High-speed interband cascade infrared photodetectors: photo-response saturation by a femtosecond oscillator.

Interband cascade infrared photodetectors (ICIPs) combine interband optical transitions with fast intraband transport to achieve high-frequency and broad-wavelength operation at room temperature. Here we study the bias-dependent electronic impulse response of ICIPs with a mid-infrared synchronously pumped optical parametric oscillator (OPO). Since the OPO produces ultrashort 104-fs pulses, it is possible to probe the impulse response of the ICIP. From this impulse response, we identify two characteristic decay times, indicating the contribution of electron as well as hole carriers. A reverse bias voltage applied to the ICIP reduces both time scales and leads to an increased electrical cut-off frequency. The OPO emits up to 500 mW average power, of which up to 10 mW is directed to the ICIP in order to test its saturation characteristics under short-pulse illumination. The peak of the impulse response profile as well as the average photocurrent experience a gradual saturation behavior, and we determine the corresponding saturation powers by measuring the photo-response as a function of average power directed to the ICIP. We demonstrate that an increasing reverse bias increases the saturation power as well as the responsivity of the ICIP.

Watt-level and sub-100-fs self-starting mode-locked 2.4-µm Cr:ZnS oscillator enabled by GaSb-SESAMs.

Femtosecond lasers with high peak power at wavelengths above 2 µm are of high interest for generating mid-infrared (mid-IR) broadband coherent light for spectroscopic applications. Cr2+-doped ZnS/ZnSe solid-state lasers are uniquely suited since they provide an ultra-broad bandwidth in combination with watt-level average power. To date, the semiconductor saturable absorber mirror (SESAM) mode-locked Cr:ZnS(e) lasers have been severely limited in power due to the lack of suitable 2.4-µm SESAMs. For the first time, we develop novel high-performance 2.4-µm type-I and type-II SESAMs, and thereby obtain state-of-the-art mode-locking performance. The type-I InGaSb/GaSb SESAM demonstrates a low non-saturable loss (0.8%) and an ultrafast recovery time (1.9 ps). By incorporating this SESAM in a 250-MHz Cr:ZnS laser cavity, we demonstrate fundamental mode-locking at 2.37 µm with 0.8 W average power and 79-fs pulse duration. This corresponds to a peak power of 39 kW, which is the highest so far for any saturable absorber mode-locked Cr:ZnS(e) oscillator. In the same laser cavity, we could also generate 120-fs pulses at a record high average power of 1 W. A comparable laser performance is achieved using type-II InAs/GaSb SESAM as well. These results pave the way towards a new class of high-power femtosecond SESAM mode-locked oscillators operating directly above 2-µm wavelength.

Digital mammography screening: sensitivity of the programme dependent on breast density.

OBJECTIVES: To analyse the impact of breast density on the sensitivity of a population-based digital mammography screening programme (SP) as key evaluation parameter. METHODS: 25,576 examinations were prospectively stratified from ACR category 1 to 4 for increments of 25 % density during independent double reading. SP was calculated as number of screen-detected cancers divided by the sum of screen-detected plus interval cancers (24-months period) per ACR category, related to the first reading (a), second reading (b) and highest stratification if discrepant (c). Chi-square tests were used for comparison. RESULTS: Overall sensitivity of the programme was 79.9 %. SP in ACR 4 (a: 50 %, b: 50 %, c: 50 %) was significantly lower than in ACR 3 (a: 72.9 %, b: 79.4 %, c: 80.7 %, p < 0.001), ACR 2 (a: 83.9 %, b: 85.7 %, c: 83.2 %, p < 0.001) and ACR 1 (a: 100 %, b: 88.8 %, c: 100 %; p < 0.001). Frequencies of ACR 4 were a: 5.0 %, b: 4.3 %, c: 6.9 %. CONCLUSION: Digital mammography screening with independent double reading leads to a high overall SP. In the small group of women with breast density classified as ACR 4 SP is significantly reduced compared to all other ACR categories. KEY POINTS: • Overall sensitivity of a population-based digital mammography screening programme (SP) was 79.9 %. • In women with ACR 1, 2, or 3, SP ranged between 72.9 %-100 %. • ACR 4 was rare in participants (<7 %) and SP was only 50 %. • SP in ACR 4 differed significantly from ACR 3 (p < 0.001).

Reduction of Advanced Breast Cancer Stages at Subsequent Participation in Mammography Screening.

