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L M Lopez

Publications and source records attributed to L M Lopez.

At least 19 recordsLinked to original sources
PubMed2006

Scalpel versus no-scalpel incision for vasectomy.

BACKGROUND: Currently, the two most common surgical techniques for approaching the vas during vasectomy are the incisional method and the no-scalpel technique. Whereas the conventional incisional technique involves the use of a scalpel to make one or two incisions, the no-scalpel technique uses a sharp-pointed, forceps-like instrument to puncture the skin. The no-scalpel technique aims to reduce adverse events, especially bleeding, bruising, hematoma, infection and pain and to shorten the operating time. OBJECTIVES: The objective of this review was to compare the effectiveness, safety, and acceptability of the incisional versus no-scalpel vasectomy approach to the vas. SEARCH STRATEGY: We searched the computerized databases of CENTRAL, MEDLINE, EMBASE, POPLINE and LILACS in May 2006. In addition, we searched the reference lists of relevant articles and book chapters. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials were included in this review. No language restrictions were placed on the reporting of the trials. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts located in the literature searches and two authors independently extracted data from the articles identified for inclusion. Outcome measures included safety, acceptability, operating time, contraceptive efficacy, and discontinuation. MAIN RESULTS: Two randomized controlled trials evaluated the no-scalpel technique and differed in their findings. The larger trial demonstrated less perioperative bleeding (Odds ratio (OR) 0.49; 95% Confidence Interval (CI) 0.27 to 0.89) and pain during surgery (OR 0.75; 95% CI 0.61 to 0.93), scrotal pain (OR 0.63; 95% 0.50 to 0.80), and incisional infection (OR 0.21; 95% CI 0.06 to 0.78) during follow up than the standard incisional group. Both studies found less hematoma with the no-scalpel technique (OR 0.23; 95% CI 0.15 to 0.36). Operations using the no-scalpel approach were faster and had a quicker resumption of sexual activity. The smaller study did not find these differences; however, the study could have failed to detect differences due to a small sample size as well as a high loss to follow up. Neither trial found differences in vasectomy effectiveness between the two approaches to the vas. AUTHORS' CONCLUSIONS: The no-scalpel approach to the vas resulted in less bleeding, hematoma, infection, and pain as well as a shorter operation time than the traditional incision technique. Although no difference in effectiveness was found between the two approaches, the sample sizes might have been too small to detect actual differences. Additional well-conducted randomized trials would help answer this question.

Controlled Clinical Trials as Topic↗
PubMed2006

Steroidal contraceptives: effect on bone fractures in women.

BACKGROUND: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. However, osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally. OBJECTIVES: To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women SEARCH STRATEGY: We searched MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of fracture or bone health and hormonal contraceptives. We wrote to investigators to find additional trials. SELECTION CRITERIA: Randomized controlled trials were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Studies were excluded if hormones were provided for treatment of a specific condition rather than for contraception. Interventions could include comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive. Interventions could also include the provision of a supplement versus a placebo. DATA COLLECTION AND ANALYSIS: We assessed for inclusion all titles and abstracts identified through the literature searches with no language limitation. The weighted mean difference (WMD) was computed with 95% confidence interval (CI) using a fixed-effect model. MAIN RESULTS: No trial had fracture as an outcome. Combination contraceptives did not appear to affect bone health. Of progestin-only methods, depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density, while results were inconsistent for implants. The two placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Due to different interventions, no trials could be combined for meta-analysis. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Bone Density↗
PubMed2006

Non-steroidal anti-inflammatory drugs for heavy bleeding or pain associated with intrauterine-device use.

