were chosen from among a group of 254 outpatients affected by migraine, diagnosed according to the International Headache Society criteria. The control group consisted of ten healthy female subjects. As far as CCTs were concerned no differences emerged between patients and controls. However in the patient group we found a significant increase in the excitability threshold values, both in the ictal and the interictal period, and in both hemispheres. If confirmed, the increased excitability threshold may be a useful neurophysiological correlate of migraine without aura.

Adult↗
PubMed2003

Response properties of TMJ units in superficial laminae at the spinomedullary junction of female rats vary over the estrous cycle.

Neurons responsive to stimulation of the temporomandibular joint (TMJ) region were recorded from superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C(2)) junction region of cycling female rats under barbiturate anesthesia. To determine if receptive field (RF) properties or sensitivity to algesic chemicals of TMJ units vary over the estrous cycle, animals were selected from proestrous (high estrogen) or early diestrous (low estrogen) stages. More than 90% of TMJ units from each group received convergent nociceptive input [wide dynamic range (WDR) or nociceptive specific (NS)-like] from facial skin. The cutaneous high-threshold RF areas of WDR units from proestrous rats were 30% larger than diestrous units, while RF areas of NS units were similar. Bradykinin (BK, 0.1-10 microM) injection into the TMJ region excited a high percentage of units (>80% of total) from both groups in a dose-related manner. However, BK-evoked response magnitude (R(mag), +140%) and duration (+64%) were greater for proestrous than diestrous units. Both WDR and NS-like TMJ units of proestrous females displayed enhanced BK-evoked R(mag) values and response duration. Glutamate or mustard oil excitation of TMJ units was not affected by stage of the estrous cycle. Several TMJ units from proestrous and diestrous females were activated antidromically from the contralateral posterior thalamus, indicating that projection and nonprojection units were included in the sample population. These results were consistent with the hypothesis that factors related to stage of the estrous cycle modify the processing of deep craniofacial inputs by superficial dorsal horn neurons at the spinomedullary junction, a key region for the initial integration of sensory signals from the TMJ.

Animals↗
PubMed1999

The bone marrow plasma cell labeling index by flow cytometry.

The bone marrow plasma cell labeling index is the most important prognostic indicator for patients with multiple myeloma. Traditionally, this test has been performed as a two color immunofluorescent microscope technique which is time consuming and requires a degree of subjectivity in its interpretation. We have assessed various adaptations of this method to flow cytometry. A bromodeoxyuridine method has been compared with a propidium iodide DNA method to detect cells in S phase and CD38-FITC has been compared with CD38-FITC + CD138-FITC and CD38-biotin + streptavidin FITC to identify plasma cells. The mean channel fluorescent intensity of the plasma cell peaks for each of these markers was 12. 7, 17.4 and 35.3 respectively demonstrating the superiority of CD38-biotin + streptavidin FITC. Analysis after propidium iodide staining provided a good correlation with the slide technique (r = 0. 71; P < 0.0001) but the bromodeoxyuridine method did not correlate with the slide method (r = 0.09; P = NS). The labeling index values obtained from either of the flow methods were greater than the microscopic method. Thus a labeling index of >4% will replace the traditional >1% threshold for identifying patients with a significantly increased labeling index. The advantages of the new method are that it takes less time to perform, is more objective and provides additional data on ploidy and cell cycle status.

ADP-ribosyl Cyclase↗
PubMed1988

Are differences in FSH concentrations involved in the control of ovulation rate in Romanov and Ile-de-France ewes?

Despite differences in FSH concentrations ranging from 1.5 ng/ml (Romanov ewes) to 4 ng/ml (Ile-de-France ewes) between the follicular and luteal phases, follicular growth (numbers of follicles growing, growth rates, maximum size reached) was morphologically similar between the two stages of the cycle. Injection of 750 i.u. hCG at Day 6 or 16 of the cycle triggered ovulation of 4.1 +/- 0.7 and 4.0 +/- 1.3 follicles in Romanov and 2.2 +/- 0.5 and 1.7 +/- 0.5 follicles in Ile-de-France ewes, respectively, demonstrating that functional differentiation was similar between the two stages of the cycle. As gonadotrophin environment differs between these two stages of the cycle, this suggests that there is a wide flexibility in the amount of gonadotrophins required to trigger terminal follicular growth and that ovarian requirements for gonadotrophins might work through thresholds. When Romanov and Ile-de-France ewes were given similar amounts of exogenous gonadotrophins (1250 i.u. PMSG, 750 i.u. hCG) after hypophysectomy, ovulation rates were close to the usual values (Romanov, 5.5 +/- 3.9; Ile-de-France, 1.4 +/- 0.5), demonstrating that differences in gonadotrophin concentrations during the follicular phase do not play a major role in the high ovulation of the Romanov compared to the Ile-de-France ewes.

