Cross sections of the 36Ar(d,α)34mCl, 40Ar(d,α)38Cl, and 40Ar(d,p)41Ar nuclear reactions below 8.4 MeV.

We have measured the cross section for production of the medically interesting isotope (34m)Cl, along with (38)Cl and (41)Ar, using deuteron bombardments of (36)Ar and (40)Ar below 8.4 MeV. ALICE/ASH analytical codes were employed to determine the shape of nuclear excitation functions, and experiments were performed using the University of Wisconsin tandem electrostatic accelerator to irradiate thin targets of argon gas.

A superconducting beta spectrometer.

We have designed and constructed a superconducting beta spectrometer with a momentum resolution of about 2% and a peak solid angle of 0.5 sr. The performance of the spectrometer is described and the results of calibrations with line sources are presented.

Improved understanding of the effect of food on drug absorption and bioavailability for lipophilic compounds using an intestinal pig perfusion model.

The purpose of this study was to investigate the relative importance of mechanisms behind the effect of food on the intestinal absorption and bioavailability for low solubility compounds by applying a porcine single-pass perfusion model. Nanoparticle suspensions of the model compounds, danazol and cyclosporine were perfused through the jejunum in isotonic fluid alone (control) and isotonic fluid with a P-glycoprotein (P-gp) inhibitor (verapamil) or dietary and endogenous lipids added. The drugs were also administered as saturated solutions in the isotonic fluid containing lipids. Administration of cyclosporine together with verapamil increased the absorption compared to the control (1.6 times) suggesting an effect on jejunal permeability. However, addition of dietary lipids to the media led to a 50% reduction in the absorption of cyclosporine indicating lack of major effects by P-gp inhibition by lipids in vivo. The absorption of danazol was increased (2.6 times) when administered as a nanosuspension in lipid containing media compared to the control, but decreased (60%) when administered as a solution in the same media. This shows how important dissolution of the drug nanoparticles is in drug absorption. The difference in the effect of lipids in the absorption of cyclosporine and danazol when administered as nanosuspensions may be due to different distribution to the colloidal structures present in the media, thereby rendering the drugs' different diffusion rates in the perfused segment. In conclusion, solubilisation seems to be a more important factor than P-gp inhibition as an explanation for the food-drug interaction observed for several low solubility drugs. In addition, the partition into different colloidal structures seems to play a major role in the dissolution and absorption of poorly soluble drugs.

Rapid modulation of Ca2+ uptake in human jejunal enterocytes.

The active metabolite of D vitamin, 1,25(OH)2D3, has been suggested to promote acute uptake of calcium through the intestinal lining in cell lines and murine models. In this study, the effects of D vitamin on the cytoplasmic Ca2+ of single human jejunal enterocytes, obtained with LOC-I-GUT technique, was analyzed in vivo in a fluorometric system using fura-2 as the Ca2+-sensing probe. Vitamin-promoted acute Ca2+ influx exhibited dual kinetics, indicating initial release from intracellular Ca2+ pools and fast entry from the extracellular space. Furthermore, providing a chemical clamp of membrane potential close to 0 mV did not activate voltage-sensitive calcium channels in the cellular membrane, neither was the hormone-induced Ca2+ influx affected by verapamil. This advocates that voltage-operated channels like L-type Ca2+ channels do not participate in the process of Ca2+ uptake. In fact, the existence of calcium-release-activated-calcium channels (I(CRAC)) was implied by the findings that irreversible depletion of intracellular Ca2+ stores by thapsigargin promoted Ca2+ entry. In the thapsigargin-treated enterocytes, D vitamin lost its ability to promote calcium entry indicating an important role for intracellular store-operated Ca2+ stores in the acute effects of 1,25(OH)2D3.

Revalidation of the isobaric multiplet mass equation.