BACKGROUND: Heavy bleeding and pain are the most common reasons why women discontinue IUDs. Non-steroidal anti-inflammatory drugs, which inhibit prostaglandin synthesis, have been shown to be effective in reducing menstrual bleeding and pain in women without IUDs. OBJECTIVES: This review summarizes all randomized controlled trials studying use of nonsteroidal anti-inflammatory drugs for treatment of bleeding or pain associated with IUD use. Trials of prophylactic use of these drugs around the time of IUD insertion were also included. SEARCH STRATEGY: We performed searches of PubMed, CENTRAL, POPLINE, EMBASE, LILACS, and CINAHL for relevant trials. We also wrote to the authors of all trials identified to seek other published or unpublished trials. SELECTION CRITERIA: We included all randomized controlled trials in any language that tested one or more nonsteroidal anti-inflammatory drugs for treatment or prevention of bleeding or pain associated with IUD insertion or use. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data from relevant trials, and we entered data into RevMan for analysis. MAIN RESULTS: We found 15 trials from 10 countries; the total number of participants was 2702. Nonsteroidal anti-inflammatory drugs (naproxen, suprofen, mefenamic acid, ibuprofen, indomethacin, flufenamic acid, alclofenac, and diclofenac) were effective in reducing menstrual blood loss associated with IUD use. This held true for women with and without complaints of heavy bleeding. Similarly, these drugs were effective in reducing pain associated with IUD use. In contrast, prophylactic use of nonsteroidal anti-inflammatory drugs had mixed results; studies with ibuprofen found no effect on pain after insertion on IUD discontinuation. No important differences emerged in the one trial comparing the effect of different NSAIDs on bleeding. AUTHORS' CONCLUSIONS: Nonsteroidal anti-inflammatory drugs reduce bleeding and pain associated with IUD use. NSAIDs should be considered first-line therapy; if NSAIDs are ineffective, tranexamic acid may be considered as second-line therapy. Prophylactic ibuprofen administration with the first six menses after insertion appears unwarranted.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Oral contraceptives for functional ovarian cysts.

BACKGROUND: Functional ovarian cysts are a common gynecological problem among women of reproductive age worldwide. When large, persistent, or painful, these cysts may require operations, sometimes resulting in removal of the ovary. Since early oral contraceptives were associated with a reduced incidence of functional ovarian cysts, many clinicians inferred that birth control pills could be used to treat cysts as well. This became a common clinical practice in the early 1970s. OBJECTIVES: This review examined all randomized controlled trials that studied oral contraceptives as therapy for functional ovarian cysts. SEARCH STRATEGY: We searched the computer databases of CENTRAL, PubMed, POPLINE, and EMBASE for randomized controlled trials. We also examined the reference lists of articles and wrote to authors of all studies identified to seek articles we had missed. SELECTION CRITERIA: We included randomized controlled trials in any language that included oral contraceptives used for treatment and not prevention of functional ovarian cysts. Criteria for diagnosis of cysts were those used by authors of studies. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data from the articles and entered them into RevMan 4.2. We used Peto odds ratios with 95% confidence intervals for dichotomous outcomes. MAIN RESULTS: We identified four randomized controlled trials from three countries; the studies included a total of 227 women. Treatment with combined oral contraceptives did not hasten resolution of functional ovarian cysts in any trial. This held true for cysts that occurred spontaneously as well as those that developed after ovulation induction. Most cysts resolved without treatment within a few cycles; persistent cysts tended to be pathological (e.g., endometrioma or para-ovarian cyst) and not physiological. AUTHORS' CONCLUSIONS: Although widely used for treating functional ovarian cysts, combined oral contraceptives appear to be of no benefit. Watchful waiting over several cycles is appropriate. Should cysts persist, surgical management is often indicated.

Contraceptives, Oral, Combined↗
PubMed2006

Triphasic versus monophasic oral contraceptives for contraception.

