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PubMed1985

Ibuprofen stereoisomer hepatic clearance and distribution in normal and fatty in situ perfused rat liver.

Ibuprofen is a 2-arylpropionic acid anti-inflammatory agent that undergoes stereoselective chiral inversion (R to S configuration) as well as oxidative metabolism in humans and rats. The present study was undertaken to define more clearly the role of the liver in ibuprofen stereoisomer clearance in both normal and disease states. Liver perfusion experiments were conducted with normal and fatty rat liver; chronic fatty liver was induced by nutritional deficiency and was used as a model of hepatotoxin-induced fatty liver in humans. Total (R)-ibuprofen clearance (ClRtot), chiral inversion-related clearance (ClRinv), (S)-ibuprofen clearance (ClS) and hepatic distribution coefficients for each stereoisomer (KR and KS) were calculated with a model that corrected for perfusate reservoir sampling. In both normal and fatty liver, ClRinv accounted for 60% of ClRtot, but ClRtot was 30% lower in fatty liver than in normal liver (P less than .001). ClS was 40% of ClRtot in normal liver and was not significantly different from the noninversion clearance of (R)-ibuprofen. ClS was unchanged between normal and fatty liver and KS was greater than KR in normal liver (P = .01) but not in fatty liver. The results indicate that the fatty liver condition stereoselectively affects (R)-ibuprofen clearance and eliminates preferential (S)-isomer hepatic distribution. Based on model simulations, these effects are predicted to have minimal impact on total ibuprofen plasma levels or area-under-curve measurements following a dose of rac-ibuprofen unless ClRtot is reduced by more than 50%.

Animals↗

PubMed1994

Trace element reference values in tissues from inhabitants of the European Union. VIII. Thallium in the Italian population.

In order to establish reference values of thallium in tissues of the general population the element was determined in blood (TlB) and urine (TlU) of 123 healthy inhabitants living in the Marche region, Central Italy. The analysis was carried out by inductively coupled plasma-mass spectrometry (ICP-MS; detection limit in our experimental conditions, 0.001 micrograms Tl/I), which was validated by neutron activation analysis (NAA) and laser induced fluorecence (LIF) spectroscopy. The check of pre-analytical factors indicated a low risk of contamination and loss of Tl during sampling, handling and storage before the instrumental analysis (blank of the entire procedure less than the detection limit). Mean values of TlU and TlB were 0.066 micrograms Tl/l and 0.063 micrograms Tl/l, respectively (median in both cases 0.057 microgram Tl/l). No conclusive evidence concerning the distribution followed by our data set, normal or log-normal, were drawn, although Lilliefors test and Kolmogorov's D-test showed a tendency for TlB to follow both the normal and the log-normal while TlU followed a log-normal distribution. Overall correlations between TlU and TlB are rather weak. A significant, but not high, correlation (P < 0.0004, r = 0.44) was observed in females. Age, sex, smoking habits and alcohol consumption did not seem to play any role on TlU and TlB. Tentatively proposed reference intervals are 0.019-0.17 microgram Tl/l (urine) and 0.014-0.19 microgram Tl/l (blood).

Adult↗

PubMed2001

A mixture model for occupational exposure mean testing with a limit of detection.

Information from detectable exposure measurements randomly sampled from a left-truncated log-normal distribution may be used to evaluate the distribution of nondetectable values that fall below an analytic limit of detection. If the proportion of nondetects is larger than expected under log normality, alternative models to account for these unobserved data should be considered. We discuss one such model that incorporates a mixture of true zero exposures and a log-normal distribution with possible left censoring, previously considered in a different context by Moulton and Halsey (1995, Biometrics 51, 1570-1578). A particular relationship is demonstrated between maximum likelihood parameter estimates based on this mixture model and those assuming either left-truncated or left-censored data. These results emphasize the need for caution when choosing a model to fit data involving nondetectable values. A one-sided likelihood ratio test for comparing mean exposure under the mixture model to an occupational exposure limit is then developed and evaluated via simulations. An example demonstrates the potential impact of specifying an incorrect model for the nondetectable values.

Algorithms↗

PubMed1998

Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies.