Animals↗
PubMed2001

Determination of RhD zygosity: comparison of a double amplification refractory mutation system approach and a multiplex real-time quantitative PCR approach.

BACKGROUND: Rh isoimmunization and hemolytic disease of the newborn still occur despite the availability of Rh immunoglobulin. For the prenatal investigation of sensitized RhD-negative pregnant women, determination of the zygosity of the RhD-positive father has important implications. The currently available molecular methods for RhD zygosity assessment, in general, are technically demanding and labor-intensive. Therefore, at present, rhesus genotype assessment is most commonly inferred from results of serological tests. The recent elucidation of the genetic structure of the prevalent RHD deletion in Caucasians, as well as the development of real-time PCR, allowed us to explore two new approaches for the molecular determination of RhD zygosity. METHODS: Two methods for RhD zygosity determination were developed. The first was based on the double Amplification Refractory Mutation System (double ARMS). The second was based on multiplex real-time quantitative PCR. For the double ARMS assay, allele-specific primers were designed to directly amplify the most prevalent RHD deletion found in RhD-negative individuals in the Caucasian population. The multiplex real-time quantitative PCR assay, on the other hand, involved coamplification and quantification of RHD-specific sequences in relation to a reference gene, albumin, in a single PCR reaction. A ratio, DeltaCt, based on the threshold cycle, was then determined and reflects the RHD gene dosage. RESULTS: The allele-specific primers of the double ARMS assay reliably amplified the RHD-deleted allele and therefore accurately distinguished homozygous from heterozygous RhD-positive samples. The results were in complete concordance with serological testing. For the multiplex real-time quantitative PCR assay, the DeltaCt values clearly segregated into two distinct populations according to the RHD gene dosage, with mean values of 1.70 (SD, 0.17) and 2.62 (SD, 0.29) for the homozygous and heterozygous samples, respectively (P: <0.001, t-test). The results were in complete concordance with the results of serological testing as well as with the double ARMS assay. CONCLUSION: Double ARMS and real-time quantitative PCR are alternative robust assays for the determination of RhD zygosity.

Albumins↗
PubMed2004

[Are there olfactory evoked alterations of breathing patterns?].

BACKGROUND: It is controversially discussed whether strictly olfactory stimuli are able to evoke changes of breathing patterns. A number work groups argue that the more or less noticeable irritative component of odors are responsible for a respiratory response. Other work groups regard changes of breathing pattern as an indicator for an intact smell ability during "pure" olfactory stimulation. METHODS: 12 normosmic young volunteers were repeatedly challenged with hydrogensulfide (H (2)S) for two seconds on inspiration in concentrations just above the threshold using a flow olfactometer. Clean air stimuli were presented randomly as control blanks. The breathing patterns were registered with a differential pressure transducer occluding one nostril via a tube. The signals were digitized and recorded on a PC. Nine parameters were calculated for each breath using a custom made LabView (R) software. The breath during stimulation was compared to the average of five breathing cycles prior to stimulation. An increase or reduction of each parameter was equally regarded by means of their absolute value. The sum was termed respiration index (RI). RESULTS: The mean RI (all trials of each test person) stimulated with H (2)S varied from 201 to 570; stimulated with clean air from 85 to 188. The difference was significant (p < 0,001). A significant group-difference for each single trial was seen as well. There was no significant increase or decrease of RI during 15 successive stimulations with H (2)S. CONCLUSIONS: Detectable short H (2)S-stimuli are able to evoke alterations of breathing patterns which can be identified by computer. Respiration-olfactometry is suitable to objectify odor perception.

Adult↗
PubMed2001

Reproducibility of the parameters of the on-transient cardiopulmonary responses during moderate exercise in patients with chronic obstructive pulmonary disease.

