'Trig-onometry': non-high-density lipoprotein cholesterol as a therapeutic target in dyslipidaemia.

Targeting elevations in low-density lipoprotein cholesterol (LDL-C) remains the cornerstone of cardiovascular prevention. However, this fraction does not adequately capture elevated triglyceride-rich lipoproteins (TRLs; e.g. intermediate-density lipoprotein, very low density lipoprotein) in certain patients with metabolic syndrome or diabetic dyslipidaemia. Many such individuals have residual cardiovascular risk that might be lipid/lipoprotein related despite therapy with first-line agents (statins). Epidemiological evidence encompassing > 100,000 persons supports the contention that non-high-density lipoprotein cholesterol (non-HDL-C) is a superior risk factor vs. LDL-C for incident coronary heart disease (CHD) in certain patient populations. In studies with clinical end-points evaluated in the current article, a 1:1 to 1:3 relationship was observed between reductions in non-HDL-C and in the relative risk of CHD after long-term treatment with statins, niacin (nicotinic acid) and fibric-acid derivatives (fibrates); this relationship increased to 1:5 to 1:10 in smaller subgroups of patients with elevated triglycerides and low HDL-C levels. Treatment with statin-, niacin-, fibrate-, ezetimibe-, and omega 3 fatty acid-containing regimens reduced non-HDL-C by approximately 9-65%. In a range of clinical trials, long-term treatment with these agents also significantly decreased the incidence of clinical/angiographic/imaging efficacy outcome variables. For patients with dyslipidaemia, consensus guidelines have established non-HDL-C treatment targets 30 mg/dl higher than LDL-C goals. Ongoing prospective randomised controlled trials should help to resolve controversies concerning (i) the clinical utility of targeting non-HDL-C in patients with dyslipidaemia; (ii) the most efficacious and well-tolerated therapies to reduce non-HDL-C (e.g. combination regimens); and (iii) associations between such reductions and clinical, angiographic, and/or imaging end-points.

A strong astrophysical constraint on the violation of special relativity by quantum gravity.

Special relativity asserts that physical phenomena appear the same to all unaccelerated observers. This is called Lorentz symmetry and relates long wavelengths to short ones: if the symmetry is exact it implies that space-time must look the same at all length scales. Several approaches to quantum gravity, however, suggest that there may be a microscopic structure of space-time that leads to a violation of Lorentz symmetry. This might arise because of the discreteness or non-commutivity of space-time, or through the action of extra dimensions. Here we determine a very strong constraint on a type of Lorentz violation that produces a maximum electron speed less than the speed of light. We use the observation of 100-MeV synchrotron radiation from the Crab nebula to improve the previous limit by a factor of 40 million, ruling out this type of Lorentz violation, and thereby providing an important constraint on theories of quantum gravity.

A rapidly expanding Bose-Einstein condensate: an expanding universe in the lab.

We study the dynamics of a supersonically expanding ring-shaped Bose-Einstein condensate both experimentally and theoretically. The expansion redshifts long-wavelength excitations, as in an expanding universe. After expansion, energy in the radial mode leads to the production of bulk topological excitations - solitons and vortices - driving the production of a large number of azimuthal phonons and, at late times, causing stochastic persistent currents. These complex nonlinear dynamics, fueled by the energy stored coherently in one mode, are reminiscent of a type of "preheating" that may have taken place at the end of inflation.

The effect of a perioperative ketamine infusion on the incidence of chronic postsurgical pain-a pilot study.