BACKGROUND: Side effects of oral contraceptive pills (OCs) discourage adherence to and continuation of OC regimens. Strategies to decrease adverse effects led to the introduction of the triphasic OC in the 1980s. Whether triphasic OCs have higher accidental pregnancy rates than monophasic pills is unknown. Nor is it known if triphasic pills give better cycle control and fewer side effects than the monophasic pills. OBJECTIVES: To compare triphasic OCs with monophasic OCs in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH STRATEGY: We searched the computerized databases of MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. Additionally, we searched the reference lists of relevant articles and book chapters. We also contacted researchers and pharmaceutical companies in Europe and the U.S. to identify other trials not found in our search. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any triphasic OC with any monophasic pill used to prevent pregnancy. Interventions had to include at least three treatment cycles. DATA COLLECTION AND ANALYSIS: We assessed the studies found in the literature searches for possible inclusion and for their methodological quality. We contacted the authors of all included studies and of possibly randomized trials for supplemental information about the methods and outcomes studied. We entered the data into RevMan 4.2 and calculated odds ratios for the outcome measures of efficacy, breakthrough bleeding, spotting, withdrawal bleeding and discontinuation. MAIN RESULTS: Of 21 trials included, 18 examined contraceptive effectiveness: the triphasic and monophasic preparations did not differ significantly. Several trials reported favorable bleeding patterns, i.e. less spotting, breakthrough bleeding or amenorrhea, in triphasic versus monophasic OC users. However, meta-analysis was generally not possible due to differences in measuring and reporting the cycle disturbance data as well as differences in progestogen type and hormone dosages. No significant differences were found in the numbers of women who discontinued due to medical reasons, cycle disturbances, intermenstrual bleeding or adverse events. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine whether triphasic OCs differ from monophasic OCs in effectiveness, bleeding patterns or discontinuation rates. Therefore, we recommend monophasic pills as a first choice for women starting OC use. Large, high-quality RCTs that compare triphasic and monophasic OCs with identical progestogens are needed to determine whether triphasic pills differ from monophasic OCs. Future studies should follow the WHO recommendations on recording menstrual bleeding patterns and the CONSORT reporting guidelines.

Contraception↗
PubMed2006

Non-latex versus latex male condoms for contraception.

BACKGROUND: The male condom, which consists of a thin sheath placed over the glans and shaft of the penis, is designed to prevent pregnancy by providing a physical barrier against the deposition of semen into the vagina during intercourse. Beginning in the 1990s, nonlatex male condoms made of polyurethane film or synthetic elastomers were developed as alternative male barrier methods for individuals with allergies, sensitivities or preferences that prevented the consistent use of condoms made of latex. OBJECTIVES: The review sought to evaluate nonlatex male condoms in comparison with latex condoms in terms of contraceptive efficacy, breakage and slippage, safety, and user preferences. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of nonlatex condoms. We also wrote to the manufacturers of nonlatex condoms and known investigators in an attempt to locate any other trials not identified in our search. SELECTION CRITERIA: The review included all randomized controlled trials identified in the literature search that evaluated a male nonlatex condom made of polyurethane film or synthetic elastomers in comparison with a latex condom. DATA COLLECTION AND ANALYSIS: We evaluated all titles and abstracts located in the literature searches for inclusion. Two authors independently extracted data from the identified studies. We analyzed data with RevMan. The Peto odds ratio (Peto OR) with 95% confidence interval (CI) was calculated for each outcome of contraceptive efficacy, condom breakage and slippage, discontinuation of use, safety, and user preference. Contraceptive efficacy, early discontinuation, and safety outcomes were also measured with survival analysis techniques. MAIN RESULTS: While the eZ.on condom did not protect against pregnancy as well as its latex comparison condom, no differences were found in the typical-use efficacy between the Avanti and the Standard Tactylon and their latex counterparts. The nonlatex condoms had significantly higher rates of clinical breakage than their latex comparison condoms: the Peto OR for clinical breakage ranged from 2.6 (95% CI 1.6 to 4.3) to 5.0 (95% CI 3.6 to 6.8). Few adverse events were reported. Substantial proportions of participants preferred the nonlatex condom or reported that they would recommend its use to others. AUTHORS' CONCLUSIONS: Although the nonlatex condoms were associated with higher rates of clinical breakage than their latex comparison condoms, the new condoms still provide an acceptable alternative for those with allergies, sensitivities, or preferences that might prevent the consistent use of latex condoms. The contraceptive efficacy of the nonlatex condoms requires more research.

Condoms↗
PubMed2006

Combination contraceptives: effects on weight.

