Showing papers by "Tufts University published in 1980"
TL;DR: In this paper, it is argued that if the Hamiltonian of a system of charged fermions does not conserve parity, then an equilibrium electric current parallel to the value of the magnetic field can develop in such a system in an external magnetic field.
Abstract: It is argued that if the Hamiltonian of a system of charged fermions does not conserve parity, then an equilibrium electric current parallel to $\stackrel{\ensuremath{\rightarrow}}{\mathrm{B}}$ can develop in such a system in an external magnetic field $\stackrel{\ensuremath{\rightarrow}}{\mathrm{B}}$. The equilibrium current is calculated (i) for noninteracting left-handed massless fermions and (ii) for a system of massive particles with a Fermitype parity-violating interaction. In the first case a nonzero current is found, while in the second case the current vanishes in the lowest order of perturbation theory. The physical reason for the cancellation of the current in the second case is not clear and one cannot rule out the possibility that a nonzero current appears in other models.
496 citations
TL;DR: The preliminary data suggest that parathyroid gland function may be enhanced in essential hypertension, and there is a need for derivative experiments directed at defining the importance of the preliminary findings In the patbogenesis of human and experimental hypertension.
Abstract: Disorders of calcium metabolism are not generally considered important either clinically or pathophysiologically in essential hypertension Recent reports, though, suggest that increased parathyroid gland function may be one of the more common endocrine disturbances associated with hypertension We measured serum parathyroid hormone (PTH) concentrations as well as routine blood and urine chemistries in 34 hypertensives Their mean PTH, 791 +/- 31 muliter Eq/muliter, was significantly higher (p less than 0025) than the mean PTH, 669 +/- 33, of an age- and sex-matched normotensive control population The mean serum calcium, 95 +/- 01 mg%, was identical in the two populations Compared to a second age- and sex-matched normotensive population, the hypertensives demonstrated a significant (p less than 0005) relative hypercalciuria For any level of urinary sodium, hypertensives excreted more calcium These preliminary data suggest that parathyroid gland function may be enhanced in essential hypertension This increased gland activity appears, in part, to be an appropriate, physiologic response to a previously unrecognized relative hypercalciuria, or renal calcium leak, associated with essential hypertension We conclude that the increased prevalence of hypertension in subjects with hyperparathyroidism probably represents the final event in a continuum that begins with obligatory urinary calcium losses in hypertensives, but whose pathological presentation is hyperparathyroidism The results of this pilot study indicate a need for derivative experiments directed at defining the importance of our preliminary findings in the pathogenesis of human and experimental hypertension
328 citations
TL;DR: Tear flow and volume were measured in 15 normal volunteers, divided into young and old age groups, using subjective fluorophotometric analysis and Schirmer testing with and without topical anesthesia.
301 citations
TL;DR: Using restriction enzyme analyses and DNA-DNA hybridization to specific 32P-labeled genetic probes, at least four genetically distinct tetracycline resistance determiants are defined: Class A (the determinant on prototype plasmid RP1), Class B ( that on R222), and Class C (that onplasmid pSC101).
255 citations
TL;DR: Calculations indicate that the high RQ's observed during the highest glucose infusion rate could be attributed to the synthesis of fat from infused glucose, and that about 30% of the increase in VO2 above the basal level could also been attributed to fat synthesis.
Abstract: We have used the primed constant infusion of U-13C-glucose to study glucose metabolism during conventional total parenteral nutrition (TPN) in five postoperative surgical patients. Glucose production from nonrecycled carbon sources was suppressed to 17% of the basal level at the lowest rate of glucose infusion tested (4 mg/kg x min). Subsequent increases in glucose infusion rate had minimal effect in further suppressing glucose production. Additional nitrogen-sparing effects of glucose when glucose is infused at rates in excess of 4 mg/kg x min must therefore be derived from oxidation of the infused glucose. An increase in the infusion rate from 4 mg/kg x min to 7 mg/kg x min was associated with an increased rate of glucose oxidation, but a further increase in glucose infusion rate (9 mg/kg x min) was without significant effect on glucose oxidation. As the rate of TPN administration (glucose and amino acids) increased, both metabolic rate and RQ rose significantly. Our calculations indicate that the high RQ's observed during the highest glucose infusion rate (X = 1.13) could be attributed to the synthesis of fat from infused glucose, and that about 30% of the increase in VO2 above the basal level could also be attributed to fat synthesis. The progressive increase in the ability to clear glucose from the blood that occurred as TPN progressed was not due to an increase in the rate of oxidation of glucose; we found no correlation between glucose clearance and glucose oxidation.
