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Biomedical subjects

M A Russell

Publications and source records attributed to M A Russell.

At least 55 records · Page 3Linked to original sources
PubMed1994

Transdermal nicotine for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

Administration, Cutaneous↗
PubMed1994

Effect of subcutaneous nicotine injections of EEG alpha frequency in non-smokers: a placebo-controlled pilot study.

The effect of two subcutaneous injections of 0.6 mg nicotine, administered 40 min apart, was compared with placebo in four non-smoking subjects in a counter-balanced double-blind crossover design. The nicotine injections produced mean peak plasma nicotine concentrations of 5.3 ng/ml 10 min after the first injection and 8.5 ng/ml 10 min after the second injection. The nicotine injections produced an increase in mean dominant alpha frequency on the electroencephalogram (EEG) which was 2 Hz greater than the effect of placebo (P = 0.049) and also produced a heart-rate boost which was 8 beats per minute greater than that produced by placebo (P = 0.022). These effects on dominant alpha frequency and heart rate were most apparent in the 10 min following each nicotine injection. The increase in dominant alpha frequency found in non-smokers in this study was similar to that following nicotine inhalation in abstinent smokers in previous studies, and suggests that this is a primary effect of nicotine, rather than simply a reversal of withdrawal-induced EEG slowing.

Adult↗
PubMed1994

The pilE gene product of Pseudomonas aeruginosa, required for pilus biogenesis, shares amino acid sequence identity with the N-termini of type 4 prepilin proteins.

A new locus required for type 4 pilus biogenesis by Pseudomonas aeruginosa has been identified. A pilE mutant, designated MJ-6, was broadly resistant to pili-specific phages and unable to translocate across solid surfaces by the pilus-dependent mechanism of twitching motility (Twt-). Immunoblot analysis demonstrated that MJ-6 was devoid of pili (Pil-) but was unaffected in the production of unassembled pilin pools. Genetic studies aimed at localizing the pilE mutation on the P. aeruginosa PAO chromosome demonstrated a strong co-linkage between MJ-6 phage resistance and the proB marker located at 71 min. Cloning of the pilE gene was facilitated by the isolation and identification of a pro(B+)-containing plasmid from a PAO1 cosmid library. Upon introduction of the PAO1 proB+ cosmid clone into MJ-6, sensitivity to pili-specific phage, twitching motility and pilus production were restored. The nucleotide sequence of a 1 kb EcoRV-ClaI fragment containing the pilE region revealed a single complete open reading frame with characteristic P. aeruginosa codon bias. PilE, a protein with a molecular weight of 15,278, showed significant sequence identity to the pilin precursors of P. aeruginosa and to other type 4 prepilin proteins. The region of highest homology was localized to the N-terminal 40 amino acid residues. The putative PilE N-terminus contained a seven-residue basic leader sequence followed by a consensus cleavage site for prepilin peptidase and a largely hydrophobic region which contained tyrosine residues (Tyr-24 and Tyr-27) previously implicated in maintaining pilin subunit-subunit interactions. The requirement of PilE in pilus biogenesis was confirmed by demonstrating that chromosomal pilE insertion mutants were pilus- and twitching-motility deficient.

Amino Acid Sequence↗
PubMed1994

Age-specific patterns of mortality from cardiovascular disease and other major causes, 1969 to 1990.

There were substantial reductions in mortality rates for all causes of death and for cardiovascular diseases in all age groups examined and both sexes during the period 1969 to 1990. Among young and middle-aged women, cardiovascular diseases were no longer the major cause of death; cancers were. In younger men, accidents, poisonings and violence (including suicides) were the leading cause of death. In middle-aged men, cardiovascular mortality dropped to about the same level as cancer mortality. Only in older people did cardiovascular mortality still dominate. Nevertheless, the proportion of all deaths due to cardiovascular disease remained high and there are opportunities for further reductions. The relative lack of improvement in mortality from cancers suggests that these will form increasing proportions of the burden of disease and treatment costs in the next decades.

Adult↗
PubMed1994

Effect of nicotine on rectal mucus and mucosal eicosanoids.

Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel.

Animals↗
PubMed1993

Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches.

