Ga-67 lung uptake in patients with adult respiratory distress syndrome. Association with lung infection and patients' prognosis. Nine patients with adult respiratory distress syndrome (ARDS) were studied with Ga-67 imaging in search for a site of infection. Different degrees and two patterns of Ga-67 lung uptake scoring in comparison with liver uptake were demonstrated. All patients had diffuse lung uptake, whereas five of them also showed additional focal lung activity. In only one patient was an abdominal focal uptake detected. Chest radiographs of all patients revealed diffuse and focal lung infiltrates that correlated with the Ga-67 uptake patterns. Therefore, Ga-67 imaging was unhelpful in differentiating patients with ARDS with lung infection from patients without lung infection. The intensity of Ga-67 uptake, as expressed by Ga-67 scoring, correlated with the course and outcome of ARDS. Patients exhibiting a high Ga-67 score had long periods of hospitalization and eventually died (four patients), whereas those who had low Ga-67 scores had a short disease course and survived (five patients). It is concluded that Ga-67 imaging in ARDS patients is unable to detect lung infection; however, it may be useful in the assessment of patients' prognosis.


Osteitis pubis, Tc-99m MDP, and professional hockey players. Three cases of osteitis pubis detected by bone scanning with Tc-99m MDP in professional ice hockey players are presented. This entity is related to mechanical stress and aggravated by forceful contraction of the adductor and rectus abdominis muscles. The signs, symptoms, and laboratory data are relatively nonspecific, as are radiographic findings in the early stage (pubic symphysitis). The use of bone scanning in the appropriate clinical setting aids in diagnosis.


Portal vein aneurysm demonstrated by blood pool SPECT. Portal vein aneurysms are rare and are occasionally suggested by ultrasound and usually confirmed by invasive angiography. Such a case was diagnosed by scintigraphic studies, most importantly blood pool SPECT, which clearly separates it from hepatic cysts.


Pulmonary scintigraphic findings in children with pectus excavatum by the comparison of chest radiograph indices. Pulmonary scintigraphy, including Xe-133 ventilation combined with Tc-99m MAA perfusion scans, was performed in 23 children (3 girls, 20 boys, ages: 2-9 years) with pectus excavatum, and the indices from lateral chest radiography were used for comparison. The findings of pulmonary scintigraphy were analyzed as 1) ventilation fractions (VF), and 2) perfusion fractions (PF) between bilateral lungs; and 3) ventilation-perfusion ratios (V/Q ratio) of both lungs. The results showed that 6 of 23 cases had impaired VF, 11 of 23 cases had impaired PF, and 7 of 23 cases had an impaired V/Q ratio in the right and left lung, respectively. The severity of sternal depression in pectus excavatum was shown as certain indices that were obtained on routine lateral chest radiographs. However, no significant correlations existed between the differences in the fractions and the indices. Our results suggest that pulmonary scintigraphy is not necessary for children with pectus excavatum to predict the severity of sternal depression and pulmonary function, because 1) pulmonary scintigraphy is very difficult to perform in children; 2) unnecessary radiation exposure should be avoided; and 3) it is not well correlated with the severity of the depressed sternum.


Regional cerebral blood flow measured with I-123 IMP SPECT in a case of subcortical arteriosclerotic encephalopathy (Binswanger's disease). N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT studies were performed on a 75-year-old patient who could be clinically classified as subcortical arteriosclerotic encephalopathy (Binswanger's disease). Regional cerebral blood flow (rCBF) was quantitatively measured by a microsphere model, and was diffusely decreased in the whole brain (mean rCBF: 36 ml/100 g/minute). After a ventriculoperitoneal shunt operation, his clinical symptoms were markedly improved, and the improvement was validated by a 32% increase of mean rCBF. However, MRI and CT images showed no significant interval changes before and after the shunt operation. Regional rCBF measurement by I-123 IMP SPECT should be performed and plays an important role in the evaluation of Binswanger's disease.


Portacaval graft patency demonstrated by scintigraphic calculation of portal contribution to hepatic blood flow. The case presented refers to a cirrhotic patient with portal hypertension in whom a portacaval graft bypass was surgically implanted. The calculation of the portal contribution to hepatic blood flow helped to demonstrate the patency of the graft.


Clinical value of lung scintigraphy with Tc-99m gluconate in distinguishing benign from malignant lung diseases. One hundred patients were studied with three-phase lung scintigraphy with Tc-99m gluconate. The results showed that there were statistically significant differences between benign and malignant lung lesions in the intensity of accumulation, the blood supply index ratio, and the radioactive uptake ratio. However, no difference was observed between the benign lung lesions and the healthy lungs. Analysis of false negatives and false positives revealed that false negatives had something to do with the cell types of the malignancies, in addition to the relatively small size of the lesions; the false positives were mostly caused by acute inflammation, for which obstructive pneumonitis might be responsible in part. It is concluded that Tc-99m gluconate is tumor-avid and can be used as an agent for positive imaging of lung cancer, because quantitative parameters, blood supply index ratio, and radioactive uptake ratio are more objective in distinguishing malignant lung lesions from benign ones, and are of relatively higher sensitivity and specificity. Thus, lung scintigraphy with Tc-99m gluconate provides an efficient supplementary measure for differentiating between malignant and benign lung lesions.


Explanations and therapies for penicillin failure in streptococcal pharyngitis. A disturbing trend toward penicillin failure has developed in the treatment of streptococcal pharyngitis in some parts of the United States and abroad. A variety of explanations has been proposed to account for these penicillin-treatment failures. With the resurgence of serious complications from streptococcal infection, successful bacteriologic eradication has regained importance. In communities with a high incidence of penicillin failures, alternative antimicrobials should be considered. Cephalosporins, amoxicillin/clavulanate, and the extended-spectrum macrolides represent logical options under such clinical circumstances.


Cholelithiasis in infants with Down syndrome. Three cases and literature review. Only four cases of cholelithiasis have been reported in patients with Down syndrome and none in Down syndrome infants. The cases of three Down syndrome infants (all males) with cholelithiasis are reported. Each exhibited different fetal complications, and in each, Down syndrome was diagnosed at birth. Gallstones apparently were congenital (a rarity) in one infant, since they were detected on the first day of life. Cholelithiasis was an incidental finding in another of the infants when, at 12 weeks old, he had renal ultrasonography because of a urinary tract infection. The third infant was 4 months old when sonographic studies revealed a gallstone. Despite the confirmation of cholelithiasis in all three infants, none has since had any signs or symptoms that suggest the need for intervention. Cholelithiasis is probably more common in Down syndrome infants than has been supposed, but whether Down syndrome infants with gastrointestinal (GI) malformations are more likely to have gallstones than are children with similar GI malformations but with normal karyotypes is unknown.


Fractures in the under-3-year-old age cohort. One hundred twenty-four urban children under 3 years of age admitted for fractures were retrospectively reviewed to determine the frequency of accidental and nonaccidental causes in this population. The fractures were categorized according to their mechanisms: motor-vehicle passenger or pedestrian accident, other accidents, or child abuse. There were no differences in the frequency of fractures by race, date of birth, or season in which the injury occurred. Skull fractures were most frequent (62%), followed by femur fractures (11%). There was a 26% increase in fractures between 1987 and 1989, especially in the non-motor vehicle cohort. Caretaker ignorance and/or carelessness was a common cause of fractures in the infant and toddler age group. Injuries were still occurring in spite of infant care seat use. The American public must be educated in preventive medicine and safety to decrease the senseless morbidity of our greatest resource.


Screening for psychosocial dysfunction in pediatric practice. A naturalistic study of the Pediatric Symptom Checklist. This study examined the routine implementation of the Pediatric Symptom Checklist (PSC), a brief questionnaire which screens for psychosocial dysfunction in school-aged children in an outpatient pediatric practice. Results indicated that the PSC was well-accepted by parents and adequately tolerated by busy clinic staff. When the PSC was included as part of the standard procedure for well-child visits, the referral rate for psychosocial problems due to positive PSC scores rose to 12% from the clinic baseline referral rate of 1.5%, a significant increase (P < .01). Half of the children who screened positive on the PSC had not been previously identified by their pediatricians as having psychosocial problems, and more than half had never received any psychological treatment. When implementation of the PSC was discontinued, the referral rate fell to 2%, a rate similar to baseline. The findings suggest that it is possible to incorporate the PSC into routine pediatric practice and that the PSC can help pediatricians identify and better serve children experiencing psychosocial difficulties. The study also suggests that further work is needed to understand the barriers to ongoing implementation.