204 citations
TL;DR: It is proved that the liver is capable of SAA production and to identify the specific cell responsible for synthesis, as has been shown for another acute phase reactant, C-reactive protein8.
Abstract: Infection or inflammation triggers the rapid appearance in the blood of a group of proteins known as acute phase reactants1 Serum amyloid A protein (SAA) is an acute phase protein which is believed to be the precursor for the secondary amyloid fibril protein, known previously as amyloid of unknown origin, and now as amyloid A protein (AA) The site of synthesis of SAA has been controversial, with previous evidence suggesting that AA related proteins arise in liver2–4, connective tissues5, polymorphonuclear neutrophil leukocytes6 and spleen7 However, in none of these systems could SAA synthesis be induced in vitro and the evidence rested on studies of tissues or cells arising from pre-stimulated animals Our aim in the present studies was to prove that the liver is capable of SAA production and to identify the specific cell responsible for synthesis The experiments demonstrate that SAA is synthesized in the liver by hepatocytes In addition, colchicine, currently used for the treatment of amyloidosis, blocks the secretion of SAA from the hepatocyte, as has been shown for another acute phase reactant, C-reactive protein8
178 citations
TL;DR: In this article, the finite-temperature Green's-function formalism is extended to the case of relativistic rotating systems and free scalar, spinor, and electromagnetic Green's functions for a rotating system are obtained.
Abstract: The finite-temperature Green's-function formalism is extended to the case of relativistic rotating systems. Free scalar, spinor, and electromagnetic Green's functions for a rotating system are obtained. As an application of the formalism, the neutrino parity-violating current is calculated. The result agrees with previous calculations where different methods have been used.
171 citations
170 citations
TL;DR: Using Dowex ion-exchange chromatography, gel chromatography on Sephadex G-75, and preparative disc acrylamide gel electrophoresis, several polypeptides with the full biological multiplication-stimulating activity have been isolated and one of them, designated MSA II-1, previously has been used to study the relationship of the activity to the insulin-like growth factors purified from human plasma.
Abstract: Multiplication-stimulating activity (MSA) refers to a family of insulin-like growth factors that have been purified from serum-free medium conditioned by a Buffalo rat liver cell line (BRL-3A). Using Dowex ion-exchange chromatography, gel chromatography on Sephadex G-75, and preparative disc acrylamide gel electrophoresis, several polypeptides with the full biological multiplication-stimulating activity have been isolated. One of these polypeptides, designated MSA II-1, previously has been used to study the relationship of the activity to the insulin-like growth factors (somato-medins) purified from human plasma. Polypeptide II-1 is a single chain polypeptide of molecular weight 8700. Glycine is the COOH-terminal amino acid. Edman degradation of carboxymethylated MSA II-l did not reveal a free NH2-terminus. A polypeptide of lower molecular weight than MSA II-1 has also been purified. This polypeptide (MSA III-2) has been shown to be more potent than MSA II-1 in the rat-liver-membrane radioreceptor assay and in a competitive binding assay utilizing the rat-serum somatomedin-binding protein(s). The relationship of these various polypeptides has been investigated by gel filtration in guanidine hydrochloride and by acrylamide gel electrophoresis of the reduced and native polypeptides.
168 citations
TL;DR: The experience emphasizes the importance of adequate followup in patients treated with oral vancomycin for antibiotic-associated diarrhea or colitis due to C. difficile despite susceptibility to this agent with in vitro testing.
157 citations
TL;DR: It is concluded that spectrin dimers possess a single binding site for F actin, an actin-binding protein found in erythrocytes, and may represent the first in vitro assembly of a cytoskeletal complex resembling that of the native cell both biochemically and structurally.
TL;DR: It is suggested that albumin synthesis in the elderly is controlled at a lower set point, which prevents its response to higher protein intakes, as well as whole body protein synthesis from urinary 15N-urea enrichment using the Picou and Taylor-Roberts model.