OBJECTIVES: (a) To evaluate the efficacy of transdermal nicotine patches as an aid to stopping smoking when used as an adjunct to brief advice and support in a general practice setting; (b) to see whether an increase in nicotine patch dosage enhances the rate of initial cessation. DESIGN: Randomised double blind placebo controlled parallel group study with one year of follow up. SETTING: 30 general practices in 15 English counties. SUBJECTS: 600 dependent heavy smokers (> or = 15 cigarettes daily) who were well motivated to give up. INTERVENTIONS: Brief general practitioner advice, booklet, and 16 hours per day patch treatment for 18 weeks with brief support and follow up at one, three, six, 12, 26, and 52 weeks. MAIN OUTCOME MEASURES: Self reported complete abstinence for up to one year with biochemical validation at all follow up points. RESULTS: Nicotine patches reduced the severity of craving and adverse mood changes in the first weeks of withdrawal and doubled the rate of initial cessation at week 3 (nicotine group 36% of patients (144/400), placebo group 16.5% of patients (33/200)) and of continuous abstinence throughout one year (nicotine group 9.3% (37), placebo group 5.0% (10)). A dose increase at week 1 among patients experiencing difficulty in quitting increased the proportion who achieved abstinence at week 3. There were no adverse systemic effects attributable to nicotine, but the incidence of moderate or severe local irritation or itching at the patch site was 16.4% (63 patients), compared with 3.8% (seven) with placebo. CONCLUSION: Transdermal nicotine patches used as an adjunct to brief advice and support in a general practice setting are an effective aid to long term cessation of smoking in highly dependent smokers.

Administration, Cutaneous↗
PubMed1993

Transdermal nicotine patches with low-intensity support to aid smoking cessation in outpatients in a general hospital. A placebo-controlled trial.

OBJECTIVE: To assess whether transdermal nicotine patches combined with low-intensity support can help outpatients in a general hospital stop smoking. DESIGN: Randomized, double-blind, placebo-controlled trial with 12 weeks of follow-up. SETTING: Department of Thoracic Medicine in an inner-city public general hospital, London, England. SUBJECTS: Two hundred forty-eight outpatients in a general hospital, who smoked at least 10 cigarettes per day (the majority were being treated for smoking-related diseases), referred by clinicians at the hospital. INTERVENTION: Brief advice to stop smoking and daily application of transdermal nicotine patches (delivering 15 mg over 16 hours) or placebo, with follow-up appointments at 1, 3, 6, and 12 weeks, with a doubling of the dosage for continuing smokers at week 1. MAIN OUTCOME MEASURE: Sustained abstinence from tobacco from week 3 to week 12 validated with measurement of expired-air carbon monoxide concentration at weeks 3, 6, and 12. RESULTS: Twenty-nine (23.4%) of 124 subjects assigned to the nicotine group were validated as having abstained from smoking at both weeks 3 and 6, compared with 16 (12.9%) of 124 subjects receiving placebo (P = .008). At week 12, 22 (17.7%) of the subjects in the nicotine group were validated as having abstained at all three points as were 15 (12.1%) of the subjects in the placebo group (P = .058). CONCLUSION: Transdermal nicotine patches combined with low-intensity support are effective in helping outpatients in a general hospital stop smoking but do not prevent relapse after 6 weeks.

Administration, Cutaneous↗
PubMed1993

Biological homogeneity and precision of measurement: the boundary conditions for normal in body composition.

For compartments most urgently important to clinical medicine we have satisfactory levels of measurement precision, and the clinical considerations now are the availability of the methods, and the collection of data for normal subjects. Our colleagues in physics and imaging will improve measurement precisions, but the work most needed is to refine the biological side of the measurement equation. Large numbers of measurements, carefully done with carefully calibrated and unchanging systems, exist only for the special case of measuring body calcium in women, in the large cohort of approximately 2,500 women, studied by Aloia and Cohn with neutron activation, and for body potassium, in these women, and in the larger numbers of diverse age, sex, race, and size in the Rosetta study in our laboratory. Can we benefit from the "orthogonal measurements" and "orthogonal physiologic constraints" approaches, in which triangulation is used to combine measurements from several techniques to establish upper-lower bounds estimates by different techniques, with convergence on a "best fit" result? We have noted that the intrinsic homeostatic mechanisms of the body function with great precision to control body temperature, osmotic and ionic concentrations in the water phase, hypertrophy of muscle with exercise, and remodeling of bone by stress. We consider it unlikely that the control mechanisms are more loosely hinged for such secondary parameters as K/FFM and bone density.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

Glycerol particle cigarettes: a less harmful option for chronic smokers.