Regional anesthesia in the preterm neonate. The physiologic immaturity of respiratory musculature and central respiratory control centers leads to an increased risk of apnea and respiratory complications following general anesthesia in the neonate. Regional anesthetic techniques, such as spinal and caudal epidural anesthesia, may obviate the need for general anesthesia and lessen the risks of perioperative morbidity. Although these techniques have been previously described in infants, most reports focus on regional anesthesia in the former preterm infant outside the actual neonatal period. There is relatively little or no information concerning regional anesthesia in neonates during the first week of life. We present four neonates (weight, 1.07 to 2.8 kg; gestational age, 27 to 35 weeks) who required anesthetic care during the first week of life for various surgical procedures, including vesicostomy placement, gastroschisis closure, and debridement of a lower-extremity wound. Either caudal epidural or spinal anesthesia was successfully used in the four neonates. Regional anesthesia was used as the sole technique without supplementation with intravenous or inhalational agents in three of the four neonates. The advantages, risks, and applications of regional anesthesia in the neonate are discussed.


Taking it to the streets. Helmet use and bicycle safety as components of inner-city youth development. A three-week bicycle safety module (BSM) featuring helmet use was developed for an inner-city, comprehensive youth development program in East Wheeling, West Virginia. Prior to BSM intervention, no helmet use had been observed in the test neighborhood. After a three-week program focusing on safety behaviors and helmet use, students demonstrated significant improvements in knowledge, a positive relationship between skill and knowledge, and nearly 100 percent helmet usage rates. Unfortunately, neighborhood helmet use rates fell to nearly zero after the summer camp was over. The data suggest that helmet use and improved knowledge and skills could become the norm in an inner-city day-camp context, but periodic, model-oriented reinforcement of the BSM is recommended for maintenance of observed knowledge and usage improvements.


Pharmacokinetics and pharmacodynamics of intravenous meperidine in neonates and infants. The pharmacokinetics of meperidine (pethidine) was studied in 21 infants who received a single intravenous dose of 1 mg/kg after surgery (n = 18) or during mechanical ventilation because of respiratory distress (n = 3). Eleven patients were younger than 1 week old, 10 patients were aged from 3 weeks to 5 months, and five of the patients were premature. The pharmacokinetics of meperidine varied greatly between the subjects, with a median elimination half-life of 10.7 hours (range, 3.3 to 59.4 hours), median clearance of 8.0 ml/kg/min (range, 1.8 to 34.9 ml/kg/min), median volume of the central compartment of 2.4 L/kg (range, 0.5 to 4.8 L/kg), and median steady-state volume of distribution 7.2 L/kg (range, 3.3 to 11.0). The great interindividual variability in meperidine pharmacokinetics should be taken into consideration when meperidine is administered to neonates. Although no life-threatening or serious side effects were observed in this study, appropriate care should be exercised when prescribing meperidine for this age group.


Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. In 26 hospitalized patients with depression, a combined pharmacogenetic test with dextromethorphan, a substrate of cytochrome P450IID6, and mephenytoin, the S-form of which is hydroxylated by a P450IIC isozyme, was carried out before amitriptyline therapy. Metabolites were determined in 24-hour urine samples collected on treatment day 8, and the contributions of individual compounds, including the four isomers of 10-hydroxyamitriptyline and 10-hydroxynortriptyline to total excretion were calculated. Formation of (-)-E-10-hydroxyamitriptyline and (-)-E-10-hydroxynortriptyline apparently depends on the activity of cytochrome P450IID6 because negative correlations existed between the log metabolic ratio of dextromethorphan and the relative quantities of these enantiomers. In contrast, correlations were positive for nortriptyline, (+)-E-10-hydroxynortriptyline, (-)-Z-10-hydroxynortriptyline, and (+)-Z-10-hydroxynortriptyline. The mephenytoin hydroxylase seems to participate in side-chain demethylation to the secondary and primary amines, because the log metabolic ratio of mephenytoin correlated negatively with the relative quantity of E-10-hydroxydidesmethylamitriptyline and positively with that of amitriptyline and its N-glucuronide.


Classic conditioning and placebo effects in crossover studies. To find evidence of classically conditioned placebo effects in a placebo-controlled crossover drug study. Specifically, we tested a prediction of the conditioning model that the placebo response will be greater after drug exposure than before. Twenty-four patients with mild to moderate essential hypertension and no contraindications to atenolol participated in the study. The study design required randomized assignment to one of three groups: placebo followed by 50 mg atenolol daily, followed by no treatment, each for 1 week; atenolol followed by placebo; and atenolol followed by nothing (to show residual drug effects). Twice-daily blood pressure measurements were made by patients at home; once-weekly measurements of blood pressure and heart rate were made by a research nurse. Before drug treatment, there were no differences in the antihypertensive responses of patients taking placebo and patients taking nothing (difference, 0.98 mm Hg; 95% confidence interval, -0.98 to 2.93). After atenolol treatment, placebo treatment produced a significantly greater antihypertensive response than no treatment (difference, -6.09 mm Hg; 95% confidence interval, -11.81 to -0.38). Thus the placebo response after atenolol administration was more than a residual drug effect. Similar patterns were observed for heart rate but not for blood pressure readings taken in the office. These observations are consistent with a conditioning model of placebo effects. These findings warrant further investigation in larger studies and in other disease models.


Pharmacokinetic and pharmacodynamic interaction between toloxatone, a new reversible monoamine oxidase-A inhibitor, and oral tyramine in healthy subjects. We examined the influence of toloxatone, a new reversible monoamine oxidase-A inhibitor used in the treatment of depression, on tyramine-induced pressor effect in healthy volunteers. The maximum increase in systolic blood pressure produced by four single oral doses of tyramine administered during a meal and ranging from 100 mg to 800 mg was compared during repeated (3 to 5 days) administration of placebo, 200 mg toloxatone three times a day and 400 mg toloxatone three times a day in a single-blind, three-period crossover study. Toloxatone by itself had no significant influence on blood pressure. During administration of toloxatone, no significant increase in tyramine-induced increase in systolic blood pressure was observed for tyramine doses of 200 mg or less that are consistently higher than those associated with normal food intake. However, toloxatone increased the tyramine-induced increase in blood pressure after 400 mg tyramine (400 mg toloxatone three times a day) and 800 mg tyramine (200 mg toloxatone three times a day and 400 mg toloxatone three times a day). This pharmacodynamic interaction could be explained by an increase in tyramine systemic bioavailability in the presence of toloxatone. It is concluded that interaction between tyramine in meals and toloxatone is unlikely to occur in patients after long-term administration of the drug at therapeutic dosages.


Hemodynamic effects of the use of oral snuff. The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system.


Effects of temazepam on saccadic eye movements: concentration-effect relationships in individual volunteers. Saccadic eye movements were analyzed after single oral doses of 20 mg temazepam and placebo in a randomized, double-blind crossover study in eight healthy volunteers. For an optimal evaluation of concentration-effect relationships, 18 blood samples and 43 effect measures were obtained over 33 1/2 hours. After placebo, saccadic peak velocity decreased within the first hour, with average values remaining 6.2% to 12.1% below baseline up to 15 hours after intake. After temazepam, significant changes in peak velocity occurred for 5 hours, with maximum decreases averaging 29.2% (95% confidence interval, 10.0 to 37.2). The apparent duration of effects ranged from 3 to 9 hours in individual subjects. Linear concentration-effect relationships were demonstrated for peak velocity, with individual slopes ranging from -0.11 to -0.46 deg/sec.(ng/ml)-1 (average r = -0.82, all p < 0.01). Differences in protein binding of temazepam did not account for the approximate fourfold variability in individual sensitivities to temazepam. By increasing the frequency of measurements, the accuracy of pharmacodynamic evaluations was clearly enhanced in this study.


Pharmacodynamics and tolerability of L-654,066, a steroid 5 alpha-reductase inhibitor, in men. A four-period, two-panel single rising-dose study (0.1 to 100 mg) was conducted in healthy men to investigate the pharmacodynamics and tolerability of L-654,066, a steroid 5 alpha-reductase inhibitor. Within each panel, six subjects received L-654,066 and two subjects received placebo at each dose level; the placebo subjects changed between periods so that each subject received placebo once. Testosterone and dihydrotestosterone were measured in serum at 0, 4, 24, and 48 hours after each treatment. L-654,066 was associated with a significant reduction in serum dihydrotestosterone concentrations, which was maximal at 48 hours after dose. Forty-eight hours after treatment, mean percentage of inhibition was 24% and 39% for the 0.1 and 0.5 mg doses, respectively, and ranged from 50% to 65% at doses from 1 to 25 mg and from 70% to 75% at doses from 50 to 100 mg. Testosterone serum levels did not show any significant difference between the various treatments, including placebo.


