Una imagen atípica para un tumor típico / An atypical imaging for the most typical intracranial tumor

Los meningiomas son los tumores intracraneales benignos más frecuentes en adultos, suponen el 20% de todos los tumores cerebrales. Solamente el 1-4% presentan cambios quísticos. La relación entre el componente quístico y sólido de los meningiomas mixtos fue utilizada por varios autores para crear hasta cuatro clasificaciones diferentes de este subtipo de meningiomas. El diagnóstico mediante TC resulta muy complejo ante este subtipo de meningiomas por la dificultad de discernir entre diferentes lesiones intracraneales que también presentan componente quístico asociado. Presentamos el caso de un paciente varón de 49 años que presenta episodios de amaurosis fugax. En la TC se identificó una lesión sólida en localización frontotemporal izquierda, con gran componente quístico que producía importante efecto de masa y desplazaba la línea media. Se completó estudio mediante RM y arteriografía y finalmente fue diagnosticado como meningioma mixto, que tras embolización tumoral desde arteria meníngea media, se resecó quirúrgicamente.

Meningiomas are the most common benign intracranial tumors in adults, accounting for 20% of all brain tumors. Only 1-4% have cystic changes. The relationship between the cystic and solid component of mixed meningiomas was used by several authors to create up to four different classifications of this subtype of meningiomas. CT diagnosis is challenging in this subtype of meningiomas because of the difficulty of distinguishing between different intracranial lesions that also have associated cystic component. We present the case of a 49-year-old male patient with episodes of amaurosis fugax. On CT, a solid lesion was identified in the left frontotemporal region, with a large cystic component that produced an important mass effect and midline displacement. A study was completed by MR and arteriography and finally was diagnosed as mixed meningioma, which after tumor embolization via the middle meningeal artery, was surgically resected.

Detection of an explosive simulant via electrical impedance spectroscopy utilizing the UiO-66-NH2 metal-organic framework.

Electrical impedance spectroscopy, in conjunction with the metal-organic framework (MOF) UiO-66-NH2, is used to detect trace levels of the explosive simulant 2,6-dinitrotoluene. The combination of porosity and functionality of the MOF provides an effective dielectric structure, resulting in changes of impedance magnitude and phase angle. The promising data indicate that MOFs may be used in low-cost, robust explosive detection devices.

Chronic diarrhoea: Definition, classification and diagnosis / Diarrea crónica: definición, clasificación y diagnóstico

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

La diarrea crónica es un síntoma de presentación frecuente, tanto en las consultas de medicina de familia como en las de digestivo. Se estima que >5% de la población sufre diarrea crónica y que cerca del 40% de estos sujetos son mayores de 60 años. El clínico se enfrenta con frecuencia a la necesidad de decidir cuál es el mejor enfoque diagnóstico de estos pacientes y elegir entre las múltiples pruebas diagnósticas existentes. En 2014 la Societat Catalana de Digestologia creó un grupo de trabajo con el objetivo principal de crear algoritmos diagnósticos en base a la práctica clínica y evaluar las pruebas diagnósticas disponibles y la evidencia científica para su utilización. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Se han establecido 28 recomendaciones y 6 algoritmos diagnósticos. Se describen los criterios de derivación desde medicina primaria a digestivo de un paciente con diarrea crónica.

Optimised empiric triple and concomitant therapy for Helicobacter pylori eradication in clinical practice: the OPTRICON study.