BACKGROUND: Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. OBJECTIVES: The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. SEARCH STRATEGY: We searched the computerized databases MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of combination contraceptives. We also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. SELECTION CRITERIA: All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, and/or study length. DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan, and a second author verified the data entered. Depending on the data available, the weighted mean difference using a fixed effects model with 95% confidence intervals (CI) was calculated for the mean change in weight between baseline and post-treatment measurements or the Peto odds ratio with 95% confidence intervals was calculated using the proportion of women who gained or lost more than a specified amount of weight. MAIN RESULTS: The three placebo-controlled, randomized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight gain did not differ between groups where this was studied. AUTHORS' CONCLUSIONS: Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident.

Body Weight↗
PubMed2005

Combination injectable contraceptives for contraception.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

Algestone↗
PubMed2001

Ibutilide: efficacy and safety in atrial fibrillation and atrial flutter in a general cardiology practice.

BACKGROUND: Published experience with ibutilide (IB) in randomized clinical trials reveals that conversion to sinus rhythm (SR) occurs in 31% of patients with atrial fibrillation (AF) and in 63% of patients with atrial flutter. HYPOTHESIS: The study was undertaken to test the efficacy and safety of IB in patients with AF and with atrial flutter and to compare them with those reported in previous studies. METHODS: In a general cardiology practice, 54 consecutive patients with AF or atrial flutter, no contraindication to IB, and a normal QTc interval, were treated with intravenous IB (0.4-2.0 mg). Duration of arrhythmia, left atrial (LA) size, ejection fraction (EF), time to conversion, QTc interval, and adverse drug events were determined. Patients were observed for a minimum of 6 h. Successful cardioversion was defined as arrhythmia termination within 6 h. RESULTS: Twenty-four of 34 (70.6%) patients with AF and 15 of 20 (75%) patients with atrial flutter converted to SR. Conversion of AF to SR was more likely to occur if duration of AF was approximately 96 h compared with > 96 h (81 vs. 17%, respectively; p = 0.006). The mean time to arrhythmia termination was 68.8 min. Left atrial size, determined by echocardiogram, was 44 +/- 13 mm in 43 patients. Patients with LA size approximately 45 mm had a conversion rate of 55% in both AF and flutter, compared with a conversion rate of 72% in patients with LA size < 45 mm. Ejection fraction was not a predictor of drug success. The QTc intervals were significantly prolonged after IB administration, with a mean change of 47.1 ms for successfully treated patients. Sustained polymorphic ventricular tachycardia occurred in one patient within 1 min of IB infusion, requiring electrical cardioversion to SR. This patient's serum electrolytes and QTc interval were normal prior to IB infusion; however, the QTc increased by 160 ms (from 387 to 547 ms) during drug infusion. No systemic or pulmonary emboli occurred. CONCLUSION: The efficacy of IB for conversion of AF to SR in this prospective observational study was considerably better than previously reported. Duration of AF remains an important predictor of conversion to SR. Complications are rare and without long-term adverse effects.

Aged↗
PubMed2001

New recommendations from the 1999 American College of Cardiology/American Heart Association acute myocardial infarction guidelines.