Protection against aspirin-induced gastric lesions by lansoprazole: simultaneous evaluation of functional and morphologic responses. The protective effect of lansoprazole, a new proton pump inhibitor, against aspirin-induced gastric lesions was studied in a double-blind crossover trial with a simultaneous measure of the functional capacities of the mucosal barrier (by a recording of the gastric potential difference) and of the morphologic changes in the mucosa (by gastric endoscopy). After 1 week of treatment with lansoprazole (30 mg per day) or placebo, each healthy volunteer received 1 gm aspirin by mouth. Recording of the gastric potential difference lasted for 3 hours and was followed by gastric endoscopy. Morphologic lesions induced by aspirin were effectively prevented by lansoprazole: Lanza score was 0.67 +/- 0.98 (mean +/- SD) versus 2.25 +/- 1.1 with placebo (p < 0.005, ANOVA). Conversely, the decrease in the gastric potential difference was similar. The inhibition of acid secretion induced by lansoprazole was therefore sufficient to prevent aspirin-induced mucosal lesions without reinforcing the defense capacities of the mucosa. This simple pharmacologic model makes it possible to simultaneously evaluate the functional and morphologic effects of aspirin intake on the gastric mucosa.


Prediction of sotalol-induced maximum steady-state QTc prolongation from single-dose administration in healthy volunteers. The relationship between racemic sotalol plasma concentrations and QTc interval prolongation after both single-dose and repeated administration of three sotalol oral doses was studied in a randomized crossover protocol performed in 10 healthy volunteers. QTc interval increase was significant after the three single-dose sotalol administrations and was significantly related to the administered dose (p < 0.0001). In 21 of 30 analyses, QTc interval was linearly correlated with sotalol plasma concentrations. After the 320 mg dose, the linear model was a best fit for 90% of the cases, and no hysteresis was observed. After repeated sotalol administration, 69 of 87 QTc interval measurements at steady state could be predicted from the plasma concentration versus effect relationship established after single-dose 320 mg administration. Seventeen of 18 errors (94%) corresponded to QTc intervals that were significantly lower than predicted. These findings suggest that a short-term individual linear model determined after a 320 mg test dose of sotalol allows a good prediction of expected maximal increase in QTc duration in healthy subjects.


Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function. To assess whether fluvoxamine alters the pharmacokinetics of alcohol or potentiates alcohol-related impairment of cognitive function. The study design required partially "blinded" balanced crossover studies, each involving 12 healthy male volunteers who each received a 40 gm dose of intravenous or oral alcohol after single and multiple doses of 50 mg fluvoxamine. Main outcome measures for pharmacokinetics were venous blood alcohol and plasma fluvoxamine. Main outcome measures for pharmacodynamics were word recall, simple and choice reaction time, number vigilance, memory scanning, and word recognition. The pharmacokinetics of intravenous alcohol were not affected by concomitant administration of fluvoxamine. Compared with placebo-alcohol, alcohol slightly increased the rate of fluvoxamine absorption, but the area under the plasma concentration-time curve from 0 to 12 hours at steady state was unchanged. As expected, alcohol significantly impaired cognitive function in volunteers. However, fluvoxamine did not potentiate the effects of alcohol and in some instances appeared to reverse the effects or reduce their duration. Fluvoxamine was well tolerated: only mild adverse effects were reported, and none of those required intervention. Fluvoxamine does not interact significantly with alcohol or potentiate alcohol-related impairment of cognitive function.


Comparison of intravenous ketorolac with morphine for postoperative pain in children. Ninety-two children from 3 to 12 years of age were given intravenous morphine or ketorolac by titration, or ketorolac by bolus injection for moderate or severe postsurgical pain in a double-blind randomized parallel-group study. Pain scores were assessed every 5 minutes until pain relief was complete, and then every 15 minutes for 8 hours or until pain returned. Twenty-nine of 30 patients receiving morphine and 25 of 30 patients in each group receiving ketorolac achieved pain relief. The subjects in the morphine group required statistically fewer doses for analgesia than the subjects in the ketorolac groups. The sums of pain intensity differences calculated from the start of the study numerically favored morphine, but the sum of pain intensity differences from pain relief until 50% withdrew were significantly better in the ketorolac groups. Median durations of analgesia from initial drug administration were 170, 190, and 225 minutes in the morphine, ketorolac titration, and ketorolac bolus groups, respectively. The most common side effect was injection site pain. Analgesia after intravenous ketorolac developed more slowly but was sustained better than morphine.


Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. The pharmacokinetics of cyclosporine was studied in six healthy volunteers after administration of the drug orally (10 mg/kg) and intravenously (3 mg/kg) with and without concomitant rifampin administration. Both blood and plasma (separated at 37 degrees C) samples were analyzed for cyclosporine concentration. For blood and plasma, respectively, clearances of cyclosporine were calculated to be 0.30 and 0.55 L/hr/kg, values for volume of distribution at steady state were 1.31 and 1.68 L/kg, and bioavailabilities were 27% and 33% during the pre-rifampin phase. Post-rifampin phase clearances of cyclosporine were 0.42 and 0.79 L/hr/kg, values for volume of distribution at steady state were 1.36 and 1.35 L/kg, and bioavailabilities were 10% and 9% for blood and plasma, respectively. Rifampin not only induces the hepatic metabolism of cyclosporine but also decreases its bioavailability to a greater extent than would be predicted by the increased metabolism. The decreased bioavailability most probably can be explained by an induction of intestinal cytochrome P450 enzymes, which appears to be markedly greater than the induction of hepatic metabolism.


Influence of lansoprazole treatment on diazepam plasma concentrations. The possible influence of long-term treatment with lansoprazole on the single-dose pharmacokinetics of diazepam was investigated in 12 healthy male volunteers. In this double-blind randomized crossover study, 60 mg lansoprazole or placebo was administered once daily for 10 days. One hour after administration on day 7, 0.1 mg/kg diazepam was administered intravenously, and blood was collected up to 96 hours after the injection for plasma diazepam and desmethyldiazepam measurement. During the placebo session, the plasma elimination half-life, clearance, and volume of distribution of diazepam were 26.0 +/- 1.6 hours, 22.5 +/- 1.1 ml/hr/kg, and 0.82 +/- 0.04 L/kg, respectively. These parameters were not significantly different during the lansoprazole session. The mean plasma concentrations of desmethyldiazepam were similar in both sessions. These findings illustrate that long-term treatment with a therapeutic dose of lansoprazole does not interfere with the metabolism of diazepam.


Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine. This was designed as a randomized, two-period, two-treatment, crossover study. The patients were 12 men infected with human immunodeficiency virus who had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. On two separate occasions 14 days apart, patients received either zidovudine alone (200 mg every 4 hours while awake) or zidovudine (200 mg every 4 hours while awake) and naproxen (500 mg every 12 hours for 4 days). On the morning of the fifth day, each patient received the final dose of each regimen and blood and urine were serially collected for 8 hours. Pharmacokinetic parameters (area under the serum concentration-time curve [AUC], maximum plasma concentration, terminal half-life, renal clearance, and urinary recovery) were assessed for zidovudine and its glucuronide metabolite. Naproxen had no significant effect (< 10% difference between treatment means, p > 0.15, ANOVA) on the above pharmacokinetic parameters for both zidovudine and its metabolite. Although the power of the study to detect these small differences was < 80% at the 5% significance level, differences ranging from 12.6% for AUC to 38.8% for urinary recovery could be detected with 80% power. Therapeutic doses of naproxen do not significantly affect the pharmacokinetic disposition of zidovudine.


Erythromycin breath test predicts oral clearance of cyclosporine in kidney transplant recipients. It has been shown recently that cyclosporine is largely metabolized by P450IIIA (CYP3A), an enzyme whose catalytic activity varies significantly among patients. To determine whether heterogeneity in P450IIIA activity contributes to interpatient differences in cyclosporine dosing requirements, the oral pharmacokinetics of the drug were determined in 20 stable kidney transplant recipients. P450IIIA activity was then measured in each patient by use of the erythromycin breath test. In the 16 patients who were at steady state, the logarithm of the apparent oral clearance of cyclosporine correlated significantly with the rate of 14CO2 exhaled in breath after intravenous administration of [14C N-methyl]erythromycin (r = 0.55, p = 0.03). No significant correlations existed between apparent oral clearance and age, high-density lipoprotein cholesterol or low-density lipoprotein cholesterol, or hematocrit in these patients. We conclude that heterogeneity in P450IIIA activity significantly contributes to interpatient differences in dosing requirements of cyclosporine in kidney transplant patients.


