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Biomedical subjects

D Gonzales

Publications and source records attributed to D Gonzales.

13 recordsLinked to original sources

Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial.

BACKGROUND: Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse. OBJECTIVE: To evaluate the efficacy of bupropion to prevent smoking relapse. DESIGN: Randomized, placebo-controlled trial. PARTICIPANTS: 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day. INTERVENTION: The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking. MEASUREMENT: Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less. RESULTS: The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016). CONCLUSIONS: In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain.

Adult↗

Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial.

BACKGROUND: Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD. METHODS: In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat. FINDINGS: All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events. INTERPRETATION: Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.

Adult↗

Synchronous water-clear cell double parathyroid adenomas a hitherto uncharacterized entity?

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of the water-clear cell type are exceptionally rare, and only 2 cases have been reported. We describe a patient with synchronous water-clear cell double parathyroid adenomas, an entity that has not previously been reported. In our case, the enlarged superior parathyroid glands were completely replaced by water-clear cells, with only a minute rim of extracapsular, histologically unremarkable parathyroid tissue. The inferior parathyroid glands were grossly unremarkable, and incisional biopsy specimens were histologically normal (no foci of water-clear cells were identified). The findings in this case are most consistent with the diagnosis of double adenomas of the water-clear cell type. We acknowledge that despite molecular proof of monoclonality of the 2 lesions, it is not possible to entirely exclude the possibility that this unusual case could be due to asymmetric hyperplasia.

Adenoma↗

Instability studies of porcine somatotropin in aqueous solutions and the possible reagents for its stabilization.

The instability of porcine somatotropin (pST) in various solutions and possible stabilization of the hormone by sugars and mild detergents were studied. Aggregation and decomposition of the hormone molecules in various pH solutions and under presence of sugar or detergent were monitored by gel permeation chromatography (GPC) or ultraviolet spectroscopy (UV). The pST is a very unstable hormone in an aqueous environment. It was found in this project that the peptide hormone underwent aggregation or decomposition quickly in acidic and alkaline solutions but slowly in neutral pH solutions. High losses of pST monomers were seen in concentrated solutions of the hormone. On the other hand, pST monomers were stabilized to a certain degree in glucose solutions and at a low concentration of urea. These results should facilitate the development of efficient controlled-release systems which are essential for commercializing porcine somatotropin.

Animals↗

Modular elements of the MLC 1f/3f locus confer fiber-specific transcription regulation in transgenic mice.

The two proteins encoded by the fast alkali myosin light chain (MLC) 1f/3f locus are developmentally regulated, muscle specific, and expressed exclusively in fast-twitch fibers. Their expression is independently regulated by two separate promoters and a downstream enhancer. Previous studies showed a reporter gene directed by the rat MLC If promoter and MLC enhancer to exhibit correct skeletal muscle-specific expression in transgenic mice during development and to be preferentially expressed in fast-twitch Type IIB fibers [Donoghue et al., (1991) J. Cell B.ol. 115:423-434]. The MLC 3f promoter also directed muscle-specific expression of a CAT reporter gene in adult transgenic mice and showed little dependence upon the enhancer. Here, we show that the MLC 3f promoter also directs transgene expression in the fast-twitch fibers of adult skeletal muscle, but almost exclusively to fiber Types IIA and IIX. MLC 3f transgene expression occurs in only a subset of the fiber types that express the endogenous locus, indicating modular elements included in the transgene confer fiber-specific transcription regulation. MyoD protein was also found to be restricted to fiber Types IIA and IIX, providing evidence for its possible role in mediating fiber-specific gene expression.

Animals↗

Predictors of initial smoking cessation and relapse through the first 2 years of the Lung Health Study.

Analyses were made separately for men and women of the predictors of end-of-treatment (4 months) smoking cessation and subsequent relapse at 12 and 24 months among 3,923 participants enrolled in the Lung Health Study's 12-week cognitive-behavioral group smoking cessation program. Nicotine gum (2 mg) was available to all participants. Men were more likely than women to quit smoking initially, but relapse rates were similar for both genders. Baseline variables associated with initial quitting for both genders included greater education, lower nicotine dependence, and fewer respiratory symptoms. The best predictor of relapse between 4 and 12 months was smoking at least 1 cigarette between quit day and 4 months. Nicotine gum use at 12 months predicted relapse by 24 months for both genders. Greater social and environmental support for quitting smoking were the only factors that predicted both initial quitting and relapse for both genders. Clinical implications are discussed.

