PubMed Health⌕ Search

Biomedical subjects

R A Buchanan

Publications and source records attributed to R A Buchanan.

At least 19 recordsLinked to original sources
PubMed1994

Quantitative dark-field mass analysis of ultrathin cryosections in the field-emission scanning transmission electron microscope.

The availability of a cryotransfer stage, highly efficient electron energy loss spectrometers, and ultra-thin-window energy-dispersive x-ray spectrometers for the VG Microscopes HB501 field-emission scanning transmission electron microscope (STEM) provides this instrument with the potential for high resolution biological microanalysis. Recent technical advances offer cryosections that are thin enough to take advantage of the analytical capabilities of this microscope. This paper first discusses the quantitative characterization of freeze-dried, ultrathin cryosections of directly frozen liver and brain by low-dose dark-field STEM imaging. Such images reveal high-quality sections with good structural detail, mainly due to reduced preparation artifacts and electron beam damage. These sections are thin enough for dark-field mass analysis, so that the mass of individual organelles can be measured in situ, and their water content deduced. This permits the measurement of mass loss-corrected subcellular elemental concentrations. The results suggest several new applications for cryosections as illustrated by data on synaptic activity-dependent calcium regulation in Purkinje cells of mouse cerebellum. Low-dose mass analysis of cryosections in combination with x-ray and electron spectroscopy is a promising approach to quantitating physiological changes in mass distribution and elemental composition.

Animals↗
PubMed1993

Measurement of low calcium concentrations in cryosectioned cells by parallel-EELS mapping.

Electron energy loss spectroscopy (EELS) in the scanning transmission electron microscope provides a high sensitivity for microanalysis of certain important biological elements such as calcium whose physiological concentrations in cells are rather low. Application of parallel-EELS mapping to the analysis of freeze-dried cryosections of rapidly frozen tissue provides a means of detecting small amounts of calcium in structures with diameter approximately 50 nm. Detector pattern noise due to channel gain variations can be reduced by acquiring difference spectra at each pixel. By segmenting nitrogen maps that reflect the structure through the protein distribution it is possible to sum spectra from specific compartments. These are then processed by fitting reference spectra for the Ca L23-edge and the carbon background. It has been found that useful data can be collected at 100 keV beam energy from freeze-dried cryosections of cerebellar cortex cut to nominal thickness of 100 nm. The analysis results in a sensitivity of +/- 0.4 mmol Ca/kg dry weight with a total acquisition time of 400 s, a significant improvement over that achievable with energy-dispersive X-ray spectroscopy.

Animals↗
PubMed1990

Surface modification of biomaterials through noble metal ion implantation.

Studies are described involving effects of noble-metal ion implantation on corrosion inhibition and charge-injection capabilities of surgical Ti-6A1-4V alloy. A major factor linked to excellent long-term biological performance is resistance to metal-ion release to tissues. The elements most resistant to corrosion in aqueous solutions are the noble metals. Disadvantages include expense and general inadequacy of mechanical properties. However, if small quantities can be used to surface-modify a surgical device in the last stage of manufacture, that device could possess an optimum combination of environmental integrity, biological response, mechanical properties, and charge-injection capability at minimum expense. Results for ion-implanted Ir are presented. Iridium has been described as the most corrosion-resistant element known, and its activated oxide as having the highest charge-injection capability of any material known. Ti-6A1-4V samples, ion implanted with 2.5 and 5.0 atomic % peak-maximum concentrations of Ir, were subjected to corrosion treatments to enrich the surface with Ir. Corrosion potential and cyclic voltammetry measurements indicated enrichment in H2SO4, and continued enrichment in isotonic saline, with corrosion potentials approaching that of pure Ir, and charge densities in isotonic saline exceeding that of pure Ir for the 5.0% peak-max Ir implanted material. X-ray photoelectron spectroscopy confirmed the high levels of Ir surface enrichment.

Alloys↗
PubMed1990

Associations between pericytes and capillary endothelium in the eel rete mirabile.

Morphometric analysis of electron micrographs of the eel rete mirabile revealed that pericytes occupied nearly one-third of the cellular volume of this organ with over 75% of the pericyte volume associated with arterially derived capillaries. These pericytes were highly arborized, extending processes which encircled the capillaries and covering, on average, more than 85% the ablumenal surface of arterially derived capillaries. Pericytes and endothelial cells interacted in a manner suggesting that pericyte activity modulates both capillary blood flow and permeability.