Chronic postsurgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study at three hospitals to assess the feasibility of a proposed large multicentre placebo-controlled randomised trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine, 0.5 mg/kg pre-incision, 0.25 mg/kg/hour intraoperatively and 0.1 mg/kg/hour for 24 hours, or placebo, was administered to 80 patients, recruited over a 15-month period, undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at six-month telephone follow-up using a structured questionnaire. Fourteen patients (17.5%) reported CPSP (relative risk [95% confidence interval] if received ketamine 1.18 [0.70 to 1.98], P=0.56). Four patients in the treatment group and three in the control group reported ongoing analgesic use to treat CPSP and two patients in each group reported their worst pain in the previous 24 hours at ≥3/10 at six months. There were no significant differences in adverse event rates, quality of recovery scores, or cumulative morphine equivalents consumption in the first 72 hours. Numeric Rating Scale pain scores (median [interquartile range, IQR]) for average pain in the previous 24 hours among those patients reporting CPSP were 17.5 [0 to 40] /100 with no difference between treatment groups. A large (n=4,000 to 5,000) adequately powered multicentre trial is feasible using this population and methodology.

Use of postmenopausal hormone replacement therapy by African American women. The importance of physician discussion.

BACKGROUND: Although nationally the use of hormone replacement therapy (HRT) has increased dramatically in the last decade, little is known about its use by disadvantaged, minority women or the role that physician discussion plays in determining its use. METHODS: In 1994, we surveyed a total of 328 predominantly indigent, African American women (refusals, 22) who attended public hospital medical continuity of care clinics staffed by internal medicine house officers. RESULTS: Of the 328 women who completed the survey, the mean age was 63 years, 302 women (92%) were African American, and 286 (87.3%) had yearly incomes of less than $10000. Of the 328 women, 52 (15.6%) were receiving HRT at the time of the survey, varying from 22 (28.2%) of 78 women aged 50 to 59 years to 1 (3%) of 33 women older than 80 years (P = .006). In a logistic regression model adjusting for age and ethnicity, women who had previously undergone a hysterectomy were significantly more likely to use HRT, with an odds ratio of 2.76 (95% confidence interval, 1.44-5.30; P = .002). The levels of education and income and the history of myocardial infarction were not significantly associated with the use of HRT (P > .20). Although all women who were currently receiving HRT recalled discussing HRT with their physicians, of the 276 women who were not receiving HRT, only 62 (22%) recalled any such discussion (P < .001). CONCLUSIONS: In poor, African American women who reside in the inner city, younger age, undergoing a hysterectomy, and physician discussion of HRT are significantly associated with current use of HRT. Physician discussion of HRT may need greater emphasis in internal medicine training programs.

New perspectives on the management of low levels of high-density lipoprotein cholesterol.

A low serum high-density lipoprotein cholesterol (HDL-C) level is a potent predictor of coronary heart disease (CHD). It has been estimated that 11% of US men have isolated low HDL-C levels, and there is uncertainty regarding the management of these patients. A cause-and-effect relationship between low HDL-C levels and CHD is supported by epidemiological, animal, and human clinical studies. We reviewed the structure and function of HDL-C and its role in preventing atherosclerosis. We then suggested an approach to the patient with isolated low HDL-C that may be useful to the primary care physician. An algorithm was proposed for use in patients with existing CHD, while the decision to treat patients without CHD was based on their score on the Framingham Heart Study risk prediction chart.

The fats of life: the role of omega-3 fatty acids in the prevention of coronary heart disease.

Epidemiological and clinical trial evidence suggests that omega-3 polyunsaturated fatty acids (PUFAs) might have a significant role in the prevention of coronary heart disease. Dietary sources of omega-3 PUFA include fish oils rich in eicosapentaenoic acid and docosahexaenoic acid along with plants rich in alpha-linolenic acid. Randomized clinical trials with fish oils (eicosapentaenoic acid and docosahexaenoic acid) and alpha-linolenic acid have demonstrated reductions in risk that compare favorably with those seen in landmark secondary prevention trials with lipid-lowering drugs. Several mechanisms explaining the cardioprotective effect of omega-3 PUFAs have been suggested, including antiarrhythmic, hypolipidemic, and antithrombotic roles. Although official US guidelines for the dietary intake of omega-3 PUFAs are not available, several international guidelines have been published. Fish is an important source of omega-3 PUFAs in the US diet; however, vegetable sources, including grains and oils, offer an alternative source for those who are unable to regularly consume fish.

Maximizing the cost-effectiveness of lipid-lowering therapy.