BACKGROUND: Empiric triple therapy for Helicobacter pylori should be abandoned when clarithromycin resistance rate is >15-20%. Optimisation of triple therapy (high-dose acid suppression and 14-day duration) can increase eradication rates by 10%. AIM: To compare the efficacy and safety of optimised triple (OPT-TRI) and nonbismuth quadruple concomitant (OPT-CON) therapies. METHODS: Prospective multicentre study in 16 Spanish centres using triple therapy in clinical practice. In a 3-month two-phase fashion, the first 402 patients received an OPT-TRI therapy [esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin (500 mg b.d) for 14 days] and the last 375 patients an OPT-CON treatment [OPT-TRI therapy plus metronidazole (500 mg b.d)]. RESULTS: Seven-hundred seventy-seven consecutive patients were included (402 OPT-TRI, 375 OPT-CON). The OPT-CON therapy achieved significantly higher eradication rates in the per-protocol [82.3% (95% CI = 78-86%) vs. 93.8% (91-96%), P < 0.001] and intention-to-treat analysis [81.3% (78-86%) vs. 90.4% (87-93%), P < 0.001]. Adverse events (97% mild/moderate) were significantly more common with OPT-CON therapy (39% vs. 47%, P = 0.016), but full compliance with therapy was similar between groups (94% vs. 92%, P = 0.4). OPT-CON therapy was the only significant predictor of successful eradication (odds ratio, 2.24; 95% CI: 1.48-3.51, P < 0.001). The rate of participating centres achieving cure rates ≥ 90% favoured OPT-CON therapy (OPT-TRI 25% vs. OPT-CON 62%). CONCLUSIONS: Empiric OPT-CON therapy achieved significantly higher cure rates (>90%) compared to OPT-TRI therapy. Addition of metronidazole to OPT-TRI therapy increased eradication rates by 10%, resulting in more mild adverse effects, but without impairing compliance with therapy.

Trastornos funcionales y motores digestivos / Functional and motility gastrointestinal disorders

Como cada año en el congreso de la Asociación Gastroenterológica Americana (Digestive Diseases Week [DDW] ), se han presentado muchísimos trabajos, unos mejores y otros no tan buenos, de los que hemos intentado hacer una labor de discriminación y de síntesis. En términos generales, podemos decir que se consolidan ciertos avances tecnológicos, con incorporación plena a la práctica clínica, como la impedanciometría y la manometría de alta resolución. Surgen nuevos datos fisiopatológicos que apuntan aún más a la unificación y conexión inexorable de los aspectos orgánicos y psicológicos (modelo biopsicosocial) en los trastornos funcionales digestivos (TFD). Se pusieron muchas esperanzas en los criterios de Roma III para mejorar el diagnóstico de los TFD y, en especial, de la dispepsia funcional. Sin embargo, su aplicación práctica ha sido bastante desalentadora. Además, al menos 2 estudios han comprobando que dichos criterios son poco discriminativos para diferenciar los subtipos de DF y que existe mucho solapamiento con la enfermedad por reflujo gastroesofágico. Respecto a los 2 principales TFD, la dispepsia funcional y el síndrome del intestino irritable (SII), se presentaron nuevos datos sobre la importancia de los factores genéticos, microinflamatorios o psicológicos en la etiopatogenia de ambos trastornos. Desde el punto de vista terapéutico se presentaron resultados de la eficacia y seguridad de acotiamida en la dispepsia funcional, y de linaclotida y prucaloprida en el estreñimiento, tanto idiopático como asociado al SII. Diversos estudios, e incluso metaanálisis, han demostrado la utilidad del biofeedback en el tratamiento del estreñimiento. Aun así, su eficacia se ha puesto en duda debido a ciertas deficiencias metodológicas de algunas investigaciones. En este DDW se presentaron trabajos que confirman la utilidad del biofeedback, ya sea hospitalario o domiciliario, en el estreñimiento por disinergia. Se recogen también algunos aspectos de especial interés en el diagnóstico y tratamiento del síndrome de rumiación, del dolor torácico de posible origen esofágico y del síndrome de hiperemesis por canabinoides (AU)