OBJECTIVE: To review literature relating to significant changes in drug therapy recommendations in the 1999 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for treating patients with acute myocardial infarction (AMI). DATA SOURCES: 1999 ACC/AHA AMI guidelines, English-language clinical trials, reviews, and editorials researching the role of drug therapy and primary angioplasty for AMI that were referenced in the guidelines were included. Additional data published in 2000 or unpublished were also included if relevant to interpretation of the guidelines. STUDY SELECTION: The articles selected influence AMI treatment recommendations. DATA SYNTHESIS: Many clinicians and health systems use the ACC/AHA AMI guidelines to develop treatment plans for AMI patients. This review highlights important changes in AMI drug therapy recommendations by reviewing the results of recent clinical trials. Insights into evolving drug therapy strategies that may impact future guideline development are also described. CONCLUSIONS: Several changes in drug therapy recommendations were included in the 1999 AMI ACC/AHA guidelines. There is emphasis on administering fibrin-specific thrombolytics secondary to enhanced efficacy. Selection between fibrin-specific agents is unclear at this time. Low response rates to thrombolytics have been noted in the elderly, women, patients with heart failure, and those showing left bundle-branch block on the electrocardiogram. These patient groups should be targeted for improved utilization programs. The use of glycoprotein (GP) IIb/IIIa receptor inhibitors in non-ST-segment elevation MI was emphasized. Small trials combining reduced doses of thrombolytics with GP IIb/IIIa receptor inhibitors have shown promise by increasing reperfusion rates without increasing bleeding risk, but firm conclusions cannot be made until the results of larger trials are known. Primary percutaneous coronary intervention (PCI) trials suggest lower mortality rates for primary PCI when compared with thrombolysis alone. However, primary PCI, including coronary angioplasty, is only available at approximately 13% of US hospitals, making thrombolysis the preferred strategy for most patients. Clopidogrel has supplanted ticlopidine as the recommended antiplatelet agent for patients with aspirin allergy or intolerance following reports of a better safety profile. The recommended dose of unfractionated heparin is lower than previously recommended, necessitating a separate nomogram for patients with acute coronary syndromes. Routine use of warfarin, either alone or in combination with aspirin, is not supported by clinical trials; however, warfarin remains a choice for antithrombotic therapy in patients intolerant to aspirin. Beta-adrenergic receptor blockers continue to be recommended, and emphasis is placed on improving rates of early administration (during hospitalization), even in patients with moderate left ventricular dysfunction. New recommendations for drug treatment of post-AMI patients with low high-density lipoprotein cholesterol and/or elevated triglycerides are included, with either niacin or gemfibrozil recommended as an option. Supplementary antioxidants are not recommended for either primary or secondary prevention of AMI, with new data demonstrating lack of efficacy vitamin E in primary prevention. Estrogen replacement therapy or hormonal replacement therapy should not be initiated solely for prevention of cardiovascular disease, but can be continued in cardiovascular patients already taking long-term therapy for other reasons. Bupropion has been added as a new treatment option for smoking cessation. As drug therapy continues to evolve in treating AMI, more frequent updates of therapy guidelines will be necessary.

Adrenergic beta-Antagonists↗
PubMed2001

Low-molecular-weight heparins are essentially the same for treatment and prevention of venous thromboembolism.

The pharmacodynamic properties of low-molecular-weight heparins differ. Data from randomized clinical trials show that despite these differences, the agents have similar efficacy and safety profiles in preventing and treating new and recurrent venous thromboembolism in patients who underwent general surgery or total hip or knee replacement. Dalteparin, enoxaparin, or tinzaparin, when administered at the dosages used in the reviewed clinical trials, are essentially indistinguishable.

Clinical Trials as Topic↗
PubMed2001

Effect of dyskinetoplastic agents on ultrastructure and oxidative phosphorylation in Crithidia fasciculata.

Ethidium bromide (EB) is an intercalating agent which binds specifically to the kinetoplast (mitochondrial) DNA (kDNA) of trypanosomatids. Accordingly, EB inhibits DNA replication, thus inducing dyskinetoplasty. Since in eukariotic organisms mitochondrial DNA encodes the genetic information for cytochromes b, aa3 and F0F1 ATPase, it seemed of interest to establish whether a similar effect occurs in Crithidia fasciculata, a trypanosomatid used for assay of potential trypanocidal drugs. Culturing of C. fasciculata in the presence of EB inhibited growth and induced dyskinetoplasty, as confirmed by electron microscopy. The kinetoplast of EB-cultured crithidia lost its characteristic arc shape, it was misplaced in the cell cytoplasm its matrix structure and membrane differentiation were specifically modified. Dyskinetoplasty decreased crithidia respiration and oxidative phosphorylation, as indicated by the lower ATP level, ATP/ADP ratio and adenylate energy charge. The interference of EB with kinetoplastic constituents synthesis was confirmed by the lack of action of EB on crithidia in the stationary phase of growth, that ruled out direct inhibition of oxidative phosphorylation enzymes. The lipophilic o-naphthoquinone beta-lapachone produced structural alterations in kinetoplast membranes, that correlated with inhibition of oxidative phosphorylation. These latter effects involved free radicals since they were prevented by free radical scavengers.