Cardiovascular disease, including coronary heart disease, is the leading cause of death both in men and in women in the United States. The purpose of this review is to describe the effectiveness of lipid-lowering therapy in reducing cardiovascular morbidity and mortality, which has recently been extended to patients with mild to moderate hypercholesterolemia, and the cost of providing therapy, which would be prohibitive if all persons with hypercholesterolemia received treatment. Cost-effectiveness analysis provides a rational means of allocating limited health care resources by allowing the comparison of the costs of lipid-lowering therapy, in particular, therapy with beta-hydroxy-beta-methylglutaryl-CoA (coenzyme A) reductase inhibitors (statins), with the costs of atherosclerosis that could be prevented by lowering cholesterol. To extend the benefits of treatment to the large number of persons not receiving therapy, we need to implement more cost-effective treatment by improving risk assessment, increasing treatment effectiveness, and reducing the cost of therapy.

Impact of evidence-based "clinical judgment" on the number of American adults requiring lipid-lowering therapy based on updated NHANES III data. National Health and Nutrition Examination Survey.

BACKGROUND: When the National Cholesterol Education Program Adult Treatment Panel II (ATP II) guidelines were published, National Health and Nutrition Examination Survey III data for 1988 to 1991 were used to estimate the number of Americans requiring lipid-lowering therapy based on ATP II cut points. However, the guidelines recommend using clinical judgment to determine whether to initiate drug therapy in individuals whose low-density lipoprotein cholesterol levels remain above treatment goals with diet therapy but below the initiation level for drug therapy. METHODS: We analyzed updated (1988-1994) National Health and Nutrition Examination Survey III data, based on a sample of 6796 adults aged 20 years and older, to estimate the numbers of American adults with an elevated low-density lipoprotein cholesterol level and requiring drug therapy using cut points vs clinical judgment as specified in ATP II guidelines. RESULTS: Assuming a 10% low-density lipoprotein cholesterol reduction with diet, an estimated 10.4 million American adults require drug therapy based on ATP II cut points. If we include individuals for whom the guidelines recommend clinical judgment, the estimate increases to 28.4 million. The largest increase occurs in individuals without known coronary heart disease but with 2 or more risk factors: from 5.5 to 17.5 million. These high-risk individuals have low-density lipoprotein cholesterol concentrations similar to those in patients with coronary heart disease. CONCLUSIONS: Since the ATP II guidelines were published, clinical judgment has been informed by abundant clinical trial evidence establishing the safety and benefit of lipid-lowering therapy. The large number of individuals at high risk for coronary heart disease emphasizes the need for cost-effective therapy to extend treatment to the greatest number of individuals who may benefit.

Efficacy and safety of pravastatin in African Americans with primary hypercholesterolemia.

BACKGROUND: Coronary artery disease strikes early and may prove particularly severe in persons of African-American descent. Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia. METHODS: After 4 weeks on an American Heart Association phase I low-fat diet, patients were randomized in a double-blind manner to either pravastatin or placebo in a 3:1 ratio. RESULTS: After 12 weeks of pravastatin treatment, low-density lipoprotein cholesterol levels declined 25.8%, total cholesterol levels 20.3%, and triglyceride levels 6.2%, while high-density lipoprotein cholesterol levels remained essentially unchanged. Overall, 72% of pravastatin-treated patients achieved reductions in low-density lipoprotein cholesterol level in excess of 20%, and 44% attained declines in excess of 30% (both P < .01 vs placebo). Pravastatin was generally well tolerated in this population, with one patient (0.5%) exhibiting a reversible myopathy with creatine kinase elevations to 10 times the upper limit of normal. No substantial elevations of aminotransferase levels of two to three times the upper limit of normal occurred in either the pravastatin or the placebo group. Drug compliance was high, exceeding 90%. CONCLUSION: Pravastatin appears to be an effective and safe lipid-lowering agent and is the first 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be studied extensively in this underrepresented population.

Effects of aging and xerosis on the amino acid composition of human skin.

