Precise Measurement of Differential Cross Sections of the Σ

The differential cross sections of the Σ^{-}p→Λn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise angular information about the Σ^{-}p→Λn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 [statistical error(stat.)] ±0.65 [systematic error(syst.)] mb and 15.8±0.83(stat)±0.52(syst) mb for 470

A multiple-pathway model for the diffusion of drugs in skin.

A mathematical model for the diffusion of drugs in skin is presented. The penetration of the drug by both transcellular and intercellular pathways, as well as its interchange between these pathways, is considered. A pharmacologically motivated asymptotic limit is identified and analysed to obtain, in particular, an analytical expression for the flux of drug to the blood at steady state. Relevant model data is discussed, and some numerical results are also presented.

A method for the enumeration of bacterial adhesion to epithelial cells using image analysis.

Computerised image analysis was utilised to enumerate the attachment of Staphylococcus epidermidis to HEp2 cell monolayers. A differential staining technique was employed such that individual staphylococcal cells stood out in sharp contrast against the uneven cell surface and granular contents of the epithelial cells. The primary image analysis operation involved subtracting an out-of-focus image from an in-focus image of the bacteria on the monolayer, thereby accentuating the bacterial image. Enumeration, using a particle counting routine, was rapid and reproducible, facilitating counting in excess of 700 bacteria per field at x 500 magnification. The computerised programme compared favourably with manual counting and would provide a rapid, objective and morphologically discriminatory method for evaluating bacterial attachment to various tissues.

Epi-fluorescence microscopy and image analysis used to measure diffusion coefficients in gel systems.

A method using epi-fluorescence microscopy and image analysis has been developed to follow and quantify the diffusion of fluorescent compounds through gels. Two mathematical approaches were employed to calculate diffusion coefficients. The spatial resolution provided by the fluorescence microscope allowed diffusion to be followed over very short distances; accordingly diffusion coefficients were obtained within minutes, even for slowly diffusing systems. The method was successfully applied to the diffusion of macromolecules into agar, carbopol and mucus gel systems.

Synthesis and anticonvulsant activity of 2-benzylglutarimides.

A series of 2-benzylglutarimides (4) and their N-methyl analogues (5) were prepared according to the Topliss scheme for the selection of benzyl substituents to maximize anticonvulsant activity. A total of 22 such compounds were subjected to initial (phase I) screening in mice against seizures induced by maximal electroshock (MES) and pentylenetetrazol (scMet) and in the rotorod assay for neurotoxicity. From this series of test compounds, 10 were advanced to quantitative (phase II) testing. Of these, 2-(4-chlorobenzyl)glutarimide (4b) emerged as the most promising anticonvulsant drug candidate by demonstrating both good anti-scMet and anti-MES activity combined with low neurotoxicity after intraperitoneal administration in mice. In drug differentiation tests, 4b was also effective in nontoxic doses against seizures induced by bicuculline, picrotoxin, and strychnine. When compared with the clinically useful drugs phenytoin, carbamazepine, phenobarbital, valproate, and ethosuximide, 4b exhibited an overall pharmacological profile most closely resembling that of valproate.

Outcome following standardized 185 MBq dose 131I therapy for Graves' disease.

The clinical outcome of 199 patients with Graves' disease treated with standardized 185MBq 131I therapy doses has been analysed. Most patients were controlled with antithyroid drugs prior to the 131I therapy, and also received antithyroid drugs for several months following 131I. The median follow-up period was 5.5 years. The single 185MBq 131I dose successfully treated 72.4% of patients. The 1, 2 and 5 year hypothyroid figures were 15.5%, 19.3% and 27.3%, respectively. Previous thyroidectomy was associated with an increased hypothyroid rate. Retreatment was required by 25.6%, with 3.5% requiring more than two 131I doses. Discriminant analysis of pretreatment variables suggests that patients with large goitres or severe disease (serum T3 greater than 10nmol/l) should be treated with higher doses of 131I.

Radionuclide perfusion scans in the assessment of acute renal transplant rejection.

