PubMed Health⌕ Search

Biomedical subjects

R Spector

Publications and source records attributed to R Spector.

At least 73 records · Page 4Linked to original sources
PubMed1985

Search for DNA alterations in Alzheimer's disease.

The DNA of brain cortex obtained from autopsy specimens of eight patients with Alzheimer's disease and eight controls was examined for content of normal and abnormal bases. DNA, purified by hydroxyapatite chromatography, was hydrolyzed under mild conditions and the deoxynucleosides were measured by high performance liquid chromatography (HPLC). No differences in the mole percentages of deoxynucleosides in DNA were detected in patients with Alzheimer's disease compared to controls, nor were abnormal deoxynucleosides found. Restriction-nuclease digests examined by agarose gel electrophoresis also showed no changes. Thus, diffuse and persistent damage to the DNA in brain in Alzheimer's disease was not detected by these methods.

Aged↗
PubMed1985

Lack of effect of oral activated charcoal on imipramine clearance.

The effect of oral activated charcoal on the pharmacokinetics of intravenous imipramine was studied in a randomized, crossover trial. Four normal men received intravenous imipramine (12.5 mg/70 kg) on two separate occasions, followed by either water or water plus high-surface-area activated charcoal (180 gm) in divided doses over 24 hours. Serum imipramine concentrations were measured from 0 to 24 hours after the imipramine infusion. There was no difference in the mean (+/- SE) t1/2 (9.0 +/- 0.8 vs. 10.9 +/- 1.6 hours), apparent volume of distribution (11.2 +/- 2.1 vs. 12.4 +/- 2.1 L/kg), or systemic clearance (992.2 +/- 138.3 vs. 930.3 +/- 101.9 ml/min/70 kg) of imipramine after dosing without and with oral activated charcoal, respectively (P greater than 0.05; paired t test). These results suggest that multiple oral doses of activated charcoal do not increase the clearance of imipramine in man.

Absorption↗
PubMed1985

Uridine transport and metabolism in the central nervous system.

The mechanisms by which uridine enters and leaves brain, choroid plexus, and cerebrospinal fluid (CSF) were investigated in the isolated choroid plexus in vitro and by injecting [3H]uridine intravenously and intraventricularly. Consistent with its postulated role in transporting uridine from blood into CSF, the isolated rabbit choroid plexus concentrated uridine with 10 microM uridine in the medium. [3H]Uridine, with and without unlabeled uridine, was infused at a constant rate into conscious adult rabbits. At 180 min, [3H]uridine entered CSF, choroid plexus, and brain more rapidly than mannitol. In brain, approximately 60-80% of the nonvolatile radioactivity was [3H]uridine phosphates. The addition of 2.1 mmol/kg of unlabeled uridine to the infusion syringe decreased the relative entry of [3H]uridine into brain by approximately 75% due mainly to the decreased formation of [3H]uridine phosphates and increased formation of [3H]uracil. Two hours after the intraventricular injection of [3H]uridine, [3H]uridine was cleared from CSF more rapidly than mannitol, in part to brain, where approximately 75% of the [3H]uridine was converted to [3H]uridine phosphates. The intraventricular injection of 42 mumol unlabeled uridine with the [3H]uridine decreased the phosphorylation of [3H]uridine in brain significantly and also decreased the clearance of [3H]uridine from the CSF. From blood, uridine enters CSF and the extracellular space of brain. Uridine then can enter brain cells, be phosphorylated to uridine phosphates, and subsequently incorporated into RNA or be catabolized to uracil.

Animals↗
PubMed1985

Regression to the mean: a potential source of error in clinical pharmacological studies.

The design and interpretation of clinical trials in clinical pharmacology must avoid certain pitfalls to be useful in guiding drug therapy decisions. Here, we discuss one important problem in clinical trial design, the problem of regression to the mean. Because certain disease states tend to wax and wane in severity and because patients tend to present for treatment when disease activity is high, the expected course of the disease is improvement. Therefore, any treatment begun will appear to lessen disease activity. We give four examples of diseases where improper and inadequate recommendations for drug therapy have been made based on clinical trials that ignored the problem of regression to the mean: vasospastic angina, rheumatoid arthritis, chronic congestive heart failure, and renal stones. Studies of drug therapy in diseases such as these should be conducted with concurrent placebo controls rather than having each patient serve as his own control.

