Search PubMed⌕ Search

Biomedical subjects

S E Sherman

Publications and source records attributed to S E Sherman.

At least 19 recordsLinked to original sources
PubMed1994

Physical activity and mortality in women in the Framingham Heart Study.

Men who are more active live longer, but it is not clear if the same is true for women. We monitored 1404 women aged 50 to 74 who were free of cardiovascular disease. We assessed physical activity levels and ranked subjects into quartiles. After 16 years, 319 (23%) women had died. The relative risk of mortality, compared to the least active quartile, was as follows: second quartile, 0.95 (95% confidence interval [CI] 0.72 to 1.26); third quartile, 0.63 (95% CI 0.46 to 0.86); most active quartile, 0.67 (95% CI 0.48 to 0.92). The relative risks were not changed by adjustment for cardiac risk factors, chronic obstructive pulmonary disease, or cancer or by excluding all subjects who died in the first 6 years (to eliminate occult disease at baseline). There was no association between activity levels and cardiovascular morbidity or mortality. We conclude that women who were more active lived longer; this effect was not the result of decreased cardiovascular disease.

Age Factors↗
PubMed1994

Does exercise reduce mortality rates in the elderly? Experience from the Framingham Heart Study.

Regular physical activity decreases the mortality rate in middle-aged men and probably in middle-aged women. It is unknown whether this is also true in the elderly. We studied 285 men and women aged 75 years or older who were free of cardiovascular disease. Subjects were ranked by baseline physical activity levels and grouped into quartiles. After adjustments were made for cardiac risk factors, chronic obstructive pulmonary disease, and cancer, women in the second most active quartile had a much lower risk of mortality at 10 years (relative risk 0.24, 95% confidence interval 0.12 to 0.51). There was no statistically significant difference in men. There appeared to be an excess of sudden cardiac deaths in the most active women, although this group still lived longer than the least active women. We conclude that women aged 75 years or older who are more active live longer. This benefit may be attenuated in those who are extremely active.

Aged↗
PubMed1992

Intrathecal oxymetazoline does not produce neurotoxicity in the spinal cord of the rat.

To determine if intrathecal (i.t.) oxymetazoline (OXY) induces histological evidence of spinal neurotoxicity, male, Sprague-Dawley rats (300-450 g; implanted with an i.t. catheter) were treated with i.t. saline or 100 nmol OXY twice daily for 3 days, or 200 or 300 nmol OXY once daily for 3 days. Spantide (D-Arg1, D-Try7,9, Leu11-substance P; 0.067 nmol = 0.1 microgram, 0.167 nmol = 0.25 microgram or 0.334 nmol = 0.5 microgram) or capsaicin (0.164 mumol = 50 micrograms), given as a single i.t. injection, were used as positive controls. Animals were killed 12 h after the last injection of saline or OXY, and 72 h after spantide or capsaicin. Spinal cord sections (L1 and adjacent segments) were examined by light microscopy for changes in gross morphology, substance P-like immunoreactivity (SP-IR) and calcitonin gene related peptide-like immunoreactivity (CGRP-IR). All doses of i.t. OXY produced antinociception (tail-flick ED50 = 53.7 nmol, paw pressure withdrawal ED50 = 93.3 nmol). Rectal temperature decreased by 1.5-2.4 degrees C up to 12 h after 100 nmol of i.t. OXY. There were no signs of inflammation or necrosis, and no detectable loss or damage to either spinal afferents or motor neurons as judged by SP-IR and CGRP-IR structures in spinal cords of OXY-treated animals (all doses) as compared to i.t. saline controls. Spantide (0.1 microgram) had no antinociceptive or neurotoxic effect; 0.25 microgram induced irreversible loss of the TF reflex and transient hind limb paralysis; 0.5 microgram induced irreversible loss of TF and PP responses, permanent hind limb paralysis, bladder and bowel dysfunction. The spinal cords from these animals showed signs of extensive necrosis, cavitation, and haemorrhage in the ventral horn accompanied by a loss of CGRP-IR motor neurons. Capsaicin-treated rats exhibited a permanent loss of the TF but not the PP response and a marked reduction of SP-IR spinal afferents in the dorsal horn. It is concluded that i.t. OXY produces antinociception in the rat with no detectable spinal neurotoxicity as assessed by parameters which are sensitive to the neurotoxins, spantide and capsaicin.

Analgesics↗
PubMed1992

Long-term diabetes alters the hepatobiliary clearance of acetaminophen, bilirubin and digoxin.