We do not have an estimate of how much tissue is needed for a reliable measure of bronchial epithelial reticular basement membrane (RBM) thickness or for counts of inflammatory cells. An assessment of the frequency distribution and variance of data from repeat measurements of RBM thickness and biopsy section inflammatory cell counts in cases with asthma (n=6), chronic obstructive pulmonary disease (COPD; n=5), and normal healthy subjects (n=7) was made. Tissue sections were stained with haematoxylin and eosin or by immunohistochemistry for EG2, mast cell tryptase and CD3-positive cells. Measurements of RBM thickness in individuals followed a log-normal distribution. For a precision of approximately +/-15%, 31-45 measurements were required. In contrast, inflammatory cell counts for each individual did not follow a normal distribution. There was high variance such that the cumulative weighted mean did not become stable until at least 5-10 mm of tissue underlying the RBM had been included. In conclusion multiple measurements of reticular basement membrane thickness or tissue section cell counts should be made for each individual in studies of bronchial biopsies. It is recommended that reticular basement membrane thickness should be measured at 20 mm intervals over a 1 mm reticular basement membrane length and that a zone beneath it of at least 5-10 mm of reticular basement membrane should be included for counts of inflammatory cells.

Adult↗

PubMed1976

The computer analysis of volume distribution curves. Demonstration of two erythrocyte populations of different size in the young guinea pig and analysis of the mechanism of immune lysis of cells by antibody and complement.

Guinea pig, rat and sheep erythrocytes were sized electrically using the hydrodynamic focusing technique. The experimental curves were approximated with a computer by linear and logarithmic normal distributions. Rat and guinea pig erythrocytes from adult animals were best approximated by one linear normal distribution. Two populations (I, II) of erythrocytes with different mean volume could be demonstrated in young guinea pigs by this analysis. Population I erythrocytes are small, have a lower electrophoretic mobility and are mainly present at birth. They are gradually replaced by the larger population II erythrocytes. Both types of erythrocytes are probably the result of separate differentiation pathways. The analysis of erythrocyte volume distribution curves during immune lysis by antibody and complement shows that intact and ghost erythrocytes are measured by electrical sizing. No volume changes were observed up to the EAC1-8 intermediate. After the addition of C9, a C9 dose-dependent part of the erythrocytes swell permanently to spheroids. The spheroid transformation is a temperature-dependent, all or nothing reaction which is independent of protein osmotic forces from the interior of the cell.

Animals↗

PubMed1994

Electric field distribution within normal cat spinal cord.

Electric currents of small magnitude have been used successfully to induce regrowth of injured spinal cord fibers. The purpose of this study was to determine the potentials and current density distributions on the surface, as well as within the spinal cord, after the application of exogenous electric fields. A 10 microA DC current was applied epidurally to the spinal cord using two different electrode configurations. The two electrode configurations studied were: anode and cathode dorsal (D-D) and anode ventral and cathode dorsal (V-D). Two types of recording electrodes were used to map the potentials on the surface and within the spinal cord. The recording system consisted of glass microelectrodes connected to differential amplifiers. The output was recorded on a polygraph. The current density was more localized on the dorsal surface of the spinal cord for the D-D configuration. In contrast, in the V-D configuration, the current density was greater near the anode on the ventral surface and near the cathode on the dorsal surface of the spinal cord. As a result of the anode being located ventrally, there was a more uniform current density distribution within the spinal cord.

Animals↗

PubMed1982

The growth rate of bone sarcomas and survival after radiotherapy with tourniquet-induced hypoxia: a clinical study.

The volume doubling time of primary bone sarcomas and lung metastases was determined by measurements made on serial radiographs. For the primary tumors, the volume doubling times were log-normally distributed and varied in the range of 20--200 days with a mean around 50 days. The volume doubling times of the metastases also showed a log-normal distribution in the range of 10--100 days, but with a mean twice as short as that of the primates. Radiation therapy was given with three--four doses of 20--25 Gy to the tumors that, together with the surrounding normal tissues, had been made hypoxic by the application of a tourniquet. Amputations were not performed unless required eventually by some serious late radiation damage, such as grave functional deficiency, and/or painful fibrosis and ankyloses. In no case did microscopic examination of the amputated tissues reveal the persistence of any viable, neoplastic cells. The five-year survival of a total of 69 patients was 26%. Survival expectancy was found to be closely related to the volume doubling time of the tumors, as was the incidence of the metastases. The data stress the importance of volume doubling time as a predictive factor and indicate, furthermore, that treatment with a few massive radiation doses in combination with tourniquet-induced hypoxia is effective in the local control of bone sarcomas. The several late reaction of the normal tissues to the treatment will, however, require amputations in most of the five-year survivors.

Adolescent↗

PubMed1987

Evaluation and comparison of the distributions of gastric pH and hydrogen ion concentration.