PURPOSE: The decline in advanced breast cancer stages is presumably the most relevant surrogate parameter in mammography screening. It represents the last step in the causal cascade that is expected to affect breast cancer-related mortality. To assess the effectiveness of population-based screening, we analyzed the 2-year incidence rates of advanced breast cancers between women participating in the initial and in the first subsequent round. MATERIALS AND METHODS: The study included data from 19,563 initial and 18,034 subsequent examinations of one digital screening unit (2008 - 2010). Data on tumor stages, detected by screening or within the following interval of two years (2-year incidence), were provided by the epidemiological cancer registry. Rates of all and combined UICC stages 2, 3 and 4 (advanced stages) were reported for a two-year period. Proportions were tested for significance by using chi-square tests (p < 0.001). RESULTS: The 2-year incidence rate of all stages was significantly lower in participants in subsequent screening than in initial screening (0.85 vs. 1.29 per 100 women (%); p < 0.0001). A significantly lower 2-year incidence of advanced stages was observed for subsequent screening compared to initial screening (0.26 % vs. 0.48 %; p = 0.0007). Among women aged 50 to 59 years, the incidence of advanced stages was less clearly different (0.21 % vs. 0.35 %; p = 0.07) than in women aged 60 to 69 years (0.31 % vs. 0.70 %; p = 0.0008). CONCLUSION: During the change from prevalent to incident phase mammography screening, a program impact is seen by a lower 2-year incidence of advanced breast cancers within subsequent compared to initial participants, predominately in women aged 60 to 69 years. KEY POINTS: • The incidence of advanced tumor stages represents the most relevant surrogate parameter for screening effectiveness. • For the first time the 2-year incidence of advanced breast cancer stages after subsequent mammography screening was analyzed. • We observed a significant effect of screening on the 2-year incidence of advanced stages, predominately in the age group 60 to 69 years.

Experimental ELISA for diagnosis of ovine dicrocoeliosis and application in a field survey.

Dicrocoeliosis is a parasitic disease caused by trematodes belonging to the genus Dicrocoelium. It usually produces mild symptoms, and for this reason, dicrocoeliosis often remains undetected. Its diagnosis is mostly based on postmortem examination of the liver or on coprological assays for in vivo diagnosis. However, the latter method has scant sensitivity and because of the long pre-patency of Dicrocoelium spp. only permits late diagnosis. In the present study, an enzyme-linked immunosorbent assay (ELISA) was developed based on excretory/secretory antigen of Dicrocoelium dendriticum. The ELISA detected antibodies (IgG) in experimental infected sheep starting from day 30 post-infection (d.p.i.), whereas coprological samples were positive from 58 d.p.i. The ELISA was used in a field study in order to assess dicrocoeliosis seroprevalence in ovine flocks from the province of Trento (northeastern Italy), and this was the first sero-epidemiological study of ovine dicrocoeliosis in northern Italy. Altogether, 842 sheep sera were tested. In accordance with previous surveys carried out in other regions of Italy, a high prevalence of 80% to 100% was found.

Liver flukes in dogs and treatment with praziquantel.

Opisthorchiid eggs were found in 6 out of 27 (22%) huskies while an ELISA detected antibodies against Opisthorchis felineus and Metorchis bilis in 24 (89%) and 25 (93%) sera taken from these dogs, respectively. All dogs showed an increased activity of glutamate dehydrogenase while aspartate aminotransferase was normal in all samples. Ten weeks after treatment with praziquantel no fluke eggs were found in the faeces from any animal and antibody titres dropped in all animals.

Variations in the use of diagnostic procedures after acute stroke in Europe: results from the BIOMED II study of stroke care.

Valid classification of stroke is essential to initiate effective acute management and early secondary prevention strategies. To accurately evaluate stroke subtype a number of diagnostic procedures have to be performed. This study sought to investigate variations in use of diagnostic procedures across selected European hospitals. First-ever stroke patients were sampled over a 1-year period through 11 hospital-based registers across 10 European countries. We defined a diagnostic standard for valid aetiological classification of ischemic stroke including brain imaging, vascular imaging and echocardiography. The impact of socio-demographic, clinical and structural characteristics on performance of the diagnostic standard was assessed using multivariate logistic regression analyses. A total of 1721 patients were included in the study. 83.1% received brain imaging, ranging from 32.8% to 100%. The diagnostic standard was performed in 40.4% of stroke patients, ranging from 0% to 77.2%. Patients with increasing age (P < 0.001) and with more severe strokes (P = 0.001) were less probably to receive the diagnostic standard. Patients treated in stroke units and neurological departments were more frequently investigated with the diagnostic standard (P < 0.001). Less than half of hospitalized stroke patients across Europe underwent diagnostic procedures to allow for aetiological classification of stroke, which may hamper the initiation of effective early management and secondary prevention.