Adenosine Triphosphate↗
PubMed2000

Effects of age on gene expression during estrogen-induced synaptic sprouting in the female rat.

Age and estrogen treatment influenced fiber outgrowth and compensatory neuronal sprouting after unilateral entorhinal cortex lesions (ECL) which model Alzheimer disease-like deafferentation in the dentate gyrus of the hippocampus. In young F344 rats (3 months old), ovariectomy (OVX) decreased reactive fiber outgrowth by 60%. Sprouting in middle-aged rats (18 months old) was reduced in intact females; no further reduction was caused by OVX. Several astrocyte mRNAs were measured in the dentate gyrus of young and middle-aged female rats in three different estrogen states (sham OVX, OVX, or OVX + estradiol) 1 week after ECL. Glial fibrillary acidic protein (GFAP) mRNA was twofold greater in middle-aged rats than young, although both ages showed threefold increases in response to ECL. In prior studies GFAP was found to be decreased by estradiol treatment 3-4 days after ECL; in this study GFAP mRNA had returned to sham OVX levels in young rats by 7 days post-ECL. Surprisingly, estradiol treatment increased GFAP mRNA levels by 25% above OVX in middle-aged rats. Apolipoprotein E (apoE) mRNA was decreased 20% by age in the dentate, although both age groups showed a 25% increase in apoE mRNA in response to ECL. Apolipoprotein J (apoJ) mRNA was increased 20% in the dentate gyrus of middle-aged rats, and both age groups responded to ECL with a 65% increase in apoJ mRNA. The estrogen state did not alter levels of either apolipoprotein mRNA in the deafferented dentate. The data suggest that the estrogen-induced decrease of GFAP in response to lesions does not persist at 7 days post-ECL during sprouting. Overall effects of age on the dentate gyrus include elevated GFAP mRNA and decreased apoE mRNA. The cortical wound site showed consistent enhancement of GFAP mRNA in both age groups by estradiol above sham OVX and greater responses in middle-aged rats.

Afferent Pathways↗
PubMed1998

Endothelial dysfunction: implications for therapy of cardiovascular diseases.

OBJECTIVE: To review current literature regarding endothelial dysfunction in cardiovascular diseases and examine implications of these findings for the treatment of various cardiovascular disorders. DATA SOURCE: A MEDLINE search of basic science articles pertinent to understanding the role of the endothelium in the atherosclerotic process and of clinical trials examining the presence and treatment of impaired endothelium-dependent vascular relaxation was conducted. STUDY SELECTION: Selected basic science articles and reviews were included to explain the foundation for subsequent clinical trials. All clinical trials examining the treatment of impaired endothelium-dependent vascular relaxation were reviewed. DATA SYNTHESIS: Endothelial dysfunction characterized by impaired endothelium-dependent vascular relaxation is an early physiologic event in atherogenesis. Endothelial dysfunction in peripheral vasculature serves as a marker for impairment in coronary arteries. Techniques for measuring endothelium-dependent vascular relaxation are specific and have a high positive predictive value for coronary artery disease, but low sensitivity. Various pharmacologic agents have been used in an attempt to improve endothelial function, but only lipid-lowering agents and estrogen supplementation have been shown to improve endothelium-dependent vascular relaxation consistently. Treatments used in patients with heart failure or hypertension fail to demonstrate consistent improvement. CONCLUSIONS: Endothelial dysfunction serves as a marker for cardiovascular disease, but pharmacologic treatment does not consistently restore normal endothelial function. Nevertheless, some of these agents are known to have positive clinical outcomes. Future research using these techniques will provide greater insight into the effects of many commonly used therapies for cardiovascular disease on the pathobiology of endothelial dysfunction.