We have determined the energy of the J(pi) = 1/2(+), T = 3/2 resonance in 32S(p,p) to be E(p) = 3374.7+/-0.8 keV. This disagrees with the previously accepted value of E(p) = 3370+/-1 keV by Abbondanno et al. [Nuovo Cimento 70A, 391 (1970)] and solves a problem raised by recent observations of unexpected deviations from the isobaric multiplet mass equation. This resonance is also important in calibrating the beta-delayed proton spectra from 33Ar and 32Ar, and our findings may modify previous conclusions.

Upper body movement during walking in children with lumbo-sacral myelomeningocele.

Eight children with lumbo-sacral myelomeningocele (MMC) underwent three-dimensional movement analysis to determine whether or not differing levels of lower extremity strength affected the extent of shoulder, trunk and pelvis movement during independent walking when wearing orthoses. Fourteen control children were also investigated. The patterns of upper body movements in all MMC children were well defined and consistent, showing small standard deviations from the mean. In the frontal and transverse planes, segment displacements of the MMC children assigned into Group II (hip extensor and abductor muscle strength grade 0-2) were almost twice that of the MMC children in Group I (hip extensor and abductor muscle strength grade 3-4). All segment displacements in the frontal, transverse and sagittal planes for Group I and Group II children were significantly greater than those for the controls. In the frontal plane these differences were approximately 4-10 times greater, with the Group II children having the largest peak-to-peak displacements. These results indicate that the motion amplitudes of the upper body segments are related to the degree of muscle weakness of the lower limbs. No significant differences were found when comparing segment motions during walking with either the Ferrari type knee-ankle-foot or ankle-foot orthoses.

The effect of amiloride on the in vivo effective permeability of amoxicillin in human jejunum: experience from a regional perfusion technique.

The purpose of this human intestinal perfusion study (in vivo) was twofold. Firstly, we aimed to determine the effective in vivo jejunal permeability (P(eff)) of amoxicillin and to classify it according to the Biopharmaceutics Classification System (BCS). Secondly, we investigated the acute effect of amiloride on the jejunal P(eff) of amoxicillin. Amoxicillin, a beta-lactam antibiotic, has been reported to be absorbed across the intestinal mucosa by both passive diffusion and active transport. A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut perfusion tube in 14 healthy volunteers. Each perfusion lasted for 200 min and was divided into two periods of 100 min each. The concentration of amoxicillin entering the jejunal segment was 300 mg/l in both periods, and amiloride, an inhibitor of the Na+/H+ exchanger, was added at 25 mg/l in period 2. The concentrations of amoxicillin and amiloride in the outlet jejunal perfusate were measured with two different HPLC-methods. Antipyrine and [14C]PEG 4000 were added as internal standards to the perfusion solution. Amiloride had no significant effect on the jejunal P(eff) of amoxicillin. The human in vivo jejunal P(eff) for amoxicillin was 0.34+/-0.11 x 10(-4) and 0.46+/-0.12 x 10(-4) cm/s in periods 1 and 2, respectively. The high jejunal P(eff) for amiloride was 1.63+/-0.51 x 10(-4) cm/s which predicts an intestinal absorption of more than 90%. Following the BCS amoxicillin was classified as a low P(eff) drug, and amiloride had no acute effect on the in vivo jejunal P(eff) of amoxicillin.

The A(y) problem for p-3He elastic scattering.

We present evidence that numerically accurate quantum calculations employing modern internucleon forces do not reproduce the proton analyzing power, A(y), for p- 3He elastic scattering at low energies. These calculations underpredict new measured analyzing powers by approximately 30% at E(c.m.) = 1.20 MeV and by 40% at E(c.m.) = 1.69 MeV, an effect analogous to a well-known problem in p-d and n-d scattering. The calculations are performed using the complex Kohn variational principle and the (correlated) hyperspherical harmonics technique with full treatment of the Coulomb force. The inclusion of the three-nucleon interaction does not improve the agreement with the experimental data.

Lower extremity isometric joint torque in children with juvenile chronic arthritis.