Adult↗

A new endotracheal tube for carbon dioxide and KTP laser surgery of the aerodigestive tract.

We have tested the fire-resistance of a new endotracheal tube designed for use in laser surgery of the upper aerodigestive tract. This Teflon/metallic-wrapped silicone tube seems capable of withstanding occasional, accidental pulsed laser impact at power settings used clinically (1 to 10 watts) without fire. On rare occasions when continuous mode is used, the tube seems capable of withstanding at least several seconds of continuous irradiation at clinical power settings without igniting. When used with other recommended safety procedures, this tube should minimize the risk of endotracheal tube fire from accidental laser impact.

Digestive System Diseases↗

A congenic line of the BALB/c mouse strain with the endogenous mouse mammary tumor virus proviral gene Mtv-3: tissue-specific expression and correlation with resistance to mouse mammary tumor virus infection and tumorigenesis.

Mouse mammary tumor virus (MMTV) expression and MMTV-induced tumorigenesis were studied in a congenic line of the BALB/cHeA strain, termed BALB/c-Mtv-3+, that carries the Mtv-3 proviral gene. BALB/c-Mtv-3+ mice were free of milk-transmitted MMTV and did not spontaneously develop mammary tumors. A specific Mtv-3 expression was observed in the mammary gland and spleen, but not in other lymphoid tissues, such as thymus and bone marrow. This expression was hormone dependent, as shown by the increase of MMTV mRNA during pregnancy. At the protein level, large amounts of p28, but only traces of gp52, the main MMTV core and envelope antigens, respectively, were observed, in agreement with the already described "partial" expression of the Mtv-3 gene products. The presence of the 24S (3.8 kilobases) mRNA encoding the MMTV env antigens in the spleen and the low gp52 reactivity in lactating mammary glands showed that this noncoordinate expression was probably due to a defect in translation or posttranslational processing of env proteins. The susceptibility of BALB/c-Mtv-3+ to experimental MMTV infection was studied. The presence of Mtv-3 conferred to BALB/c mice resistance to MMTV infection, as shown by measuring viral antigens released in the milk of infected mice and by recording the incidence of early mammary tumors. The presence of a nontumorigenic endogenous MMTV gene was therefore protective against exogenous MMTV infection.

Animals↗

Effects of inhibitory and stimulatory photoperiods and sexual maturation on the ability of hamster testes to respond to hCG in vitro.

The decrease in gonadal weight produced in adult golden hamsters by exposure to short photoperiods was accompanied by a marked reduction in the ability of the testes to produce testosterone from endogenous precursors in vitro, both without and with hCG stimulation. These changes were significant after 4-7 weeks in short photoperiod (5L: 19D) and were even more pronounced after 17-20 weeks. Production of testosterone in vitro by testes of immature hamsters was comparable to values obtained in adult animals with short photoperiod-induced gonadal atrophy. Delay of sexual maturation induced by daily injections of bromocriptine was accompanied by a further decrease in testicular testosterone production in vitro. Exposure of gonadally-regressed adult hamsters to a long, stimulatory photoperiod (14L: 10D) produced a rapid and marked increase in testicular testosterone production, which was coincident with the previously demonstrated increase in serum gonadotrophin levels after 1-5 days of photostimulation. Furthermore, testosterone production in vitro by regressed testes of animals exposed to short photoperiod was increased significantly by one large dose of hCG administered 26 h before killing the animals. It is concluded that the suppressive effects of short photoperiods on the ability of the hamster testis to produce testosterone and to respond to hCG stimulation are due to reductions in endogenous LH, FSH and prolactin release, with a consequent loss of testicular LH/hCG receptors and decreased activity of enzymes involved in the biosynthesis of testosterone.

Animals↗

Age-related change in parathyroid hormone-dependent cyclic AMP formation in rat kidney.

Parathyroid hormone (PTH) dependent cyclic AMP (cAMP) accumulation was evaluated in renal cortex from 2- and 12-month-old rats. Basal cAMP was lower, and responses to PTH were greater at all concentrations of hormone in kidney from 2-month-old rats. This difference was obliterated by prior removal of parathyroid glands. cAMP responses to calcitonin and both basal and hormone-stimulated adenylate cyclase activity were the same at both ages. The results suggest progressive loss of responsiveness to PTH with age, but at a site other than the receptor-adenylate cyclase complex. Blunted cAMP accumulation in year-old rats most likely reflects agonist-specific desensitization.

Adenylyl Cyclases↗