[Treatment of a subsequently detected, iatrogenic colonic perforation via minimal-invasive rendezvous procedure]. / Versorgung einer spät entdeckten, iatrogenen Kolonperforation via minimalinvasivem Rendezvous-Verfahren.

Laparoscopic surgery as primary therapeutical option for iatrogenic colonic perforation after colonoscopy can be complemented by intraoparative colonoscopy in order to detect and treat even difficult accessible lesions. Via the presented method minimal invasisve detection and therapy of perforation can be conducted safely and can lead to reduction of morbidity.

Influence of procalcitonin on decision to start antibiotic treatment in patients with a lower respiratory tract infection: insight from the observational multicentric ProREAL surveillance.

Procalcitonin (PCT)-guided antibiotic stewardship is a successful strategy to decrease antibiotic use. We assessed if clinical judgement affected compliance with a PCT-algorithm for antibiotic prescribing in a multicenter surveillance of patients with lower respiratory tract infections (LRTI). Initiation and duration of antibiotic therapy, adherence to a PCT algorithm and outcome were monitored in consecutive adults with LRTI who were enrolled in a prospective observational quality control. We correlated initial clinical judgment of the treating physician with algorithm compliance and assessed the influence of PCT on the final decision to initiate antibiotic therapy. PCT levels correlated with physicians' estimates of the likelihood of bacterial infection (p for trend <0.02). PCT influenced the post-test probability of antibiotic initiation with a greater effect in patients with non-pneumonia LRTI (e.g., for bronchitis: -23 % if PCT ≤ 0.25 µg/L and +31 % if PCT > 0.25 µg/L), in European centers (e.g., in France -22 % if PCT ≤ 0.25 µg/L and +13 % if PCT > 0.25 µg/L) and in centers, which had previous experience with the PCT-algorithm (-16 % if PCT ≤ 0.25 µg/L and +19 % if PCT > 0.25 µg/L). Algorithm non-compliance, i.e. antibiotic prescribing despite low PCT-levels, was independently predicted by the likelihood of a bacterial infection as judged by the treating physician. Compliance was significantly associated with identification of a bacterial etiology (p = 0.01). Compliance with PCT-guided antibiotic stewardship was affected by geographically and culturally-influenced subjective clinical judgment. Initiation of antibiotic therapy was altered by PCT levels. Differential compliance with antibiotic stewardship efforts contributes to geographical differences in antibiotic prescribing habits and potentially influences antibiotic resistance rates.

A 24-week, multicentre, open evaluation of the clinical effectiveness of the rivastigmine patch in patients with probable Alzheimer's disease.

BACKGROUND: Cholinesterase inhibitors form the mainstay of treatment for persons with mild-to-moderate Alzheimer's disease (AD). The rivastigmine patch may increase compliance and the proportion of patients maintaining an efficacious dose compared with oral cholinesterase inhibitors. OBJECTIVE: To investigate the proportion of patients who reached and maintained the target rivastigmine patch dose compared with the target rivastigmine capsule dose reported in clinical trials. METHODS: This was a multicentre, 24-week, open-label study in persons with probable AD and a Mini-Mental State Examination (MMSE) score of ≥ 10 and ≤ 26. The primary outcome was the proportion of patients (ITT population) treated with 9.5 mg/24 h rivastigmine patch for at least 8 weeks at week 24. Secondary outcomes included week 24 MMSE, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), Trail Making Test Part A (TMT-A) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores. RESULTS: Overall, 208 participants received treatment and 155 (74.5%) completed the study. Within the ITT population, 147/182 patients (80.8%; 95% CI 75.0-86.5%) were treated for at least 8 weeks with the 9.5 mg/24 h rivastigmine patch; 135/182 patients (74.2%; 95% CI 67.8-80.5%) were treated for at least 8 weeks and completed the study. The most common adverse events were nausea (10.1% of patients), erythema (8.7%), pruritus (8.2%) and vomiting (7.2%). At week 24, patients treated with the rivastigmine patch showed improvements on MMSE, ADCS-ADL, ADCS-CGIC and TMT-A scores. Caregivers reported acceptance, preference and satisfaction with the patch. CONCLUSION: Transdermal delivery may allow more patients to reach and maintain therapeutic doses of rivastigmine compared with oral rivastigmine.