To be clinically useful as indices reflective of altered physiological function consequent to interventions in patients with chronic obstructive pulmonary disease (COPD), the time constant (tau) and steady-state amplitude of the kinetic responses for oxygen uptake (VO2) carbon dioxide output (VCO2) ventilation (VE) and heart rate (HR) have to be appropriately differentiable and reproducible. We therefore assessed the reproducibility of tau and steady state amplitude values in 41 patients with severe COPD [mean (SD)] [forced expiratory volume in 1 s = 41 (7)% predicted], aged 64 (5) years. Of the total, 6 of the patients (15%) did not produce breath-by-breath data of sufficient quality to warrant kinetic analysis. The remaining 35 patients completed two moderate-intensity 10 min square-wave exercise tests separated by 2 h, both before and after an endurance training programme. Tests were conducted on an electromagnetically-braked cycle ergometer at an exercise intensity corresponding to 80% of the estimated lactate threshold (thetaLa) or 50% of peak oxygen uptake if thetaLa was insufficiently differentiable. Breath-by-breath measurements of VO2, VCO2, VE and HR were averaged into 10 s bins and the on-transient response kinetics were estimated using a mono-exponential model. Analysing the pre-training and the post-training test 1 and test 2 comparisons together, the test 1- test 2 differences were not significantly different from 0 for either tau or A. The standard deviation of the test 1- test 2 differences allowed us to define the magnitude of change that would reach statistical significance. For tau, this averaged some 8, 10, 11 and 8 s, for VO2, VCO2, VE and HR, respectively, for a one-tailed paired-comparisons test (i.e. appropriate for assessing hypothesised improvements resulting from an intervention); for a two-tailed comparison, the differences were approximately 2 s greater. The corresponding one-tailed values for A were 100 ml x min(-1), 95 ml x min(-1), 2.5 1 x min(-1) and 4 beats x min(-1), respectively; the two-tailed values were 10%-15% greater. We therefore conclude that both tau and A for moderate-intensity exercise can be reproducibly estimated in patients with COPD when the data set provides a sufficiently large amplitude of response and sufficiently low sample variability to allow appropriate parameter estimation.

Aged↗
PubMed1980

The relation of ventilation to metabolic rate during moderate exercise in man.

To characterize more precisely the relationship between ventilation (VE) and CO2 output (VCO2) during incremental exercise, 35 healthy males were studied at rest and during upright cycle ergometry, with the work rate incremented every 4 min up to each subject's anaerobic threshold (Oan). Twenty-one subjects had arterial blood sampled at rest and in the steady state at each work rate to determine the relationship between physiological dead space ventilation (VD) and VCO2. At these work rates arterial PCO2 was regulated at the resting, control value. VE (BTPS) was linearly related to VCO2 from rest Oan with a slope of 24.6. However, the regression had a significant positive intercept of 3.2 L/min-1. This causes the ventilatory equivalent for CO2 (i.e., VE/VCO2) to decrease with increasing work rates. VD also increased linearly with increasing VCO2. However, this was consequent to increased breathing frequency as VD remained constant. Thus, the observed fall in VE/VCO2 with increasing work rates is due to the positive intercept but the inherent relationship between VE and VCO2, reflected by the linear regression slope, remains unchanged from rest through moderate exercise.

Adult↗
PubMed2002

Formation of monolayers and bilayer foam films from lamellar, inverted hexagonal and cubic lipid phases.

This study revealed large distinctions between the lamellar and non-lamellar liquid crystalline lipid phases in their spreading at the air/water interface and propensity to form bilayer foam films. Comparative measurements were made for the lamellar L(alpha), the inverted hexagonal H(II) and the bicontinuous cubic Pn3m phases of the phospholipid dipalmitoleoylphosphatidylethanolamine (DPoPE). With regard to monolayer formation, followed as the decrease of surface tension with time, the best spreading (lowest surface tension) was observed for the L(alpha) phase, and poorest spreading (highest surface tension) was recorded for the H(II) phase. The cubic Pn3m phase of DPoPE, induced by temperature cycling, retained an intermediate position between the L(alpha) and H(II) phases. According to their ability to lower surface tension and disintegrate at the air/water interface, the three phases thus order as L(alpha)>Pn3m>H(II). Clearly expressed threshold (minimum) bulk lipid concentrations, C(t), required for formation of stable foam bilayers from these phases, were determined and their values were found to correlate well with the bulk lipid phase behaviour. The C(t) values for L(alpha) and H(II) substantially increase with the temperature. Their Arrhenius plots, ln C(t) versus 1/ T, are linear and intersect at approximately 36-37 degrees C, coinciding with the onset of the bulk L(alpha)-->H(II) phase transition, as determined by differential scanning calorimetry. However, the C(t) value for the Pn3m phase, equal to 30 micro g/mL, was found to be constant over the whole range investigated between 20 degrees C and 50 degrees C. The horizontal C(t) versus T plot for the Pn3m phase crosses the respective plot for the L(alpha) phase at the temperature bounding from below the hysteretic loop of the L(alpha)<-->H(II) transition (approximately 26 degrees C), thus providing a certain insight about the thermodynamic stability of the Pn3m phase relative to the L(alpha) phase. The established strong effect of the particular lipid phase on the formation of monolayers and stable black foam films should be of importance in various in vitro and in vivo systems, where lipid structures are in contact with interfaces and disintegrate there to different extents.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