Abstract: Albumin synthesis was evaluated in 5 young adult males (19–25 yr) and 6 elderly males (64–78 yr) by a procedure involving oral administration of 15 N-glycine every 3 hr over a 60-hr period From about 40 hr onwards, urinary urea achieved a plateau of 15 N-enrichment, which was estimated from the average of the last five (low protein) or seven (adequate protein) consecutive three-hourly urinary samples of the 60-hr period This enrichment plateau was used as an index of the 15 N-enrichment of the guanidine N of hepatic free arginine The 15 N-enrichment of the guanidine N of arginine in serum albumin was determined and albumin synthesis was estimated by comparing this value with the estimated enrichment of precursor hepatic arginine Using this methodology, serum albumin concentration, synthesis, rate and plasma volume were measured when the young and elderly subjects had received an adequate protein intake (15 g · kg −1 for 7 days) or a low protein intake (04 g · kg −1 for 14 days) Serum albumin concentration was lower in the elderly at both levels of protein intake; protein intake did not affect this parameter in either age-group Plasma volume (per kg body weight) did not differ between young and old, but increased in both groups when they were given the low-protein diet, so that the total intravascular albumin mass increased in both age groups significantly in the case of the young, and was probably due to net transfer of albumin from the extravascular pool The fractional synthesis rate of the whole body albumin pool with adequate intake of protein was 40%/day in the young and 34%/day in the elderly This fractional rate was reduced significantly by giving the low-protein diet to the young subjects, but was not reduced in the elderly Absolute synthesis rates, calculated per kg body weight and per kg body cell mass, led to a similar conclusion Whole body protein synthesis was also estimated from urinary 15 N-urea enrichment using the Picou and Taylor-Roberts model Albumin synthesis as a percentage of whole body protein synthesis (5%–6%) was reduced in the young adults by giving the low-protein diet, but was unchanged in the elderly In conclusion, the rate of albumin synthesis in the young, but not in the elderly, is sensitive to changes in protein intake It is suggested that albumin synthesis in the elderly is controlled at a lower set point, which prevents its response to higher protein intakes
TL;DR: It is found that the photoreceptor-retinal pigment epithelial (RPE) complex accounts for two thirds of total oxygen consumption and substantially influences oxygen transport between the choroid and the inner retina.
TL;DR: Oviposition and larval feeding behaviors of the crucifer specialist Pieris napi macdunnoughii correlate with leaf glucosinolate profils of plant species in a natural community, and it is suggested that allelochemically similar community associates influence the coevolution of individual plant species with insect herbivores.
TL;DR: It was concluded that the accumulation of intramitochondrial adenine nucleotides, via the net uptake of ATP or ADP, probably accounted for the postnatal maturation of adenin nucleotide translocase activity and State 3 respiration.
TL;DR: It is shown that transformation of spectrin tetramers to dimers, as induced by ghost incubation in hypotonic conditions, diminishes the structural stability of the Triton-insoluble membrane skeletons.
Abstract: The inner side of the red-cell membrane is laminated by a two-dimensional network of membrane proteins which include spectrin, actin and some other components1–4. After extraction of lipids and integral proteins from the membrane, this membrane skeleton can be visualized as a ball-shaped network consisting of twisted fibres1–4 and globular protrusions4; however, the assembly of the individual proteins in the membrane skeleton is not well understood. Spectrin can be eluted from the membrane in the form of dimers and tetramers5–8. Electron microscopic study with low-angle shadowing technique shows that spectrin dimers are two parallel strands of twisted fibres presumably representing bands 1 and 2 of spectrin9. Spectrin tetramers presumably formed by head-to-head associations of two dimers are twice as long9. In solution, the spectrin dimer–tetramer equilibrium depends on temperature and salt concentration7,8; however, it is not known whether the same equilibrium exists in the membrane and whether it affects the physical properties of the membrane, such as its structural stability and deformability. We now demonstrate that spectrin dimers and tetramers are in a reversible equilibrium in the membrane and that in physiological conditions this equilibrium favours spectrin tetramers. Furthermore, we show that transformation of spectrin tetramers to dimers, as induced by ghost incubation in hypotonic conditions, diminishes the structural stability of the Triton-insoluble membrane skeletons.
TL;DR: The heat-labile enterotoxin of Escherichia coli, like cholera toxin, activates adenylate cyclase by catalyzing the transfer of adenosine diphosphate-ribose from HAD+ to the guanyl nucleotide-dependent regulatory component of the cyclase.