[Changes in the perception of risk factors for stroke in the German population between 1995-1996 and 2000-2001. Results of two representative EMNID surveys]. / Veränderungen in der Wahrnehmung der Risikofaktoren für einen Schlaganfall in der deutschen Bevölkerung zwischen 1995/1996 und 2000/2001. Ergebnisse zweier repräsentativer EMNID-Befragungen.

BACKGROUND AND OBJECTIVE: Stroke is one of the leading causes for death and disability worldwide. A better understanding of the perception of modifiable stroke risk factors in the population is the first step to initiate effective prevention strategies on population level. Changes over 5 years in the risk perception in the general population were investigated by two representative surveys in Germany. METHODS: Nationwide programs to screen voluntary participants for stroke risk were undertaken in 1995-1996 and 2000-2001 by the German Stroke Foundation, in cooperation with the health insurance company BARMER and the Sanofi-Synthelabo Company. As part of these programmes two surveys were performed by TNS-EMNID to collect data on population knowledge. A representative sample of the German population was selected and asked to categorize their perception of stroke risk for common vascular risk factors. RESULTS: A total of 8193 participants were interviewed (4081 in 1995-1996 and 4112 in 2000-2001); 43.5% were (3) 50 years of age and 52.5% were female. Hypertension was rated by 68.3% to be in the highest risk category for stroke, followed by smoking (52.3%), hypercholesterolemia (48.0%), overweight (48.0%), excessive alcohol consumption (32.9%) and diabetes (26.6%). The proportion of participants who graded these factors to be important for stroke occurrence was persistently higher in 2000-2001 than in 1995-1996. CONCLUSION: Perception of modifiable risk factors for stroke increased over a 5-year time period in two representative surveys in Germany. The importance of diabetes mellitus as a risk factor for stroke is especially underestimated in the general population.

[Differences in the extent of diagnostic procedures after acute stroke in patients treated in departments of neurology, internal medicine and geriatric medicine]. / Art und Umfang der Diagnostik bei der Akutbehandlung von Schlaganfallpatienten in neurologischen, internistischen und geriatrischen Abteilungen.

BACKGROUND AND PURPOSE: In Germany, data about variations in acute stroke treatment between different facilities are lacking. The aim of the present study was to compare the extent of diagnostic procedures for acute stroke between departments of neurology, internal medicine, and geriatric medicine. METHODS: Stroke patients admitted to hospitals cooperating within the Westphalian Stroke Register between January 1, 2000 and December 31, 2001 were analyzed. Forty-two hospitals participated in the study including 24 departments of neurology, 13 of internal medicine, and 5 of geriatric medicine. The register is based on a standardized data assessment including sociodemographic and clinical characteristics of the patient, in the acute phase, as well as diagnostic and treatment procedures, complications, and status at discharge. The performance of brain imaging, Doppler, and echocardiography was defined as diagnostic standard for diagnosis and etiological classification of ischemic stroke. RESULTS: A total of 12,232 stroke patients were included. Mean age was 72 years, 49 % were men. In general, diagnostic procedures were administered more often in neurological departments compared to departments of internal or geriatric medicine. In all participating hospitals, the application of diagnostic techniques was less frequent in older patients. The defined diagnostic standard was performed more often in those neurological departments providing acute stroke unit services compared to neurological departments without stroke unit services. CONCLUSION: Our study detected variations in the extent of diagnostic procedures in acute stroke between different medical disciplines. However, further studies are required to clarify whether a more frequent performance of diagnostic techniques yields relevant therapeutic consequences.

Influence of methods for Trichinella detection in pigs from endemic and non-endemic European region.