The shapes of the distributions of gastric pH and hydrogen ion concentration [H+] were determined for each of 68 groups of patients scheduled for elective surgery under general anesthesia. The 68 groups comprised a total of 1,326 patients who had served as subjects in 13 of the authors' previously published studies. In general, the results showed that neither pH nor H+ was normally distributed; most of the pH distributions (47 of 68 = 69%) and most of the H+ distributions (53 of 68 = 78%) showed significant departure from the normal distribution. Moreover, the shapes of the distributions varied, depending upon the conditions under which gastric acidity was assessed. Groups receiving no medication for gastric acidity had positively skewed pH distributions (nonsymmetrical distribution with tail pointing to right and majority of cases in lower range), and groups receiving medications for the reduction of acidity had negatively skewed pH distributions (nonsymmetrical with tail pointing to left and majority of cases in upper range). The medications produced an inverse relationship between mean pH and skewness such that the skewness of the groups decreased from positive to negative as mean pH increased. For H+, all groups had positively skewed distributions, but the distributions were more positively skewed for groups receiving medications for gastric acidity. Again, the medication conditions produced an inverse relationship between mean acidity and skewness such that the groups became more positively skewed as the mean H+ decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric Acidity Determination↗

PubMed2003

Micro-lightguide spectrophotometry as an intraoral monitoring method in free vascular soft tissue flaps.

PURPOSE: The aim of this prospective study was to measure the hemoglobin oxygen saturation (HbO(2)%) and relative Hb concentration of free vascular soft tissue flaps using micro-lightguide spectrophotometry. The objective was to measure the normal range and topographic differences in HbO(2)% and rel. Hb conc. in tissue transfers before establishing this as a clinical method for monitoring perfusion and vitality. PATIENTS AND METHODS: In 39 patients who had received free vascular soft tissue flaps (34 radial forearm flaps; 8 latissimus flaps) to cover defects after tumor surgery, the capillary HbO(2)% in transferred tissue was measured spectrophotometrically preoperatively at the donor site and postoperatively up to the third postoperative day. On average about 500 hemoglobin spectra (200 to 800 spectra) were measured over each 24-hour period. Additionally, the relative Hb concentration was determined for the individual measuring times. The measurements were carried out topographically on the flap base, flap center, and flap periphery. RESULTS: The preoperative HbO(2) values at the donor site of free soft tissue flaps were between 20% and 40% in all topographic regions. In the case of clinically successful flaps, a normal distribution of the HbO(2) values of 20% to 80% was obtained in the immediate postoperative period, and from the second day on, a normal distribution of 45% to 60%. In the case of 2 flaps with partial necrosis, HbO(2) values of less than 10% to 15% were measured from the second postoperative day on. The relative Hb concentration had no influence on the amount of HbO(2)% measured in the transferred capillaries. In the postoperative phase, here was no topographic difference between the individual flap regions. CONCLUSIONS: As a noninvasive method, micro-lightguide spectrophotometry permits quantitative determination of HbO(2)% and relative Hb concentration over the entire surface of soft tissue flaps. In the case of partially unsuccessful flaps, HbO(2) values of less than 10% to 15% were measured beforehand, thus indicating that these HbO(2) values are not sufficient to support the vitality of the free tissue transfer. When combined with clinical observation, application can be recommended for the vitality measurement of free soft tissue flaps and permits more information to be obtained on topographic capillary perfusion conditions.

Adolescent↗

PubMedDate not supplied

Statistical analysis of cost outcomes in a randomized controlled clinical trial.

This paper suggests an approach to deal with an estimation problem which is often encountered in analyzing the longitudinal cost data gathered in a clinical trial. The source of that estimation problem is twofold: 1) a considerable number of missing data due to treatment-related withdrawal of severely affected patients with high health care costs in only one the treatment groups and 2) a heavily skewed cost distribution due to rare high-cost events. The approach is illustrated using data from a trial comparing 3 different drug regimes. In order to calculate costs per patient-year in case of selectively missing data we extrapolated the costs of patients with incomplete follow-up. Due to the skewness and the associated large variance in costs per patient-year, these costs cannot be analyzed using common parametric statistical methods relying on underlying normal distributions. A logarithmic transformation was performed to approximate a normal distribution, reduce the impact of extreme values and create similar size variances in the treatment groups. An ordinary least squares regression analysis of transformed data then standardized for differences in patient characteristics between the groups. For the retransformation, the so-called smearing estimate was used. This 'transformation-standardization-retransformation' approach enabled us to provide more consistent and efficient estimates of cost differences that were shown to be statistically significant and judged to be important.