OBJECTIVE: To determine the intratester reliability of joint torque testing with a hand-held dynamometer (HHD) during contractions of four major lower extremity muscles in children with juvenile chronic arthritis (JCA) and to compare results for children with JCA to results for children without disability. METHODS: Eleven children with JCA and 14 children with normal musculoskeletal function were tested with a HHD using isometric muscle contractions of the right quadriceps, hamstrings, tibialis anterior and triceps surae. RESULTS: Intratester reliability values exceeded the 0.92 level, regardless of the number of trials, for all motions tested. Statistically lower joint torque values were found in a subgroup of children with JCA for contractions of the tibialis anterior (p=0.003) and triceps surae (p=0.05) muscles. CONCLUSIONS: HHD offers a reliable means of testing the joint torque generated with contraction of these lower extremity muscles in children with JCA. Findings in children with JCA compared to children without disability agree with previous reports concerning quadriceps muscle function, but also point to concerns for muscles associated with generating ankle joint torque.

Direct estimation of the in vivo dissolution of spironolactone, in two particle size ranges, using the single-pass perfusion technique (Loc-I-Gut) in humans.

AIM: The objective of this in vivo dissolution study was to investigate the usefulness of the Loc-I-Gut technique for differentiating between the in vivo dissolution rate of two particle sizes of spironolactone, and to compare these in vivo results with corresponding in vitro data. METHODS: The study included six volunteers, and consisted of three sequential parts (I, II, III). In parts I and III the in vivo dissolution was measured directly by perfusing a semi-open segment in the proximal jejunum. In part II, a solution of spironolactone was administered orally, and the plasma concentration time profile was followed for 48 h. The in vitro dissolution was measured using flow-through cells and different dissolution media simulating human gastrointestinal fluids. RESULTS: A difference in in vivo dissolution rate of the two different particle sizes was observed, based on perfusion data. This difference was not pronounced in the relative bioavailability of spironolactone administered in two different particle sizes. The relative bioavailability was dependent on the bile acid concentration in vivo. In vitro, dissolution rate of the smaller particles was improved at fasted state bile acid concentrations, while the larger particles were only significantly affected at fed state bile acid concentrations. CONCLUSION: In vivo dissolution studies discriminated between the dissolution rate of the two different particle sizes of spironolactone, based on the perfusate samples. The lack of difference in relative bioavailability, might be explained by the insufficient wash-out of particles after ending the perfusion, reabsorption of surface active ingredients along the GI tract, relatively small difference in particle size and the large inter- and intra-individual differences in pharmacokinetic variables.

A guide for use and interpretation of kinesiologic electromyographic data.

Physical therapists are among the most common users of electromyography as a method for understanding function and dysfunction of the neuromuscular system. However, there is no collection of references or a source that provides an overview or synthesis of information that serves to guide either the user or the consumer of electromyography and the data derived. Thus, the purpose of this article is to present a guide, accompanied by an inclusive reference list, for the use and interpretation of kinesiologic electromyographic data. The guide is divided into 4 major sections: collecting, managing, normalizing, and analyzing kinesiologic electromyographic data. In the first of these sections, the issues affecting data collection with both indwelling and surface electrodes are discussed. In the second section, data management through alternative forms of data processing is addressed. In the third section, various reasons and procedures for data normalization are discussed. The last section reviews qualitative descriptors once used as the only means of analyzing data, then focuses on more quantitative procedures that predominate today. The guide is intended as a tool for students, educators, clinicians, and beginning researchers who use and interpret kinesiologic electromyographic data. Modifications will likely be needed as alternative forms of collecting, managing, normalizing, and analyzing electromyographic data are proposed, used in various settings, and reported in the literature.

Extraordinary feeding behaviour in Diptera Sciomyzidae, snail-killing flies.

In the laboratory, the larva of Sepedonella nana, Diptera Sciomyzidae, were only able to develop at the expense of small aquatic oligochets collected in adult habitats. Up till now, larval cycles have been elucidated for 38% of the Sciomyzidae; all these larvae proved to be strict consumers of aquatic or terrestrial molluscs (including slugs). This specific predation was considered as a major distinguishing characteristic of Sciomyzidae among Diptera. The unusual nutritional behaviour of S. nana reported in the present note is in contradiction with well-established prior knowledge. The species presented all the characteristics of the family, particularly the ventral arch sclerite present on the larva cephalopharyngeal skeleton. It was considered as a derived species; this behaviour, probably of secondary type, revealed new nutritional types for Afrotropical Sciomyzidae for which the biology of only five species was elucidated out of about 60 species described.