A total of 1401 German and 226 Croatian pigs raised either indoors or outdoors were tested for Trichinella infection by direct and indirect detection methods. A 10 g sample of diaphragm were examined for muscle larvae by the artificial digestion method; the species was determined by multiplex polymerase chain reaction (PCR). For detection of anti-Trichinella IgG, serum samples diluted 1:100, and meat juice samples diluted 1:10, were tested by enzyme-linked immunosorbent assay. All German pigs and those Croatian pigs raised indoors proved to be Trichinella-negative by all methods. Muscle larvae were detected in a total of eleven of the Croatian pigs, which were raised on small outdoor farms. For eight isolates, PCR results demonstrated that recovered larvae were Trichinella spiralis. Anti-Trichinella-IgG was detected in serum and meat juice of digestion positive animals when the worm burdens exceeded 0.38 larvae per gram of muscle. Positive results in Croatian pigs indicate a higher risk of infection for outdoor farming in areas where Trichinella is endemic. Results of direct and indirect detection were compared and are discussed with special regard to specificity and sensitivity of methods.

Educational level and risk profile of cardiac patients in the EUROASPIRE II substudy.

STUDY OBJECTIVE: To ascertain, whether, conventional risk factors and readiness of coronary patients to modify their behaviour and to comply with recommended medication were associated with education in patients with established coronary heart disease. DESIGN AND METHODS: EUROASPIRE II was a cross sectional survey undertaken in 1999-2000 in 15 European countries to ascertain how effectively recommendations on coronary preventions are being followed in clinical practice. Consecutive patients, men and women

[Classical risk factors for myocardial infarction and total mortality in the community--13-year follow-up of the MONICA Augsburg cohort study]. / Klassische Risikofaktoren für Herzinfarkt und Gesamtsterblichkeit in der Bevölkerung. 13-Jahres-Follow-up der MONICA Augsburg-Kohortenstudie.

PURPOSE: The MONICA (MONItoring of trends and determinants in CArdiovascular disease) project in the region of Augsburg, Southern Germany, is the first population-based cohort study in Germany investigating the association of the risk factors hypertension, hypercholesterolemia and smoking with incident myocardial infarction and total mortality, and to assess their impact at the population level. METHODS: At baseline, 1074 men and 1013 women aged 45-64 years were randomly selected from the population in the Augsburg region and extensively interviewed and examined regarding their cardiovascular risk profile. They were traced over 13 years from 1984-1997. We calculated incidence rates, hazard rate ratios, population attributable risks (PAR), and rate advancement periods (RAP) according to the three risk factors and their combinations. RESULTS: Among men, 107 myocardial infarctions and 204 total mortality events occurred during the study period; in women the number of total mortality cases was 102. The three classical risk factors were associated with incident myocardial infarction in men and with total mortality in men and women over a period of 13 years. Heavily smoking men had a particularly high risk of total mortality (HRR=4.2; 95% CI 2.5-7.0) and myocardial infarction (HRR=3.8; 1.9-7.6). Men with treated hypertension were at equally high risk for both total mortality (HRR=2.4; 1.5-3.7) and myocardial infarction (HRR=2.4; 1.3-4.3). In women, treated hypertension (HRR=2.5; 1.5-4.1) and hypercholesterolemia (HRR=2.0; 1.2-3.3) were most strongly related to total mortality. Regarding the association of risk factor combinations and myocardial infarction among men, the presence of all three risk factors simultaneously (HRR=7.9; 3.6-17.3) and the combination smoking/hypercholesterolemia (HRR=5.8; 3.2-10.5) were particularly hazardous. In total, the three risk factors contributed 54% of the burden of myocardial infarction in the male study population. The rate advancement periods for myocardial infarction related to treated hypertension, hypercholesterolemia and heavy smoking were 10.5, 5.8 and 15.8 years, respectively. CONCLUSIONS: Our results confirm the outstanding impact of the classical risk factors on myocardial infarction and total mortality in a southern German population. Coronary heart disease is largely preventable through risk factor reduction. Therefore, risk factor counselling, education and treatment are crucial to prevent people from developing the disease or dying prematurely.

[Secondary prevention of coronary heart disease. Results from EuroASPIRE I and II in the region of Münster, Germany]. / Sekundärprävention der koronaren Herzkrankheit - Ergebnisse der EuroASPIRE I- und II-Studien in der Region Münster, Germany.