The effect of insulin-dependent diabetes on hepatobiliary clearance of acetaminophen, bilirubin and digoxin was determined using Sprague-Dawley rats that were treated with a 45 mg/kg dose of streptozotocin 28 days before experimentation. Urinary excretion of acetaminophen was increased 280%, whereas biliary excretion was decreased 65% and total clearance was unchanged. Both steady-state volume of distribution and elimination half-life of acetaminophen were decreased in diabetic rats by 23 and 25%, respectively. Biliary excretion of glucuronide and sulfate conjugates was decreased by 75 and 50%, respectively, whereas parent acetaminophen excretion was unchanged. The glutathione conjugate was only detected in normal and insulin-treated rats; however, comparable levels of a cysteine conjugate were detected in bile of diabetic rats. Administration of insulin reversed the hyperglycemia and the changes in volume of distribution, elimination half-life and glutathione excretion. Other diabetes-induced alterations were unchanged. In contrast, digoxin plasma disappearance, volume of distribution and total clearance were significantly increased in diabetic rats, whereas the elimination half-life was decreased. Administration of insulin reversed the changes in serum disappearance and partially reversed the increased biliary excretion of digoxin. No differences were observed for the serum disappearance, glucuronidation or biliary excretion of bilirubin in diabetic vs. normal rats. These data indicate that insulin deficiency for 1 month can alter hepatic excretory function and the pharmacokinetics of commonly used drugs.

Acetaminophen↗
PubMed1990

Molecular structure of the complex formed between the anticancer drug cisplatin and d(pGpG): C222(1) crystal form.

The three dimensional molecular structure of the adduct formed between the anticancer drug cisplatin and a DNA dinucleotide d(pGpG) has been determined by x-ray diffraction analysis at 1.37 A resolution and refined to a final R-factor of 0.11. This structure, solved by using data from a previously reported crystal form in the space group C222(1), resembles that found in the space group P2(1)2(1)2 (Sherman, et al., Science, 230, 412-417, 1985; ibid, J. Amer. Chem. Soc. 110, 7368-7381, 1988). In both structures, four crystallographically independent cis-[Pt(NH3)2(d(pGpG]] molecules aggregate into a tetrameric cluster that is stabilized by a large number of intermolecular hydrogen bonds and base-base stacking interactions. In each molecule, the platinum atom is coordinated to the N7 atoms of two guanine bases arranged in a head-to-head orientation, resulting in a large dihedral angle between the guanines. Intermolecular guanine-guanine base pairings between different intrastrand crosslinked molecules are used extensively in the crystal lattice.

Base Composition↗
PubMed1988

Intrathecal oxymetazoline produces analgesia via spinal alpha-adrenoceptors and potentiates spinal morphine.

The intrathecal (i.t.) injection of 100 nmol of oxymetazoline to male, Sprague-Dawley rats significantly increased tail flick latency and paw pressure threshold for 10 h as compared to i.t. saline-treated rats. Oxymetazoline-induced antinociception was accompanied by a 2 degree C decrease in rectal temperature and a delayed but mild sedative effect. Intrathecal phentolamine (50 micrograms), injected 8 h after i.t. oxymetazoline, completely reversed the analgesic and hypothermic effects but did not affect sedation. The intravenous injection of oxymetazoline (100 nmol) had no effect in the paw pressure test and virtually no effect in the tail flick test. Co-injection of i.t. morphine and i.t. oxymetazoline in a molar ratio of 1:28 resulted in significant potentiation of their antinociceptive effects as determined by isobolographic analysis. For i.t. morphine alone, the ED50 and 95% confidence interval (95% CI) was 3.8 nmol (2.8-5.6) in the tail flick test and 7.7 nmol (5.4-12.8) in the paw pressure test. In the combination, the ED50 (95% CI) of i.t. morphine was 0.7 nmol (0.6-0.8) in the tail flick test and 1.2 nmol (1.1-1.4) in the paw pressure test, corresponding to an approximate 6-fold increase in potency. The data indicate that: (1) the antinociceptive and hypothermic effects of i.t. oxymetazoline at 8 h are mediated by spinal alpha-adrenoceptors; (2) peripheral sites, and probably supraspinal sites, do not contribute to i.t. oxymetazoline-induced antinociception [corrected]; and (3) oxymetazoline potentiates the analgesic effects of morphine in the spinal cord of the naive rat.

Analgesics↗
PubMed1988

Altered leukocyte protein kinase activity in atopic dermatitis.

Previous studies have demonstrated elevated cyclic-AMP-specific phosphodiesterase (PDE) activity in mononuclear leukocytes (MNL) from patients with atopic dermatitis (AD). We questioned whether increased kinase activation could account for this observation. In these studies, we measured abnormally lower basal calcium/phospholipid-dependent protein kinase (PK-C) phosphorylation in MNL from patients with AD. Basal cAMP-dependent protein kinase (PK-A) phosphorylation was concomitantly higher in MNL from patients with AD. These results are in agreement with earlier reports that PK-A activity may have a negative influence on PK-C activity in certain cell systems. Stimulation with the H1-histamine agonist, thiazolylethylamine (TEA), of MNL from normal donors but not patients with AD, resulted in statistically significant increases in PK-C phosphorylation. This implies receptor down regulation or functional desensitization in AD cells. Altered basal protein kinase phosphorylation and abnormal response to selective histamine agonists seen in MNL from patients with AD could explain elevated PDE activity.