Adolescent↗

PubMed1979

Distribution functions of variables characterizing the mycelial morphology of Streptomyces hygroscopicus grown in glucose-limited chemostat cultures.

The distribution of variables characterizing the morphology of the mycelium of Streptomyces hygroscopicus grown in glucose-limited chemostat cultures at different specific growth rates were investigated statistically. The values of the hyphal growth unit (L/N) and the values of the distance from the apex to the first branch (Lp) are normally distributed, but the values of the distance between neighbouring branches are logarithmically normal distributed. The distribution functions are discussed from the biological point of view.

Glucose↗

PubMed2004

Variability in pain intensity, physical and psychological function in non-acute, non-traumatic neck pain.

BACKGROUND AND PURPOSE: Variability in clinical presentation among patients with neck pain disorders, in relation to symptom severity and the effect of the disorder on their physical and psychological function, has not been well documented. The present study examined the variability in pain intensity, physical and emotional or cognitive function in patients with non-acute, non-traumatic neck pain, and the extent to which these factors are associated at the time of referral for physiotherapy treatment. METHOD: The study utilized a survey of patients referred for physiotherapy treatment for non-acute, non-traumatic neck pain. Seventy-two patients (mean age 58 years; SD 15.5 years) with a symptom duration ranging from four weeks to 30 years were recruited. Each completed measures of pain intensity using a visual analogue scale, and neck-pain related disability by use of the 'Neck Pain and Disability' scale (NPAD). Frequency distributions were calculated to examine variability in pain intensity, the total NPAD score and the effect of the disorder on different aspects of physical and emotional or cognitive function. Relationships between pain intensity, and physical and psychological function, were also examined. RESULTS: Pain intensity was normally distributed with a mean score of 6.3 cm (SD 2.5 cm). NPAD scores were normally distributed (mean 54.8%; SD 18%). Similar variability was noted in each of the NPAD factor scores for neck function, pain intensity, emotional or cognitive function and activities of daily living. Pain intensity was significantly (p < 0.01) correlated with the total NPAD score (r = 0.55) and with each of the four effects of neck pain represented in the NPAD sub-domains (r = 0.42-0.63). Symptom duration was not significantly correlated with pain intensity, or with the severity of disability, as reflected in the total NPAD score. CONCLUSIONS: The results highlight the variability between patients with neck pain, in relation to pain intensity and the effect of the disorder on physical and psychological function. Identifying the specific effects of the neck pain disorder in individual cases is important when defining the treatment objectives and selecting measures of treatment response.

Adult↗

PubMed1995

The all ulnar motor hand without forearm anastomosis.

Anomalous ulnar innervation of intrinsic hand muscles, inferred in a number of clinical series, has been documented only rarely in electrophysiological studies. Using near-nerve and standard conduction studies we evaluated 2 cases with nearly exclusive ulnar innervation of hand muscles. There was no evidence of anomalous communication in the forearm. Digital sensory fibers were normally distributed in median and ulnar nerves. The anomalous motor innervation most likely results from palmar communication between ulnar and median branches (Riche-Cannieu anastomoses). The normal distribution of digital afferents suggests that such anastomoses are formed primarily by motor axons.

Action Potentials↗

PubMed1985

Reference values for automated cytochemical differential count of leukocytes in children 0-16 years old: comparison with manually obtained counts from Wright-stained smears.

Reference values for the differential leukocyte count using an automated cytochemical method (Hemalog D) were determined in 1216 healthy children aged 0-16 years. Log-normal distributions for the absolute counts of all the separate cell types and for the total leukocyte counts were determined. For the relative values, a log-normal distribution for the eosinophils and basophils was also established. The Hemalog D gives narrower limits compared with the manual count, but the differences between the two methods are smaller than expected. It appears that the lower limit of the separate cell types is not zero.

Adolescent↗

PubMed2006

Hematology, plasma biochemistry, and antibodies to select viruses in wild-caught Eastern massasauga rattlesnakes (Sistrurus catenatus catenatus) from Illinois.