BACKGROUND: EuroASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) is a European multicenter study on secondary prevention in patients with coronary heart disease (CHD). The first cross-sectional survey was undertaken in 1995/96 among 3569 patients from nine countries. A second cross-sectional survey (EuroASPIRE II) was conducted in 1999/2000 among 5556 patients from 15 countries to evaluate among others whether coronary prevention had improved since the first. METHODS: The present study was conducted in the region of Münster, Germany, as part of the EuroASPIRE study. Consecutive patients, men and women up to 70 years of age with established CHD, were identified retrospectively. A total of 392 (EuroASPIRE I) and 402 (EuroASPIRE II) patients participated. Information on cardiovascular risk factors, lifestyle and medication were obtained through medical records, interviews and examinations. RESULTS: Both studies demonstrate a high prevalence of risk factors among CHD patients. At the time of the interview more than 60% of the patients in both surveys had two or more risk factors. The comparison of EuroASPIRE I and II reveals a substantial decrease of 20% in the prevalence of hypercholesterolemia, but an increase in the prevalence of hypertension and obesity. ACE-inhibitors, betablockers and lipid lowering drugs, especially statins, were used more frequently in EuroASPIRE II. CONCLUSIONS: We conclude that secondary prevention of CHD in the region of Münster like in the other European study regions is less than optimal and has not substantially improved between 1996 and 2000. Potential reasons are discussed.

Field methodology for lateral cranial radiography of nonhuman primates.

The historical lack of field-based radiographic studies of nonhuman primates within the field of anthropology is likely due to the perceived difficulty of transporting and operating X-ray equipment. Here we present a method for taking lateral cranial radiographs of nonhuman primates in the field that is simple to employ, and that produces exposed films suitable for collection of measurement data useful for growth and development studies, as well as for investigating bone and soft-tissue pathology. Several different X-ray units, film types, and portable power sources were used, all producing suitable images of similar quality, indicating that this methodology is likely not overly sensitive to these important parameters.

Aspects of clinical features, diagnosis, notification and tracing back referring to Trichinella outbreaks in north Rhine-Westphalia, Germany, 1998.

52 cases of human trichinellosis were notified from 11 towns in North Rhine-Westphalia from November 1998 to March 1999. After non-typical symptoms in the enteral phase, fever, muscular ache, headache, oedema, disorder of vision and rash occurred in the parenteral phase. Trichinellosis was serologically confirmed by ELISA, IFAT or western blot. Raw sausage and minced meat produced from raw pork could be determined as probable source of infection with 44 and eight notified cases, respectively. Whereas questionable raw sausage was not available for examination, frozen minced meat from the second outbreak could be secured in households of infected people. Larvae were isolated from minced meat and were identified by PCR as Trichinella spiralis. Tracing back to the source of infection was difficult because of the long time between clinical symptoms, laboratory diagnosis and notification as well as complex trade routes for pork and its products. Trichinella cases emphasize the necessity to meet the prescribed slaughter inspection and to guarantee a reliable prove of origin for meat products especially in view of specific consumer habits, i.e. the consumption of raw meat.

[Mitral valve endocarditis caused by Erysipelothrix rhusiopathiae]. / Mitralklappenendokarditis durch Erysipelothrix rhusiopathiae.

HISTORY AND CLINICAL FINDINGS: A 67 year-old country woman was admitted to the hospital because of a four weeks history of continuous catarrh, arthralgia and fever. Recently, she had also developed upper abdominal pain after oral ibuprofen treatment. The clinical examination showed a patient of impaired general condition. The heart and lungs were auscultatory normal and there were no signs of dyspnea, cyanosis or inflammatory skin lesions. EXAMINATIONS: Physical examination of heart and lung, electrocardiography and transthoracic echocardiography were without pathological findings. CLINICAL COURSE: Gastroscopy revealed acute antral gastritis and duodenitis with presence of Helicobacter pylori. Eradication therapy resolved the abdominal symptoms but fever returned after the antibiotic therapy was stopped. The patient developed a severe endocarditis with progressive mitral regurgitation within a few days. Erysipelothrix rhusiopathiae was isolated from blood cultures and identified by conventional and molecular methods. The patient was treated successfully with 3 x 2 g ampicillin daily, applied parenterally for six weeks, and a mitral valve replacement. CONCLUSION: This was an unusual manifestation of systemic Erysipelothrix rhusiopathiae infection. The bacterium Erysipelothrix rhusiopathiae has still to be considered in the diagnosis and treatment of endocarditis in patients with increased risk of exposure (e.g. farmers, butchers and fishermen).

Detection of Trichinella infection in food animals.