Fluoxetine impairs clearance of alprazolam but not of clonazepam. Volunteer male subjects received single 1.0 mg oral doses of alprazolam and of clonazepam on two occasions, during coadministration of 40 mg/day fluoxetine or of placebo. When the sequence of trials was placebo first and fluoxetine second, fluoxetine coadministration significantly prolonged alprazolam half-life (20 versus 17 hours) and reduced clearance (48 versus 61 ml/min). No effect of fluoxetine was seen when fluoxetine was given first and placebo second, because norfluoxetine persisted into the placebo phase even though fluoxetine had been discontinued 2 weeks earlier. Fluoxetine had no significant effects on clonazepam elimination half-life or clearance regardless of the sequence of fluoxetine and placebo administration. In the fluoxetine-placebo sequence, fluoxetine significantly increased the rate of clonazepam absorption. Thus fluoxetine appears to impair clearance of alprazolam by way of microsomal oxidation but does not alter clearance of clonazepam by way of nitroreduction. The very slow elimination of norfluoxetine should be considered in the design of clinical or pharmacokinetic studies that involve fluoxetine.


Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. The single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone have been determined in patients with moderate to severe cancer pain. The mean +/- SD elimination half-life after single-dose administration of intravenous (4.6 mg to 9.1 mg) and oral (9.1 mg) oxycodone was 3.01 +/- 1.37 hours and 3.51 +/- 1.43 hours, respectively. After intravenous administration, the mean +/- SD volume of distribution was 211.9 +/- 186.6 L, and the mean +/- SD total plasma clearance was 48.6 +/- 26.5 L/hr. The mean absolute oral bioavailability of oxycodone was 87%, and the mean +/- SD volume of distribution after oral administration was 249.1 +/- 204.3 L. When administered orally as 10 mg oxycodone hydrochloride every 4 hours, there was no accumulation of oxycodone at steady state and the mean +/- SD steady-state concentration was 34.6 +/- 10.3 micrograms/L. Intravenous oxycodone produced a faster onset of pain relief than oxycodone tablets, but the duration of analgesia was approximately the same (4 hours). However, the incidence of side effects and their severity were significantly higher (p < 0.05) for intravenous oxycodone than for oxycodone tablets. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study supports the need for individualized dosing regimens.


Clinical pharmacology of nicorandil in patients with congestive heart failure. Nicorandil is a nicotinamide derivative with a potential role in human therapeutics because of its potent vasodilating properties. The pharmacokinetics of oral nicorandil administration and the relationships between plasma nicorandil concentration and hemodynamic responses were examined in 25 patients with moderate to severe congestive heart failure. The dose range from 10 to 60 mg was studied. Elimination half-life for this dose range was substantially longer than that previously reported in normal volunteers. Total area under the curve increased in a curvilinear fashion with progressive dose increments, indicating a disproportionate increase in systemically available drug at higher doses. Hemodynamic responses generally correlated well with plasma nicorandil concentration, with rapid loss of cardiovascular activity corresponding to the efficient clearance of nicorandil.


Time course of tolerance to apomorphine in parkinsonism. We sought to determine if tolerance developed to the antiparkinsonian effects of apomorphine and, if so, what temporal factors influenced its development. Seven patients with parkinsonism and motor fluctuations received short (6-hour) and long (22- to 31-hour) apomorphine infusions. Tolerance was evaluated by comparison of the responses to test doses of apomorphine that were administered before and after each infusion. The responses to the test doses that followed either infusion were reduced by 35% after the short infusion and by 68% after the long infusion, although plasma apomorphine levels were similar to or higher than levels achieved with preinfusion test doses. The duration of improvement in parkinsonism after discontinuation of the long infusion was briefer than that after the short infusion. We conclude that tolerance to apomorphine occurs in parkinsonism, and the loss of response is greater after longer periods of drug administration.


Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations. The power spectrum of instantaneous heart rate fluctuations was used to determine the optimal doses of atropine that induce a maximal vagolytic or vagomimetic effect. In a crossover placebo controlled study, eight volunteers received increasing bolus doses of intravenous atropine (0.1 to 2.3 mg per subject) or placebo, and frequency bands of the power spectrum were integrated. During atropine administration a significant bimodal dose dependence was observed for the respiratory peak (0.2 to 0.4 Hz, p = 0.0006), the midfrequency band (0.09 to 0.15 Hz, p = 0.0035), and mean heart rate (p < 0.0001). Low doses (< 0.4 mg per subject) increased the respiratory and midfrequency band power, with maximal response at 0.2 mg per subject. Larger doses of atropine, 0.5 to 2.3 mg per subject, markedly reduced the power in all frequency bands in a dose-dependent way. The corresponding changes in mean heart rate were simultaneous, but in the opposite direction. We suggest that the respiratory peak of the power spectrum can be used to optimize drug effects on cardiac parasympathetic control.


Population pharmacodynamics of doxacurium. The nonlinear mixed-effects modeling (NONMEM) computer program was used to investigate the variability in the duration of doxacurium-induced neuromuscular block in 408 patients enrolled in phase II and phase III clinical trials of doxacurium. Spontaneous recovery data in the 10% to 90% block range from all patients were pooled and fitted to a linear model. Two parameters were estimated: (1) the slope, which is related to the pharmacokinetics and to the steepness of the dose-response curve, and (2) the intercept, which is linearly related to dose but has no physiologic meaning. The primary goal was to determine the factors affecting the slope by use of univariate and multivariate analyses techniques. Estimates of the slope ranged from 0.67% to 1.1% block/min (interindividual variability, 39%). Factors with clinically significant effects on the slope included the following: age, obesity, and anesthesia type. Thus these factors influence the time course of doxacurium-induced block and may require individualization of dose.


The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. The effect of the selective serotonin reuptake inhibitor citalopram on diabetic neuropathy symptoms was examined in a double-blind, placebo-controlled, crossover study for two 3-week periods. Citalopram was given as a fixed dose of 40 mg/day. Data from 15 patients could be included in the statistical analysis. Citalopram significantly relieved the symptoms of neuropathy as measured by both observer- and self-rating in comparison with placebo. The steady-state plasma concentration of citalopram was 10 to 890 nmol/L. There was no significant relationship between the plasma concentration of citalopram and the effect of treatment as measured by observer- or self-rating. Two of 17 patients, both receiving citalopram, left the study because of side effects (nausea and vomiting or gastric upset and diarrhea). Side-effect ratings were significantly higher during administration of citalopram than during administration of placebo, but citalopram was generally well tolerated. Compared with earlier results obtained with imipramine administered on the basis of plasma level monitoring, citalopram appeared to be less effective, but seemed to be better tolerated.


Pharmacologic maintenance of abstinence in patients with alcoholism: no efficacy of 5-hydroxytryptophan or levodopa. Pharmacologic enhancement of central nervous system serotonin and dopamine functions has been postulated to improve maintenance of abstinence in patients with alcoholism. To test this hypothesis, patients with alcoholism who completed a 42-day inpatient treatment program were randomized to be administered, in a double-blind fashion, either 5-hydroxytryptophan and carbidopa, levodopa and carbidopa, or placebo for 1 year. Eight of 31 patients who entered the analysis remained abstinent from alcohol for 1 year; however, there was no significant effect of the treatment condition on maintenance of abstinence. Baseline psychologic measures showed that patients who abstained from alcohol had more education and higher scores on memory function tests. Measures of cerebrospinal fluid obtained before the start of the study indicated that all patients who had higher concentrations of the dopamine metabolite homovanillic acid relapsed, suggesting that further research is needed to elucidate the role of dopamine in alcoholism.


Enantioselective pharmacokinetics and pharmacodynamics of dl-threo-methylphenidate in children with attention deficit hyperactivity disorder. Nine boys with attention-deficit hyperactivity disorder took part in a study in which d-methylphenidate, l-methylphenidate, dl-methylphenidate, or placebo were administered in a double-blind, four-way, randomized, crossover design. Plasma levels of the isomers of methylphenidate were monitored by means of an enantioselective assay method. The ability of the children to perform tasks that required sustained attention was monitored by a battery of computer tests. There was no evidence of interconversion between the enantiomers in vivo, although the presence of the d-isomer significantly altered the pharmacokinetics of the l-antipode. The presence of the l-isomer did not affect the pharmacokinetics of d-methylphenidate. The computer tests revealed a drug-induced improvement in sustained attention that was entirely attributable to the d-enantiomer. There was no evidence to suggest that the effectiveness of d-methylphenidate was in any way compromised by the presence of its antipode.


Biosynthesis and distribution of fibronectin in normal and osteoarthritic human cartilage. The biosynthesis of fibronectin was determined in explants from normal and osteoarthritic human cartilage after metabolic labeling and immunoprecipitation. Each sample of osteoarthritic cartilage was divided into three regions taken at different distances from the eburnated bone area. Only full depth cartilage samples were taken into consideration. We could detect a low level of fibronectin biosynthesis in normal cartilage. In osteoarthritic cartilage increased synthesis of fibronectin was demonstrated, the most important in the region close to the eburnated area. Increased synthesis, although to a lower extent, was also demonstrated in the two other regions at increasing distances from the eburnated areas. Immuno-histological examinations performed on tissue samples and similar studies on articular chondrocyte cell cultures confirmed the accumulation of newly synthesized fibronectin in pathological conditions.


