Cessation of screening for intestinal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae in a low-endemicity intensive care unit with universal contact precautions.

OBJECTIVES: The usefulness of screening for carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) with active surveillance cultures (ASC) remains equivocal in low-endemicity intensive care units (ICUs). Our primary objective was to appraise the impact of ceasing ASC on the incidence of ICU-acquired ESBL-E infections in an ICU with universal contact precautions (CP). Patient outcomes and carbapenem consumption were also investigated. METHODS: A single-ICU, retrospective, uncontrolled before-and-after study including all patients admitted for ≥3 days during two consecutive 1-year periods with and without ASC. RESULTS: A total of 524 and 545 patients were included during the ASC and the no-ASC periods, respectively. Twenty-eight patients (5.3%) from the ASC period were ESBL-E carriers. An ICU-acquired ESBL-E infection (median duration of risk exposure, 4 (range 2-9) days for both periods) occurred in 1.1% and 1.5% of patients admitted during the ASC and the no-ASC periods (p = 0.64), with no inter-period variation in incidence after adjustment on competing risks of death and ICU discharge (standardized hazard ratio (SHR) 2.32, 95% CI 0.80-6.73, p = 0.12). An admission during the no-ASC period exerted no independent impact on the hazards of ESBL-E infections (adjusted OR 1.16, 95% CI 0.38-3.50, p = 0.79), in-ICU death (SHR 1.22, 95% CI 0.93-1.59, p = 0.15) and extended length of stay (SHR for discharge 0.89, 95% CI 0.79-1.01, p = 0.08). Carbapenem exposure in patients without ESBL-E infection decreased between the ASC and no-ASC periods (75 versus 61 carbapenem-days per 1000 patient-days, p = 0.01). CONCLUSIONS: In a low-endemicity ICU with universal CP, the withdrawal of routine screening for ESBL-E carriage had no significant effect on the incidence of ICU-acquired ESBL-E infections and patient outcomes. Carbapenem consumption decreased in patients without ESBL-E infection.

The incidence of Staphylococcus aureus ST8-USA300 among French pediatric inpatients is rising.

Methicillin-resistant Staphylococcus aureus (MRSA) formerly colonized and infected only inpatients in hospitals, but have been reported in community settings worldwide over the last 20 years. In France, the prevalence of such MRSA remains low and outbreaks have, until now, been mainly due to the ST80 clone. However, there were two outbreaks of MRSA clone ST-USA300 recently in France, including one involving children. To investigate epidemiological developments, we studied the 77 MRSA isolated from pediatric patients hospitalized between 2008 and 2013 in three French hospitals. The median incidence of MRSA was stable and low (0.137 per 100 admissions). The prevalence of Panton-Valentine leukocidin (PVL)-positive MRSA was high (33.8 %). The 26 PVL-positive MRSA were genetically diverse, with two clones being predominant: ST80 (12 isolates, 46.1 %) and ST8-USA300 (8 isolates, 30.8 %). The incidence of ST8-USA300 increased over the 6-year period. We believe that screening for ST8-USA300 should be improved: medical biologists should be encouraged to search for PVL genes in all MRSA isolates recovered from abscesses, whatever the susceptibility pattern of the isolate, and not only when suggestive of ST80.

[Outbreak of dermatophytosis in a high-level French judo team: prospective study 2006/2011. Efficacy of a therapeutic protocol introduced in 2004/2005]. / Épidémie de dermatophytoses chez les judokas du pôle France d'Orléans : étude prospective 2006/2011 et évaluation de l'efficacité des mesures instaurées en 2004/2005.

BACKGROUND: Outbreaks of dermatophytosis have been reported more and more frequently in combat sports such as wrestling and judo. Such outbreaks are difficult to treat due to the involvement of numerous actors and structures. The main aim of our study was to determine whether the use of a standardized treatment in a high-level judo team could successfully reduce the outbreak. Our secondary objectives were to study the topography of lesions and ascertain whether consultations for suspected dermatophytosis were significantly more frequent during the 4 weeks following a judo training course. MATERIALS AND METHODS: We conducted a prospective follow-up study from October 2004 to the end of June 2005 (series 1) and then from September 2006 to June 2011 (series 2) during which all new suspected cases of dermatophytosis in a judoka from Pôle France Orléans were examined at the Orléans Dermatology Department. For each consultation, we prepared a map of lesions and mycological samples, and patients received standardized treatment. RESULTS: We compared the two series and a considerable decrease was noted in dermatophytosis outbreaks after the introduction of these measures. The mean number of visits per training season was 97 for series 1 and 21.6 per training season for series 2. The mean numbers of episodes of cutaneous lesions clinically active per training season were 74 for series 1 and 16.8 for series 2. Lesions were localized mainly on the forearms, face and neck (40% for series 1 and 73% for series 2). "Waves" of visits (at least two visits per week) occurred significantly more frequently (68%) during the 4 weeks following a training period than during the rest of the year. CONCLUSION: Standardized management of this outbreak reduced the number of infectious episodes.