Animals↗
PubMed1997

Clinical trials in thrombolytic therapy, Part 2: The open-artery hypothesis and RAPID-1 and RAPID-2.

The open-artery hypothesis as supported by thrombolytic study results is discussed. The open-artery hypothesis states that survival after acute myocardial infarction (AMI) is maximized by achieving early and sustained patency of the infarct-related artery. However, two large multicenter trials did not detect any difference in mortality between patients given alteplase and patients given streptokinase, despite previous evidence that alteplase led to earlier recanalization of infarct-related arteries. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial suggested that early and complete patency is essential for short-term survival after AMI. Subsequent observations indicated that an open infarct-related artery at the time of hospital discharge is associated with improved long-term survival. In the Reteplase Angiographic Phase II International Dose-Finding (RAPID-1) trial, complete patency was more frequent in patients who received a double-bolus regimen of reteplase than in patients who received standard-dose alteplase. Similar results were obtained in the Reteplase versus Alteplase Patency Investigation during Myocardial Infarction (RAPID-2) trial, which compared the same double-bolus reteplase regimen with an accelerated regimen of alteplase. In both RAPID studies, mortality was lower and other outcomes were more favorable in reteplase recipients. Reteplase seems more likely to produce normal blood flow soon after AMI than either standard-dose or accelerated alteplase and may be associated with a lower mortality rate. This lends further support to the open-artery hypothesis.

Clinical Trials as Topic↗
PubMed1997

Effects of intermittent transdermal nitroglycerin on occurrence of ischemia after patch removal: results of the second transdermal intermittent dosing evaluation study (TIDES-II).

OBJECTIVES: We sought to evaluate the effects of intermittent transdermal nitroglycerin (TD-NTG) on the occurrence of ischemia during patch-off hours in patients with stable angina pectoris receiving a beta-adrenergic blocking agent or calcium antagonist, or both. BACKGROUND: The current recommendations for the use of intermittent TD-NTG may be associated with the occurrence of rebound ischemia. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, crossover trial with three study periods. Tolerability to TD-NTG was assessed in Period I. Seventy-two patients were assigned to receive either double-blind transdermal placebo or maximally tolerated TD-NTG for 2 weeks (Period II) and were then crossed over to the alternative treatment for another 2 weeks (Period III). The patients were instructed to apply medication daily at 8 AM, to remove it at 10 PM and to note symptoms and sublingual nitroglycerin (SL-NTG) use in a diary. The occurrence of ischemia was assessed from patient-perceived angina, symptom-limited exercise treadmill test (ETT) and 48-h ambulatory electrocardiographic (AECG) monitoring. RESULTS: Transdermal NTG (0.2 to 0.4 mg/h) significantly reduced the magnitude of ST segment depression at angina onset during ETT compared with placebo. Total angina frequency was not significantly different between TD-NTG (mean [+/-SD] 3.2 +/- 4.2) and placebo (3.3 +/- 5.2). During patch-off hours, angina frequency increased with TD-NTG (1.1 +/- 2.1) compared with placebo (0.7 +/- 1.6) (p = 0.03). Similar trends for an increase in ischemia after TD-NTG were also observed from AECG analyses. Specifically, ischemia frequency tended to be lower during patch-off hours for placebo than with TD-NTG (0.05 +/- 0.09 vs. 0.08 +/- 0.20 episodes/h, respectively, p = 0.08), even though frequency of ischemia tended to be higher during patch-on hours for placebo than with TD-NTG (0.12 +/- 0.19 vs. 0.07 +/- 0.15 episodes/h, respectively, p = 0.11). During placebo, ischemia frequency decreased 58% (patch-on to patch-off, p = 0.01) compared with a 14% increase with TD-NTG. These changes attenuate the usual circadian variation in ischemia. CONCLUSIONS: An increase in ischemia frequency during patch-off hours after use of intermittent TD-NTG was perceived by patients, and this subjective finding was supported by a corresponding trend for AECG ischemia to increase during these same hours.

Administration, Cutaneous↗