Air Sacs↗
PubMed1988

A comparison of the efficacy and safety of alprazolam and desipramine in depressed outpatients.

Fifty-two adult depressed outpatients fulfilling Research Diagnostic Criteria for Definite Major Depressive Disorder were enrolled in a double-blind study comparing the antidepressant effects of alprazolam versus desipramine. Twenty-nine patients completed the seven week (one week placebo followed by six weeks of active drug) study. The mean daily dose of alprazolam and desipramine at study termination was 3.34 mg and 192 mg respectively. Based on psychometric ratings of depression (Hamilton Scale) and severity of illness (Clinical Global Impressions) there was no significant difference between alprazolam and desipramine at the end of six weeks of active drug treatment. Both medications were well tolerated with drowsiness being the most common side effect of alprazolam, and insomnia, dry mouth, and constipation, the complaints most associated with desipramine.

Adult↗
PubMed1988

Preparation of isolated blood capillaries.

Blood capillaries have been isolated from various tissue sources yielding suspensions of capillary segments. These have provided opportunities to study the cellular properties of capillary endothelium under conditions uncomplicated by the presence of stromal tissues and in which measured parameters can be attributed to endothelial cells. Fresh capillary isolates have been used directly as experimental systems but the yield of endothelium is quite low. Amplification of endothelial biomass has been accomplished by using freshly isolated capillaries as explants for primary tissue culture. It has not been previously possible, however, to obtain large amounts of capillary endothelium from a single preparation nor have different capillary types been isolated from the same tissue. The rete mirabile of the eel swim bladder is a copious source of capillaries of two types: thick-walled, continuous capillaries heavily invested with pericytes and thin-walled, fenestrated capillaries. These can be isolated in large numbers free of large blood vessels and contaminating stromal tissue. The two types of capillaries can be isolated from each other by perfusing magnetic beads into one type prior to isolation and separating them from the other type in a magnetic field. This provides a system in which the cellular properties of the two types of endothelium can be studied in vitro and, due to a common isolation procedure, direct comparisons can be made.

Adipose Tissue↗
PubMed1987

Ion implantation of surgical Ti-6Al-4V for improved resistance to wear-accelerated corrosion.

The influence of nitrogen-ion implantation on the wear-accelerated corrosion behavior of surgical Ti-6Al-4V was studied. Nonpassivated and prepassivated unimplanted Ti-6Al-4V specimens were employed as controls for comparison. Corrosion rates as a function of time at open-circuit corrosion potentials were electrochemically measured in saline and serum solutions under both static and wear conditions. The wear parameters simulated those of a total artificial hip under average walking conditions. The results indicated that prepassivation of the control material was beneficial under static-corrosion conditions, but not under wear-corrosion conditions. The nitrogen-ion implantation process was found to significantly improve the material's resistance to wear-accelerated corrosion in both saline and serum solutions.

Alloys↗
PubMed1987

Wear-accelerated corrosion of Ti-6Al-4V and nitrogen-ion-implanted Ti-6Al-4V: mechanisms and influence of fixed-stress magnitude.

Wear-accelerated corrosion rates at constant anodic potentials were evaluated for unimplanted and nitrogen-ion-implanted surgical Ti-6Al-4V while wearing against ultrahigh-molecular-weight polyethylene at stress levels up to 6.90 MPa (1000 psi). The ion implantation processing was found to reduce the wear corrosion rates in both saline and serum solutions at all applied stress levels. During wear testing, all of the ion-implanted surfaces remained visually unchanged from the polished condition. However, many of the unimplanted surfaces developed damage zones characterized by wear tracks and black wear debris. A surface-damage mechanism is proposed and discussed which involves disruption of the Ti-6Al-4V protective oxide film, subsequent entrapment of oxide particles in the polyethylene, then self-perpetuating damage due to the abrasive action of the embedded particles.

Aluminum↗
PubMed1986

Comparative pharmacokinetics of zonisamide (CI-912) in epileptic patients on carbamazepine or phenytoin monotherapy.

