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Biomedical subjects

T Richardson

Publications and source records attributed to T Richardson.

At least 19 recordsLinked to original sources

Developmental responses of amphibians to solar and artificial UVB sources: a comparative study.

Many amphibian species, in widely scattered locations, currently show population declines and/or reductions in range, but other amphibian species show no such declines. There is no known single cause for these declines. Differential sensitivity to UVB radiation among species might be one contributing factor. We have focused on amphibian eggs, potentially the most UVB-sensitive stage, and compared their resistance to UVB components of sunlight with their levels of photolyase, typically the most important enzyme for repair of the major UV photoproducts in DNA, cyclobutane pyrimidine dimers. Photolyase varied 100-fold among eggs/oocytes of 10 species. Among three species-Hyla regilla, Rana cascadae, and Bufo boreas-for which resistance of eggs to solar UVB irradiance in their natural locations was measured, hatching success correlated strongly with photolyase. Two additional species, Rana aurora and Ambystoma gracile, now show similar correlations. Among the low-egg-photolyase species, R. cascadae and B. boreas are showing declines, and the status of A. gracile is not known. Of the two high-photolyase species, populations of H. regilla remain robust, but populations of R. aurora are showing declines. To determine whether levels of photolyase or other repair activities are affected by solar exposures during amphibian development, we have initiated an extended study of H. regilla and R. cascadae, and of Xenopus laevis, laboratory-reared specimens of which previously showed very low photolyase levels. Hyla regilla and R. cascadae tadpoles are being reared to maturity in laboratories supplemented with modest levels of UV light or light filtered to remove UVB wavelengths. Young X. laevis females are being reared indoors and outdoors. Initial observations reveal severe effects of both UVA and UVB light on H. regilla and R. cascadae tadpoles and metamorphs, including developmental abnormalities and high mortalities. Assays of photolyase levels in the skins of young animals roughly parallel previous egg/oocyte photolyase measurements for all three species.

Amphibians

Adjunctive desipramine in the treatment of cocaine abusing schizophrenics.

Because schizophrenic patients have a lifetime prevalence rate for cocaine abuse between 15 and 50 percent, the use of adjunctive pharmacotherapy should be considered in cocaine-abuse treatment programs. This 12-week, open-label outpatient study compares 12 cocaine-abusing schizophrenic patients treated with desipramine (DMI) 100 to 150 mg and antipsychotic agents to 15 patients treated with only antipsychotic agents (no DMI). All 27 patients participated in a Dual Diagnosis Relapse Prevention (DDRP) program, which integrates traditional substance-abuse relapse prevention and psychiatric social skills training. The DMI group was more likely to complete the study (83% vs. 60%, odds ratio = 3.3, NS) and had fewer cocaine-positive urines during the last 6 weeks (20% vs. 50%, odds ratio = 4.0, p < .01). In the context of a specialized dual diagnosis treatment program, patients receiving DMI substantially decreased cocaine usage and had improved psychiatric symptoms.

Adult

Solid and cystic ultimobranchial body remnants in the thyroid.

In this study we determined the incidence rate (89%) and characterized the morphology of ultimobranchial body (UBB) remnants found in 18 serially sectioned neonatal thyroid glands. Although UBB remnants are often referred to as solid cell nests, we found cystic features in 55%. Ciliated columnar cells were seen in 23%. One contained a large pseudo-papilla. The UBB cells had nuclei with features reminiscent of papillary carcinoma nuclei in that they were enlarged, oval, and contained finely dispersed chromatin when compared with follicular cell nuclei. Both papillary carcinomas and UBB remnants are common, occur as tiny, solid, or cystic thyroid entities in patients of all ages, may contain papillary structures, and share some common nuclear features. Therefore, it is important to include UBB remnants in the differential diagnosis of minute thyroid entities and to recognize their morphologic features.

Animals

Equivalence of conventional and sustained release oral dosage formulations of acetazolamide in primary open angle glaucoma.