Abstract: The heat-labile enterotoxin of Escherichia coli, like cholera toxin, activates adenylate cyclase by catalyzing the transfer of adenosine diphosphate-ribose from HAD+ (oxidized nicotinamide adenine dinucleotide) to the guanyl nucleotide-dependent regulatory component of the cyclase. A preparation of enterotoxin that had been released from E. coli following exposure to polymyxin B and then partially purified was found to contain two enzymatically active peptides, one of about 29,000 and the other of about 24,000 daltons, which correspond in molecular size to the enzymatically active subunit A and fragment A1 of cholera toxin, respectively. As with cholera toxin, the enzymatic activity of E. coli enterotoxin was elevated by incubation with sodium dodecyl sulfate to release active peptides. Treatment with dithiothreitol, however, had no effect. Dithiothreitol activates subunit A of cholera toxin by reducing an internal disulfide bond, but no corresponding bond appears to be present in the partially purified E. coli enterotoxin.
TL;DR: The data suggest that the therapeutic benefit of cholestyramine in some patients with antibiotic-associated pseudomembranous colitis is due to its binding of the C. difficile cytotoxin.
Abstract: Cholestyramine and colestipol were tested for binding of Clostridium difficile cytotoxin with use of batch absorption and column chromatography. The toxin was bound by both resins and could not be eluted from cholestyramine with either an ionic of a pH gradient. Vancomycin bound to cholestyramine more strongly than to colestipol. Cholestyramine and vancomycin were also tested for therapeutic efficacy in the hamster model of clindamycin-induced cecitis. Both compounds delayed death and reduced levels of cytotoxin in stool; these effects were greatest for vancomycin. Use of the two compounds in combination reduced concentrations of biologically active vancomycin in stool, but the levels still exceeded the minimum inhibitory concentration for C. difficile. These data suggest that the therapeutic benefit of cholestyramine in some patients with antibiotic-associated pseudomembranous colitis is due to its binding of the C. difficile cytotoxin. Since anion-exchange resins also bind vancomycin, caution is necessary if resins are used concurrently with vancomycin for therapy.
TL;DR: The aggression-enhancing effects of alcohol and CDP in the neutral cage situation are consistent with the view that both drugs can lead to behavioral disinhibition and provide evidence for an additive interaction of both drugs in their depressant effects and, also, in their aggressionheightening effects.
Abstract: The purpose of the present experiments was to investigate conditions under which alcohol and chlordiazepoxide (CDP) enhance aggression. Alcohol (300, 600, and 1200 mg/kg orally) and CDP (5, 10, and 20 mg/kg) failed to alter attack behavior in male mice confronting intruder mice in their home cages. When confrontations between attack-experienced mice and group-housed mice occurred in a neutral cage, attack and threat behavior was suppressed to about 50% of that in the resident's home cage. A low dose of alcohol (300 mg/kg) more than doubled the frequency of attacks and threats in the neutral cage. Higher doses of both drugs decreased attacks in the neutral cage. Combined administration of low doses of alcohol (150 and 300 mg/kg) and CDP (2.5 and 5.0 mg/kg) increased attack and threat frequency in the neutral cage to a larger extent than when either drug was given itself. The aggression-enhancing effects of alcohol and CDP in the neutral cage situation are consistent with the view that both drugs can lead to behavioral disinhibition. Alternatively, the results could reflect simply the ratedependency of alcohol effects on attack behavior, that is, low rates are increased whereas high rates remain unaffected. The present results also provide evidence for an additive interaction of both drugs in their depressant effects and, also, in their aggressionheightening effects.
TL;DR: Dietary self-selection of the three macronutrients, protein, carbohydrate and fat, was examined in male rats following the administration of three doses of morphine sulphate, resulting in an overall increase in fat intake.
Abstract: Dietary self-selection of the three macronutrients, protein, carbohydrate and fat, was examined in male rats following the administration of three doses of morphine sulphate: 10 mg, 15 mg, and 30 mg/kg body weight. Intakes of all three macronutrients were suppressed in a dose-dependent manner for a two-hour period following morphine administration. Both protein and carbohydrate intakes remained suppressed for a six-hour feeding period after morphine injections. In contrast, animals increased fat intake during the final four hours of the six-hour feeding period resulting in an overall increase in fat intake.
TL;DR: Findings indicate that normal diets cause only small elevations in plasma choline; purified lecithin supplements are likely to have greater effects in treating neurologic diseases.