[1997-2007, 10 years of monitoring the evolution of resistance of Streptococcus pneumoniae to antibiotics in the region Centre; review of the Pneumococcus network]. / 1997-2007, dix ans de suivi de l'évolution de la résistance de Streptococcus pneumoniae aux antibiotiques en région Centre; bilan de l'observatoire du pneumocoque.

Regional pneumococcal observatories in region Centre, created in 1997, participate with the others pneumococcal observatories alongside the National Reference Center for Pneumococci and the Institut de Veille Sanitaire at the monitoring of the evolution of resistance of pneumococci to antibiotics in France. Between 1997 and 2007, 2427 strains of Streptococcus pneumoniae were isolated in part from cerebrospinal fluids, blood and middle ear fluid, from children and adults. The prevalence of pneumococci with a decreased susceptibility to penicillin (PDSP) decreased strongly in region Centre: 56.8 % in 2001, 39.6 % en 2007. These data are similar to the French national data over the same period.

Heart rate variability in mice: a theoretical and practical guide.

The mouse is the animal model principally used to study biological processes in mammals. The mutation, overexpression or knockout of one or several genes can provide insight into human disease. In cardiovascular research, evaluation of autonomic nervous function is an essential tool for a better understanding of the pathophysiological conditions in which cardiomyopathy arises and develops. Analysis of heart rate variability is the least invasive method to evaluate the sympathovagal balance on the sino-atrial level. The need to perform this technique on freely moving mice emerged in the 1990s, but despite previous studies it has been difficult to set up and standardize a common protocol. The multitudes of techniques used, plus subtle differences in methodology, impede the comparison and clear interpretation of results. This article aims to make a survey of heart rate variability analysis and to establish a standardized protocol for the assessment of the autonomic neural regulation of heart rate in mice.

[Outbreak of cutaneous dermatophytosis in the Judo French Programme in Orleans: September 2004-June 2005]. / Epidémie de trichophyties cutanées chez les judokas du pôle France d'Orléans: septembre 2004-juin 2005.

BACKGROUND: High contact sports regularly allow transmission of infectious agents, including fungi such as dermatophytes. The occurrence of dermatophytosis outbreaks among wrestlers has been extensively described since the 90s. The emergence of such outbreaks among judokas was described for the first time in December 2004. We report here an outbreak which occurred in a high level judo team and is, to our knowledge, the largest ever published. PATIENTS AND METHODS: From October 2004 to June 2005, every judokas of the Pôle France Orléans who were suspect of dermatophytosis were addressed to one single dermatologist. Lesions were sampled for fungal culture and their anatomical cartography was extensively raised. Two protocols of treatment were defined. RESULTS: 97 medical appointments occurred over the period, leading to 74 clinically-defined episodes of dermatophytosis, distributed as 51 primo-contaminations and 23 re-contaminations (new episode in an individual who was considered cured). The distribution of the lesions on the body was: forearms > anterior trunk > neck and face > scalp. Among the 74 episodes, 53 could grow Trichophyton tonsurans. Infected athletes received oral and topical antifungal treatments. No adverse effects were noticed. DISCUSSION: This series among judokas is the largest ever published. It allowed the description of the specific clinical and anatomical presentation of tinea corporis gladiatorum, emphasising that contamination takes place through direct skin to skin contacts during practice. T. tonsurans is regularly the responsible fungus in recently published series. Caring for such an outbreak raises specific problems because of the numerous structures involved and of the nature of these structures and of the sportive goals they aim at. CONCLUSION: This outbreak is probably part of a wider one diffusing among high level judo teams. Stopping it requires the cooperation of several distinct actors, among which sports federations as well as sports-related physicians and dermatologists should play a major role.

Outbreak of tinea corporis gladiatorum, a fungal skin infection due to Trichophyton tonsurans, in a French high level judo team.