Angina Pectoris↗
PubMed1985

The effects of activated charcoal on digoxin and digitoxin clearance.

The effect of multiple oral doses of activated charcoal on digitalis glycoside kinetics was studied to determine whether an activated charcoal regimen might have utility in treating patients with digitalis toxicity. Normal subjects were given intravenous infusions of digoxin 0.75 mg/70 kg or digitoxin 1 mg/70 kg iv followed by either water alone or water with activated charcoal in divided doses in a randomized crossover design. A subject with chronic renal failure was also given digoxin 0.5 mg/70 kg iv followed by water alone or water with activated charcoal. In six normal subjects, treatment with activated charcoal did not increase digoxin clearance (Cl) significantly (16.79 +/- 1.70 vs. 22.68 +/- 3.51 L/h). However, digitoxin Cl did increase significantly, from 0.24 +/- 0.01 to 0.47 +/- 0.04 L/h. In the renal failure subject, digoxin Cl increased from 3.6 L/h to 10.1 L/h. We conclude that the activated charcoal regimen is probably useful in patients with digitoxin toxicity. Although similar benefit is limited in patients with normal renal function who develop digoxin toxicity, it is possible that activated charcoal will be useful in patients with prolonged digoxin elimination due to renal dysfunction.

Adult↗
PubMed1985

Thymidine transport and metabolism in choroid plexus: effect of diazepam and thiopental.

Choroid plexus contains an active transport (influx) and a facilitated diffusion (efflux) system for nucleosides. The ability of diazepam and thiopental to inhibit active transport or facilitated diffusion of thymidine in choroid plexus was measured in vitro under various conditions. When isolated rabbit choroid plexuses were incubated in artificial cerebrospinal fluid containing 1 microM [3H] thymidine for 10 min at 37 degrees C under 95% O2-5% CO2, diazepam (10 microM) and thiopental (500 microM) doubled the tissue-to-medium ratios of [3H] thymidine from 8 to 15 to 16. These results were not due to metabolism or intracellular binding but rather to inhibition of [3H] thymidine efflux from choroid plexus. Diazepam, unlike thiopental, inhibited [3H] thymidine efflux in a concentration-dependent manner. When isolated choroid plexuses were incubated in artificial cerebrospinal fluid containing low concentrations of [3H] thymidine (6 nM) to allow intracellular conversion of [3H] thymidine into [3H] thymidine phosphates and [3H] DNA, both diazepam (10 microM) and thiopental (500 microM) altered [3H] thymidine accumulation and metabolism consistent with inhibition of facilitated diffusion but not active transport of thymidine. These studies provide evidence that, at toxic but not therapeutic concentrations, diazepam and thiopental alter facilitated nucleoside transport in the choroid plexus.

Animals↗
PubMed1984

Treatment of essential blepharospasm. I. Comparison of facial nerve avulsion and eyebrow-eyelid muscle stripping procedure.

Benign essential blepharospasm is an incurable disease for which many treatment modalities have been suggested. The two surgical procedures that have been used most commonly are avulsion of the facial nerve and stripping of the protractor muscles of the eyelid and brow. We compare two matched series of 22 patients; one group underwent facial nerve avulsion ("Reynold's" procedure), and the other underwent "muscle stripping" ("Anderson's" procedure). We noted the number of procedures required for the patient to obtain a functional visual result and the side effects produced. Additional surgical procedures required by patients undergoing facial nerve avulsion were additional facial nerve avulsion, repair of ectropion, and correction of dermatochalasis and brow droop. Additional procedures required in patients who had muscle stripping were excision of lower lid orbicular fibers or residual brow fibers. The Reynold group required 16 additional procedures (38 separate procedures) to obtain functional results, as opposed to the four additional procedures (26 separate procedures) required in the Anderson group. Two patients in the Reynold group who needed surgery have not yet undergone it at this writing. If they did, that would boost the total number of procedures to 40. Secondary procedures are needed 4.5 times more often with the Reynold procedure than with the Anderson procedure. The patient's subjective response to and acceptance of the procedure are much greater for the Anderson procedure.