Conversion from carbamazepine or oxcarbazepine to topiramate in adolescents and adults with epilepsy.

OBJECTIVE: To explore effectiveness, tolerability and changes in quality of life in patients with epilepsy converting to topiramate (TPM) from carbamazepine (CBZ) or oxcarbazepine (OXC) due to insufficient effectiveness and/or tolerability. METHODS: A multicenter, open-label, non-interventional trial was used to examine patients (> or = 12 years) with epilepsy, changing to TPM monotherapy from baseline mono- or combination therapy with CBZ or OXC. TPM was added to the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1-2 weeks, until a final dose between 50 and 200 mg/day was reached. On the basis of clinical judgment, the treating physician decided whether or not the existing AED treatment with CBZ or OXC could then be withdrawn. Type and number of seizures, preferred TPM dose, quality of life (QOLIE-10 questionnaire), subjective perception of improvement and adverse events (AE) were documented. RESULTS: 140 patients (53.5% women, mean age 47 years) decided to switch to TPM due to insufficient effectiveness (75% of patients) and/or poor tolerability (80%) of the CBZ/OXC treatment. Average duration of follow-up was 24 weeks with an overall discontinuation rate of 19.3%, mainly due to AEs (12.1%). At study endpoint, the intended shift to TPM monotherapy was achieved in 73% of patients at a median TPM dose of 100 mg/day. A seizure reduction of > or = 50% was achieved in 91% of patients in the last scheduled period (weeks 12-26); 62% of patients entering that period remained seizure free. Quality of life at endpoint improved significantly when compared with baseline for all domains of QOLIE-10 (P < 0.001). Most frequent AEs (reported by > or = 5% of patients) were paresthesia (9.3%), weight loss (7.9%), convulsions (5.7%) and memory disorders (5.0%). CONCLUSION: In patients with epilepsy, previously not satisfactorily treated with CBZ or OXC, conversion to TPM may result in an improvement in seizure control as well as in quality of life.

Microencapsulation of essential thyme oil by spray drying and its antimicrobial evaluation against Vibrio alginolyticus and Vibrio parahaemolyticus.

The aims of this research were first, to evaluate the antibacterial potential of commercial thyme essential oil against V. alginolyticus and V. parahaemolyticys and second, using the spray drying technique to produce microcapsules. chemical compounds of thyme oil and microcapsules were identified and quantified being thymol the chemical component present at the highest concentration. Oil-in-water (O/W) emulsions were prepared and the microcapsules were obtained with a spray dryer using maltodextrin as wall material (ratio 1:4). Thyme oil and the microcapsules exhibited antimicrobial activity against V. parahaemolyticus and V. alginolyticus. The spray drying process did not affect the antimicrobial activity of thyme essentialoil.

Bioconjugation strategies to couple supramolecular exo-functionalized palladium cages to peptides for biomedical applications.

Supramolecular Pd2L4 cages (L = ligand) hold promise as drug delivery systems. With the idea of achieving targeted delivery of the metallacages to tumor cells, the bioconjugation of exo-functionalized self-assembled Pd2L4 cages to peptides following two different approaches is reported for the first time. The obtained bioconjugates were analyzed and identified by high-resolution mass spectrometry.

Movement of voltage sensor S4 in domain 4 is tightly coupled to sodium channel fast inactivation and gating charge immobilization.