An outbreak of 49 cases of tinea corporis gladiatorum due to Trichophyton tonsurans infection occurred in a high level judo team of 131 members in Orleans, central France, between October 2004 and April 2005. The team was divided into 5 groups: cadet-junior boys (n=44), cadet-junior girls (n=33), male university students (n= 15), female university students (n=21), and a group called 'pole technique' made up of high level judokas who have finished academic study (n=18). The outbreak involved 86% of the cadet-junior boys, but only 6 men in the 'pole technique' (33%) and only 5 of the 69 other team members (7%) (cadet-junior girls and university students). We describe the outbreak and the results of a survey that found a known risk factor for the 'pole technique': sharing an electric hair shaver. Personal hygiene practices were found to be very good among the cadet-junior boys. The high attack rate in this group may be linked to the poor shower facilities in the gymnasium where they practiced that led them to have their showers several hours after the end of daily practice.

A "true" polymicrobial endocarditis: Candida tropicalis and Staphylococcus aureus--to a drug user. Case presentation and literature review.

Polymicrobial endocarditis is more frequent in intravenous drug user (IVDU). Combined therapy--medical and surgical--represents the standard of care, but long-term suppressive therapy duration in fungal endocarditis is still debated. The polymicrobial endocarditis is rare: 1-3%. It is being observed with increasing frequency among drug users; a predominance of tricuspid valve involvement exists. We report a case of dual etiology infective endocarditis (IE) - Candida tropicalis and Staphylococcus aureus - in a IVDU; the treatment was combined, medical and surgical, and was followed by a suppressive antifungal therapy. We review the other published Candida tropicalis endocarditis cases and discuss their optimal management.

Treatment difficulties of a listerial rhombencephalitis in an adult patient allergic to penicillins.

Rhombencephalitis is not a rare presentation of listerial central nervous system infections in healthy adults. This report describes a case with several management difficulties linked to antibiotic related adverse events, pointing to alternative solutions to aminopenicillins. In addition, the role of dexamethasone in the management of inflammation and neurological symptoms is discussed.

[Digital purpura revealing septicaemical rat-bite fever]. / Purpura digital isolé révélant une streptobacillose septicémique après morsure de rat.

INTRODUCTION: Infection with Streptobacillus moniliformis is an uncommon illness which can lead to death if untreated. We report the case in which initially cutaneous signs permitted diagnosis and further identification of the organism. CASE REPORT: A 42 year-old woman presented with a three-day history of acrally distributed purpuric macules on her fingers. Two days later, she was admitted for arthritis of the knees and wrists. There were two large pustules on the left elbow and the right knee. Laboratory studies showed inflammatory changes. The diagnosis of streptobacillary rat-bite fever was made after isolation of Gram-negative bacilli from a blood-culture and from cutaneous lesions. Finally identification of the organism was made by molecular biology analysis. The patient received intravenous ofloxacin and imipenem with complete resolution of arthritis and the cutaneous lesions. DISCUSSION: Streptobacillary rat-bite fever is a systemic infectious disease. It is caused by Streptobacillus moniliformis, organism found in the oropharyngeal flora of small rodents, especially rats. The illness is uncommon in urban settings. It starts by fever, followed by arthritis and rash. Septicaemical rat-bite fever may start only with cutaneous involvement such as acral purpura, like in our case. This clinical manifestation must be recognized by the dermatologist, because the illness can lead to death if untreated.

Comparative effects of melatonin, zolpidem and diazepam on sleep, body temperature, blood pressure and heart rate measured by radiotelemetry in Wistar rats.

RATIONALE: The role of melatonin (MLT) in mediating the sleep-wake cycle has been previously suspected of indicating that this substance could be a candidate for a new generation of hypnotics. OBJECTIVES: We investigated whether MLT acted as a sleep promoter or a modulator of sleep temporal timing related to cardiovascular and body temperature (Tb) adaptations to sleep induction. The pharmacological effects of MLT on sleep were compared with zolpidem (ZP) and diazepam (DZ). METHODS: The radiotelemetry system was used to record the electrocorticogram [slow wave sleep (SWS), paradoxical sleep (PS)], Tb, blood pressure and heart rate in six Wistar rats. DZ (3 mg/kg and 6 mg/kg), ZP (1, 3, 5 and 10 mg/kg) and MLT (2.5 and 5 mg/kg) were delivered intraperitoneally during light (L) and dark (D) periods. RESULTS: MLT increased the number of sleep cycles (L: 30%, D: 110%) and total duration (P<0.05) of PS (L: 70%, D: 150%). In return, ZP (10 mg/kg) presented no effect during L but increased total (40%) and mean duration (37%) of SWS during the D period. DZ modified mean duration of SWS (L: -27%, D: +26%) and increased total duration of SWS (+47%). ZP and DZ induced a more pronounced decrease in Tb than MLT but only DZ induced tachycardia and hypertension. CONCLUSIONS: We showed that MLT could not promote sleep and its cardiovascular adaptations despite hypothermia, but modulated the period of ultradian sleep cycles. DZ and ZP promoted sleep and induced hypothermia during the D period. Only DZ disrupted sleep architecture and induced adverse effects on cardiovascular parameters.

