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Attitude of Health Personnel↗
Biomedical subjects
K Doan
Publications and source records attributed to K Doan.
A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.
BACKGROUND AND METHODS: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. RESULTS: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. CONCLUSIONS: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.
Administration, Cutaneous↗
A novel endothelial-derived lipase that modulates HDL metabolism.
High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease. At least 50% of the variation in HDL cholesterol levels is genetically determined, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism and the HL (LIPC) locus has been associated with variation in HDL cholesterol levels in humans. We describe here the cloning and in vivo functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells in vitro and thus has been termed endothelial lipase (encoded by the LIPG gene). EL is expressed in vivo in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and in vivo effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.
Amino Acid Sequence↗
Efficacy of a nicotine inhaler in smoking cessation: a double-blind, placebo-controlled trial.
A non-combustible nicotine inhaler, administered orally, has been developed for treatment of smokers. The inhaler allows weaning from nicotine while maintaining partial reinforcement of the ritual/sensory phenomena of smoking. Subjects were randomly assigned to active (n = 112) and placebo (n = 111) groups. Some behavioral intervention occurred as a function of participation. Strict abstinence (primary outcome criterion) was defined by CO < or = 8 ppm with no slips allowed at any time and cotinine values < or = 14 at 1 year. Survival analysis showed active inhaler was superior to placebo (p < 0.01). Active vs. placebo success rates were: 63% vs. 47% (day 3), 46% vs. 28% (week 1), 36% vs. 19% (week 2), 33% vs. 16% (week 3), 29% vs. 14% (week 6), 24% vs. 10% (3 months), 17% vs. 9% (6 months) and 13% vs. 8% (1 year). chi 2 analyses were significant through 3 months but not at 6 months (p < 0.08) or 1 year. Craving was relieved with active inhalers at day 3 and week 1. Subjects averaged six inhalers/day. Cotinine levels were 57-61% of smoking levels. Common side effects included throat/mouth irritation and coughing. Failure was predicted by early slips. The inhaler is clearly useful for short-term smoking cessation with potential for long-term efficacy. Extended access to the inhaler and relapse prevention training could improve success rates. Another promising approach would be to combine the inhaler with a nicotine patch.
Adult↗
Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial.
Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation but absolute success rates are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safety and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8-32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO < or = 8 ppm; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.
Administration, Intranasal↗
Cloning and sequencing of the cDNA encoding a human testis phospholipid hydroperoxide glutathione peroxidase.
A human cDNA that encodes a polypeptide that has 94% deduced amino-acid sequence identity to porcine phospholipid hydroperoxide glutathione peroxidase was cloned from a testis library. The sequence shows preservation of the UGA selenocysteine codon, putative active-site Trp and Glu residues and a Tyr residue that is phosphorylated in the porcine protein. The 3'-UTR shows some conservation of sequences implicated in the insertion of selenocysteine at an opal codon in human glutathione peroxidase-1.
Amino Acid Sequence↗
Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents.
We analyzed the expression of plasma glutathione peroxidase (GSHPx-P) messenger RNA (mRNA) in mouse, rat, and human tissues, using a human GSHPx-P cDNA clone as the probe. Unlike the classical cellular glutathione peroxidase (GSHPx-1), GSHPx-P expression appears to be tissue-specific. In the mouse and rat, kidney expresses an mRNA at a high level detected with the human probe. A signal is also detected in mRNA isolated from mouse and rat heart, rat cardiac myocytes, mouse lung, epididymis, and the mammary gland of midpregnant mice. No signal is detected in mRNA isolated from mouse and rat liver, mouse brain, uterus, and testis. In human tissues, an mRNA hybridizing to GSHPx-P cDNA is present in liver, as well as kidney, heart, lung, breast, and placenta. We have shown that human kidney expresses a GSHPx-P mRNA, and not a GSHPx-P-like message, by isolating a cDNA clone from a human kidney library in lambda gt11. From the 412-nucleotide partial sequence of the kidney cDNA, which codes for the 40-170 amino acids of GSHPx-P including the TGA codon for selenocysteine, we found complete sequence identity of the kidney cDNA with GSHPx-P isolated from placenta. The expression of GSHPx-P mRNA in cell lines was also studied. There is some correlation of the expression of GSHPx-P in these cell lines with that in normal tissues. Cell lines that expressed GSHPx-P mRNA or protein included the human hepatocarcinoma HepG2, Hep3B cells, human kidney carcinoma A498 cells, and the human breast cancer SK-BR-3, T47D, MDA-MB-231, and AdrrMCF-7 cells. Cell lines that did not express GSHPx-P included human choriocarcinoma BeWo cells, human breast cancer MCF-7, ZR-75-1, and Hs578T cells, and mouse hepatoma Hepa-1 cells.