Myocardial creatine kinase-MB concentration in normal and explanted human hearts and released from hearts of patients with acute myocardial infarction. Using an enzyme immunoassay of creatine kinase (CK)-MB concentration commercially available for diagnosis of acute myocardial infarction (AMI), we studied CK-MB concentrations in myocardium of subjects who died from noncardiac causes and in cardiac explants of patients with either coronary heart disease or cardiomyopathy who underwent cardiac transplantation. Secondly, CK-MB concentrations were measured in serial plasma samples of 93 patients with AMI. By calculation of cumulatively released amounts of CK-MB and cumulatively released activities of CK, aspartate aminotransferase (AST) and alpha-hydroxybutyrate dehydrogenase (HBDH), we obtained values of the proportions in which these quantities were released from the myocardium. Taking a myocardial HBDH activity of 152 U/g as a reference value, the released activities of CK and AST, and the released mass of CK-MB per gram of myocardium were calculated. These values were compared to the corresponding quantities in myocardium of normal hearts and in explanted myocardium. Normal hearts differ from explanted myocardium and from "infarcted" hearts with respect to CK-MB concentration, but not with respect to CK, AST and HBDH activities. The wide range of CK-MB concentrations in normal hearts (1-515 micrograms/g) suggests variable expression of the CK-MB gene. The presence of CK-MB is not confined to cardiac tissue. CK-MB concentration in 12 samples of human skeletal muscle equalled 27 +/- 1 micrograms/g (2.1 +/- 0.5% of total CK activity). In conclusion, the mean concentration of CK-MB in normal hearts is low (139 micrograms/g) with a high variation coefficient (127%), but is high (369 micrograms/g) with a small variation coefficient (31%) in explanted hearts.(ABSTRACT TRUNCATED AT 250 WORDS)


Non-invasive assessments of compliance of the aortic wind-kessel in man derived from pulse pressure/storage volume ratio and from pulse wave velocity. Two noninvasive methods for assessment of the compliance (1/E') of the aortic windkessel in man are presented and were tested for their ability to detect increases in stiffness of the aorta induced by atropine (0.012 and 0.024 mg/kg sequentially) in the presence and absence of a beta-blockade with propranolol 240 mg (n = 9). Method A, based on the calculation of the relation between pulse pressure and systolic storage volume of the aorta, requires measurement of blood pressure, systolic and diastolic time intervals and stroke volume. Method B, based on measurement of pulse wave velocity along the aorta also requires several anthropometric data (body surface area, age). Both methods were able to detect a dose-dependent increase in E' following atropine injections; method A has greater relative changes than method B. The average maximal increases were 90 and 40 percent of the baseline before atropine. The daily baselines of E' averaged 0.6 Torr x cm-3 for method A and 0.9 Torr x cm-3 for method B. Propranolol itself did not influence E' but dampened the atropine effects. The results from method A and B were correlated with r = 0.70 and 0.60 resp. (p < 0.01). The results suggest the use of these relatively simple techniques for evaluation of aortic compliance under influence of varying pathophysiological conditions or/and pharmacological interventions.


Anticholinergic influences of biperidene on the EEG effects of haloperidol. 15 normal volunteers demonstrated after 14 days of haloperidol (HA) medication (3 mg/day) a higher mean power density (mpd) in all frequency bands of the EEG power spectra combined with a higher theta and a lower alpha center frequency (cf). After further 7 days of HA medication together with the additionally applied anticholinergic biperidene (BI) (6 mg/day) the HA effects were antagonized especially in the theta cf and the alpha mpd. The higher delta and theta mpd were not antagonized. The EEG spectra of the pre- and posttreatment condition did not differ. There was a significant effect of HA on the "Adjective Mood Scale" and on the "Complaint List", which disappeared during the additional BI medication. The reaction times were prolonged with HA and decreased with BI. Blocked dopaminergic impulses on the cholinergic EEG mechanisms possibly produce higher amplitudes during HA medication. Schizophrenic patients treated with neuroleptic drugs showed similar EEG spectra in previous studies during rest but not during motor activation.


Differential effects of transition metal ions on in vitro lipid peroxidation of human serum and protein precipitated from serum. Elevated concentrations of lipid peroxidation products in serum have been documented in some common human diseases. In addition, several reports indicate that peroxidative damage of tissues in laboratory animals are enhanced in acute toxicity from transition metal ions. We studied the effects of four commonly encountered transition metal ions in human acute toxicity: copper, iron, mercury and lead on in vitro lipid peroxidation of human sera. Cupric and ferric ions caused a significant increase in lipid peroxidation products while mercuric and lead ions had no effects. Lipid peroxidation products in sera incubated with 1 mM cupric ion were increased by 210-248% following 24 h of incubation and 340-480% after 48 h of incubation, while the increases were significantly lower in the aliquots of same serum pools supplemented with same molar concentration of ferric ions (110-115% after 24 h and 137-141% following 48 h). On the other hand the effects were reversed when lipoproteins coprecipitated with other serum proteins were incubated with cupric and ferric ions. Under such conditions increases of lipid peroxidation products were significantly higher with ferric ions (240% after 24 h and 600% after 48 h) compared to cupric ions (20% following 24 h and 25% following 48 h). Such differential behavior of cupric and ferric ions in promoting lipid peroxidation can be explained with a different degree of binding of such ions with serum proteins.


Molecular analysis of the fragile X syndrome. Carriers of the fragile X mutation possess more than the normal number of copies of a trinucleotide repeat (CGG) within the coding region of a gene designated as FMR-1 in Xq27. The clinical phenotype is determined by the number of copies of the CGG repeat. DNA-based methods for the detection of the fragile X mutation are now available which greatly assist in the genetic diagnosis of this disorder. Direct detection of the mutation enables the identification of fragile X negative normal transmitting males and fragile X negative carrier females.


High-resolution computed tomography of drug-induced lung disease. In order to determine the potential clinical utility of high-resolution CT (HRCT) in the assessment of drug-induced lung disease, we reviewed the chest radiographs and HRCT scans of 23 patients and five normal controls. The radiographs and HRCT scans were reviewed separately in random order by two independent observers who were not aware of the relative numbers of patients and controls. Abnormal findings were detected in the affected patients in 17/23 radiographs compared to 23/23 HRCT scans. The patients included five cases of bleomycin toxicity, five cases of nitrofurantoin toxicity, two cases each of penicillamine, busulphan, BCNU and amiodarone toxicity, and one case each of cyclophosphamide, procainamide, mitomycin and methotrexate toxicity. The HRCT appearances could be grouped into four categories according to their dominant pattern and distribution of disease. These include fibrosis with or without consolidation (n = 12), ground-glass opacities (n = 7), widespread bilateral consolidation (n = 2), and bronchial wall thickening with areas of decreased attenuation (n = 2). The results of this study indicate that HRCT is more sensitive than the radiograph in the detection of drug-induced lung disease. The appearances demonstrated by HRCT reflect the pathological mechanisms of drug-induced lung disease.


Primary immunodeficiencies in the USSR: update of a nine-year study. During the period January 1982-January 1991, 372 patients with primary immunodeficiencies from all the regions of the USSR were detected in a specialized unit. Incidence of main clinical manifestations and death rates are reported. Differences with other national registries are discussed.


Imaging of orbitofrontal cholesterol granuloma. The radiological findings in 31 patients with a histologically proven orbitofrontal cholesterol granuloma are presented. Plain films and computed tomography (CT) both show a characteristic lytic lesion allowing a reasonably confident diagnosis to be made preoperatively, thus facilitating appropriate surgery. The most important differential diagnoses on clinico-radiological grounds are lacrimal gland carcinoma and dermoid cyst. On plain films cholesterol granulomas typically show constancy of site, lysis of the superior orbital margin, frequent extension into the frontozygomatic process and absent or minimal surrounding sclerosis. On CT ragged bone destruction with a soft tissue mass no denser than brain extending extraperiosteally into the orbit are the most typical features. MRI and other imaging modalities are discussed.


Tongue cancer treated with irradiation: assessment with MR imaging. We examined the usefulness of MRI in differentiating post-radiation scar tissue from the residual tumour. Ten consecutive patients who underwent MR imaging before and after radiation therapy were assessed prospectively. T1- and T2-weighted images using a 1.5 unit were obtained in 10 patients (3 T1, 6 T2, 1 T3) at 1 week before irradiation, and 2 weeks, 2 months, 4 months, 6 months and every 6 months thereafter following completion of radiation. Although all T2 and T3 tumours demonstrated high signal intensity compared to muscle on T2-weighted images, the T1 tumour could be demonstrated in only one of three patients. Six patients in whom the primary tumour clinically disappeared demonstrated low signal intensity on T2-weighted images until 4 months after completion of radiation therapy (range 1 week to 4 months). This study suggests that MRI can detect primary tumours larger than T2 (2 cm), and may be useful in assessing the effectiveness of therapy for tongue cancer.