Commitment to division in Paramecium: effect of nutrient level on the macronuclear DNA increment.

In Paramecium, a fixed macronuclear DNA increment is associated with commitment to cell division. This study shows that this threshold DNA increment is about 70% of the final DNA increment in well-fed cells. The DNA increment is reduced when growth rate is decreased and decreases in parallel with growth rate to a minimum of 30% of the normal DNA increment. This minimum value is obtained when the growth rate is 20% of its normal level or lower. Further reduction in the growth rate produces no further reduction in the DNA increment. Following abrupt nutrient-level shifts, both the threshold DNA increment and the final DNA increment change progressively as the time of the shift is moved to later stages of the cell cycle. The threshold DNA increment is reset following nutrient-level shifts up to the point of commitment to division. These observations are consistent with the notion that the magnitude of the threshold DNA increment is strongly correlated with the rate of growth and is rapidly reset by factors which alter the growth rate. The implications of these observations for growth-driven regulation of the cell cycle are discussed.

Animals↗
PubMed2001

Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity.

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APB muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested.

Adult↗
PubMed1999

High-throughput real-time reverse transcription-PCR quantitation of hepatitis C virus RNA.

We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in serum samples. The method combines Taqman technology (Roche) and the ABI Prism 7700 (Perkin Elmer) real-time sequence detection system. We have optimized a single-tube reverse transcription-PCR (RT-PCR) that contains a dual-labeled fluorogenic probe to quantify the 5' noncoding region (5' NCR) of HCV. The probe contains a fluorescent reporter at the 5' end and a fluorescent quencher at the 3' end. The use of such a probe combined with the 5'-3' nuclease activity of Taq polymerase allows direct quantitation of the PCR product by the detection of a fluorescent reporter released in the course of the exponential phase of the PCR. For accurate quantitation of the number of copies of HCV in samples containing unknown quantities, we have used serial dilutions of a synthetic 5' NCR RNA standard of HCV that was previously quantified with an isotopic tracer. The method has a 5-log dynamic range (10(3) to 10(7)). The coefficient of regression of the standard curve was, on average, 0.98. The intra-assay and the interassay coefficients of variation of the threshold cycle were 1% and 6.2%, respectively. Seventy-nine RNA samples from the sera of infected patients were quantified by this method. Comparison of the results with those obtained by other quantitation methods (the Quantiplex 2.0 branched-DNA assay and the Superquant assay from the National Genetics Institute) revealed a significant correlation with all of the results. The mean values were also statistically comparable. In conclusion, the high sensitivity, simplicity, and reproducibility of the real-time HCV RNA quantitation which allows the screening of large numbers of samples, combined with its wide dynamic range, make this method especially suitable for monitoring of the viral load during therapy and tailoring of treatment schedules.

Adult↗
PubMed1987

Levels of short (1-15 ms) electrical shocks from a 50 Hz supply inducing ventricular fibrillation in hyperbaric helium and oxygen.

An investigation was undertaken to determine the ventricular fibrillation (VF) threshold of anaesthetised dogs subjected to external application of electric shocks between a foreleg and a hindleg. The shocks were 2-15 ms sections of 50 Hz sine waveform starting at peak current and were applied at a known time in the heart cycle. The object of the experiment was to determine if there was an increase in cardiac susceptibility to electrically induced VF at 31 atmospheres absolute (atm abs) in a helium and oxygen environment. The duration and position of that part of the cardiac cycle most vulnerable to induction of VF by electrocution was found (seven animals) using 4 ms shocks and then the minimum fibrillating current for shocks of 2-15 ms (min FC2-15) delivered at the most vulnerable point of the cycle (five animals). Body resistance was calculated from the data so gathered. Fibrillation thresholds were not changed by compression and there were no significant changes in the vulnerable period of the cardiac cycle. Min FC2 was significantly higher than for other durations under both control (3.21 A, SD 1.08) and test conditions (3.26 A, SD 0.39), p = 0.001. There was no difference in body resistance at 31 atm abs (395.5, SD 12.9) from control values at 1 atm abs (396.7, SD 10.9). From these data it was concluded that the heart is no more susceptible to the induction of VF at 31 atm abs in a helium oxygen environment and additional safety factors are unnecessary from this point of view.