Amino acid compositions of skin samples from young and old subjects and from age-matched donors with dry skin syndrome (xerosis) were examined. The amino acid contents of the free amino acid (FAA) fraction, soluble hydrolysate (SH) fraction, and whole cell hydrolysate (WCH) were determined. The greatest differences were observed between the FAA compositions of the young and old normal subjects. Xerosis did not appear to affect the amino acid compositions of samples from young subjects as much as old subjects. Overall, the effect of aging on the amino acid contents was more pronounced than the effect of xerosis. The amino acid composition of the FAA showed a high degree of similarity to filaggrin, whereas the WCH showed a similarity to keratin.

Clinical context: current concepts of coronary heart disease management.

Coronary heart disease (CHD) is the single greatest cause of death among adults in the United States. It is also a major cause of disability and is associated with direct and indirect costs that exceed $118 billion annually. Elevation of serum lipid levels, particularly low-density lipoprotein cholesterol (LDL-C) levels, is closely linked to the development of CHD. Lipid levels that increase the risk of CHD are present in nearly one third of the US population. Large-scale intervention studies have shown that decreasing LDL-C can significantly reduce the risk of cardiovascular mortality, adverse cardiovascular events, and the requirement for revascularization procedures. Statins are now thought the most effective agents for lowering LDL-C, and they also have positive effects on other components of the serum lipid profile. These drugs are also better tolerated than other lipid-lowering agents. Statin therapy significantly decreases the risk of cardiovascular disease and is a cost-effective cardiovascular treatment according to current standards. Because statins vary substantially in acquisition cost, using statins in the most cost-effective manner is important for controlling health-care costs. Optimizing the cost-effectiveness of statin therapy is a particular concern to managed care organizations in light of the large number of patients who are now considered candidates for this treatment.

Fluvastatin and niacin in hypercholesterolemia: a preliminary report on gender differences in efficacy.

A total of 74 hypercholesterolemic patients were randomized to receive double-blind treatment for 6 weeks with either 20 mg of fluvastatin daily or placebo. Open-label niacin, to a maximum of 3 g daily, was added to each treatment for a further 9 weeks. Changes in lipid parameters were derived from averaged data, with monotherapy at weeks 3 and 6 and with combination therapy at weeks 12 and 15. The reduction in low-density lipoprotein cholesterol (LDL-C) was significantly greater with fluvastatin (20.8%) compared with placebo (p < 0.001) after 3-6 weeks of treatment. At the end of 12-15 weeks, the addition of niacin potentiated the response to 43.7% with the fluvastatin+niacin combination and to 26.5% with the placebo+niacin combination (p < 0.001, vs baseline and between treatment groups). Significant gender differences were noted in the LDL-C response to the fluvastatin+niacin combination. Women achieved LDL-C reductions of 54.6% whereas men achieved reductions of 38.2% (p < 0.0005, between gender groups). Women also tended to have greater LDL-C reductions with the placebo+niacin combination, compared with men (p < 0.05). At the end of 12-15 weeks, there were HDL-C increases of 33.1% (p < 0.001) whereas triglyceride levels declined by 32.3% (p < 0.001). In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective and well-tolerated alternative for the treatment of hypercholesterolemia. The differential response in LDL-C between men and women should be further explored in other trials of lipid-lowering therapy.

Long-term treatment of hypercholesterolemia with dietary fiber.

PURPOSE: To evaluate the hypocholesterolemic effects of long-term treatment (36 to 51 weeks) with a mixture of dietary fibers (guar gum, pectin, soy, pea, corn bran) administered twice a day. PATIENTS AND METHODS: Fifty-nine subjects with moderate hypercholesterolemia who completed a 15-week, placebo-controlled study with the dietary fiber were treated for an additional 36 weeks with 20 g/day of fiber. Subjects were counseled and monitored on a National Cholesterol Education Program (NCEP) Step-One Diet before starting and during treatment. Analyses of changes in lipoprotein values during the additional 36 weeks of treatment took into account changes in weight, diet, and other variables that might have affected the response to treatment. RESULTS: There were no significant effects on the levels of either triglycerides or high-density lipoprotein cholesterol (HDL-C). Levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and the LDL/HDL ratio were significantly reduced during treatment. The mean percentage reductions from baseline after 51 weeks of treatment were approximately 5% for TC, 9% for LDL-C, and 11% for the LDL/HDL ratio. Changes were apparent after 3 weeks of treatment, with the maximum reductions occurring by the 15th week of treatment. CONCLUSIONS: For subjects on a Step-One Diet who complied with the treatment regimen, the moderate cholesterol-lowering effects of the fiber persisted throughout the 36-to-51 week treatment period.