Zonisamide (CI-912) is an experimental antiepileptic drug. Since this drug is to be evaluated initially as an add-on medication, an investigation was conducted to study its kinetics in the presence of two standard antiepileptic drugs. Patients in two groups, one on maintenance phenytoin (PHT) monotherapy and the other on maintenance carbamazepine (CBZ) monotherapy, each received a single dose of four 100-mg capsules of zonisamide; and blood samples were obtained at periodic intervals. Plasma and red blood cell (RBC) concentrations of zonisamide were measured by high performance liquid chromatography. Plasma and RBC areas under the curve produced by single doses of zonisamide in patients receiving CBZ were significantly higher than those receiving PHT (p less than 0.05). Clearance values, although not statistically significantly different, were lower for the CBZ group; and consistent with this, plasma and RBC concentrations decreased more rapidly in the PHT group. The approximate values for t1/2 were 36.4 h in plasma and 54.2 h in RBC for patients treated with CBZ, and 27.1 h in plasma and 35.8 h in RBC for patients treated with PHT. The RBC/plasma ratio varied eightfold within a given curve. These findings suggest that the dosage of zonisamide in epileptic patients might need to be varied depending on the comedication.

Adolescent↗
PubMed1985

Intraocular pressure, ocular pulse pressure, and body position.

Intraocular pressures (IOP's) were measured using the Digilab Pneuma-tonometer with the subject in both the sitting and supine positions. The IOP with the Pneuma-tonometer was greater (17.03 mm Hg) in the supine position than in the sitting position (12.90 mm Hg). The IOP measured with the Pneuma-tonometer, with the subject sitting, was similar to the IOP measured with the Goldmann applanation tonometer (13.42 mm Hg). Inasmuch as IOP tends to be lower with the patient in a sitting position, the clinician should be alert to the possibility that some patients with borderline Goldmann IOP's may have pressures well above the normal range when they are lying down. Due to the continuous recording provided by the Pneuma-tonometer, the ocular pulse pressure can be measured. We found a mean ocular pulse pressure amplitude of 1.77 mm Hg. All values are shown plus or minus 1 SD. Comparison of the ocular pulse pressure amplitude for the two eyes could aid in detecting patients with suspected carotid artery stenosis.

Adult↗
PubMed1985

A comparison of the safety and efficacy of alprazolam and desipramine in moderately severe depression.

Fifty-four patients (34 outpatients, 20 inpatients) fulfilling Research Diagnostic Criteria for Definite Major Depressive Disorder were enrolled in a double-blind study comparing the antidepressant effects of alprazolam versus desipramine. The mean daily dose of alprazolam and desipramine at study termination was 3.78 mg and 208 mg respectively. As there were no significant demographic or clinical differences between outpatients and inpatients, both groups were combined in data analysis. Using the Hamilton Depression Rating Scale (HAM-D) both drug groups showed highly significant improvement beginning with the first week of active drug treatment. HAM-D scores continued to decrease through study termination (six weeks of active drug). There were no significant differences when comparing alprazolam and desipramine (outpatients, inpatients, or both groups combined) on any of the subjective or objective psychometrics used in this study. Clinically, only twelve of thirty-four outpatients (35.3%) were felt to be "markedly or moderately" improved, suggesting that neither the outpatient alprazolam nor desipramine patients did particularly well with drug treatment. In terms of drug safety there was no difference between the alprazolam and desipramine in the number of excessive or serious drug side effects. However, five of twenty-nine alprazolam patients had to discontinue therapy because of excessive drowsiness, and two of the alprazolam outpatients had motor vehicle accidents directly related to this adverse event. Alprazolam appeared as effective as desipramine in the pharmacotherapy of this group of depressed outpatient and inpatients. Alprazolam appeared well-tolerated by most subjects although drowsiness was a common--and at times serious--medication side effect.

Adult↗
PubMed1983

Bioavailability of calcium valproate in normal men compared with the free acid and sodium salt.

Calcium valproate has been formulated into tablets containing the equivalent of 250 mg valproic acid (VPA). The bioequivalence of this preparation (Valontin, Parke-Davis) has been studied in 12 normal adult males in parallel with other products containing the free acid (Depakene capsules, Abbott) and the sodium salt (Depakene syrup, Abbott). Each subject received a single 500-mg oral dose of each product at 2-week intervals in a randomized three-way crossover study. Assays were carried out for VPA in blood and urine specimens which were collected over extended time periods. Peak plasma levels were attained on the average within 30 min with the syrup, 1.13 h with the capsules, and 1.38 h with the tablets. There were no significant differences in the peak plasma levels attained with the three products, or in the plasma half-lives of VPA and areas under the time-concentration curves. The plasma level curves appeared to be biexponential, with terminal half-lives that averaged 16.6 h. One subject showed a remarkably long half-life (28-38 h) after each of the three doses, indicating the possibility of genetic differences between individuals in the disposition of VPA. The urinary excretion of VPA in most subjects ran parallel to the plasma levels and could not be detected 96 h after dosing; however, the subject with the long plasma half-life continued to excrete VPA in his urine for at least 2 additional days. The mean recovery of VPA in 6-day urine represented 12-14% of the dose and ranged from 5.5 to 27.9% in different individuals. There were no significant differences between the three formulations in the pattern of urinary excretion.