As in previous years, a huge number of studies were presented at the Congress of the American Gastroenterology Association (Digestive Diseases Week [DDW] ), some of which were bet ter than others. The present article at tempts to extract and summarize the most interesting findings reported. In general terms, certain technological advances have been consolidated, with full incorporation into clinical practice, such as impedancemetry and high-resolution manometry. New physiopathological data are coming to light that increasingly indicate the in extricable link between organic and psychological factors (the biopsychosocial model) in functional gastrointestinal disorders (FGID). Despite the high hopes that the Rome III criteria would improve the diagnosis of FGID and especially that of functional dyspepsia, their practical application has been fairly discouraging. Moreover, at least two studies have demonstrated that these criteria cannot be used to differentiate subtypes of functional dyspepsia and that there is wide overlap with gastroesophageal reflux disease. New data were presented on the role of genetic, microinflammatory and psychological factors in the etiopathogenesis of the two main FGID: functional dyspepsia and irritable bowel syndrome (IBS). The results on the safety and efficacy of acotiamide in functional dyspepsia and of linaclotide and prucalopride in idiopathic and IBS-associated constipation were also presented. Several studies, and even meta-analyses, have demonstrated the utility of biofeedback in the treatment of constipation. Even so, the efficacy of this therapy has been questioned due to certain methodological deficiencies in some studies. In DDW 2011, studies confirming the utility of biofeedback, whether hospital- or home-based were presented, in dyssynergy constipation. The present article also mentions certain features of special interest in the diagnosis and t reatment of rumination syndrome, thoracic pain of possible esophageal origin and cannabinoid-induced hyperemesis syndrome (AU)

Change over time of bowel habit in irritable bowel syndrome: a prospective, observational, 1-year follow-up study (RITMO study).

BACKGROUND: Evolution of bowel habit in irritable bowel syndrome (IBS) is not well known. AIM: To evaluate the change over time of bowel habit in IBS patients followed-up during 1 year. METHODS: Five hundred and seventeen patients with IBS were prospectively included in an observational study with five evaluations over a 1-year period. Symptoms were recorded daily in diary cards during four 4-week periods along the study. Bristol Stool Scale (BSS) was used to define bowel habit. RESULTS: Four-hundred patients completed the study. Rome II showed low-moderate agreement (42%) with BSS to define bowel habit. Frequency of constipation and diarrhoea showed little changes throughout the study. Over 50% of the patients had the same bowel habit when each diary was compared with the next one. A third of patients maintained the same habit throughout the study. Most changes occurred from/to mixed or unsubtyped IBS. Only 14% of cases changed from constipation to diarrhoea or vice versa. This change was associated to female gender (OR: 2.65). CONCLUSIONS: The frequency of constipation and diarrhoea remains relatively stable over time. Changes in IBS subtypes are common, but changes between constipation and diarrhoea are rare. Alternating IBS is more frequent in women.

Predictive factors of irritable bowel syndrome improvement: 1-year prospective evaluation in 400 patients.

BACKGROUND: The natural history of the irritable bowel syndrome is poorly understood. AIM: To assess the clinical course of the irritable bowel syndrome and the factors that might predict it. METHODS: An observational prospective study, involving 400 irritable bowel syndrome patients meeting Rome II criteria. Symptoms were recorded in a diary over four non-consecutive months (1, 4, 7 and 10). Demographic data, associated disorders, psychological status and health-related quality of life were obtained. RESULTS: At 1-year follow-up, half of the patients and half of their physicians considered irritable bowel syndrome to have improved, but improvement was minor. Diary data showed that, according to the type of symptom, improvement was small and quite different: diarrhoea in 19% of patients, abdominal pain frequency in 26%, constipation in 33% and abdominal pain intensity in 60%. Factors related to improvement at one year were: severe symptoms and poor health-related quality of life at first visit, irritable bowel syndrome-constipation, good improvement at 3 months, anxiety/depression, stress, symptoms related to meals and absence of comorbidity. By multivariate logistic regression, predictors were: severe basal symptoms and good improvement at 3 months (OR:CI 95%, 1.32:1.09-1.59 and 4.44:2.81-7.05). CONCLUSIONS: At 1-year follow-up, half the patients and their physicians considered the irritable bowel syndrome to have had some improvement but, symptom diaries demonstrated that improvement was small and heterogeneous. Severe basal symptoms and improvement at 3 months were related to better prognosis.