Cost-effectiveness of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy in the managed care era.

More than $100 billion is spent in the United States each year on cardiovascular disease, primarily for hospitalizations and revascularization procedures. This is more than for any other disease state. As the clinical practice of medicine shifts from the paradigm of private practice to the managed care environment, cost-effectiveness is becoming increasingly important. A primary measure in analyzing cost-effectiveness is the cost-effectiveness ratio, or the dollar cost per unit of improvement for a given expenditure. This measure allows healthcare planners to compare completely different interventions. With approximately 52 million adult U.S. citizens having elevated low-density lipoprotein (LDL) cholesterol levels, lipid-lowering therapy---with diet or 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors---is an important consideration for primary care physicians and managed care providers. The National Health and Nutrition Examination Survey (NHANES) III indicates that 75-88% of adults who have coronary artery disease (CAD) risk factors or CAD require only a moderate (20--30%) reduction in LDL cholesterol levels to reach National Cholesterol Education Program goals. The clinical literature shows that all 4 of the currently available HMG-CoA reductase inhibitors can provide appropriate, moderate LDL cholesterol reductions within their recommended dosage ranges. For the majority of patients who need a 20--30% reduction in LDL cholesterol, fluvastatin 20 or 40 mg once daily provides the most cost-effective HMG-CoA therapy, expressed as cost of therapy per 1% LDL cholesterol reduction. For patients who need a >30% LDL cholesterol reduction, a high-dose HMG-CoA reductase inhibitor (e.g., simvastatin 20 or 40 mg/day) or a combination of a lower-dose HMG-CoA reductase inhibitor and a bile acid resin is the preferred initial therapy. Although a true cost-effectiveness analysis would incorporate morbidity and mortality data from clinical trials, analysis using intermediate endpoints, such as LDL cholesterol reduction, suggests that fluvastatin is the preferred initial HMG-CoA reductase inhibitor for the treatment of moderate hyperlipidemia.

Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety.

A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin-placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia.

Fluvastatin with and without niacin for hypercholesterolemia.

Seventy-four patients with plasma low-density lipoprotein cholesterol levels > or = 160 mg/dl after an American Heart Association phase 1 diet were randomized to double-blind treatment with fluvastatin, 20 mg/day, or placebo for 6 weeks. Immediate-release niacin was then added to both treatment regimens and titrated to a maximum of 3 g/day for a further 9 weeks. After 6 weeks of fluvastatin monotherapy, low-density lipoprotein cholesterol levels decreased by 21% (p < 0.001 vs placebo), and after the addition of niacin, response was potentiated to 40% compared with 25% for the niacin control group at study end point (p < 0.001). Fluvastatin, alone and in combination with niacin, also significantly improved high-density lipoprotein cholesterol (increases of about 30%) and triglyceride profiles (decreases of approximately 28%) from baseline. Lipoprotein(a) decreased by 37% in those receiving fluvastatin-niacin but was unaltered in those receiving fluvastatin alone. No serious adverse events were ascribed to fluvastatin, and no cases of myositis were observed. Small, transient, asymptomatic increases in aspartate aminotransferase were noted with fluvastatin-niacin treatment but were not considered clinically relevant. Although the fluvastatin-niacin combination in this study was without evidence of significant transaminitis, myopathy, or rhabdomyolysis, it would seem prudent to continue to monitor its safety with longer term use. In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective, safe, and well-tolerated therapeutic alternative for hypercholesterolemia.