The effect of ketoconazole on the jejunal permeability and CYP3A metabolism of (R/S)-verapamil in humans.

AIMS: The purpose of this human intestinal perfusion study was to investigate the effect of ketoconazole on the jejunal permeability and first-pass metabolism of (R)- and (S)-verapamil in humans. METHODS: A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut(R) perfusion tube in six healthy volunteers. Each perfusion lasted for 200 min and was divided into two periods of 100 min each. The inlet concentration of (R/S)-verapamil was 120 mg l-1 in both periods, and ketoconazole was added at 40 mg l-1 in period 2. (R/S)-verapamil was also administered as a short intravenous infusion of 5 mg, over a period of 10 min. The appearance ratios of the CYP3A formed metabolites (R)- and (S)-norverapamil were also estimated in the outlet jejunal perfusate. RESULTS: The effective jejunal permeability (Peff) of both (R)- and (S)-verapamil was unaffected by the addition of ketoconazole in period 2 suggesting that ketoconazole had no effect on the P-glycoprotein mediated efflux. However, the appearance ratio of both (R)- and (S)-norverapamil in the outlet jejunal perfusate decreased in the presence of ketoconazole. The rate of absorption into plasma of (R)- and (S)-verapamil increased despite the low dose of ketoconazole added, indicating an inhibition of the gut wall metabolism of (R/S)-verapamil by ketoconazole. CONCLUSIONS: Ketoconazole did not affect the jejunal Peff of (R/S)-verapamil, but it did increase the overall transport into the systemic circulation (bioavailability), probably by inhibition of the gut wall metabolism of verapamil. This might be due to ketoconazole being less potent as an inhibitor of P-glycoprotein than of CYP3A4 in vivo in humans.

Increased intestinal non-substance P tachykinin concentrations in malignant midgut carcinoid disease.

BACKGROUND: Diarrhoea is an important feature of the carcinoid syndrome, and various agents which may be released from carcinoid tumours have been considered to contribute pathophysiologically. The aim of the present study was to determine luminal concentrations of possible chemical mediators in an uninvolved small intestinal segment using a two-balloon six-channel tube in nine patients with malignant midgut carcinoid disease. METHODS: All patients were treated with interferon and/or octreotide to alleviate the most severe flush. Ion transport was measured during luminal perfusion and luminal perfusate concentrations of calcitonin gene-related peptide, neurotensin, prostaglandin E (PGE)2, neuropeptide Y, somatostatin, vasoactive intestinal polypeptide, substance P and other tachykinins (neurokinin A, neurokinin B, neuropeptide K, eledoisin) were determined by separate assays. RESULTS: Carcinoid patients showed decreased absorption of Cl-, Na+, K+ and water and increased luminal content of non-substance P tachykinins to 424.5 fmol/cm per h, compared with 255.5 fmol/cm per h in control subjects. There were also increased luminal concentrations of PGE2, commonly claimed as a more general mediator of diarrhoea. CONCLUSIONS: The observed increase in intestinal tachykinins may involve extended activity from tachykinin-containing intrinsic neurones in the enteric nervous system, contributing to enhanced intestinal motility and secretory diarrhoea in patients with carcinoid syndrome.

Jejunal permeability in humans in vivo and rats in situ: investigation of molecular size selectivity and solvent drag.