Irritable bowel syndrome prevalence varies enormously depending on the employed diagnostic criteria: comparison of Rome II versus previous criteria in a general population.

BACKGROUND: Irritable bowel syndrome (IBS) prevalence estimates are essential for measuring the importance of the problem and the burden of the illness. However, IBS diagnosis is based on clinical criteria which have changed over time. The aim of this study was to assess how the use of different diagnostic criteria influences estimated IBS prevalence and, in particular, to compare how this prevalence varies using the new Rome II criteria and previous diagnostic criteria. METHODS: An epidemiological survey was conducted in the general population using personal interviews in a home setting. Two thousand individuals stratified by gender, age, social class and geographic location were randomly selected from the general population of Spain. Participants were classified as 'potential IBS subjects' (n = 281) or 'non-potential IBS subjects' (n = 1719) as a result of their response to a screening question regarding the presence of abdominal pain, constipation or diarrhoea. Thus, we estimated IBS prevalence according to the following diagnostic criteria: Manning, Rome I, Rome II, Drossman, Talley and Kay & Jorgensen. RESULTS: Prevalences of IBS according to the Manning and Rome I criteria were 10.3% and 12.1%, respectively. These were higher than the prevalences obtained with the other criteria used, which varied from 2.1% to 4.9%. IBS was more prevalent in females than males irrespective of the criteria used (the female:male ratio ranged from 2.33 to 4.33). Subjects who fulfilled the Rome II, Drossman, Talley or Kay & Jorgensen criteria also fulfilled the Rome I and Manning criteria. However, between 44% and 80% of subjects who fulfilled the Rome I or Manning criteria did not fulfil the more stringent diagnostic criteria. CONCLUSIONS: The prevalence of IBS varies enormously depending on the diagnostic criteria employed. Criteria based on the frequency of symptoms, such as the Rome II criteria, produce much lower prevalence values compared to criteria based solely on the presence of symptoms. In fact, more than two-thirds of subjects who fulfilled the Rome I criteria would not have been diagnosed with IBS if Rome II criteria had been employed.

Caracteristicas epidemiológicas e importancia socioeconómica del síndrome del intestino irritable / Epidemiological characteristics and socioeconomic importance of irritable bowel syndrome

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Epidemiological characteristics and socioeconomic importance of irritable bowel syndrome.

In summary, in light of the flood of figures, statistics, and epidemiological evidence, the socioeconomic importance of IBS cannot be questioned. The development of new, effective treatments that would control the symptoms is a huge challenge for researchers and the pharmaceutical industry. Drugs able to relieve the symptoms of IBS would provide great relief to a large number of patients, and would save the health system considerable effort and resources.

Placebo in functional dyspepsia: symptomatic, gastrointestinal motor, and gastric sensorial responses.