The highly charged transmembrane segments in each of the four homologous domains (S4D1-S4D4) represent the principal voltage sensors for sodium channel gating. Hitherto, the existence of a functional specialization of the four voltage sensors with regard to the control of the different gating modes, i.e., activation, deactivation, and inactivation, is problematic, most likely due to a functional coupling between the different domains. However, recent experimental data indicate that the voltage sensor in domain 4 (S4D4) plays a unique role in sodium channel fast inactivation. The correlation of fast inactivation and the movement of the S4D4 voltage sensor in rat brain IIA sodium channels was examined by site-directed mutagenesis of the central arginine residues to histidine and by analysis of both ionic and gating currents using a high expression system in Xenopus oocytes and an optimized two-electrode voltage clamp. Mutation R1635H shifts the steady state inactivation to more hyperpolarizing potentials and drastically increases the recovery time constant, thereby indicating a stabilized inactivated state. In contrast, R1638H shifts the steady state inactivation to more depolarizing potentials and strongly increases the inactivation time constant, thereby suggesting a preferred open state occupancy. The double mutant R1635/1638H shows intermediate effects on inactivation. In contrast, the activation kinetics are not significantly influenced by any of the mutations. Gating current immobilization is markedly decreased in R1635H and R1635/1638H but only moderately in R1638H. The time courses of recovery from inactivation and immobilization correlate well in wild-type and mutant channels, suggesting an intimate coupling of these two processes that is maintained in the mutations. These results demonstrate that S4D4 is one of the immobilized voltage sensors during the manifestation of the inactivated state. Moreover, the presented data strongly suggest that S4D4 is involved in the control of fast inactivation.

Effect of cocaine on the coronary circulation and systemic hemodynamics in dogs.

This study investigated the effect of intravenous cocaine (0.5 to 2 mg/kg body weight) on the coronary circulation and systemic hemodynamics in closed chest sedated dogs. The role of alpha- and beta-adrenoceptor stimulation in mediating these effects was also investigated. Cocaine produced dose-dependent increases in mean arterial pressure and rate-pressure product. Although the lower doses of cocaine had no significant effect on the coronary circulation, the 2 mg/kg dose produced a 55 +/- 14% increase in coronary vascular resistance (p less than 0.05 versus baseline) and a 19 +/- 3% reduction in diameter of the left anterior descending coronary artery (p less than 0.05 versus baseline). Despite these potentially deleterious effects on the coronary circulation (occurring at a time of markedly increased myocardial oxygen demand), the electrocardiogram did not demonstrate ischemic changes and there was no myocardial lactate production. Cocaine-induced coronary vasoconstriction was abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, but not by pretreatment with the beta-adrenoceptor antagonist propranolol. The findings that cocaine did not change systemic vascular resistance in dogs without adrenergic blockade, reduced systemic vascular resistance in dogs after alpha-blockade (p less than 0.05) and increased systemic vascular resistance in dogs after beta-blockade (p = 0.06) suggest that epinephrine (rather than norepinephrine) is primarily responsible for the peripheral vascular actions of cocaine. Thus, in this canine preparation with normal coronary arteries, cocaine produced vasoconstriction of both epicardial and coronary resistance vessels that was not associated with evidence of myocardial ischemia. The pharmacologic mechanism for the effect of cocaine on the coronary circulation is alpha-adrenoceptor stimulation, whereas systemic hemodynamic effects are mediated by combined alpha- and beta-adrenoceptor stimulation.

Pmg-1 and pmg-2 constitute a novel family of KAP genes differentially expressed during skin and mammary gland development.