Adult↗
PubMed1984

Effect of the surface area of activated charcoal on theophylline clearance.

The effect of the surface area of activated charcoal on theophylline clearance was studied. Eight fasting, healthy men received intravenous infusions of either aminophylline (6 mg/kg, N = 3) or theophylline (5 mg/kg, N = 5) over 1 hour followed by either 5 Gm standard activated charcoal every 2 hours, 20 Gm every 2 hours, or 5 Gm PX-21 activated charcoal (with 3.6 times the surface area) every 2 hours. Theophylline t 1/2 and AUC with each regimen were respectively 6.3 +/- 0.5 (S.E.) hours and 88.9 +/- 8.4 mg/liter X hr with 5 Gm standard activated charcoal, 5.3 +/- 0.3 hours and 75.4 +/- 4.9 mg/liter X hr with 5 Gm PX-21, and 4.9 +/- 0.2 hours and 67.7 +/- 3.6 mg/liter X hr with 20 Gm standard activated charcoal. There was a relationship between the activated charcoal surface area and the reduction in theophylline t 1/2 and AUC. We conclude that the clearance of theophylline is related to the surface area of activated charcoal administered and that PX-21 may be a more potent activated charcoal product for enhancing theophylline removal.

Administration, Oral↗
PubMed1984

Model for theophylline overdose treatment with oral activated charcoal.

The effect of repeated oral doses of activated charcoal on theophylline kinetics was studied in six subjects with hepatic cirrhosis and five patients with moderate theophylline poisoning to determine whether an activated charcoal regimen would be a useful strategy in patients with theophylline poisoning who did not require hemoperfusion. Six subjects with cirrhosis were injected IV with 6 mg/kg aminophylline followed by either water or water with activated charcoal (140 gm) in divided doses over 12 hr. In these subjects, treatment with activated charcoal decreased the mean (+/- SE) serum theophylline t1/2 from 12.7 +/- 4.0 hr to 4.0 +/- 0.7 hr. Subjects with the longest control t1/2s demonstrated the greatest charcoal effect. We developed a mathematical model that predicts that treatment with repeated oral doses of activated charcoal would result in an average serum theophylline t1/2 of 7.1 hr or less even if the subject's endogenous theophylline t1/2 is very long. In a pilot study of five patients with moderate theophylline poisoning, treatment with repeated oral doses of activated charcoal was well tolerated and led to a mean (+/- SE) t1/2 that was shorter than expected (4.9 +/- 0.8 hr, range 3.1 to 7.1 hr). We conclude that repeated oral doses of activated charcoal are relatively more effective in decreasing the serum theophylline t1/2 in persons with long endogenous t1/2s and that this may be useful for certain patients with mild or moderate theophylline poisoning.

Adult↗
PubMed1984

Accumulation of pantothenic acid by the isolated choroid plexus and brain slices in vitro.

In vitro, the transport of [14C]pantothenic acid into and from the isolated rabbit choroid plexus, an anatomical locus of the blood-CSF barrier, and brain slices was studied. The choroid plexus accumulated [14C]pantothenic acid from the medium against a concentration gradient, although at low concentrations (less than 1 microM) there was substantial intracellular phosphorylation and binding of the [14C]pantothenic acid. The saturable accumulation process in choroid plexus was inhibited by probenecid and caproic acid but not by nicotinic acid or by weak bases. The accumulation process was markedly inhibited by N-ethylmaleimide, poly-L-lysine (which blocks sodium transport), and low temperatures. [14C]Pantothenic acid was readily released from choroid plexus by a temperature-dependent process. Brain slices also accumulated and, at low concentrations, phosphorylated [14C]pantothenic acid from the medium by a temperature-, probenecid-, and N-ethylmaleimide-sensitive saturable process. However, unlike choroid plexus, brain slices did not concentrate free pantothenic acid and [14C]pantothenic acid accumulation was not sensitive to poly-L-lysine. [14C]Pantothenic acid was readily released from brain slices by a temperature-sensitive process. These results are consistent with the view that [14C]pantothenic acid enters the isolated choroid plexus and brain slices by active transport and facilitated diffusion, respectively.