Animals↗
PubMed2006

Physicochemical analysis of acid-base responses to prolonged moderate exercise in late gestation.

Stewart's physicochemical approach was employed to investigate the safety of an average recreational and occupational activity (prolonged moderate exercise) on maternal acid-base homeostasis. The responses of 10 healthy, physically active pregnant women (PG, gestational age 34-38 weeks) were compared with those of 10 non-pregnant female controls (CG). Subjects cycled for 40 min at 85% of their measured ventilatory threshold (VT). During the transition from rest to exercise, hydrogen ion concentration ([H+]) increased significantly and bicarbonate concentration ([HCO3-]) decreased significantly in both groups. Total weak acid ([Atot]) increased significantly with exercise in both groups, whereas the strong ion difference ([SID]) and CO2 tension (PaCO2) did not change significantly with exercise. Values for [H+], [HCO3-], PaCO2, [Atot] and [SID] were significantly lower in the PG vs. CG under all experimental conditions. Acid-base responses to prolonged moderate exercise are quantitatively similar in the pregnant vs. non-pregnant state. However, pregnant women maintain a lower plasma [H+] (approximately 3 neq/L (1 neq/L=1 nmol/L)) throughout rest, exercise, and recovery, as a result of lower values for PaCO2 and [Atot], which is partly offset by a lower [SID]. The results indicate that prolonged moderate exercise appears to be well tolerated by healthy recreationally and occupationally active pregnant women.

Acid-Base Equilibrium↗
PubMed1992

Chronopharmacological study of valproic acid in mice: comparison of oral and rectal administration.

This study was performed to investigate the influence of the dosing route on chronopharmacological aspect of valproic acid (VPA) in mice, comparing the oral and rectal route. ICR male mice, housed under a standardized light-dark cycle (lights on from 0700 to 1900), were orally or rectally administered 400 mg/kg VPA each at the following scheduled time: 0900, 1300, 1700, 2100, 0100 and 0500. VPA concentrations in plasma and brain were determined by gas-liquid chromatography. There was a circadian rhythm in the electroshock seizure (ES) threshold 30 min after oral VPA administration, with the highest value at the midlight (1300) and the lowest at the middark (0100) (p < 0.01). A significant circadian rhythm was also found in plasma and brain VPA concentrations 30 min after oral administration (p < 0.01). This finding is related to the rhythm in the ES threshold. In contrast to oral administration, no circadian rhythm in the ES threshold, plasma and brain VPA concentrations was observed after rectal administration. These values after rectal dosing showed higher levels in comparison to those after oral dosing. Thus, the rectal route for VPA might have merit to eliminate the time-dependent changes in VPA pharmacologic action and kinetics. The timing of drug administration is an important factor that must be carefully controlled in drug pharmacokinetic and pharmacodynamic studies and must be considered in planning dosing routes.

Administration, Oral↗
PubMed1984

Sensibility testing in patients with carpal tunnel syndrome.

We evaluated the sensibility of the hand preoperatively and at intervals postoperatively in twenty-three hands of twenty patients with idiopathic carpal-tunnel syndrome who underwent carpal tunnel release. Tests of sensibility included the threshold tests (vibrometry, 256-cycles-per-second vibration, and Semmes-Weinstein monofilaments) and one innervation-density test (two-point discrimination). In addition the wrist-flexion test, nerve-percussion test, and tourniquet test were performed preoperatively. Only five of the twenty-three hands had abnormal two-point discrimination and each of these also had markedly abnormal threshold-test values. Nineteen of twenty-three hands preoperatively had decreased sensibility detected by both Semmes-Weinstein monofilament testing and vibrometry. Six weeks after carpal tunnel release, all of the hands demonstrated improvement on threshold testing, and 65 per cent had normal values.

Adult↗