The epidermis, by invagination of the undifferentiated ectodermal cells, gives rise to several distinct structures including hair, sebaceous, eccrine sweat and mammary glands. We have recently isolated a novel gene, pmg-1, expressed in the pubertal mouse mammary gland. While investigating its genomic structure, we identified a related gene in close proximity, which we have termed pmg-2. pmg-1 and pmg-2 are intron-less, are transcribed in opposite directions and are separated by a potential promoter region of 2.8 kb containing putative binding motifs for the developmental transcription factors Lef-1, Sox5 and D-STAT. pmg-1 and pmg-2 encode small proteins rich in G, S, F, Y and Q and contain characteristic repeats reminiscent of the keratin-associated proteins (KAPs). Both genes are expressed in growing hair follicles in skin as well as in sebaceous and eccrine sweat glands. Interestingly, expression is also detected in the mammary epithelium where it is limited to the onset of the pubertal growth phase and is independent of ovarian hormones. Their broad, developmentally controlled expression pattern, together with their unique amino acid composition, demonstrate that pmg-1 and pmg-2 constitute a novel KAP gene family participating in the differentiation of all epithelial cells forming the epidermal appendages.

Treatment of chronic rhinosinusitis with high-dose oral terbinafine: a double blind, placebo-controlled study.

OBJECTIVES: To evaluate antifungal terbinafine in patients with chronic rhinosinusitis. STUDY DESIGN: Randomized, double-blind, placebo-controlled multicenter pilot study. METHODS: Fifty-three adults with chronic rhinosinusitis received terbinafine 625 mg/day (n = 25) or placebo (n = 28) once daily for 6 weeks. Sinus secretions were collected at screening for mycology. Computed tomography was graded for extent of opacification at baseline and at week 6 using a modification of the Lund-Mackay scoring system. Patients recorded rhinosinusitis symptoms on a visual analogue scale and completed the Rhinosinusitis Disability Index. RESULTS: Positive fungal cultures were found in 41 of 53 patients (17 terbinafine, 24 placebo). (Two subjects from the Terbinafine group and one subject from the control group had no week 6 data). The mean opacification scores pre- and posttreatment for the entire study group improved from 24.2 to 22.5 in placebo (n = 26) and from 26.3 to 24.2 in terbinafine group (n = 23). The least squares means for percent change from baseline (SE) were -6.0 (8.7) for placebo compared with -7.2 (8.1) for terbinafine; 95% confidence interval for treatment difference (-18.9, 21.1); P = .91. Results were similar when only patients with positive fungal cultures were evaluated in the efficacy analysis. Investigator therapeutic evaluations and sinus symptom scores were not significantly different between the two groups at baseline or at treatment completion. CONCLUSION: Treatment with terbinafine failed to improve the symptoms or radiographic appearance of chronic rhinosinusitis even when nasal irrigation samples were positive for fungus on culture. One consideration is that the fungi isolated were not a major pathologic factor in this cohort. It is also possible that, even at high dose, terbinafine may not have maintained therapeutic levels in the nasal secretions.

[Balloon dacryocystoplasty: interventional radiological therapy of congenital dacryostenosis]. / Ballondakryozystoplastie: Interventionell-radiologische Therapie konnataler Dakryostenosen.

PURPOSE: To evaluate the results of balloon dacryocystoplasty in the treatment of complicated development of connatal obstructed nasolacrimal duct system. MATERIALS AND METHODS: Dacryocystography under general anaesthesia was performed on 46 children with epiphora from birth and recurrent infection of the nasolacrimal duct system. 54 nasolacrimal ducts (8 children bilaterally) were treated with balloon catheter dilatation and antibiotic irrigation of the nasolacrimal sac. In all cases previous conservative treatment with eye drops and superficial massage of the lacrimal sac had failed. 11 children without clinical improvement were irrigated before catheter dilatation by an ophthalmologist. The ages ranged from 6 weeks to 7.5 years (mean 23.5 months). 39 dilatations were carried out as an out-patient procedure. The clinical results were confirmed by a questionnaire filled in by the parents. RESULTS: 15 incomplete obstructions and 39 occlusions of the Hasner valve (n = 45) or of the nasolacrimal duct system (n = 9) were demonstrated with dacryocystography. Dilatation with a 2.5 mm ballon was successfully performed in all cases and the mean radiation time was 2.1 minutes. No relevant complications occurred. The mean follow up time was 18.4 months (3 - 41 months). 39 of 46 children showed no symptoms, 6 children seldomly experienced onset of epiphora. The symptoms did not improve in only one child. The cumulative clinical success rate is 98 %. CONCLUSION: Following diagnostic dacryocystography, balloon catheter dilatation is a low risk and very successful treatment of complicated connatal obstructed nasolacrimal duct system.