During the 2004 field season, blood was collected from Eastern massasauga rattlesnakes (Sistrurus catenatus catenatus) in the Carlyle Lake (Carlyle, Illinois, USA) and Allerton Park (Monticello, Illinois, USA) populations to derive baseline complete blood count and plasma biochemistry data and to assess the prevalence of antibodies to West Nile virus (WNV) and ophidian paramyxovirus (OPMV). Massasaugas were located for sampling through visual encounter surveys. Body weight, snout-vent length, total protein, globulins, sodium, and potassium were normally distributed among the survey population. Aspartate aminotransferase, creatine kinase, albumin, calcium, uric acid, white blood cell count, heterophils, lymphocytes, monocytes, eosinophils, and basophils were non-normally distributed within these animals. Female snakes had significantly shorter tail lengths; lower blood glucose, packed cell volumes, and absolute azurophil counts; and higher plasma calcium and phosphorus concentrations than did males. None of the snakes tested (n=21) were seropositive for WNV, whereas all (n=20) were seropositive for OPMV.

Animals↗

PubMed2001

Quantification and variability analysis of bacterial cross-contamination rates in common food service tasks.

This study investigated bacterial transfer rates between hands and other common surfaces involved in food preparation in the kitchen. Nalidixic acid-resistant Enterobacter aerogenes B199A was used as a surrogate microorganism to follow the cross-contamination events. Samples from at least 30 different participants were collected to determine the statistical distribution of each cross-contamination rate and to quantify the natural variability associated with that rate. The transfer rates among hands, foods, and kitchen surfaces were highly variable, being as low as 0.0005% and as high as 100%. A normal distribution was used to describe the variability in the logarithm of the transfer rates. The mean +/- SD of the normal distributions were, in log percent transfer rate, chicken to hand (0.94 +/- 0.68), cutting board to lettuce (0.90 +/- 0.59), spigot to hand (0.36 +/- 0.90), hand to lettuce (-0.12 +/- 1.07), prewashed hand to postwashed hand (i.e., hand washing efficiency) (-0.20 +/- 1.42), and hand to spigot (-0.80 +/- 1.09). Quantifying the cross-contamination risk associated with various steps in the food preparation process can provide a scientific basis for risk management efforts in both home and food service kitchens.

Animals↗

PubMed1994

The significance of vesicoureteric reflux on kidney development assessed by dimercaptosuccinate renal scintigraphy.

OBJECTIVE: To study the influence of vesicoureteric reflux on kidney parenchyma and renal length, and identify typical distribution patterns by dimercaptosuccinate (DMSA) renal scintigraphy. PATIENTS AND METHODS: DMSA renal scintigraphies in 101 children (152 renal units) with vesicoureteric reflux grade 1-5 were reviewed. RESULTS: Three main types of pathological DMSA patterns were found: (i) dysplasia; (ii) medial defect; and (iii) pole defects. In children with no history of pyelonephritis a normal distribution pattern was found in 31%, dysplasia in 23%, medial defect in 25%, pole defects in 17% and no typical pattern in 4%. In those with a history of pyelonephritis a normal distribution pattern was found in 28%, dysplasia in 24%, medial defect in 21%, pole defects in 24% and no typical pattern in 3%. A normal pattern was significantly more frequent in kidneys with reflux grade 1-2. Dysplasia was significantly more frequent in kidneys with reflux grade 4-5. In children with no history of pyelonephritis 42% of the renal units had reduced length, 8% with no other sign of pathology. The frequency of reduced kidney length at reflux grade 1-2 did not differ significantly from that at higher grades of reflux. In children with a history of pyelonephritis 52% of the renal units had reduced length, 13% with no other sign of pathology. The frequency of reduced kidney length with a normal DMSA pattern did not differ significantly from that with a pathological pattern. CONCLUSION: The pathological DMSA distribution with vesicoureteric reflux generally conforms to one of three main patterns. Reduced kidney length is frequent even at lower grades of vesicoureteric reflux even in patients with no history of pyelonephritis, and can be the only sign of pathology.

Adolescent↗

PubMed1985

Immunolocalization of prealbumin: distribution in normal human tissue.

Using an indirect immunoperoxidase staining technique we have demonstrated the plasma protein, prealbumin, in the cells of the pancreatic islets of Langerhans. Serial sections stained with antisera to glucagon, insulin and somatostatin revealed that the distribution of the prealbumin stained cells matched that of the glucagon A-cells. Absorption and cross-absorption experiments with prealbumin and glucagon showed that the staining was specific. We also found positive staining for prealbumin in single cells in the mucosa of the gastrointestinal tract, mainly stomach and colon, and kidney tubules.

Glucagon↗