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Biomedical subjects

R Watkins

Publications and source records attributed to R Watkins.

At least 19 recordsLinked to original sources
PubMed1995

Determination of a cyclic guanine monophosphate phosphodiesterase inhibitor (SCH 51866) in rat serum using capillary zone electrophoresis.

A capillary zone electrophoretic (CZE) assay was developed for the determination of cis-5,6a,7,8,9,9a-hexahydro-2-[4-(trifluoromethyl)phenylmethyl]-5-methyl - cyclopent[4,5]imidazo[2,1-b]purin-4(3H)-one, SCH 51866 (I), a cyclic guanine monophosphate phosphodiesterase inhibitor, in rat serum using acetonitrile deproteination as a clean-up step before injection. The calibration curve was linear over a serum concentration range of 0.5 to 10 micrograms/ml serum with a correlation coefficient (r) > 0.99. The limit of quantitation (LOQ) was established at 0.5 micrograms/ml. Fifty microliters of serum were used for analysis, which allowed serial bleeding (8 samples) from a single rat to characterize the pharmacokinetic profile of I after either oral or intravenous drug administration. In traditional pharmacokinetic and toxicokinetic studies in rodents, one animal provides only one serum sample since 1 to 2 ml of sample volume is required for chromatographic analysis, resulting in the use of a large number of animals per study. This assay yields a significant reduction in the use of animals, hence providing a large reduction in resources and time in drug discovery and development.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1995

Optimal temporal frequencies in oscillatory movement hyperacuity measurements of visual function in cataract patients.

Hyperacuity tasks have been suggested for the assessment of potential visual function in the presence of cataracts. To test this suggestion, hyperacuity thresholds for an oscillating bar were measured in 30 subjects with idiopathic cataract and in 24 age-matched normals over a range of oscillation frequencies. Each subject's cataract was categorized using the Oxford Clinical Cataract Classification and Grading System. Cataract was found to have a significant effect on thresholds, although a differential morphological effect on thresholds was equivocal. Thresholds at higher temporal frequencies were significantly raised when compared to the normal group. The main conclusion to be drawn from this study is that motion hyperacuity thresholds appear unaffected by cataract at low oscillation frequencies and should be used in preference to higher frequencies in the assessment of such patients.

Aged↗
PubMed1992

Visual dysfunction in type II diabetic patients revealed by a hyperacuity test.

Displacement thresholds for an oscillating bar, which fall into the hyperacuity range, were determined in 21 subjects with non-insulin dependent diabetes mellitus and 19 age-matched visually normal controls. The diabetic subjects were classed as either having minimal or no retinopathy. Whilst thresholds for the diabetic group were significantly raised above those of the normal group, there were no significant differences in thresholds between the diabetic subgroup with retinopathy and the subgroup without. Greater thresholds tended to be found at higher frequencies of oscillation as the known duration of the diabetes increased.

Diabetes Mellitus, Type 2↗
PubMed1992

Anterior lumbar interbody fusion surgical complications.

Complications of anterior lumbar fusion may be divided into several categories. The first of these is complications related to patient selection, the second is visceral complications, and the third is vascular complications. Complications of anterior lumbar fusion and complications of interbody fusion technique occur at the graft site and the donor site.

Blood Vessels↗
PubMed1992

The influence of stimulus luminance and contrast on hyperacuity thresholds for oscillatory movement.

Hyperacuity thresholds for oscillatory movement were determined under conditions of decreased contrast and decreased luminance. Responses were found to be resistant to contrast reduction down to 15%; below this level thresholds increased. The contrast response function is thus similar to that of the magnocellular channel of the visual system. Systematic reduction in luminance caused a corresponding rise in thresholds. It is suggested that this effect is due to undersampling of the retinal image as a result of a lowered quantal absorption and an increase in critical duration of temporal integration at lower levels of luminance.

Contrast Sensitivity↗
PubMed1991

The effect of spatial parameters on oscillatory movement displacement thresholds.

Earlier work has established that oscillatory movement displacement thresholds (OMDT) are a form of hyperacuity. There is speculation that the mechanism determining OMDT, like motion perception in general, involves direct motion sensing at high temporal frequencies of oscillation and spatial localization processes (from which motion is inferred) at low temporal frequencies, which are both hyperacuities in their own right. OMDT were determined, for three experienced observers, over the temporal frequency range 1-15 Hz, for three stimulus lengths and three stimulus widths. Both decreasing stimulus length and decreasing stimulus width increased OMDT at all temporal frequencies. Furthermore, the resulting functions consistently exhibit a "kink" in the temporal frequency midrange. The results are interpreted as evidence that there are two subsystems involved in the analysis of visual motion with the kink indicating the transition where one system begins to predominate over the other.

Humans↗
PubMed1991

Hyperacuity thresholds for oscillatory movement are abnormal in strabismic and anisometropic amblyopes.