Coronary artery disease in women. Risk factors, evaluation, treatment, and prevention.

Cardiovascular disease is the leading cause of death in women. Unfortunately, the problem of cardiovascular disease in women has been largely ignored as women have been enrolled in limited numbers or excluded entirely from many of the major trials on which treatment of cardiovascular disease have been based. Furthermore, recent evidence suggests that a gender bias against aggressive intervention and treatment of cardiovascular disease in women may exist. This article reviews the risk factors, methods of identification, and treatment of coronary artery disease in women, as well as the potential benefits of postmenopausal estrogen.

[Secondary prevention of myocardial infarction in the Basse-Normandie region]. / Prevention secondaire en post-infarctus en Basse-Normandie.

The objectives of this study were to determine post-infarction drug therapy at discharge from hospital and at one year in the Basse Normandie region (France) and the management of risk factors, to compare them with the practice recommended by the French Society of Cardiology and other recent references. Patients whose medical expenses were exonerated by the Social Security for primary myocardial infarction without a history of angioplasty or of coronary bypass grafting between February and September 2002 were reviewed. The data was researched from the hospital, the patient, the attending physician and the data bases of the Social Security. Four hundred and fifteen patients were included. At discharge from hospital the percentages of prescriptions of recommended drugs were as follows: betablockers 85%, antithrombotics 99%, ACE inhibitors 75%, lipid lowering drugs 90%; the four drug families were associated in 63% of cases. There was no significant difference in prescription between hospital discharge and the twelfth months except with regards to ACE inhibitors (68%) and the association of the four drug groups (54%). The prevalence of smoking, hypertension, diabetes, overweight, obesity and dyslipidaemia were respectively 40, 39, 9, 44, 20 and 81% at the time of infarction. At one year, the prevalence of smoking had fallen significantly to 16%; only 10.3% of patients had uncontrolled hypertension and only 29% had not obtained the recommended therapeutic target for LDL-cholesterol. The authors conclude that this analysis shows an adequation of drug prescription to current recommendations and an improvement in risk factor management which should, however, be pursued.

Trans-fat supplementation over two generations of rats exacerbates behavioral and biochemical damages in a model of mania: Co-treatment with lithium.

AIMS: We investigated whether trans-fat supplemented over two generations of rats could alter neuronal membranes and influence mania-like behaviors, as well as the effects of lithium (Li). MAIN METHODS: Two generations of female rats were supplemented with soybean oil (SO-C, rich in n-6 fatty acids - FA) or hydrogenated vegetable fat (HVF, rich in trans-fatty acids - TFA). Male rats born from the 1st and 2nd generations were maintained in the same supplementation until adulthood, when they were exposed to an amphetamine (AMPH)-induced model of mania and co-treated with Li or not. KEY FINDINGS: AMPH increased locomotion of both generations and this influence was higher in the HVF than in the SO-C group. Conversely, AMPH increased long-term memory in SO-C group of the 2nd generation. HVF supplementation allowed hippocampal TFA incorporation in rats of both generations (0.1 and 0.2%, respectively). Oxidative parameters indicated higher levels of protein carbonyl (PC) in the HVF group with no changes in catalase (CAT) activity in the 1st generation. In the 2nd generation, AMPH increased PC levels of both experimental groups, whereas CAT activity was lower per se in the HVF group only. The co-treatment with Li leveled out all behavioral parameters, PC levels and CAT activity indicating a significant neuroprotective role. SIGNIFICANCE: These findings suggest that chronic HVF consumption allows a rising incorporation of TFA in the brain, which may be reflected on the neuropsychiatric conditions related to mania, whereas the effects of Li are not modified in the course of this harmful dietary habit.