The mechanisms controlling rates and routes for intestinal absorption of nutrients and small compounds are still not fully clarified. In the present study we aimed to investigate the effect of solvent drag on intestinal permeability of compounds with different molecular sizes in humans and rats. The effective intestinal permeabilities (Peff) of hydrophilic compounds (MW 60-4000) were determined in the single-pass perfused jejunum in humans in vivo and rats in situ under iso- and hypotonic conditions. The transport mechanism(s) of water and the importance of the solvent drag effect were investigated by the use of D2O. This is the first report in humans establishing the relation between in vivo measured jejunal Peff and molecular size for hydrophilic compounds. In addition, in rats we also found a molecular-size selectivity for hydrophilic compounds similar to man. The jejunal Peff of water and urea (MW 60) in both species were several times higher than predicted from their physicochemical properties. In humans, the jejunal absorption of urea and creatinine (MW 113) was increased by solvent drag, while no effect was found for the other investigated compounds. In rats, Peff for urea and creatinine were unaffected. In conclusion, it is still unclear if solvent drag occurs mainly through the para- or transcellular route, although, results from this study further add to our earlier reports suggesting that the transcellular route is most important from a quantitative point of view regardless of physicochemical properties of the transported compounds.

A comparison between direct determination of in vivo dissolution and the deconvolution technique in humans.

AIM: The primary objective of this study was to investigate the in vivo dissolution of carbamazepine in humans and to compare it with the dissolution estimated by deconvolution of plasma concentrations as well as the in vitro dissolution. METHODS: The in vivo study included six healthy volunteers, and consisted of two sequential parts. In part 1 the dissolution was measured by perfusing a semi-open segment in the proximal jejunum in humans. In part 2 the volunteers were given a solution of carbamazepine orally. In both parts of the study, plasma samples were collected up to 48 h after administration of the dose. The in vitro dissolution was measured in a flow-through cell using dissolution medium with and without the addition of bile acids (3 mM). RESULTS: The direct measured in vivo dissolution profile of carbamazepine and the deconvoluted profile were found to be similar. The two dissolution profiles of carbamazepine obtained in vitro were statistically lower than the two in vivo dissolution profiles. The higher in vivo dissolution rate is probably due to efficient sink conditions as a consequence of the high permeability of carbamazepine and more pronounced intestinal motility. CONCLUSION: The jejunal perfusion system was successfully used for in vivo dissolution measurements of carbamazepine and agreed with the deconvoluted plasma profile regarding rate and extent of dissolution. Single-pass perfusion is therefore a meaningful tool for further studies of in vivo dissolution.

Comparison of different systems to classify the neurological level of lesion in patients with myelomeningocele.

In 73 patients with myelomeningocele (mean 17.2 years, range 5 to 40 years) the classification of level of lesion was studied according to six commonly used classification systems and to the ambulation groups of Hoffer. The distribution of the patients into classes of thoracic-level lesions was the same for four classification systems in 10 patients and for two classification systems into categories of level L3 in 14 patients. For the other patients discrepancies occurred between systems for lesions of level L3 and downward. None of the patients was consistently categorized in the functional ambulation groups of Hoffer using all classification systems. The results show that it is not possible to compare neurological lesion levels classified according to the different systems described in this study and consequently that the distribution into the functional ambulation groups of Hoffer varies. To enhance communication and facilitate comparing the results of treatment we suggest using some basic criteria for patient documentation.

Jejunal absorption and metabolism of R/S-verapamil in humans.

PURPOSE: The purpose of this human intestinal perfusion study was to investigate the transport and metabolism of R/S-verapamil in the human jejunum (in vivo). METHODS: A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut perfusion tube in 12 healthy volunteers. Each perfusion lasted for 200 min and was divided into two periods each of 100 min. The inlet concentrations of verapamil were 4.0 and 40 mg/l in period one and two, respectively. RESULTS: The effective jejunal permeability (Peff) of both R- and S-verapamil increased (p < 0.05) when the inlet concentration was increased consistent with saturation of an efflux mechanism. However, both R- and S-verapamil had high intestinal Peff, consistent with complete absorption. The Peff of antipyrine also increased, but there was no difference in the Peff for D-glucose in the two periods. The appearance of R/S-norverapamil in the intestinal perfusate leaving the jejunal segment was non-linear, presumably due to saturation of the CYP3A4 metabolism. CONCLUSIONS: The increased Peff in parallel with increased entering drug concentration is most likely due to saturable efflux by P-glycoprotein(s) in the human intestine.