Abstract: We examined plasma choline changes after ingestion of diets composed of common foodstuffs, with choline contents bracketing the average daily intake in the American diet, and ingestion of diets supplemented with exogenous purified lecithin. A diet with low choline content did not increase plasma choline concentrations; a diet with high choline content doubled plasma choline levels. A lecithin-supplemented (25 gm; 80% phosphatidylcholine) low-choline diet increased plasma choline levels 400%. These findings indicate that normal diets cause only small elevations in plasma choline; purified lecithin supplements are likely to have greater effects in treating neurologic diseases.
TL;DR: The results emphasize the heterogeneity of SLE antinative DNA antibodies, confirm that secondary structure of the antigen is important for specific binding to these antibodies, and support the suggestion that bivalent binding to one molecule may be important for high functional affinity.
Abstract: Double-stranded DNA fragments of varying sizes were isolated and tested for binding to systemic lupus erythematosus (SLE) antinative DNA antibodies. Fragments of 20-25, 40-50, 90-110, and 160-180 base pairs (bp), along with intermediate-size pieces were isolated by preparative gel electrophoresis of a limited micrococcal nuclease digest of calf thymus DNA. Larger helical polynucleotides of 160-200, 380, 600-1,000, and 1,200 bp were isolated by preparative gel electrophoresis of DNA from chicken erythrocyte nucleosomes and oligonucleosomes. The fragments behaved as base-paired structures as tested by thermal denaturation, resistance to S1 nuclease, and serological assays with antibodies to native or denatured DNA. At a concentration of 0.27 muM, fragments of 20-25 bp were able to react with two SLE sera in competition with native DNA. With these and two other sera, DNA of 40-50 bp was a much more effective competitor. One serum required DNA greater than 180 bp for competition in the concentration range tested. Denatured fragments were much less effective than native fragments. The results emphasize the heterogeneity of SLE antinative DNA antibodies, confirm that secondary structure of the antigen is important for specific binding to these antibodies, and support the suggestion that bivalent binding to one molecule may be important for high functional affinity.
TL;DR: In this article, the authors employ a device due to McGehee to discuss the qualitative behavior of orbits which reach or come close to triple collision in a special case of the planar three body problem.
Abstract: We employ a device due to McGehee to discuss the qualitative behavior of orbits which reach or come close to triple collision in a special case of the planar three body problem. We show that there exist infinitely many orbits which both begin and end in triple collision. Nearby orbits behave in different ways depending on whether they pass close to the collinear or equilateral triangle central configuration. Finally, we discuss a new type of orbit in the three body problem which we call “billiard shots”.
TL;DR: It is postulated that serotonin affects active intestinal electrolyte transport by a mechanism dependent on serosal but not mucosal calcium that involves an increase in the intestinal plasma membrane permeability to calcium, and perhaps a increase in intracellular calcium.
Abstract: These studies describe the calcium dependence of the serotonin-induced changes in active electrolyte transport in rabbit ileum in vitro. In the presence of a standard calcium concentration (1.2 mM) in the serosal bathing fluid, serosal serotonin caused a transient increase in short-circuit current and a prolonged decrease in net Na and Cl fluxes. Removing calcium from the serosal (no calcium plus 1 mM EGTA) but not the mucosal bathing fluid inhibited the serotoin-induced increase in ileal short-circuit current, and also completely blocked the serotonin effects on net Na and net Cl fluxes. This inhibition was rapidly reversed by readding calcium. Removing serosal calcium did not inhibit all active electrolyte transport processes, as the effect of a maximum concentration of theophylline (10 mM) was not altered. Similarly, d,l-verapamil, a calcium channel blocker, inhibited the serotonin-induced changes in short-circuit current and in net Na and net Cl fluxes, but did not alter the theophylline effects. In contrast, d-verapamil, a stereoisomer which does not block calcium channels, did not inhibit the serotonin-induced changes. The calcium dependence of these serotonin effects was associated with increased uptake of 45Ca into rabbit ileum, including increaed 45Ca uptake from the serosal surface. Serotonin also increased the rate of 45Ca efflux from rabbit ileum into a calcium-free solution, compatible with serotonin increasing the ileal plasma membrane permeability to calcium. It is postulated that serotonin affects active intestinal electrolyte transport by a mechanism dependent on serosal but not mucosal calcium that involves an increase in the intestinal plasma membrane permeability to calcium, and perhaps an increase in intracellular calcium.
TL;DR: Cells projecting to the median eminence were found in the periventricular regions of the hypothalamus and were particularly pronounced in dorsal portions of the rostral arcuate nucleus, the medial division of the paraventricular nucleus, and within the anterior perivocentular nucleus.