Dermatitis, Atopic↗
PubMed1988

Tolerance to intrathecal oxymetazoline-induced analgesia, with paradigm-dependent cross-tolerance to intrathecal morphine.

Male, Sprague-Dawley rats, implanted with intrathecal (i.t.) catheters, were given repeated i.t. injections of morphine (40 nmol), oxymetazoline (100 nmol) or saline (10 microliter) at 12-h intervals for 3 days. Antinociception was determined 1 or 1.5 hr after each injection using the tail-flick and paw-pressure tests. Complete tolerance to i.t. morphine and oxymetazoline developed within 72 and 24 hr, respectively. Antinociception after i.t. oxymetazoline (100 nmol) in morphine-tolerant rats, and after i.t. morphine (20 nmol) in oxymetazoline-tolerant rats, was not significantly different from their respective effects in saline-pretreated rats. These data suggest an absence of cross-tolerance between morphine and oxymetazoline in the rat spinal cord. In a separate group of rats, the continuous i.t. infusion of morphine (26 nmol/hr) produced significant antinociception; tolerance to morphine developed within 36 hr. The antinociceptive effect of i.t. oxymetazoline (100 nmol) was significantly attenuated in rats pretreated with continuous i.t. morphine as compared to saline-pretreated rats. In rats pretreated with continuous i.t. oxymetazoline, cross-tolerance to morphine could not be determined due to severe adverse effects during oxymetazoline infusion. The results of this study suggest that functional cross-tolerance between morphine and alpha adrenoceptor agonists in the spinal cord cannot be excluded on the basis of repeated i.t. injection experiments alone.

Analgesia↗
PubMed1985

X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: cis-[Pt(NH3)2(d(pGpG))].

Crystals of the adduct of the anticancer drug cis-diamminedichloroplatinum(II), cis-DDP, with d(pGpG), its putative target on DNA in the cancer cell, have been obtained and used in an x-ray crystallographic study to elucidate the molecular structure to atomic resolution. Each of the four crystallographically independent cis-[Pt(NH3)2(d(pGpG))] molecules is comprised of a square-planar platinum atom bonded to two ammonia ligands and two N(7) atoms of guanosine nucleosides from the same chain. Base stacking of the two adjacent guanine rings is completely disrupted by coordination to the cis-(Pt(NH3)2)2+ unit. Comparison of the backbone and deoxyribose ring torsion angles with those found by previous (nuclear magnetic resonance spectroscopy) studies of this adduct in solution demonstrates that the solid state geometry is substantially the same as that in solution. The relevance of these results to the molecular mechanism of action of cis-DDP is discussed.

Cisplatin↗
PubMed1979

Evaluation of an improved suture for cataract surgery.

An improved synthetic absorbable suture for ophthalmic surgery, 8-0 Dexon "S" polyglycolic acid, was evaluated in 25 cataract extractions and, in 5 cases, compared with 8-0 Vicryl polyglactin sutures. Dexon "S" sutures caused less tissue drag than Vicryl sutures; Vicryl was more easily knotted. With respect to handling, knotting, tissue drag, absorption, and postoperative complications, the improved Dexon suture was found to be well suited for use in cataract surgery.

Aged↗
PubMed1977

Clinical comparison of pilocarpine preparations in heavily pigmented eyes: an evaluation of the influence of polymer vehicles on corneal penetration, drug availability, and duration of hypotensive activity.

Heavily pigmented eyes have been shown to be relatively resistant to pilocarpine, and present special problems in management of open-angle glaucoma. Studies have suggested that the hypotensive effect of pilocarpine may be influenced by the vehicle; therefore, 13 relatively resistant black patients (26 eyes) were selected for a clinical comparison of pilocarpine as delivered in two different polymer vehicles. One vehicle was composed of 1.67% polyvinylpyrrolidone and BP water-soluble polymers (Adsorbobase); the other of hydroxypropyl methylcellulose 0.5%. All patients had been under treatment with the pilocarpine/methylcellulose preparation; 20 of the 26 eyes were judged to be uncontrolled (IOP above 21 mm Hg). Control of intraocular pressure was promptly obtained with the pilocarpine/Adsorbobase solution, and maintained at lower pilocarpine concentrations than with the previous therapy. Often, frequency of instillation could be decreased. This clinical comparison suggests that the Adsorbobase vehicle appreciably enhances corneal penetration and availability of pilocarpine. Three cases are discussed demonstrating the need for titration when instituting a new therapy with as little as one fourth the concentration of the previous pilocarpine therapy.

Aged↗
PubMed1975

Evaluation of Dexon suture in ophthalmic surgery.

6-0 Dexon (polyglycolic acid-PGA) suture was used in 30 eyes of 25 patients in surgical procedures which included cataract extraction, strabismus surgery, and ocular plastic surgery. The suture was found to hold the wound firmly, was not absorbed prematurely, was absorbed completely at a predicted time, was relatively easy to use although the knots were large, did not cause any infection or undue tissue reaction, and did not result in any wound dehiscence or vitreous loss.

Adolescent↗