Benign mimics of soft tissue sarcomas.

Benign mimics of soft tissue sarcomas. We reviewed all new patients referred for treatment to the Sarcoma Unit at the Royal Marsden Hospital with a clinical diagnosis of soft tissue sarcoma (STS) during the course of 1 year (1989-1990). Of 118 patients, 65 (55.1%) had primary STS, 26 (22.0%) had recurrent STS, 19 (16.1%) had benign soft tissue tumours and eight (6.8%) had malignant tumours other than STS involving soft tissues and presenting clinically as soft tissue tumours. All patients underwent CT scanning which was used to assist diagnosis, assess operability or for radiotherapy planning. The CT findings of the benign lesions, all clinically suspicious of sarcoma, are discussed. The role of CT in the identification and management of these cases is emphasized.


Allele-specific methylation in the 5'-regulatory region of class II DQ beta genes in the human major histocompatibility complex (MHC): relationship to autoimmune disease susceptibility. The DNA methylation state of the 5'-regulatory region of human HLA-DQ beta genes was examined. Two restriction enzymes were utilized to detect methylated (meCG) dinucleotides in the 5'-regulatory region of the DQ-beta genes: the restriction enzyme Msp I, which recognizes CCGG and CmeCGG, and Hpa II recognizes only the unmethylated CG sequence. DNA samples were prepared from 95 HLA-typed individuals including 40 B-lymphoblastoid cell lines and peripheral blood leukocytes of 55 individuals. Of these samples, 20 were from parents of individuals with insulin-dependent diabetes. Allele specific methylation was observed in particular DR-associated DQ-beta gene alleles. The DQw8 (DQw3.2) allele, most DQw7 (DQw3.1) alleles, and the DR3-associated DQw2 allele were all unmethylated. The parental methylation state was stably transmitted to offspring. Because these DQ alleles are highly associated with several autoimmune diseases, our results raise the possibility that the regulation of expression of these particular DQ-beta alleles might be different from that of other alleles, and that the 5'-regulatory DNA sequences of these particular DQ beta alleles may be responsible for, or contribute to, susceptibility to autoimmune diseases.


Imaging of alveolar soft part sarcoma.

Imaging of alveolar soft part sarcoma. The imaging investigations in six patients with alveolar soft part sarcoma (ASPS) are reviewed. Five patients presented with a pelvic or lower limb mass and one with haemoptysis from pulmonary metastases. Magnetic resonance imaging (MRI), CT, Doppler US and angiography studies demonstrated the highly vascular nature of this rare tumour and the frequent occurrence of pulmonary and intracranial metastases. Previously unreported Doppler US and MR evidence of multiple enlarged vessels and high blood flow within primary and secondary ASPS tumours is emphasized. Imaging is of considerable importance both for pre-operative localization and long term surveillance of this slow growing but invariably disseminating tumour.


Gas-containing ganglia of the hip.

Gas-containing ganglia of the hip. Three cases of ganglia related to the hip containing gas are presented. Gas may be shown by conventional radiography, linear tomography or computed tomography. All three cases had advanced degenerative disease of the joint. In degenerative disease, ganglia form through a pathway which allows the transfer of intra-articular gas into the ganglion. It is important to differentiate this phenomenon from overlying bowel gas and other causes of gas within soft tissues. It is the most specific radiological feature of ganglia around the hip.


The accessory navicular--an important cause of medial foot pain. The accessory navicular is a commonly occurring accessory ossicle of the foot. In most instances this is an incidental finding. In some patients, the accessory navicular is the direct cause of foot pain. We present 10 such cases. The typical clinical picture is of a young female patient who presents with chronic or acute on chronic medial foot pain centered over the medial side of the navicular. The patient is usually physically active on her feet and localizes the pain accurately. Plain radiography reveals an accessory navicular united to the navicular by a synchondrosis (Type II). The diagnosis can be confirmed by showing increased localized uptake of isotope on a technetium 99m MDP bone scan. In some cases, the accessory navicular is mistaken for a fracture. Awareness of this accessory ossicle causing such symptoms should lead to the correct diagnosis.


Renal transplant sonography: correlation of Doppler and biopsy results in cellular rejection. Seventy-one patients with allograft dysfunction had concomitant Doppler sonography and percutaneous biopsy. Forty-one had biopsy proven acute cellular rejection and eight had acute cellular rejection in combination with acute tubular necrosis. Real time ultrasonic appearance and various parameters of Doppler waveform were studied and compared with 30 controls who had a long period of stable function with no previous episodes of rejection or acute tubular necrosis (ATN). Morphological appearances were unhelpful in diagnosing rejection. A resistive index greater than 0.8 in the study group was highly specific for dysfunction but could not differentiate between acute rejection and ATN. However, two patients in the control group of normal transplants had a resistive index of 0.83. An early to mid diastolic notch was highly specific for acute rejection but of low sensitivity. It may be the only Doppler indication of cellular rejection and may be present when the resistive index is in the normal range.


Renal artery embolization with ethanol and gelfoam for the treatment of ureteric fistulae with one year follow-up. Two patients with ureteric fistulae who were unfit for reconstructive surgery were treated by renal ablation using intra-arterial ethanol, gelfoam fragments and in one case coils. In both cases the fistulae dried-up on the same day and both patients are well and normotensive a year later. Our conclusion is that renal ablation by arterial embolization with ethanol can be a valuable alternative to surgery to treat ureteric fistulae in patients who are poor surgical risks.


The acute contrast enema in suspected large bowel obstruction: value and technique. In order to determine the value of the acute contrast enema (ACE) as compared to the plain abdominal film for the diagnosis of colonic obstruction and to determine the optimal technique for performing this examination, we reviewed 140 cases performed over a 4 year period. The study shows that when provided with the case history and the plain abdominal films of patients referred for an ACE the diagnosis of colonic obstruction can be made with a sensitivity of 84% and a specificity of 72%, whereas the ACE has a sensitivity of 96% and a specificity of 98%. The ACE resulted in two false negatives, one false positive and one technical failure, analysis of which has enabled an optimal technique for the performance of this examination to be recommended.


Clinico-radiological meetings: are they worthwhile? The proceedings of 22 clinico-radiological meetings were analysed in order to assess some aspects of their benefits and cost. The mean duration of each meeting was 30.4 min. On average, the clinical and radiological details of eight patients were discussed at each meeting. The mean number of changes in the leading diagnosis was 1.6 per meeting, and a mean of 1.9 management decisions were made. A mean of 1.6 further radiological tests were recommended, offset by a mean of 0.7 scheduled investigations which were deemed no longer necessary. The cost of the salaries of the staff attending each meeting amounted to 73.82 pounds. Thus the cost of a revised leading diagnosis was calculated at 46.14 pounds whilst that of a management decision came to 38.85 pounds. The assumed educational benefits of these meetings and inevitable lost opportunity costs were not analysed.


Case report: chronic spinal cord compression from extramedullary haematopoiesis in thalassaemia--MRI findings. A 27-year-old-man with beta-thalassaemia/HbE presented with signs and symptoms of spinal cord compression due to epidural extramedullary haematopoiesis. Magnetic resonance images demonstrated spinal cord constriction and atrophy suggesting that the disease process was long-standing. On transverse T2-weighted images, high signal intensity was observed within the spinal cord suggestive of post-compressive spinal cord myelomalacia or gliosis.


Case report: selective occipital lobe hydrocephalus and agenesis of the left lobe of the liver in congenital myotonic dystrophy. Myotonic dystrophy (Steinert's disease) is an uncommon familial autosomal dominant disease, characterized by progressive muscular atrophy and myotonia. Mental retardation, frontal baldness, cortical lenticular opacities and testicular atrophy are other prominent features of a disease that involves predominantly striated muscle. There is little information regarding this disease in the radiological literature. The present report introduces two additional findings involving the skull and the liver.


Case report: small bowel volvulus presenting during pregnancy. The diagnostic use of ionizing radiation during pregnancy is to be avoided whenever possible due to the risk to the unborn child. However, vomiting presenting after the first trimester of pregnancy is unusual, and if severe or persistent, requires investigation. We present a case where reluctance to expose the fetus to radiation could have resulted in a potentially serious delay in the diagnosis of maternal small bowel volvulus.


Case report: CT diagnosis of nonobstructive left paraduodenal hernia. The preoperative diagnosis of paraduodenal hernias (PH) can only be made radiologically. PH are seldom diagnosed preoperatively unless they cause bowel obstruction. We report an unusual case of a nonobstructive left PH diagnosed preoperatively by computed tomography (CT). The CT findings of internal hernias are discussed.