In 20 smokers who switched to a new type of virtually tar free cigarette for three days, average nicotine intake was reduced by 44%, carbon monoxide intake increased by 19%, while estimated tar intake was reduced by about 90%. Such cigarettes pose substantially less risk of cancer and chronic obstructive lung disease than conventional cigarettes, and their acceptability and safety could be improved by increasing nicotine yield, reducing carbon monoxide yield, and improving the flavour.

Carbon Monoxide↗
PubMed1993

Gene expression during imaginal disc regeneration detected using enhancer-sensitive P-elements.

When imaginal disc fragments from Drosophila are cultured in adult female hosts, they either duplicate the part of the pattern specified by the fate map, or regenerate to replace the missing part. The new tissue is added by proliferation of a small number of cells from the cut edge, brought together when the wound heals to form a regeneration blastema. Specification of the new pattern has been explained by assuming interactions among cells of different positional value in the regeneration blastema. In order to identify genes which might mediate these events, we screened over eight hundred independently isolated autosomal insertions of an enhancer-sensitive P-element, for altered lac-z expression in regenerating discs following cell death induced by a temperature-sensitive cell-lethal mutation. Two further screens divided the positive lines into four groups based on appropriate timing of the lac-z response in the cell-lethal mutant background and the expected response to an alternate source of cell death. Expression in wing disc fragments cultured in vivo was most frequent in the target class defined by the screens. In this direct test, lac-z expression was found in 23 lines and in most cases was spatially and temporally correlated with the formation of the regeneration blastema. Our results suggest a very substantial transcriptional response during the early stages of imaginal disc regeneration. lac-z expression in control imaginal discs, embryos and adult ovaries of the positive lines was also assayed. The selected insertions included: a small class expressed only in discs undergoing regeneration and apparently not at any other stage, possibly representing genes active exclusively in regeneration; a larger class expressed in the embryo or during oogenesis, but not normally in imaginal discs, as expected for functions recruited from earlier stages of the developmental program; and finally a class with spatially patterned expression in normal discs. This class included several insertions with expression associated with compartment boundaries, including one at the decapentaplegic (dpp), and one at the crumbs (crb) locus, a growth factor homologue, and an EGF-repeat gene respectively. Some of the expression patterns observed in cultured disc fragments provide evidence for cell communication in the regeneration blastema.

Animals↗
PubMed1993

Smoking, alcohol consumption, and susceptibility to the common cold.

OBJECTIVES: This study was conducted to test the supposition that both smoking and consuming alcohol suppress host resistance to viral infections. METHODS: The relations between smoking, alcohol consumption, and the incidence of documented clinical colds were prospectively studied among 391 subjects intentionally exposed to one of five respiratory viruses and 26 subjects given saline. Clinical colds were defined as clinical symptoms verified by the isolation of virus or by an increase in virus-specific antibody titer. Analyses included control variables for demographics; body weight; virus; and environmental, immunological and psychological factors. RESULTS: Smokers were at greater risk for developing colds than nonsmokers because smokers were more likely both to develop infections and to develop illness following infection. Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness following infection. However, the benefits of drinking occurred only among nonsmokers. CONCLUSIONS: Susceptibility to colds was increased by smoking. Although alcohol consumption did not influence risk of clinical illness for smokers, moderate alcohol consumption was associated with decreased risk for nonsmokers.

Adult↗
PubMed1992

P-glycoprotein possesses a 1,4-dihydropyridine-selective drug acceptor site which is alloserically coupled to a vinca-alkaloid-selective binding site.

[3H]Vinblastine bound with high affinity to surface membranes prepared from H69/LX4 cells which express P-glycoprotein (P-gp) and as a consequence are multidrug resistant (MDR). The KD was 9.8 +/- 1.5 nM and density of sites 31.2 +/- 8.6 pmol/mg of protein. [3H]Vinblastine binding was inhibited by cytotoxics and agents known to reverse MDR. 1,4-Dihydropyridine MDR reversing agents including nicardipine and nifedipine accelerated the dissociation of [3H]vinblastine from P-gp indicating a negative heterotropic allosteric effect. Cyclosporin A, vincristine and actinomycin D did not alter [3H]vinblastine dissociation kinetics. It is concluded that P-gp possesses at least two allosterically coupled drug acceptor sites, receptor site-1 that is selective for vinca alkaloids and cyclosporin A, and receptor site-2 that is selective for 1,4-dihydropyridines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Randomised controlled trial of nasal nicotine spray in smoking cessation.