1. Outpatients with primary open angle glaucoma uncontrolled on single topical therapy with either pilocarpine or timolol were recruited for a stratified double dummy cross over trial. Once or twice daily sustained release acetazolamide (SRA) was compared with an identical regimen of conventional tablets (CA). 2. During the run in period the patients received 500 mg SRA once or twice daily as needed to control intraocular pressure (IOP). The dose was thereafter kept constant and patients were allocated randomly to 4 weeks treatment with CA followed by 4 weeks SRA or vice versa. IOP and venous plasma concentrations of acetazolamide were measured at weekly intervals. At the end of each 4 week course, patients were admitted for a 24 h profile of IOP and drug concentration measurements. 3. Thirty-five patients were recruited, but eleven were withdrawn during the run in period largely because of adverse effects; these became less troublesome when it was decided to give the once daily dose at 22.00 h. Four were withdrawn during the cross over, two because of inadequate IOP control. Twenty completed the trial. 4. The morning plasma concentration of acetazolamide measured each week showed no tendency to accumulation during the study. The mean swing (maximum minus minimum) in plasma acetazolamide concentration during the 24 h profile was less (P less than 0.005) with the SR formulation (11.6 +/- 4.9; mg l-1) +/- s.d.) than with the conventional (15.5 +/- 4.7) but the mean concentrations over the 24 h profile were indistinguishable (P greater than 0.05; 9.7 +/- 3.8 and 8.6 +/- 2.8 respectively). 5. Satisfactory control of IOP (no more than one reading above 22 mmHg) was maintained despite the changes in formulation in all but two of the patients who entered the cross over study. No close relationship between IOP and plasma concentration of acetazolamide was found. The 24 h IOP profiles whilst receiving each of the formulations were indistinguishable; thus the smoothing of the plasma drug concentration profile achieved by the SR formulation did not reduce the amplitude of swings in IOP. Similarly, no difference was observed between the formulations with respect to adverse effects. 6. It is concluded that the SR and conventional formulations were equivalent with respect to mean plasma acetazolamide concentration, IOP control and adverse effects. The SR formulation did not show practical advantages over the conventional formulation which was equally effective even with dosage intervals of 12 or 24 h.

Acetazolamide

Diagnosis and management of subclavian vein thrombosis occurring in association with subclavian cannulation for hemodialysis.

With the aim of improving the diagnosis and treatment of subclavian vein thrombosis, associated with subclavian cannulation for hemodialysis, we performed Doppler examination of the subclavian vein and clinical inspection of the ipsilateral arm at every dialysis in 50 consecutive patients who received subclavian hemodialysis catheters over 1 year. Edema of the arm and disappearance of the subclavian vein bruit correctly detected 3 cases of subclavian vein obstruction which were confirmed by X-ray venograms. All 3 cases failed to respond to systemic heparin, but were successfully recanalized within 36 h with continuous local streptokinase infusion at a rate of 10,000 U in 1 ml/h. In 4 other cases of edema of the arm, Doppler examination correctly predicted patency of the vein, also confirmed radiologically. In 2 cases of thrombosis, there was an underlying stenosis of the left innominate vein close to its union with the superior vena cava. These were dilated by balloon angioplasty; the stenosis recurred in both cases without recurrent thrombosis, and the angioplasty was repeated. Doppler surveillance seems to be a promising aid to the detection of subclavian vein thrombosis from hemodialysis catheters. Local streptokinase infusion is effective in treating thrombosis. Underlying venous stenosis should be looked for because this may be at least partly remediable by balloon angioplasty.

Angioplasty, Balloon

Cloning and sequencing of a complementary deoxyribonucleic acid coding for a bovine alpha s1-casein A from mammary tissue of a homozygous B variant cow.

A cDNA clone for bovine alpha s1-casein variant A was isolated from a mammary gland cDNA library using a synthetic degenerate oligonucleotide probe. The largest Pst I insert containing an EcoR I site was sequenced. It contained 1090 base pairs, 47 in the 5' noncoding region, 603 in the coding region and 440 in the 3' noncoding region. The nucleotide sequence was compared with three published cDNA sequences for alpha s1-casein variant B. The most obvious difference was the absence of the 39 bases encoding the 13 amino acids that are present in the B variant but absent from the A variant. In addition, five other single base positions differed within individual codons among the four sequences at the third base for each codon, but this did not change the amino acids encoded. There were, however, a number of differences found in the 3' noncoding region. The isolated cDNA was subjected to site-directed mutagenesis to replace a Val-Ile dipeptide with Phe-Phe to increase the chymosin sensitivity of the protein. When the milk proteins from mammary gland tissue extracts were typed, the alpha s1-casein A gene product was not detected.

Amino Acid Sequence

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