Case report: diagnosis of metastatic leptomeningeal melanoma by contrast enhanced MRI. A case of leptomeningeal melanoma metastases with a confusing clinical picture is presented. Despite repeated cytological examinations of the cerebrospinal fluid proving negative, the diagnosis was eventually made by magnetic resonance imaging with gadolinium DTPA enhancement.


Case report: complete lung collapse--an unusual presentation of cryptococcosis. Cryptococcosis presenting as an intrabronchial mass is not a recognized cause of complete lung collapse. This case report illustrates this extremely rare manifestation of pulmonary cryptococcosis, which mimicked primary pulmonary carcinoma clinically, radiologically and bronchoscopically.


A miniature silicon diode matrix detector for in vivo measurement of 133Xe disappearance following local tissue injection. A variety of biological processes can be studied from the washout of compounds labelled with a gamma emitter. Conventional systems for measurement of gamma radiation can detect count rates at both the low and high energy range of the indicator in question, 133Xe. However, silicon (Si) photodiodes have the capability of measuring the lowest energies (25-40 keV) of gamma and x-ray emitters with sufficient efficiency when applied on the skin surface and close to the indicator depot. The purpose of the present study was firstly to evaluate a portable Si photodiode matrix detector system, composed of 16 photodiodes, for in vivo measurement of disappearance rate constants of 133Xe following injection into subcutaneous (SC) or skeletal muscle (SM) tissues as compared with a stationary sodium iodide single crystal detector. Secondly, from these results, to evaluate the contribution from intra-tissue indicator diffusion and indicate means of avoiding influence from local diffusion in the washout curve of 133Xe. From the recorded 133Xe distribution in the depot proper, Si photodiodes in the matrix were selected for calculation of the washout. The Si matrix detector was reliable with a constant linearity and sensitivity within the range 20-38 degrees C and calibrated to +/- 1% between diodes. The in vivo investigations comprised two SC injections on humans with four measuring periods for comparison, and four SC and five SM injections on dogs, resulting in eight and five measuring periods for comparison. Only when the results obtained from the Si photodiodes at the position just above the count rate maximum were selected, was the contribution from diffusion significant. The ability to detect geometry changes is advantageous in studies with potential motion artefacts, such as during exercise.


A miniaturised force-torque sensor with six degrees of freedom for dental measurements. Force-torque sensor systems capable of simultaneously measuring all six spatial degrees of freedom on solid bodies are not very widespread in the medical field, particularly because of the hitherto unacceptably large external dimensions. A sensor based on the strain gauge technique has been developed with a diameter of only 32.5 mm and height of 29 mm. The miniaturised supporting framework for the strain gauges has been cast in a single piece from a wax-plastic model by the one-way mould principle. A sensitivity of 10 mN with an upper limit of 50 N is attained.


Non-invasive determination of systolic blood pressure by heart sound pattern analysis. A new concept of non-invasive blood pressure measurement by heart sound pattern analysis is described. The known diagnostic criterion of the 'accentuated' second heart sound of a hypertensive patient is here converted into a computer-aided pattern-recognition process for the second heart sound, applicable over the entire scale of blood pressure. After a 'learning phase', during which the second heart sound is recorded, analysed and correlated with a set of systolic blood pressure values of the individual patient, the computer is able to determine systolic blood pressure of the same patient from the acoustic spectrum of the second heart sound with sufficient precision. The method is in principle suited for automatically repeated blood pressure measurements, but further development is still needed for conversion into a widely practicable procedure.


Use of an oxygen multiwire surface electrode for the direct measurement of the distribution of alveolar PO2 at different inspired oxygen concentrations. Experiments were performed in six anaesthetised, mechanically ventilated rabbits. After thoracotomy, a multiwire surface PO2 electrode was placed at the pleural surface by means of a special holder. The local distribution of PO2 was investigated at different values of inspired oxygen concentration (FIO2). The data were analysed in order to establish (a) whether the PO2 values measured at the lung surface reflect intra-alveolar PO2 and (b) that the distribution of these values represent real physiological differences between alveoli. The mean PO2 values were related to the calculated mean alveolar PO2 (PAO2) values (r = 0.97) indicating that it is possible to study PAO2 by local measurements. It can therefore be concluded that the technique used allows the study of the influence of different FIO2 values on the distribution of PAO2. Each local PAO2 value is the result of the corresponding local ventilation/perfusion ratio (VA/Q) therefore the distribution of PAO2 values represents the distribution of VA/Q. An increasing FIO2 causes an increasing heterogeneity of PAO2 and thus VA/Q leading to a concomitant increase in the alveolo-arterial oxygen difference. At the moment it is not possible to decide if this heterogeneity is primarily caused by heterogeneities in perfusion or ventilation. The results could throw fresh light on the effect of different ventilation procedures.


Conductance studies of rat renal medulla for rapid estimation of extracellular electrolyte concentration. A method is described for estimation of tissue extracellular electrolytes in fresh excised rat renal medulla on the basis of its electrical conductance. The inner medulla was placed between two standard flat electrodes and the conductance was measured at a frequency of 3.5 kHz. The data were corrected for the surface area and thickness of the tissue fragment. The standard conductance so determined clearly correlated with total electrolyte concentration, and Na+ and 2(Na+ + K+) concentrations in the whole tissue (r = 0.84, 0.81 and 0.77, respectively; P < 0.001). The method enables a rapid and simple estimation of medullary extracellular electrolytes, a variable that is physiologically more meaningful than whole tissue electrolyte concentration.


Validation of a method of treating menorrhagia by endometrial ablation. Menstrual blood loss was measured by intravenous injection of radioactive iron (59Fe) and whole-body counting in 19 women complaining of menorrhagia due to dysfunctional bleeding. Fifteen patients were then treated by radiofrequency endometrial ablation, after which blood loss was re-measured. The majority of the patients were bleeding excessively before treatment (mean 281 (SD 156) ml per cycle averaged over two cycles, range 49-665 ml, n = 19). In the 15 treated patients, average blood loss was reduced to 52 (SD 39) ml per cycle and the mean reduction in blood loss was highly significant (P < 0.001). These quantitative data correlate well with the patients' subjective reports.


Mechanical parameters of human hair: possible application in the diagnosis and follow-up of hair disorders. Mechanical analysis of human hair may provide the dermatologists with several markers of considerable diagnostic importance. In the present paper, using a new computerised experimental system, attempts were made firstly to interpret the curves of the elastic and viscous components of the mechanical behavior of human hair and secondly to determine characteristic parameters which correlate well with its structural features. In order to overcome methodological problems due to the inhomogeneous structure of human hair, mechanical parameters were defined which either depend on the cortical microstructure or correlate well with the size of hair medulla.


Early exercise thallium-201 single photon emission computed tomography in unstable angina: a prospective study. To evaluate the safety and diagnostic value of early symptom-limited exercise electrocardiography (ECG) and exercise thallium-201 single photon emission computed tomography (SPECT) in unstable angina (UA), 39 patients were studied prospectively soon after stabilization on medical treatment. No patient had a history of myocardial infarction (MI) or revascularization and patients with left bundle branch block were excluded. Exercise ECG and exercise thallium-201 SPECT were performed 8 +/- 4 days and 11 +/- 6 days respectively after admission to hospital. Seventeen out of 39 patients (44%) had positive exercise ECGs and 22 (56%) negative or inconclusive ones. Exercise thallium-201 SPECT was positive in 26 patients (67%) and negative in 13 patients (33%). Thirty-one patients underwent coronary arteriography and 24 of them proved to have significant coronary artery disease (CAD). The sensitivity, specificity and positive predictive value of exercise ECG in detecting CAD are 62%, 86%, and 94% respectively while the corresponding results are 96%, 100%, and 100% for exercise thallium-201 SPECT. Therefore, it is concluded that the early symptom-limited exercise test is safe in medically stabilized patients with UA. Early exercise thallium-201 SPECT is highly sensitive and predictive of the presence of significant CAD among patients in the early recovery phase of UA and can be used in selecting this group of patients for coronary angiography and other therapeutic strategies.