The hyperacuity performance of amblyopic individuals is known to be abnormal, particularly on vernier tasks. Oscillatory movement displacement thresholds (OMDT's) a form of hyperacuity, were investigated over a range of temporal frequencies (1, 4, 7, 10, and 13 Hz) in 8 normal controls, 5 strabismic amblyopes, and 4 anisometropic amblyopes to see if this form of hyperacuity was also affected by amblyopia. OMDT's were found to be significantly raised in all of the strabismic amblyopes and three of the four anisometropes over all temporal frequencies investigated when compared to the control group. In the fourth anisometrope, OMDT's were raised at low temporal frequencies only. The findings are interpreted as evidence that magnocellular and parvocellular channels are affected in the amblyopic visual system. The functional loss in amblyopia cannot be described completely unless both temporal and spatial thresholds are investigated.

Adult↗
PubMed1991

Carbon-phosphorus bond cleavage activity in cell-free extracts of Enterobacter aerogenes ATCC 15038 and Pseudomonas sp. 4ASW.

Carbon-phosphorus bond cleavage activity was investigated in cell-free extracts of Enterobacter aerogenes ATCC 15038 (IFO 12010) and Pseudomonas sp. 4ASW, strains known to utilize a range of phosphonates as sole phosphorus source. In vitro phosphonatase activity was detected in extracts of both organisms; however extensive analysis failed to detect any organic product from phosphonates other than phosphonoacetal dehyde. Non-specific liberation of phosphate was observed in Pseudomonas sp. 4ASW, associated with a single fraction of FPLC-purified extract, and is believed to result from the activity of cellular phosphatases.

Chromatography, High Pressure Liquid↗
PubMed1990

Atrial natriuretic factor-potentiating and antihypertensive activity of SCH 34826. An orally active neutral metalloendopeptidase inhibitor.

The effects of SCH 34826, an orally active neutral metalloendopeptidase inhibitor, on responses to atrial natriuretic factor-(103-125) or -(99-126) and on blood pressure were evaluated in rats. SCH 34826 (10, 30, and 90 mg/kg s.c. and 90 mg/kg p.o.) potentiated the antihypertensive action of atrial natriuretic factor (30 micrograms/kg i.v.) in conscious spontaneously hypertensive rats. SCH 34826 (90 mg/kg) also potentiated the diuretic and natriuretic responses to atrial natriuretic factor (30 micrograms/kg i.v.) as well as the plasma levels achieved after peptide injection. SCH 34826 significantly reduced blood pressure in the conscious deoxycorticosterone acetate-salt hypertensive rat, at doses of 90 mg/kg s.c. (-35 +/- 12 mm Hg), 10 mg/kg p.o. (-30 +/- 7 mm Hg), and 90 mg/kg p.o. (-45 +/- 6 mm Hg). SCH 34826 was devoid of acute antihypertensive activity in the spontaneously hypertensive rat but reduced blood pressure by day 3 of a 5-day treatment schedule. SCH 34826 (90 mg/kg s.c.) enhanced urine volume output in the deoxycorticosterone acetate-salt rat (2.78 +/- 0.6 vs. 1.27 +/- 0.3 ml/100 g/3 hr in vehicle-control rats, p less than 0.05). SCH 34826 (90 mg/kg s.c.) increased plasma levels of atrial natriuretic factor at 1 hour (753 +/- 89 vs. 451 +/- 79 pg/ml in vehicle-treated rats, p less than 0.05) but not 3 hours after dosing. The renal excretion of atrial natriuretic factor (3,092 +/- 1,089 vs. 21 +/- 6 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) and cyclic guanosine monophosphate (2,131 +/- 509 vs. 879 +/- 168 pg/100 g/3 hr in vehicle-treated rats, p less than 0.05) was markedly elevated by SCH 34826 in deoxycorticosterone acetate-salt rats. These studies suggest that neutral endopeptidase inhibition may represent a new approach to treatment of some forms of hypertension.

Administration, Oral↗
PubMed1990

Automated percutaneous discectomy: a prospective multi-institutional study.

A prospective multi-institutional study was carried out to evaluate automated percutaneous discectomy in the treatment of lumbar disc herniations. Of the 327 patients who prospectively met the study criteria and were followed for longer than 1 year, 75.2% were successfully treated. When patients (n = 168) who prospectively did not meet the study criteria were treated, the success rate was 49.4%. One case of discitis was reported; otherwise, no other serious complications were noted, and specifically no vascular or nerve damage was encountered. This study indicates that automated percutaneous discectomy can be used successfully to treat lumbar disc herniations with minimal morbidity and emphasizes the need for proper patient selection.

Humans↗
PubMed1989

Overexpression of amyloid precursor protein A4 (beta-amyloid) immunoreactivity in genetically transformed cells: implications for a cellular model of Alzheimer amyloidosis.