Amino Acid Sequence↗
Helianthus annuus ssp. texanus has chloroplast DNA and nuclear ribosomal RNA genes of Helianthus debilis ssp. cucumerifolius.
Heiser [Heiser, C. B. (1951) Evolution 5, 42-51] hypothesized that Helianthus annuus ssp. texanus was derived by the introduction of H. annuus into Texas and subsequent introgression of genes from Helianthus debilis ssp. cucumerifolius into H. annuus. Although often considered to be one of the best cases of introgression in plants, alternative hypotheses to introgression, such as convergence or the joint retention of the ancestral condition, could not be ruled out in the original study. To test for the occurrence of introgression we examined 14 populations of H. annuus ssp. texanus, 14 allopatric populations of H. annuus, and three populations of H. debilis ssp. cucumerifolius with reference to diagnostic chloroplast DNA and nuclear ribosomal DNA markers. Thirteen of the 14 populations of H. annuus ssp. texanus had chloroplast DNA and/or ribosomal DNA markers of H. debilis ssp. cucumerifolius. In contrast, no chloroplast DNA or ribosomal DNA markers of H. debilis ssp. cucumerifolius were found in the 14 allopatric populations of H. annuus. Our findings provide strong support, therefore, for the hypothesized introgressive origin of H. annuus ssp. texanus.
Journal Article↗
Improved regional selectivity of hepatic arterial BCNU with degradable microspheres.
Starch microspheres 40 micrometers in diameter, which are rapidly degraded by serum amylase, have been administered through hepatic arterial catheters to five patients with primary and metastatic liver cancer to determine whether (1) arterial blood flow through the liver could be temporarily blocked, and (2) such occlusion at the level of the arteriolar capillary bed would enhance regional uptake and catabolism and decrease systemic exposure to simultaneously administered hepatic arterial bischlorethylnitrosourea (BCNU). It was possible with 10 ml of microspheres (9 X 10(6) microspheres/ml) injected into the hepatic artery to transiently (for 15-30 minutes) reduce hepatic flow by 80-100% in the five patients. When BCNU (50 mg/m2 in one minute) was given with microspheres there was a 30-90% reduction in systemic nitrosourea exposure and in peak levels. No myelosuppression was noted and hepatic toxicity consisted of acute pain due to BCNU and 1.5-2.0 fold transient enzyme elevations. One patient with cholangiocarcinoma showed a partial response lasting three months; three patients had stable disease and one patient with colon carcinoma had progressive disease. Thus, this pilot study suggests that concurrent intra-arterial microspheres and BCNU may have the potential to improve selective regional drug effect with marked diminution in systemic toxicity.
Carmustine↗
Totally implanted system for intravenous chemotherapy in patients with cancer.
A totally implanted system for improved central venous access has been investigated in 20 patients with cancer (six with solid tumors, four with leukemia, and 10 with lymphomas) who were treated with aggressive chemotherapy regimens and who lacked peripheral venous sites. The system is implanted using local anesthesia and consists of a subcutaneous injection port connected to a Silastic catheter threaded through the subclavian vein into the superior vena cava. Injections and continuous infusions (for up to three weeks) of virtually all classes of antineoplastic agents, antibiotics, blood components, and intravenous solutions were administered through the system. The system was filled with heparinized saline and not otherwise flushed between uses. The system has remained functional for periods exceeding 450 days (mean 235 days). There was no significant local irritation and no system became infected. None of 18 large-bore catheters (0.63 mm lumen) became occluded (seven to 300 days), whereas five of six small-bore catheters (0.38 mm lumen) became occluded (90 to 420 days). Three of the occluded systems were replaced. Acceptance has been excellent, and patients have had no impediment to normal activities. This system appears to be an alternate means of safe and reliable central venous access with improved convenience and cosmetic acceptability.
Antineoplastic Agents↗
Benefit from and tolerance to continuous intrathecal infusion of morphine for intractable cancer pain.