Chronic consumption of trans fat can facilitate the development of hyperactive behavior in rats.

In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors.

Cross-generational trans fat intake facilitates mania-like behavior: oxidative and molecular markers in brain cortex.

Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption of processed food, since high trans fat may facilitate the development of neuropsychiatric conditions, including bipolar disorder (BD).

pmg-1, a novel gene specifically expressed during the invasive growth phase of the mammary gland at puberty.

The acquisition of invasive properties is a crucial event during carcinogenesis, determining the clinical outcome. The mammary gland at puberty provides an ideal model for investigating the induction and control of invasive growth. During this growth phase, the mammary epithelium participates in a normal, hormonally controlled invasive penetration into the stroma. We have applied the differential display method to search for genes specifically activated during this developmental stage. We have identified and molecularly characterized a novel pubertal mammary gland specific gene, pmg-1. This gene is conserved in mammals and encodes a protein of 19.9 kDa. Northern blotting and in situ hybridization revealed that pmg-1 expression was exquisitely restricted to the epithelium at early puberty. To our knowledge this represents the first isolation of a gene specifically associated with the induction of mammary epithelial invasiveness at puberty.

Lectins and traffic in the secretory pathway.

Evidence is accumulating that intracellular animal lectins play important roles in quality control and glycoprotein sorting along the secretory pathway. Calnexin and calreticulin in conjunction with associated chaperones promote correct folding and oligomerization of many glycoproteins in the endoplasmic reticulum (ER). The mannose lectin ERGIC-53 operates as a cargo receptor in transport of glycoproteins from ER to Golgi and the homologous lectin VIP36 may operate in quality control of glycosylation in the Golgi. Exit from the Golgi of lysosomal hydrolases to endosomes requires mannose 6-phosphate receptors and exit to the apical plasma membrane may also involve traffic lectins. Here we discuss the features of these lectins and their role in glycoprotein traffic in the secretory pathway.

Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity.

Recent evidence suggests that high-density lipoprotein (HDL) cholesterol has important vasoactive properties which may contribute to its beneficial effects on atherosclerotic coronary artery disease. The endothelium-dependent vasodilator acetylcholine has been used in a number of experimental studies to assess endothelial function. The relation between serum lipoproteins and acetylcholine-induced coronary vasoreactivity was investigated in patients (n = 27) undergoing elective coronary arteriography. Mean serum cholesterol, low-density lipoprotein cholesterol, HDL cholesterol and triglyceride levels were 189 +/- 7 (4.84 +/- 0.18 mmol/liter), 134 +/- 6 (3.47 +/- 0.15 mmol/liter), 41 +/- 3 (1.06 +/- 0.08 mmol/liter) and 106 +/- 30 mg/dl (1.20 +/- 0.03 mmol/liter), respectively. After a baseline arteriogram, acetylcholine was infused into the left main coronary artery and percent change from baseline dimension was determined in 27 angiographically smooth coronary artery segments and in 14 arterial segments with evidence of mild atherosclerotic disease. Intact vascular smooth muscle function was then confirmed in all segments by dilation to intracoronary nitroglycerin. Acetylcholine produced significant vasoconstriction of both angiographically smooth (13 +/- 4%, p less than 0.05 vs baseline) and diseased (19 +/- 4%, p less than 0.05 vs baseline) coronary segments. A positive correlation was observed between HDL cholesterol and normal acetylcholine-induced coronary vasoreactivity in both angiographically smooth (r = 0.59, p less than 0.001) and diseased (r = 0.62, p less than 0.02) coronary segments. No significant correlation was observed, however, between total and low-density lipoprotein cholesterol, or between total cholesterol to HDL ratio and the response of coronary artery diameter to acetylcholine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)