Among the major obstacles to clarifying molecular mechanisms involved in amyloid metabolism in Alzheimer disease has been the unavailability of laboratory models for this uniquely human disorder. The present studies were aimed at establishing genetically engineered cell lines that overexpress amyloid immunoreactivity and that may be relevant to amyloid accumulation in the Alzheimer disease brain. We used cloned amyloid cDNA that contains a region encoding A4 (beta-polypeptide) amino acids along with recently developed tumor virus vectors derived from simian virus 40 to prepare transformed cells. After transient and permanent transfection, a variety of cell types overexpressed A4 immunoreactivity that was detected by highly specific monoclonal antibodies. We observed that the use of an amyloid subdomain containing the A4 region, but lacking the sequence of a Kunitz-type protease inhibitor found in amyloid precursor protein variants, was sufficient to obtain cells that overproduced an A4 epitope. The transformed cells were readily propagated in culture and may provide an experimental medium to elucidate aspects of the molecular pathogenesis of Alzheimer disease. The cellular models may also serve as tools for deriving potentially useful therapeutic agents.

Alzheimer Disease↗
PubMed1989

Comparison of MRI to contrast CT in the diagnosis of spinal stenosis.

Retrospectively, the MR (magnetic resonance) and contrast CT (computed tomography examinations of 41 patients (123 segments) were objectively scored to evaluate spinal stenosis and disc degeneration. Five categories to evaluate stenosis included the facet joint, foramina, central canal, disc on sagittal section, and disc on axial section. In addition, the ability to demonstrate spondylolysis was compared. The examinations were interpreted by a single observer blinded to the results. Comparisons show 96.6% agreement between MR and contrast CT in the diagnosis of spinal stenosis. Magnetic resonance showed disc degeneration in 74 of 123 segments, while CT showed disc degeneration disease in 27 of 123 segments. Spondylolysis was recognized at three segments on both MR and CT. In conclusion, MR and contrast CT are comparable in their abilities to demonstrate spinal stenosis, and MR is more sensitive in demonstrating disc degeneration.

Adult↗
PubMed1989

Comparison of disc space heights after anterior lumbar interbody fusion.

Thirty-one consecutive patients underwent anterior interbody fusion of 40 levels of the lumbar spine using autogenous, autologous, or mixed iliac crest graft. Each patient's disc space height was measured preoperatively, immediately postoperatively, and an average of 29 months postoperatively. The immediate postoperative radiograph demonstrated an average increase in disc space height of 89%, or 9.5 mm for each operated level. The late radiographic evaluation, from 7 to 54 months postoperatively, showed an average decrease of 1%, or 0.1 mm for each level. At late follow-up, no correlation could be found between the time from the operation and disc space height. One hundred percent of patients developed disc space height decreases during the postoperative period, with 46% of levels being narrower than their preoperative height at last follow-up. Loss of distraction is a normal postoperative occurrence of the procedure. Disc space distraction is temporary with anterior interbody fusion.

Adult↗
PubMed1986

Effects of several newer cardiotonic drugs on cardiac cyclic AMP metabolism.

The purpose of this study was to investigate the possible roles of selective inhibition of cyclic nucleotide phosphodiesterase (PDE) isozymes, adenylate cyclase activation, and tissue cyclic 3',5'-adenosine monophosphate (cyclic AMP) elevation in the positive inotropic action of five new cardiotonic drugs. Three PDE isozymes (PDE I, II and III), homogenates, and slices of guinea pig ventricles were used. The inotropics amrinone, milrinone, AR-L 115BS, MDL 17,043, and RMI 82,249 all inhibited cyclic AMP hydrolysis by PDE III in a concentration-dependent manner, as did the PDE inhibitors aminophylline and 1-methyl-3-isobutylxanthine (MIX). All drugs except for AR-L 115BS inhibited PDE III at concentrations lower than those producing a standard inotropic response. A significant correlation (r = 0.80, P less than 0.05) was observed between PDE III inhibition and inotropic activity for six of the drugs. Only aminophylline and MIX, but none of the cardiotonic drugs, inhibited cyclic AMP hydrolysis by PDE I and II and cyclic 3',5'-guanosine monophosphate (cyclic GMP) hydrolysis (amrinone not tested) by PDE I. Further, none of the cardiotonic drugs inhibited the calmodulin-stimulated cyclic AMP hydrolysis by PDE I, indicating their lack of calmodulin antagonist activity. These drugs also did not stimulate adenylate cyclase activity but all increased net cyclic AMP formation from ATP in guinea pig ventricular homogenates through inhibition of cyclic AMP breakdown. Amrinone, milrinone, MDL 17,043 and RMI 82,249, but not AR-L 115BS, raised cyclic AMP levels significantly (P less than 0.05) in guinea pig ventricular slices. Also, amrinone, MDL 17,043 and RMI 82,249, but not AR-L 115BS, potentiated forskolin-induced cyclic AMP increase. These data taken together suggest that the specific inhibition of cyclic AMP PDE III isozyme and the consequent elevation of tissue cyclic AMP levels in cardiac tissue are an important mechanism of action of amrinone, milrinone, MDL 17,043 and RMI 82,249. Because AR-L 115BS did not increase cyclic AMP levels, it is likely that another mechanism may participate in the inotropic response to AR-L 115BS.

1-Methyl-3-isobutylxanthine↗