Breast and cervical cancer screening in an inner-city medical walk-in clinic: taking advantage of an often missed opportunity.

BACKGROUND: Despite established evidence that screening for breast and cervical cancer reduces mortality in women, screening is underutilized, especially in poor, minority women. We hypothesized that a high percentage of women presenting for care to an inner-city medical walk-in clinic would report inadequate screening for breast and cervical cancer by current standards, accept same-day screening, and comply with recommended follow-up. METHODS: To determine how many women presenting to our medical Walk-In Clinic were inadequately screened for breast and cervical cancer and how many were willing to undergo same-day screening, we surveyed all women at this site over a three month period. We then implemented a one-year, same-day screening program and contacted patients with abnormal screening results by letter or phone to encourage follow up. We tracked patients to assess compliance with follow-up. RESULTS: Of the 2,363 women in the initial survey, 1,230 (52%) reported inadequate screening, of whom 55% reported interest in same-day screening. Over the one year screening period, we screened 403 women for breast and/or cervical cancer. Of the 48 women with abnormal Pap tests, compliance with initial Gynecology Clinic follow-up was 56%. Compliance was 49% with mammography appointments, and 77% for follow-up to Breast Clinic for clinical and/or mammographic abnormalities. These compliance rates compare favorably to those for screening performed in more traditional settings. CONCLUSION: Our results support the establishment of cancer screening programs in nontraditional settings such as walk-in clinics and emergency departments to target patients who are at high risk for remaining unscreened.

Laparoscopic surgery for pelvic pain associated with endometriosis.

OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. The review aims to compare the effectiveness of any laparoscopic procedure versus any other treatment modality, including expectant management. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Review Group was used to identify all publications that described or might have described randomised trials of laparoscopic surgery in the treatment of symptomatic endometriosis. For a full description of the Review Group strategy see the Review Group details. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis, with other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: One study had data appropriate for inclusion within the review. This study compared laparoscopic laser surgery with diagnostic laparoscopy. Pain relief was the primary outcome measure. The data was extracted independently by two reviewers. MAIN RESULTS: In comparison to expectant treatment there is a significant degree of pain relief at six months after surgery with laser laparoscopic surgery for minimal, mild and moderate endometriosis. Odds Ratio (OR) 4.97, 95% Confidence Interval (CI) 1.85,13.39 REVIEWER'S CONCLUSIONS: The combined surgical approach of laparoscopic laser ablation, adhesiolysis and uterine nerve ablation is likely to be a beneficial treatment for pelvic pain associated with minimal, mild and moderate endometriosis. As only one trial is included in the analysis, this conclusion should be interpreted with caution.

Laparoscopic surgery for subfertility associated with endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis. The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched Feb 2000), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2000), MEDLINE (1966-July 2001), EMBASE (1980-July 2001), the National Research Register (Issue 1, 2000) and reference lists of articles. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: Two studies had data appropriate for inclusion within the review. These studies compared laparoscopic surgical treatment of minimal and mild endometriosis compared with diagnostic laparoscopy only. The recorded outcomes included live birth, pregnancy, fetal losses and complications of surgery. MAIN RESULTS: Meta-analysis of the two randomised trials show improvement in infertility associated with endometriosis with laparoscopic surgery. The largest trial (Marcoux 1997) clearly supports this outcome with an increased chance of pregnancy (OR 2.03, 95% CI 1.28 to 3.24) and ongoing pregnancy rate after 20 weeks (OR 1.95, 95% CI 1.18 to 3.22) but the smaller trial (Gruppo Italiano 1999) does not show benefit (pregnancy OR 0.76, 95% CI 0.31 to 1.88; livebirth OR 0.85, 95% CI 0.32 to 2.28). Combining ongoing pregnancy and live birth rates there was a statistically significant increase with surgery (OR 1.64, 95% CI 1.05 to 2.57). REVIEWER'S CONCLUSIONS: The use of laparoscopic surgery in the treatment of minimal and mild endometriosis may improve success rates. The relevant trials have some methodological problems and further research in this area is needed.