TL;DR: DZ and DMDZ concentrations in CSF, presumed to reflect concentrations at the site of action, are determined by unbound plasma concentrations, because the intensity of pharmacologic action is more likely to correlate with unbound than with total plasma concentrations.
Abstract: Five dogs received a single 1.0 mg/kg dose of diazepam (DZ) IV. Concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were simultaneously measured in plasma and cisternal cerebrospinal fluid (CSF) for up to 8 h after the dose by electron-capture gas-liquid chromatography. DZ was rapidly eliminated from plasma (half-life 0.3--1.3 h); DZ disappearance was mirrored by formation of DMDZ, which in turn was eliminated slowly, Both DZ and DMDZ rapidly penetrated CSF and concentrations in CSF declined parallel with those in plasma. Despite rapid uptake, the extent of CSF transfer of DZ and DMDZ was limited by plasma protein binding. Mean CSF:plasma concentrtion ratios for DZ (range 0.023--0.137) and DMDZ (range 0.047--0.119) were highly correlated with the unbound fraction in plasma (r = 0.95 and 0.80, respectively). Thus DZ and DMDZ concentrations in CSF, presumed to reflect concentrations at the site of action, are determined by unbound plasma concentrations. The intensity of pharmacologic action is more likely to correlate with unbound than with total plasma concentrations.
TL;DR: Data indicate that vancomycin, given orally, decreases the concentration of toxin, but C. difficile survive as spores, by contrast, large populations of vegetative cells and high cytotoxin levels persist when clindamycin is used, even at an inhibitory concentration.
Abstract: Germfree mice associated with Clostridium difficile developed intestinal disease characterized by polymorphonuclear cell infiltration of the lamina propria, diarrhea, and cecal cytotoxin concentrations positive at a 10(-6) dilution. The numbers of viable bacteria never exceeded 10(10) colony-forming units per g (dry weight). Despite the high toxin levels and chronic inflammation over a 30-day period, the mortality rate was low (less than 2%). Daily treatment of these animals with two oral doses of 2 mg of vancomycin resulted in stool levels of greater than 200 micrograms/ml, well in excess of the minimum inhibitory concentration for C. difficile. This therapy decreased viable cell density by 2 to 3 logs and increased the spore counts from 10(5.8) to 10(7.8) colony-forming units per g (dry weight) by day 7, and animals were free of detectable toxin. However, once therapy was stopped, viable bacteria and spore counts and cytotoxin concentrations returned to previous levels. Treatment of mice with concentrations of clindamycin shown to be inhibitory in vitro had no effect on C. difficile toxin titers or bacterial counts, although the appearance of a clindamycin-resistant population was noted. These data indicate that vancomycin, given orally, decreases the concentration of toxin, but C. difficile survive as spores. By contrast, large populations of vegetative cells and high cytotoxin levels persist when clindamycin is used, even at an inhibitory concentration.
TL;DR: The value of early treatment of infantile spasms suggests that the treatment of this disease should be regarded as a medical emergency.
TL;DR: Plasma desmethyldiazepam concentrations were determined in venous blood samples drawn up to 9 days after the dose, and age can influence DMDZ kinetics, but changes in drug disposition with age may differ between sexes.
Abstract: Our subjects were 15 young (aged 22 to 42 yr) and 14 elderly (aged 62 to 85 yr) people who took single oral doses of 20 mg prazepam. Plasma desmethyldiazepam (DMDZ) concentrations were determined in venous blood samples drawn up to 9 days after the dose. Appearance in blood of DMDZ was slow, with peak plasma levels reached in an average of 10 to 20 hr. First-order DMDZ appearance was observed in only 17 subjects. Volume of distribution of total DMDZ (range, 1.33 to 6.30 l/kg) and of unbound DMDZ after correction for protein binding (range, 43 to 243 l/kg) was larger in women than in men of all ages, and in the elderly as opposed to the young. Elimination half-life (range, 29 to 224 hr) rose with age in men (r = 0.66, p < 0.01) but not in women (r = −0.02). Clearance of unbound DMDZ (range, 2.9 to 31.2 ml/min/kg) was greater in women than in men of all ages, and declined with age in men (r = −0.40) but not in women (r = −0.06). As in the case of diazepam, age can influence DMDZ kinetics, but changes in drug disposition with age may differ between sexes.
Clinical Pharmacology and Therapeutics (1980) 28, 196–202; doi:10.1038/clpt.1980.150