Adult↗
PubMed1983

Methsuximide for complex partial seizures: efficacy, toxicity, clinical pharmacology, and drug interactions.

Methsuximide (MSM; Celontin) was administered for 8 weeks to 26 patients with complex partial seizures (CPS) refractory to phenytoin and carbamazepine and phenobarbital or primidone. A 50% or greater reduction in CPS frequency was obtained in eight patients. MSM therapy was continued chronically in these eight patients, and five continued to have a 50% or greater reduction in CPS frequency after 3 to 34 months of follow-up. Drowsiness, gastrointestinal disturbance, hiccups, irritability, and headache were the common side effects of MSM. No serious toxicity occurred. N-desmethylmethsuximide was the principal substance detected in plasma and had the following pharmacokinetic values: accumulation half-life, 49.7 hours; time to steady state, 10.4 days; elimination half-life, 72.2 hours; therapeutic range of plasma concentration, 10 to 30 mg per liter. Plasma concentrations of phenytoin and phenobarbital derived from primidone rose significantly (p less than 0.05) after addition of MSM.

Adult↗
PubMed1982

Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment.

The effects of long-term gemfibrozil (Lopid) therapy on human liver structure are not known. Studies of this nature are becoming essential in determining the risk/benefit ratio since gemfibrozil is an effective agent for the control of hyperlipoproteinemia types IIa, IIb, and IV. Particularly, gemfibrozil is effective when dietary management or available therapeutic control fail to reduce serum cholesterol and triglycerides as well as normalizing the lipoprotein pattern. Percutaneous liver biopsies of 9 patients on long-term gemfibrozil therapy were evaluated by light microscopy, interference contrast optics and transmission electron microscopy. The distribution of patients according to lipoprotein phenotype was 3 Type IIa, 3 Type IIb, and 3 Type IV. Their lipoprotein patterns approached normal and the serum lipids were controlled during gemfibrozil therapy. By light microscopy, the lobular architecture and other parameters were within normal limits. Varying degrees of fatty change were found as would be expected. No preferential lobular disposition of the fat globules was evident. Coalescence of fat droplets, nuclear displacement and fatty cysts were noted. Differential interference contrast microscopy revealed several degrees of contrast amplitude in these droplets suggesting a heterogeneous lipid deposition in hepatocytes. The subcellular analysis revealed a moderate degree of glycogen deposition, absence of nuclear abnormalities and unremarkable mitochondria; the rough endoplasmic reticulum was not significantly altered and smooth surfaced membranes appeared proliferated. Detailed analysis of the peroxisome population showed matrix rarefaction, marginal plate formation and spurious densities though no significant proliferation occurred. Distribution of peroxisomes in hepatocytes varied widely from cell to cell and in different lobular areas. This study confirmed the association of hepatic fatty change with hyperlipoproteinemia irrespective of the pattern observed in circulating lipoproteins. Peroxisome proliferation, as seen in rodents when receiving gemfibrozil, did not occur and the structure of these subcellular organelles was not compromised. It was concluded that the long-term administration of this compound did not show adverse effects on the hepatocyte in hyperlipoproteinemia.

Gemfibrozil↗
PubMed1982

Phenytoin metabolism in subjects with long and short plasma half-lives.

Normal adult men with long and short phenytoin plasma half-lives were given 300-mg oral doses of phenytoin once daily for 15 days. Plasma levels of phenytoin (DPH) and its major metabolite (p-HPPH) were measured during the period of drug administration and for 5 days thereafter. Average steady-state plasma levels of DPH rose to 13.4 micrograms/ml in the long half-life group, compared with 3.6 micrograms/ml in the short half-life group. HPPH levels in the long half-life group were about one half of those observed in the short half-life group. The DPH/HPPH ratios in plasma specimens showed excellent correlation with the plasma half-lives of DPH and average steady-state levels, suggesting that this ratio could provide guidance in the selection of optimum dosage regimens for problem patients.

Adult↗