Protective effects of I(1)-antihypertensive agent moxonidine against neurogenic cardiac arrhythmias in halothane-anesthetized rabbits.

Numerous studies have addressed the antihypertensive properties of I(1)-imidazoline receptor agonists such as moxonidine, but very few authors examined their cardiac antiarrhythmic potency. Due to the important role of the sympathetic nervous system in the genesis of neurogenic cardiac arrhythmias, we investigated the antiarrhythmic effects of moxonidine and compared them to those of propranolol in an experimental model of neurogenic arrhythmias. Chronic bipolar electrodes were implanted within the posterior hypothalamus of six halothane-anesthetized rabbits. Every 15 days, after three 10-min-interval control electrical stimulations, we compared the effects of randomized i.v. administrations of moxonidine (25 microg/kg), propranolol (0.5 mg/kg), and saline (0.9% NaCl) on mean arterial pressure (MAP), heart rate (HR), and ECG during 2.5 h with six stimulations every 20 min. We observed that: 1) in control conditions, intrahypothalamic stimulation increased MAP (DeltaMAP = 17 +/- 2 mm Hg) and HR (DeltaHR = 60 +/- 1 beats/min), and triggered extrasystoles (number of extrasystoles = 55 +/- 2) and abnormal complexes (number of abnormal ECG complexes = 37 +/- 1), which occurred with a 6.4 +/- 0.4-s delay and 33 +/- 1-s duration; 2) moxonidine and propranolol induced almost equihypotensive (DeltaMAP = -12 +/- 2 and -10 +/- 2 mm Hg) and pronounced bradycardic effects (DeltaHR = -47 +/- 10 and -78 +/- 9 beats/min, respectively). Arrhythmias were significantly reduced by moxonidine and propranolol: Deltanumber of extrasystoles = -83 and -98%; Deltanumber of abnormal ECG complexes = -33 and -79%; Deltadelay = +65 and +188%; Deltaduration = -35 and -58%, respectively. Our results show that moxonidine presents an antiarrhythmic potency comparable to that of propranolol that should be predominantly related to their central action. However, additional studies are required to determine whether these antiarrhythmic effects are of central and/or peripheral origin.

Five years follow-up after 2-chloro deoxyadenosine treatment in thirty patients with hairy cell leukemia: evaluation of minimal residual disease and CD4+ lymphocytopenia after treatment.

Between March 1992 and August 1993, thirty patients with hairy cell leukemia (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2-CdA) for one course (N=27) or two courses at six month interval (N=3). Sixteen patients were previously untreated, 14 had been treated with alpha interferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy, alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable patients were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients relapsed after 18, 24 months and five years. Two were retreated successfully. Two CR patients relapsed after five years. Careful clinical survey, sequential bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of response and detection of residual disease and serially evaluation of lymphocyte subsets counts were performed. Results of bone marrow biopsies study show 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44+ cells (80% of BMB). There was a correlation between the presence of > 5% DBA44 positive cells on 6th month BMB and relapse. 60% had an absolute CD4+ lymphocyte count less than 0.2 10(9)/l at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymphopenia was less marked in splenectomized patients: 7/7 splenectomized patients tested have recovered a CD4+ lymphocyte count equal to pretherapy level compared to 3/11 non splenectomized patients (p: 0.004). Three opportunistic infections were observed early (first 6 months) after 2CdA therapy: pneumocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infection while in second CR. At five years, overall survival is 83% and progression free survival is 66%. Our study shows 1) long-lasting response in the majority of patients after 2-CdA, 2) a correlation between persistent minimal residual disease detected with DBA44 immunostaining and occurrence of relapse and 3) a profound and persistent CD4+ lymphopenia more marked in non splenectomized patients.

Effects of meal carbohydrate content on insulin requirements in type 1 diabetic patients treated intensively with the basal-bolus (ultralente-regular) insulin regimen.