OBJECTIVE: Therapeutic trials in functional dyspepsia consistently show a substantial placebo response, but there is no clear explanation for such an effect. Our aim was to evaluate symptomatic, gastrointestinal motor, and gastric sensorial responses to placebo treatment in patients with chronic and severe functional dyspepsia who were part of a therapeutic trial. METHODS: Thirty patients were treated during 8 wk with placebo (white-colored 8-mm tablets containing cellulose) by mouth, 20 min before breakfast, lunch, and dinner. We quantified the symptomatic response to placebo as a change in global health status, and also as a change in the individual and combined (global symptom index) of a five-symptom complex: upper abdominal pain, nausea, vomiting, bloating/fullness, and early satiety. Gastroduodenal motility, during fasting and postprandially, was evaluated by manometry in all patients pretreatment and in 17 patients posttreatment. Gastric sensitivity to distension was evaluated in 18 patients pretreatment and in five patients posttreatment (all of them clinical responders). RESULTS: Placebo treatment produced a striking symptomatic improvement; by 8 wk 80% of the patients reported an improved global health status and their global symptom index markedly decreased (23.9+/-1.3 pretreatment vs 9.1+/-1.2; p < 0.05). Placebo increased the number of gastric phases III starting in the antrum during the fasting period (1.1+/-0.1 vs 1.6+/-0.2; p < 0.05). As a group, no significant changes in postprandial gastroduodenal motility were observed after placebo treatment. However, after placebo a significant improvement in the antral motility index (MI) was observed in the subset of patients with antral hypomotility (MI pretreatment: 7.9+/-1.0; MI posttreatment: 11.7+/-0.4; p < 0.05). Before placebo treatment, patients with functional dyspepsia showed increased sensitivity to stepwise distension of the stomach relative to healthy individuals. After 8 wk of placebo treatment sensitivity to distension remained unchanged, even though patients' clinical status was markedly improved. CONCLUSION: In patients with functional dyspepsia, the symptomatic response to placebo is substantial. Some significant changes were also observed in gastric motility: increase in the gastric phase III number as well as in the postprandial antral motility index in those with hypomotility pretreatment. Remarkably, however, clinical improvement seems to occur independently of detectable changes in gastroduodenal motor activity or gastric hypersensitivity to distension.

How standard is a standard day during a standard ambulatory 24-hour esophageal pH monitoring?

BACKGROUND: Ambulatory 24-h esophageal pH monitoring is the gold standard method for measuring esophageal exposure to gastric acid. The method has gained acceptability because of its sensitivity, specificity, and accuracy and also because it is easy to perform, well tolerated, and quite physiologic. However, whether ambulatory esophageal pH-metry affects normal lifestyle has not been specifically evaluated. METHODS: We investigated 114 consecutive patients admitted to our Unit because of heartburn, acid regurgitation, or non-cardiac chest pain. Patients filled in a diary chart on 2 different days: 1 day while the pH-metry was performed and another normal day, to record the following variables: number, amount, and composition of the meals; time in supine position; number of cigarettes smoked; alcohol intake; degree of physical activity; and number and type of symptomatic episodes. Patients were encouraged to carry out normal activity. RESULTS: When the 2 days were compared, none of the registered variables appeared to differ, with the exception of subjective evaluation of physical activity: 65% of the patients said their physical activity was diminished during the test day relative to their usual standard. CONCLUSIONS: Normal habits are not significantly modified by 24-h esophageal pH-metry, with the exception of physical activity, which decreases, possibly owing more to aesthetic than to physical problems.

Duodenogastric bile reflux and gastrointestinal motility in pathogenesis of functional dyspepsia. Role of cholecystectomy.

To establish the pathogenic role of duodenogastric reflux in dyspeptic symptoms we have compared the clinical features, gastrointestinal motility, and rates of duodenogastric bile reflux in 12 cholecistectomized dyspeptic patients, 12 dyspeptic patients with intact gallbladder, and 12 healthy controls. Specific symptoms were scored for severity and frequency. Gastrointestinal manometry was performed during 3 hr of fasting and 2 hr postprandially. Simultaneously, samples of duodenal and gastric contents were obtained sequentially for quantification of bile acids. Results show that symptom global severity (9.6 +/- 0.4 vs 8.8 +/- 0.7) and frequency (9.9 +/- 0.8 vs 9.0 +/- 0.5) were similar in both dyspeptic groups; only abdominal pain was milder in cholecystectomized patients (1.9 +/- 0.1 vs 2.6 +/- 0.2; P < 0.05). Fasting gastric bile acid concentrations were higher in cholecystectomized patients (P < 0.05) and antral postcibal motility lower (P < 0.05) than in the groups. No relation among gastric hypomotility, duodenogastric bile reflux, and symptom scores was detected. We concluded that patients with functional dyspepsia and a prior cholecystectomy have clinical features similar to those with gallbladders, but some physiological features are dissimilar: antral motility is decreased and duodenogastric bile reflux is increased. Thus, a uniform clinical expression of various pathophysiological disturbances constitutes the basis of functional dyspepsia.

Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia?

The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension.

Forceful dilatation under endoscopic control in the treatment of achalasia: a randomised trial of pneumatic versus metallic dilator.

Forceful dilatation under endoscopic control is a well established treatment of achalasia; several different types of dilators can be used. This study prospectively compared the clinical and manometric efficacy of a single dilatation using two different dilators. Forty one patients were randomly assigned to forceful dilatation under endoscopic control with either a pneumatic dilator (n = 17) or a metallic dilator (n = 24). Thereafter, the patients received periodic clinical and manometric evaluation for one year (before and one, six, and 12 months after dilatation). One month after dilatation all but one of the subjects in each group had experienced good to excellent results and their clinical improvement persisted for the one year follow up. Two patients (one in each group) were perforated during the procedure and required surgical treatment. Recovery was uneventful in both cases. Resting lower oesophageal sphincter pressure (mean (SEM)) significantly and similarly decreased after both methods of dilatation (pneumatic dilator: before dilatation 37 (3) mm Hg, one year after dilatation 18 (3) mm Hg; metallic dilator: before dilatation 34 (2) mm Hg, one year after dilatation 17 (3) mm Hg; p < 0.05 for both). It is concluded that in the treatment of achalasia a single dilatation under endoscopic control with either pneumatic or metallic dilator yield comparable clinical and manometric results and similar complication rates. The use of one or other dilator should depend more on the preference and experience of the endoscopist than on the type of device.

A nonprimate animal model applicable to zidovudine pharmacokinetics in humans: inhibition of glucuronidation and renal excretion of zidovudine by probenecid in rats.

The monkey is considered the best animal model to study the pharmacokinetics of zidovudine (azidothymidine, AZT) because humans and monkeys eliminate 60 to 75% of AZT by metabolism to the 5'-O-glucuronide (GAZT), in contrast to other experimental animals, which excrete most of the drug unchanged in the urine. It has become increasingly difficult and costly to use monkeys in research. Therefore, we undertook studies to determine the suitability of the rat as an alternative animal model to study the pharmacokinetics of AZT. In the initial experiments, [3H]AZT was administered i.v. at doses of 19, 60 and 187 mumol/kg to male Sprague-Dawley rats with intact bile ducts. The respective values (mean +/- S.D.) for total clearance of AZT were 2.4 +/- 0.2, 2.3 +/- 0.3 and 1.8 +/- 0.4 l/hr/kg and for renal clearance were 1.7 +/- 0.2, 1.8 +/- 0.4 and 1.5 +/- 0.4 l/hr/kg. The renal clearance of AZT was approximately equal to renal plasma flow of rats (1.5 l/hr/kg), suggesting that in addition to filtration, AZT is also efficiently secreted in the kidney of the rat. The respective values for volume of distribution at steady state were 1.3 +/- 0.2, 1.0 +/- 0.2 and 0.84 +/- 0.19 l/kg (P less than .05) and elimination half-life were (harmonic mean) 0.55, 0.44 and 0.46 hr. Urinary excretion of AZT as unchanged drug in intact rats accounted for 70 +/- 6, 79 +/- 6, and 83 +/- 12% of the dose, whereas only 0.7 to 0.8% of the dose was recovered in the urine as GAZT. Rats with exteriorized bile ducts, the proposed alternative animal model, were given an i.v. dose of 60 mumol/kg of [3H]AZT. To test the effect of a concurrently administered drug on the elimination of AZT in the model, some rats with bile duct cannulas were pretreated with probenecid, a known inhibitor of AZT elimination in humans. Urine and bile were collected to quantify the formation of GAZT. GAZT was identified by fast atom bombardment mass spectrometry as the major metabolite of AZT in the rat. GAZT excretion in the bile and urine accounted for 11 +/- 3% of the dose in saline-treated rats, compared to only 1.4 +/- 0.3% in rats treated with probenecid (P less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)