Animals↗
PubMed1984

Specificity and sodium dependence of the active nucleoside transport system in choroid plexus.

The transport of [3H]deoxyuridine by the active nucleoside transport system into the isolated rabbit choroid plexus was measured in vitro under various conditions. Choroid plexuses were incubated in artificial CSF containing 1 microM [3H]deoxyuridine and 1 microM nitrobenzylthioinosine for 5 min under 95% O2-5% CO2 at 37 degrees C and the accumulation of [3H]deoxyuridine measured. Nitrobenzylthioinosine was added to the artificial CSF at a concentration (1 microM) that did not inhibit the active nucleoside transport system but did inhibit the separate, saturable nucleoside efflux system. The active transport of deoxyuridine into the choroid plexus depended on Na+ in the medium, as ouabain, substitution of Li+ and choline for Na+, and poly-L-lysine all inhibited deoxyuridine transport. Thiocyanate in place of chloride and penetrating sulfhydryl reagents also inhibited the active transport of deoxyuridine into choroid plexus. The active transport of deoxyuridine into choroid plexus, which is inhibited by naturally occurring ribo- and deoxyribonucleosides (IC50 = 7-21 microM), was not inhibited (IC50 much greater than 150 microM) by nucleosides with certain alterations on the 2', 3', or 5' positions in D-ribose or 2-deoxy-D-ribose (e.g., adenine arabinoside, 3'-deoxyadenosine, xylosyladenosine); or the pyrimidine or purine rings (e.g., 6-azauridine, xanthosine, 7-methylinosine, or 8-bromoadenosine). Other analogues were effective (IC50 = 8-26 microM; e.g., 5-substituted pyrimidine nucleosides, 7-deazaadenosine, 6-mercaptoguanosine) or less effective (IC50 = 46-145 microM; e.g., 5-azacytidine, 3-deazauridine) inhibitors of deoxyuridine transport into the isolated choroid plexus.

Animals↗
PubMed1984

Nucleoside and oxypurine homeostasis in adult rabbit cerebrospinal fluid and plasma.

In adult New Zealand white rabbits, the effects of food deprivation and of massive elevations of plasma uridine or thymidine concentrations on CSF and plasma nucleoside and oxypurine concentrations were studied. Nucleoside and oxypurine levels were determined by high performance liquid chromatography using unequivocal methods of compound identification. After 48 and 96 h of food deprivation, the concentrations of uridine, cytidine, inosine, thymidine, deoxycytidine, deoxyuridine, hypoxanthine, xanthine, and uric acid in CSF and plasma were not different than in controls, except at 96 h, when the plasma uridine concentration was 35% lower (p less than 0.05). After elevation of the plasma and CSF thymidine concentrations to approximately 200 and 100 microM, respectively, with intravenous thymidine for 5 h, there was a large increase in CSF and plasma thymidine to approximately 100 microM and a smaller increase in plasma and CSF deoxyuridine concentrations. After elevation of the plasma and CSF uridine concentrations to 0.6 and 0.2 mM, respectively, there was a large increase in CSF and plasma uracil and a smaller increase in plasma and CSF deoxyuridine concentrations. Elevated plasma concentration of thymidine and uridine significantly decreased the CSF to plasma ratios of deoxyuridine and thymidine; however, only elevated plasma uridine concentrations decreased the CSF to plasma ratio of uridine. These results document the powerful homeostatic mechanisms that regulate the concentrations of the principal nucleosides and oxypurine bases in CSF.

Animals↗
PubMed1984

Inherited snowflake cataracts.