The first part of this review article deals with classical methods used for the detection of Trichinella larvae in muscle samples of those animal species which are recognized as traditional sources of trichinellosis for human beings, as well as those species which are important for epidemiological reasons. Special consideration is given to the main applications of these methods (routine slaughter inspection, and epidemiological studies in reservoir animals), and to the major factors that may influence detection methods (sampling site, sample size). Historical, current and future aspects concerning national and EU legislation for Trichinella inspection are also presented. The latter part of this review is directed at serodiagnostic methods for the detection of Trichinella-specific antibodies in different animal species. Classical methods of serodiagnosis such as the complement fixation test and immunofluorescence antibody test are reviewed and the characteristics and performance of the ELISA are discussed. Factors dependent upon the animal species being tested or on components of the ELISA test system are considered. This paper also reviews systematic development of the ELISA in relation to improvements in test specificity and sensitivity. Additionally, remarks are made on implementing this test for surveillance and control programs in domestic pigs and wildlife.

On-line analysis of electrolytes in extracorporeally circulating blood: application of a rat model to examine the effect of a single pharmacological dose of melatonin on electrolyte levels in blood.

An experimental model was developed to study the kinetics of electrolytes under different physiological and/or pathological conditions. The model was applied to investigate in vivo the effect of a pharmacological dose of melatonin on the concentrations of Ca2+, K+, Na+, and pH in the anticoagulated blood of anaesthetized male Wistar rats (250-350 g). After the application of 0.25 mg melatonin/kg body weight, injected intraperitoneally into each of 8 rats, the electrolytes were measured by a flow-through system with highly sensitive ion-selective electrodes. The results were compared to a control group (n=8) which was treated with diluent (saline). The electrolytes were monitored continuously via an extracorporeal circulation, on-going for at least 60 min. Melatonin induced a significant increase of blood Ca2+ (p<0.02) by an average of 9.9% after 60 min. However, total calcium concentration did not increase significantly. The extracorporeal circulation provoked an elevation of K+ by hemolysis. This K+ increase was slightly diminished by melatonin (p<0.06). No melatonin effects were seen on Na+, pH and magnesium in blood and plasma, respectively. Also, the urine concentrations of the electrolytes were not altered by melatonin. The mechanism by which melatonin influences the blood concentrations of ionized calcium and potassium is not yet understood.

Investigation of skin samples from red foxes (Vulpes vulpes) in eastern Brandenburg (Germany) for the detection of Borrelia burgdorferi s. l.

During earlier investigations a high prevalence of Borrelia (B.) burgdorferi s. l. in unfed Ixodes (I.) ricinus ticks in the Federal State of Brandenburg has been demonstrated. In the present study skin samples were obtained from 100 red foxes (Vulpes vulpes) from the districts where the highest B. burgdorferi prevalences had previously been found (i.e. Uckermark, Barnim, Märkisch-Oderland, Oder-Spree). BSK- and MKP-medium including inhibitory substances were used for cultivation of spirochaetes. Non-motile spirochaete-like organisms were observed in 26% of the samples. Additionally, by subcultures it was not possible to obtain motile helical forms characteristic for B. burgdorferi. On tryptose agar, the bacteria which produced nonmotile forms appeared as corynebacterium-like-colonies. Investigations by electron microscopy showed that the immobile spiral forms were giant whips (flagellae) which belonged to the contaminant flora. These forms proved to be negative for B. burgdorferi s. l. by the use of a nested-PCR. In a further study, the same skin samples were investigated for the presence of B. burgdorferi s. l.-DNA using a nested-PCR. Seven out of 100 samples were positive.

Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.

Nuclear receptors regulate metabolic pathways in response to changes in the environment by appropriate alterations in gene expression of key metabolic enzymes. Here, a computational search approach based on iteratively built hidden Markov models of nuclear receptors was used to identify a human nuclear receptor, termed hPAR, that is expressed in liver and intestines. hPAR was found to be efficiently activated by pregnanes and by clinically used drugs including rifampicin, an antibiotic known to selectively induce human but not murine CYP3A expression. The CYP3A drug-metabolizing enzymes are expressed in gut and liver in response to environmental chemicals and clinically used drugs. Interestingly, hPAR is not activated by pregnenolone 16alpha-carbonitrile, which is a potent inducer of murine CYP3A genes and an activator of the mouse receptor PXR.1. Furthermore, hPAR was found to bind to and trans-activate through a conserved regulatory sequence present in human but not murine CYP3A genes. These results provide evidence that hPAR and PXR.1 may represent orthologous genes from different species that have evolved to regulate overlapping target genes in response to pharmacologically distinct CYP3A activators, and have potential implications for the in vitro identification of drug interactions important to humans.