Acute renal transplant rejection is a diagnostic and management problem. In the oliguric patient clinical evaluation and biochemical tests are less helpful than in those with a functioning graft. The perfusion index derived from a 99mTc-diethylenetriamine penta-acetic acid scan may be a more reliable marker of acute rejection. We studied 20 consecutive renal transplant recipients with serial radionuclide imaging to assess the usefulness of the perfusion index. Seventy-two of 74 episodes of acute rejection were evaluated. Thirty-three (46%) episodes were predicted or supported by a change in the perfusion index. In the non-functioning transplant, 12 of 15 (80%) acute rejection episodes were predicted or supported. A scan obtained the day after transplantation confirmed graft artery patency in all patients. The perfusion index is a useful diagnostic test for the diagnosis and management of acute rejection, particularly in the non-functioning transplanted kidney.

Results of lithium- 131I treatment of thyrotoxicosis.

The role of lithium as an adjunct to 131I therapy of thyrotoxicosis has been assessed. Seventeen lithium- 131I treated patients and 16 control- 131I treated patients have been followed for almost three years. Five lithium- 131I and 3 control- 131I patients have become hypothyroid with the lithium treated patients developing earlier thyroid failure. Ten lithium and 10 control patients remain clinically and biochemically euthyroid. Two lithium- 131I and 2 control- 131I patients remain on low dose antithyroid drugs.

Thyroid vascularity--documentation of the iodide effect in thyrotoxicosis.

Thyroid vascularity was measured in 101 thyrotoxic patients by analysis of 99mTc pertechnetate thyroid flow studies obtained with a gamma camera--minicomputer system. The diffusely hyperplastic goitres tended to have higher vascularity than the toxic multinodular goitres, and many of the solitary toxic nodules had vascularity results within normal limits. Potassium iodide therapy, 60 mg b.d. for 10-14 days results in a dramatic reduction in thyroid vascularity in diffuse thyroid hyperplasia and toxic multinodular goitre but the effect on toxic nodules was marginal.

Lithium as an adjunct to radioiodine therapy for thyrotoxicosis.

16 patients with diffuse thyroid hyperplasia were given lithium carbonate (400 mg daily) for 1 week before and 1 week after a standardised 5 mCi therapy dose of 131I. A comparable control group of 16 patients were treated with 5 mCi of 131I without lithium therapy. The % retention of the therapy dose was measured in all patients at 7 days (168-hour 131I uptake). In the lithium-treated group the 24-hour 131I uptake showed no significant change after the first week of lithium therapy. The mean 48-hour protein-bound 131I, however, fell considerably from 1-21 to 0.55%/dose/1. The mean 24-168 hour % thyroidal 131I uptake drop was significantly less in the lithium group. These results show that low-dosage lithium therapy increases the retention of a standard-therapy dose of 131I. Lithium promises to be a useful adjunct to 131I therapy in patients with a rapid thyroidal iodine turnover and particularly in young patients where the total body-radiation dose must be kept to a minimum.

Placental scanning with computer-linked gamma camera to detect impaired placental blood flow and intrauterine growth retardation.

By retrospective analysis of 65 placental localization studies by a computer-linked gamma camera the isotope studies by a computer-linked gamma camera the isotope uptake patterns were correlated with the eventual outcome of the pregnancies. The uptakes by anterior and lateral placentae were reduced in pregnancies which resulted in growth-retarded babies and statistically unrelated to the gestation of the pregnancy. This simple representation of placental blood flow could be a clinically useful index of placental function.

Computer-assisted thyroidal technetium uptake measurement using a short pinhole-to-surface distance.

The close pinhole view of the thyroid presents some important measurement problems. Possible errors due to gland, neck and set-up geometry are accentuated due to the effects of the inverse square law, and care is needed to control these. The nonuniform response inherent in the use of the pinhole collimator has a significant effect, but with computer processing this is readily eliminated. ENR subtraction may become difficult in certain circumstances, as insufficient "background areas" may be viewed, but it has been shown that the use of a "universal" (for the particular system) ENR subtraction may give, if anything, more accurate results. With these precautions in use, important errors will be of the same order of magnitude as those involved in more distant views, and may thus be kept within the realms of clinical significance. On the other hand, considerable improvements in both resolution and sensitivity make the use of the closer view an asset to both the research laboratory and the small department involved mainly in routine service work.