A patient with painful bilateral metastatic lumbosacral plexopathy from cervical cancer was treated with levorphanol tartrate (Levo-Dromoran), 4 mg orally every 4 hours, with poor pain relief. A lumbar subarachnoid catheter was then placed percutaneously. A bolus of 1 mg of morphine gave complete pain relief for 17 hours. Over the next week, the dose requirement increased to 10 mg/day, infused by an external pump. A permanently implantable infusion pump with a 50-cc drug chamber and flow rate of 3.4 cc/day was placed in the abdomen and attached to the lumbar subarachnoid catheter. The pump was refilled by percutaneous injection. Morphine was infused continuously at 15 mg/day, affording the patient increased mobility and no pain for 7 days. When the pain returned, the morphine dose was increased to 17.5 mg/day, and the patient was allowed to take oral Levo-Dromoran for pain. The intrathecal morphine dose was constant within 2-week periods, but was increased from 17.5 to 96 mg/day because of inadequate pain relief. Oral Levo-Dromoran intake averaged 3.4 mg/day. Levo-Dromoran intake was less during the 1st week of each 2-week cycle than the last week (mean 15.0 versus 38.0 mg/wk, p less than 0.05). No sedation or respiratory depression was seen.
Adenocarcinoma↗
Perfusion scintigraphy (Tc-99m MAA) during surgery for placement of chemotherapy catheter in hepatic artery: concise communication.
In 17 patients receiving regional hepatic chemotherapy, Tc-99m macroaggregated albumin imaging was used to aid arterial catheter placement and to assess perfusion patterns. Intraoperative imaging with a portable gamma camera allowed immediate monitoring of hepatic and extrahepatic perfusion patterns and assisted catheter manipulation when necessary to achieve optimal flow distribution. In all 12 patients with standard hepatic arterial anatomy, complete perfusion of both lobes of the liver was achieved, although three of them required intraoperative catheter manipulation and repeat imaging after initial placement. The remaining five patients had aberrant hepatic arterial anatomy, and complete perfusion was more difficult to achieve; they exemplified the need for dual catheters, ligation of accessory hepatic branches, and repeated imaging.
Adenocarcinoma↗
Totally implanted venous and arterial access system to replace external catheters in cancer treatment.
A totally implanted venous and arterial access system was tested in 30 cancer patients. The device, an injection port (Infuse-A-Port, Infusaid Corp., Sharon, Mass.), consisted of a 3.5 by 1.5 cm conical chamber with a self-sealing silicone rubber septum connected to a Silastic catheter. Ten patents had the injection port operatively placed for arterial access. A total of 39 bolus injections and 18 continuous infusions lasting an average 5.4 +/- 3.4 days were administered through the port. The total time of arterial access ranged from 70 to 370 days. No special program of heparinization was required to maintain patency. The injection port was used for central venous access in 20 patients. The first six patients had a small lumen catheter of 0.38 mm internal diameter, and five had occlusion between 142 and 447 days. Subsequently, 19 ports with a larger catheter lumen of 0.63 mm were used. These ports functioned for an average of 274 +/- 110 days (23 to 382 days). There were 380 single bolus injections and 64 continuous infusions. A variety of anticancer agents as well as whole blood, blood products, and antibiotics were administered with the device without difficulty. Patient acceptance was excellent.
Adult↗
Intra-arterial BCNU chemotherapy for the treatment of malignant gliomas of the central nervous system: a preliminary report.
We treated six patients with unilateral malignant astrocytomas with pulse doses of intra-arterial BCNU (200 mg/m2 initially, with escalating doses every 6-8 weeks) via transfemoral selective internal carotid catheterization. Four patients had had partial resections without prior radiation therapy and received no steroids. They had decreased tumor stain and surrounding edema after two to four cycles of chemotherapy. For one patient, results of the neurologic examination returned to normal, with total disappearance of her tumor as assessed by computerized tomographic scan. Objective tumor response continued for 7 months in three patients and for 3 months in one. In two of the four patients, chemotherapy was discontinued because of retinal toxicity and not because of treatment failure. Two patients had had partial resections and radiation therapy. One patient had stable disease for 4 months, and the second had progressive disease with gradual visual loss beginning in the infused eye 3 weeks after the second treatment. The catheterization procedure is safe; it was without immediate complication in 17 BCNU infusions. In summary, high-dose intra-arterial BCNU is well-tolerated and is an effective initial chemotherapeutic modality.
Adult↗