Studies with nicotine chewing gum and nicotine skin patches indicate that nicotine replacement can help people to give up smoking. The rapidity with which nicotine is absorbed when given as a nasal spray suggests that it might be effective for those for whom the other means of replacement are too slow. The efficacy and safety of a nasal nicotine spray as an adjunct to group treatment for stopping smoking were assessed in a randomised, double-blind, placebo-controlled trial in which 227 cigarette smokers attending the Maudsley Hospital Smokers Clinic received 4 weeks of supportive group treatment plus active nicotine (0.5 mg per shot) or placebo nasal spray. The main end-point was biochemically validated complete abstinence from smoking from the third week of group treatment until the 12-month follow-up. Side-effects were assessed by self-reports and, where necessary, by physical examination. Of subjects assigned to active treatment 26% (n = 30) were validated abstinent throughout the year, compared with 10% (n = 11) of those assigned to placebo (relative abstinence rate 2.6, 95% CI 1.5-4.5, p less than 0.001). The advantage of the active spray was greatest in the heaviest smokers. Plasma nicotine concentrations from the spray were typically between one-half and three-quarters of baseline smoking levels. Tobacco-withdrawal symptoms, craving for cigarettes, and weight gain in abstinent subjects were reduced by the active spray. Minor irritant side-effects were frequent in both active and placebo sprays, but only 2 subjects had the spray discontinued as a result. No serious adverse effects were encountered. Nasal nicotine spray combined with supportive group treatment is an effective aid to smoking cessation.

Administration, Intranasal↗
PubMed1992

Effect of transdermal nicotine patches on cigarette smoking: a double blind crossover study.

The effect of transdermal nicotine patches on ad libitum cigarette smoking was examined in 30 subjects by measuring behavioural, biochemical and subjective aspects of smoking during a week of smoking without patches, and then a week each of nicotine and placebo patches in a randomised double blind crossover design. While wearing nicotine patches the subjects did not reduce the number of cigarettes smoked, but their expired carbon monoxide was reduced by 14%, they obtained less satisfaction from their cigarettes, and reported fewer and weaker urges to smoke. Down-regulation of nicotine intake from cigarettes was imprecise, such that when subjects wore nicotine patches their post-cigarette plasma nicotine concentration increased to an average of 45 ng/ml compared with 37 ng/ml in both no patch and placebo patch conditions. As the nicotine patches produced a plasma nicotine concentration of 15.9 ng/ml in abstinent subjects, this suggests a 22% reduction in nicotine intake from cigarettes while wearing nicotine patches. No serious symptoms of nicotine overdose were reported. It is suggested that the continuous absorption of nicotine from the patch may cause a build-up of acute tolerance to both toxic and pleasant subjective effects from smoking.

Administration, Cutaneous↗
PubMed1992

Nicotine intake and dependence in Swedish snuff takers.

Two studies examining nicotine intake in users of Swedish moist oral snuff are reported. Absorption form a single pinch (2 g) in ten users after overnight abstinence was fairly rapid. The increment in plasma nicotine concentrations averaged 9.9 ng/ml (SD 6.5) after 10 min and peaked at 14.5 ng/ml (SD 4.6) shortly after discarding at 30 min. Among groups of habitual snuff takers (n = 27) and cigarette smokers (n = 35) studied on a day of normal snuffing/smoking, peak blood nicotine levels after use were similar [averaging 36.6 ng/ml (SD 14.4) and 36.7 ng/ml (SD 16.1), respectively], but there was a tendency to higher cotinine levels in the snuffers (399.2 ng/ml versus 306.3 ng/ml). The snuff takers and cigarette smokers reported similar levels of subjective dependence on tobacco. Epidemiological study of Swedish snuff users could clarify whether the cardiovascular risks of tobacco are attributable to nicotine or to other smoke components, as in their case nicotine intake is not accompanied by combustion products.

Adult↗
PubMed1992

Nasal nicotine spray: a rapid nicotine delivery system.

Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed.

Administration, Intranasal↗