OBJECTIVE: In this study, we evaluated the effects of high-(55%) and low-(40%) carbohydrate diets on insulin requirements in nine type 1 diabetic subjects treated intensively with ultralente as basal insulin and regular insulin as premeal insulin adjusted to the carbohydrate content of meals. RESEARCH DESIGN AND METHODS: Nine subjects were randomized in a crossover design to follow two diets consecutively for a period of 14 days each. A 3-day food diary was completed for each diet with the amount of carbohydrate in the mixed meals ranging from 21 to 188 g. Preprandial (5.9 vs. 6.1 mmol/l) and postprandial (8 vs. 8.9 mmol/l) capillary glucose and fructosamine (310 vs. 316 mumol/l) were comparable on both the low- and high-carbohydrate diets. RESULTS: The assessment of meal carbohydrate content by the patients was excellent, with > 85% of cases falling within 15% of computer-assisted evaluation. When premeal regular insulin was prescribed in U/10 g of carbohydrate, the postprandial glycemic rise remained constant (2.4 +/- 2.8 mmol/l) over a wide range of carbohydrate ingested (21-188 g) and was not affected by the glycemic index, fiber, and caloric and lipidic content of the meals. This tight control was maintained during the low- and high-carbohydrate diet without any change in insulin requirements (breakfast, 1.5 vs. 1.5 U/10 g of carbohydrate; lunch, 1.0 vs. 1.0; supper, 1.1 vs. 1.2) and in basal ultralente insulin requirements (22.5 vs. 21.4 U/day). CONCLUSIONS: These results indicate that in type 1 diabetic subjects 1) increasing the amount of carbohydrate intake does not influence glycemic control if premeal regular insulin is adjusted to the carbohydrate content of the meals; 2) algorithms based on U/10 g of carbohydrate are effective and safe, whatever the amount of carbohydrate in the meal; 3) the glycemic index, fiber, and lipidic and caloric content of the meals do not affect premeal regular insulin requirements; 4) wide variations in carbohydrate intake do not modify basal (ultralente) insulin requirements; and, finally 5) the ultralente-regular insulin regimen allows dissection between basal and prandial insulin requirements, so that each can be adjusted accurately and independently.

Effects of different glycaemic index foods and dietary fibre intake on glycaemic control in type 1 diabetic patients on intensive insulin therapy.

To evaluate the influence of a low glycaemic index (GI), high GI and high fibre diet on glycaemic control and insulin requirement in Type 1 diabetic patients on intensive insulin therapy, nine well-controlled, highly-motivated Type 1 diabetic patients were put on a control diet for 12 days and then randomized in a consecutive manner to 12 days of each diet, in a crossover design. During each experimental diet, the study subjects adjusted their premeal insulin (soluble) dose to maintain their 1-h postprandial capillary glucose at or below 10 mmol l(-1). At the end of each experimental diet, they were submitted to a standardized breakfast of the diet under study, using the same premeal insulin dose as that required for the control diet. The control diet contained 16.0+/-3.0 g of fibre day(-1) with a GI of 77.4+/-2.7 compared to 15.3+/-6.3 and 66.2+/-1.2 for the low GI diet, 17.1+/-7.2 and 92.9+/-3.6 for the high GI diet, and 56.1+/-3.6 (including 15 g of guar) and 73.5+/-2.1 for the high fibre diet. Prebreakfast capillary blood glucose (6.2+/-1.2 mmol l(-1)) on the low GI diet and postbreakfast capillary blood glucose (8.7+/-1.8 mmol l(-1)) on the high fibre diet were significantly lower than the values obtained with the control diet (8.0+/-1.8 and 10.6+/-2.4, respectively; p<0.05). No change in premeal or basal insulin dose was required. During the standardized breakfasts, the incremental area under the curve was 1.6+/-1.5 mmol l(-1) min(-1) for the control diet compared to 1.1+/-1.8 for the low GI diet, 3.2+/-1.4 for the high GI diet (p<0.05 versus low GI and high fibre; p=0.08 versus control), and 1.0+/-0.9 for the high fibre diet. These observations indicate that in well-controlled Type 1 diabetic subjects on intensive insulin therapy, major alterations in the GI and fibre content of meals induce small but significant changes in glucose profile. In everyday life, however, these differences are blunted, and plasma glucose remains within the target range for optimal metabolic control.

[Effects of alpha and beta blocker properties of parahydroxybenzonitrile on the cardiovascular system of rats]. / Etudes des effets alpha et beta bloquants du parahydroxybenzonitrile sur le système cardiovasculaire du Rat.