The authors report two unusual pedigrees of flake-like cataracts inherited as an isolated mendelian trait, presumably autosomal dominant. The most striking biomicroscopic feature is an accumulation of large white irregular flakes ('type B opacities') scattered throughout the equatorial cortex, with apparently less involvement of the nucleus. Some of these opacities are globular, but most are flattened and have feathery edges. These type B opacities are clinically and microscopically identical in the two families. Type B lesions are characterized histologically by irregular pale-staining areas. Ultrastructurally, these areas show large collections of microglobular degeneration immediately adjacent to normal-appearing lens fibers. Electron probe studies demonstrate normal calcium levels. 'Type A' opacities are biomicroscopically smaller, punctate, and clinically non-specific. Ultrastructurally, type A opacities include clusters of medium sized lenticular globules, each of which is larger than the individual microglobular abnormalities of type B lesions, although the aggregated type B lesion is considerably larger than an individual type A lesion. The microscopic appearance of this inherited cataract appears to be unique.

Adult↗
PubMed1984

Deoxynucleoside and vitamin transport into the central nervous system.

Several essential substances for the mammalian brain including certain vitamins and deoxynucleosides do not enter the brain in appreciable amounts directly through the cerebral capillaries, the blood-brain barrier; rather these substances are transported from blood into cerebrospinal fluid (CSF) by specific, carrier-mediated transport systems in the choroid plexus, the anatomic locus of the blood-CSF barrier. From the CSF, these substances then enter the brain. The evidence supporting the notion that the choroid plexus is important in the transfer of ascorbic acid, folates, and pyrimidine deoxynucleosides from blood into CSF is summarized. This evidence provides strong support for the theory that the CSF is, in fact, a nourishing liquor, although an incomplete one, for developing and adult mammalian brain.

Animals↗
PubMed1984

Adverse drug reactions in the elderly.

The physician who sees elderly patients must be on the alert for drug reactions and drug-induced illness. The authors offer guidelines to help spot reactions and prevent such complications as mental status changes, hypotension, hypoglycemia, and others.

Adult↗
PubMed1983

Determination of ribonucleosides, deoxyribonucleosides, and purine and pyrimidine bases in adult rabbit cerebrospinal fluid and plasma.

Purine and pyrimidine base and nucleoside levels were measured in adult rabbit cisternal CSF and plasma by reversed-phase high-performance liquid chromatography. The concentrations of bases, nucleosides, and nucleoside phosphates were similar in plasma and CSF except for the adenosine phosphates and uracil which were higher in the plasma. In plasma and CSF, adenosine levels were low (0.12 microM) and guanosine, deoxyadenosine, deoxyguanosine, and deoxyinosine were not detectable (less than 0.1 microM); inosine and xanthine concentrations were 1-2 microM and hypoxanthine concentrations were approximately 5 microM; uridine (approximately 8 microM), cytidine (2-3 microM), and thymidine, deoxyuridine, and deoxycytidine (0.5-1.4 microM) were easily detectable. In both plasma and CSF, guanine, and thymine were undetectable (less than 0.1 microM), adenine and cytosine were less than 0.2 microM, but uracil was present (greater than 1 microM). Adenosine, inosine, and guanosine phosphates were also detectable at low concentrations in CSF and plasma. These results are consistent with the hypothesis that purine deoxyribonucleosides are synthesized in situ in the adult rabbit brain. In contrast, pyrimidine deoxyribonucleosides and ribonucleosides, and purine and pyrimidine bases are available in the CSF for use by the brain.

Adenine↗
PubMed1983

Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma.

Purine and pyrimidine base and nucleoside levels were determined in adult human lumbar (CSF) and plasma by reversed-phase high performance liquid chromatography (HPLC). Guanine, thymine, cytosine and uracil were not detectable (less than 0.1 microM) in human CSF or plasma. Adenine was detectable in plasma (0.3 microM) but was not found in CSF (less than 0.2 microM). Hypoxanthine and xanthine levels in CSF were each approximately 2.5 microM. Plasma levels of hypoxanthine and xanthine were considerably lower (0.4-0.6 microM). Purine and pyrimidine ribonucleosides in human CSF were less than or equal to 0.2 microM with the exception of uridine which was present at concentrations of 2-3 microM. Although low concentrations of thymidine and deoxyuridine (0.2 microM) were present in human plasma, purine and pyrimidine deoxyribonucleosides were less than 0.1 microM in human lumbar CSF.

Chromatography, High Pressure Liquid↗