The study of parahydroxybenzonitrile on the cardiovascular system of the Rat shows alpha blocker properties.

Influence of neonatal focal cerebral hypoxia-ischemia on cardiovascular and neurobehavioral functions in adult Wistar rats.

No experimental studies looked at the disturbances appearing after a neonatal focal cerebral hypoxia-ischemia (HI) when animals become adults. Using radiotelemetry, we examined the effects of neonatal focal cerebral HI on blood pressure (BP), heart rate (HR), locomotor activity (LA), body temperature (BT) levels and circadian rhythm parameters of unrestrained adult Wistar rats. At 15 weeks of age, we continuously recorded the cardiovascular and neurobehavioral parameters of HI (n = 6) and sham-operated (n = 6) rats. In adult rats, HI induced persistent hypertensive effects associated with alteration in BP circadian rhythms and pronounced decreases in mesor and percent rhythm of LA. HR and BT parameters were not significantly modified. Therefore, our results suggest that the rat cardiovascular and behavioural circadian control systems may involve several structures which present selective vulnerability to early cerebral HI.

Treatment of recalcitrant plaque psoriasis with a humanized non-depleting antibody to CD4.

The presence of activated CD4(+) T lymphocytes in psoriatic skin plaques suggests an immune-mediated pathogenesis for the disease. Six patients with recalcitrant plaque psoriasis (PASI>12) received a humanized non-depleting monoclonal antibody to CD4 (ORTHOCLONE OKT(R)cdr4a). The antibody was well tolerated. Four weeks from treatment, the mean decrease in PASI score was 46%. In three patients disease remission was prolonged for up to 6 months and, in one case, up to 1 year post-treatment. In all patients, circulating CD4+ T-cell counts remained normal and peripheral OKTcdr4a-coated CD4+ lymphocytes were detected up to 10 days after antibody infusion. These results point to the relevance of CD4+ lymphocytes in psoriasis. They also emphasize that depletion of CD4+ cells is not mandatory to achieve therapeutic effectiveness.

Increased hepatic glucose production response to glucagon in trained subjects.

This study was designed to characterize the impact of endurance training on the hepatic response to glucagon. We measured the effect of glucagon on hepatic glucose production (HGP) in resting trained (n = 8) and untrained (n = 8) healthy male subjects (maximal rate of O2 consumption: 65.9 +/- 1.6 vs. 46.8 +/- 0.6 ml O2.kg-1.min-1, respectively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 micrograms/h) over 4 h. Insulin (0.15 mU.kg-1.min-1) was infused throughout the study, and glucagon (1.5 ng.kg-1.min-1) was infused over the last 2 h. During the latter period, plasma glucagon and insulin remained constant at 138.2 +/- 3.1 vs. 145.3 +/- 2.1 ng/l and at 95.5 +/- 4.5 vs. 96.2 +/- 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 +/- 1.1 mmol/l in trained subjects and at 8.9 +/- 0.8 mmol/l in untrained subjects (P < 0.001). During glucagon stimulation, the mean increase in HGP area under the curve was 15.8 +/- 2.8 mol.kg-1.min-1 in trained subjects compared with 7.4 +/- 1.6 mol.kg-1.min-1 in untrained subjects (P < 0.01) over the first hour and declined to 6.8 +/- 2.8 and 4.9 +/- 1.4 mol.kg-1.min-1 during the second hour. In conclusion, these observations indicate that endurance training is associated with an increase in HGP in response to physiological levels of glucagon, thus suggesting an increase in hepatic glucagon sensitivity.

Effect of tamoxifen on the pharmacokinetics of theophylline in rats.

The effect of tamoxifen on the pharmacokinetics of theophylline was investigated in male Sprague-Dawley rats. The oral administration of tamoxifen at a dose equal to 40 mg kg-1 48 h before the intravenous injection of theophylline 10 mg kg-1, significantly (P < 0.05) increased the clearance of theophylline by 39%, with no apparent effect on the volume of distribution. As a consequence, the elimination half-life of theophylline was significantly (P < 0.05) shortened in the tamoxifen-treated rats (3.56 +/- 0.39 h vs 5.25 +/- 0.48 h) as well as its mean residence time (5.04 +/- 0.60 h vs 7.50 +/- 0.75 h). Although these data cannot be directly extrapolated to the clinical situation, they provide experimental support to suggest that more attention should be paid to the potential risk of pharmacokinetic interactions in the presence of tamoxifen.