Use of non-invasive finger blood pressure monitoring in the estimation of aortic pressure at rest and during the Mueller manoeuvre. The aim of this investigation was to evaluate whether reliable estimates of aortic pressure can be derived using non-invasive finger blood pressure monitoring. Finger blood pressure (Ohmeda 2300 Finapres device; Finapres, Englewood, CO) was compared with simultaneous ascending aortic pressure measured with a catheter-transducer system both at rest and during acute negative intrathoracic pressure (the Mueller manoeuvre). Thirty-eight patients aged 17-73 years were studied. All were undergoing routine diagnostic or therapeutic cardiac catheterization. Beat-to-beat values of systolic, diastolic and mean non-invasive finger and invasive aortic blood pressure were measured at rest and factors which might have an influence on the difference between methods were examined. The mean finger-aortic difference was +5 +/- 14 mmHg for systolic, -2 +/- 7 mmHg for diastolic, -5 +/- 8 mmHg for mean and +6 +/- 13 mmHg for pulse pressure. In multivariate linear regression analysis, the difference in systolic pressure was related to aortic systolic pressure (standardized coefficient beta = -0.33, P = 0.01), heart rate (beta = 0.49, P < 0.000), age (beta = -0.29, P < 0.025) and height (beta = 0.40, P < 0.005). The linear regression equations to derive resting aortic pressures from the non-invasive finger pressure readings had correlation coefficients between 0.83 and 0.87 and standard errors of estimate between 6 and 14 mmHg. During the Mueller manoeuvre, Finapres reproduced average pressure changes reliably compared with intra-aortic pressure. Due to moderate inter-individual variation in the finger-aortic differences the correlation coefficients ranged from 0.83 to 0.93 and the standard errors of estimate from 3 to 6 mmHg. Non-invasive finger blood pressure monitoring could be used to estimate central aortic mean and diastolic blood pressure fairly reliably at rest, but with respect to systolic pressure the variance in finger-aortic difference was marked. The average intra-aortic pressure changes caused by the Mueller manoeuvre were reliably reproduced by the Finapres device.


Thigh composition in young and elderly men determined by computed tomography. Computed tomography (CT) was used to quantify components of the thigh in young (n = 13) and elderly (n = 11) men. Cross-sectional areas (CSA) of the total limb, total muscle plus bone, quadriceps compartment, hamstring compartment and bone were measured at each of five scan sites along the length of the thigh. Non-muscle tissue (NMT) areas within the muscle compartments were measured using changes in density based on Hounsfield units. Skin plus subcutaneous fat areas and quadriceps and hamstring lean muscle areas were calculated by subtraction. Geometric formulae were used to calculate related volumes for each thigh component. Volumes were also predicted from regression equations employing thigh length and component CSA from single mid-limb CT scans. The results showed that while total thigh CSA was not different in elderly men, they had significantly smaller total muscle plus bone (13.0%), and quadriceps (26.4%), and hamstring (17.9%) muscle areas. The elderly men also had significantly greater CSA for skin plus subcutaneous fat (37.6%), and for NMT in the quadriceps (59.4%) and hamstring (127.3%) muscle compartments. These results suggest that comparisons of relative leg muscle strength between young and elderly men may be misleading due to the decrease in actual muscle tissue associated with ageing. Appropriate quantification of muscle size and CSA must be carried out before such comparisons can be meaningful.


Plasma endothelin-1 during central hypovolaemia in man. Endothelin-1 (ET-1) is a potent vasoconstricting peptide with effect on resistance as well as capacitance vessels. We followed ET-1 in arterial plasma together with heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and thoracic electrical impedance (TI) in seven men during central hypovolaemia induced by 50 degrees head-up tilt. During tilting plasma ET-1 increased from 1.1 +/- 0.2 to 1.4 +/- 0.3 pmol l-1 (mean +/- SE) concomitant with an increase in total peripheral resistance (TPR) (from 15 +/- 2 to 25 +/- 3 mmHg min l-1) (P < 0.01), and HR (from 67 +/- 2 to 94 +/- 5 beats min-1) (P < 0.01) while MAP remained unchanged. CVP decreased (from 1.8 +/- 0.9 to -1.6 +/- 1.0 mmHg) (P < 0.01) during tilting and remained unchanged during sustained tilt despite further reduction of central blood volume as recorded by TI. Presyncopal symptoms occurred after 28 +/- 6 min associated with decreases in HR (to 70 +/- 6 beats min-1), MAP (from 90 +/- 3 to 52 +/- 4 mmHg) and TPR (to 11 +/- 2 mmHg min l-1) (P < 0.01). At this time plasma ET-1 reached its highest level of 1.6 +/- 0.3 pmol l-1 (P < 0.01). Data show that head-up tilt is associated with increased plasma concentrations of ET-1 which may play a role in maintaining vascular tone in situations with a reduced central blood volume.


Heart rate during haemorrhagic shock.

Heart rate during haemorrhagic shock. In a prospective study, heart rate and mean arterial pressure were related to estimated blood loss in 34 consecutive patients aged 23-92 years during resuscitation from haemorrhagic shock. Eighteen patients with a blood loss of less than 31 (1.9 [0.9-3.0] l) (median and range), corresponding to 34 (16-46) % of estimated blood volume, had a heart rate of 83 (60-160) beats min-1 and a mean arterial pressure of 62 (35-73) mmHg. In 16 patients with a blood loss of more than 3 l (4.0 [3.3-5.0] l) corresponding to 89 (35-100) % of the estimated blood volume, heart rate was 120 (110-160) beats min-1 (P < 0.05) and mean arterial pressure 52 (0-70) mmHg (P < 0.05). Six patients died due to severe bleeding (3.1 [2.5-5.0] l) with a heart rate of 129 (110-160) beats min-1 and a mean arterial pressure of 40 (0-70) mmHg. It is concluded that reversible hypovolaemic shock is associated with a relatively low heart rate (approximately 80 beats min-1) and that tachycardia (approximately 120 beats min-1) is associated with profound bleeding. Hypovolaemic shock with tachycardia may represent a transition to an irreversible stage.


Relationship between hyperglycaemia and aerobic power in men with newly diagnosed type 2 (non insulin-dependent) diabetes. The aim of the study described here was to evaluate aerobic function during exercise and its determinants in middle-aged men with newly diagnosed Type 2 (non insulin-dependent) diabetes. Using breath-by-breath technique, we measured O2 uptake at anaerobic (ventilatory) threshold and at peak exercise in a group of diabetic men (n = 19; fasting blood glucose 8.6 +/- 0.7 mmol l-1, mean +/- SEM) without any disease or medication that could have had an influence on exercise performance, and compared the results to those observed in non-diabetic healthy control men (n = 18). There were no differences in physical activity or smoking habits between the groups. Oxygen uptake was lower in the diabetic men than in the control men both at anaerobic threshold (15.0 +/- 0.8 vs. 18.8 +/- 1.0 ml min-1 kg-1, P < 0.01) and at peak exercise (25.3 +/- 1.5 vs. 31.1 +/- 1.4 ml min-1 kg-1, P < 0.01). In the diabetic men peak O2 uptake showed an inverse linear correlation with age (r = -0.71, P < or = 0.001), fasting blood glucose (r = -0.49, P < 0.05) and glucose response in an oral glucose tolerance test (r = -0.43, P < 0.05). In addition, long-term smoking was associated with impaired peak O2 uptake. In a stepwise multiple regression procedure 75% of the total variance of peak O2 uptake in the diabetic men was explained by age, post-load blood glucose response and smoking history. Thus, in addition to ageing and smoking, hyperglycaemia is correlated with impaired aerobic power in men with newly diagnosed Type 2 diabetes.


Myocardial reperfusion in thrombolysis A 99Tcm-Sestamibi SPECT study in patients with acute myocardial infarction. This study presents the outcome of myocardial scintigraphy performed before and after thrombolytic treatment in 16 patients with acute myocardial infarction using 99Tcm-Sestamibi (Cardiolite, Du Pont Scandinavia AB, Kista, Sweden). The patients were given 99Tcm-Sestamibi intravenously as soon as possible after the decision to give thrombolytic treatment. When the patients were in a clinically stable state after the thrombolytic treatment, myocardial perfusion was analysed with the gamma camera using single photon emission computerized tomography (SPECT). A second 99Tcm-Sestamibi tomography was carried out on the second to fourth day after the myocardial infarction. Data reconstruction was done with the 'Bull's eye technique'. Nine patients received thrombolysis < 3 h from the onset of pain. In this group six patients (66%) improved their myocardial perfusion by > 10% after treatment, while all seven patients who received treatment > or = 3 h after the onset of pain improved their myocardial perfusion by < 10%. This study emphasises the importance of early diagnosis and treatment of patients with acute myocardial infarction in order to salvage myocardium.


[Thrombolytic therapy in acute myocardial infarct]. The benefits, main pharmacological characteristics, indications, side effects and time limits for use of thrombolytic agents in acute myocardial infarction are reviewed. The authors also point out the strategies to follow in patients after thrombolytic therapy.


[Irritable colon. Physiopathologic and therapeutic aspects]. The authors review the pathophysiologic mechanisms involved in bowel motility and in its alterations. Several symptoms are present in a form of bowel disease usually defined as "irritable bowel", in which a lot of polymorphic aspects appear to coincide. The first part of the paper is concerned with the symptoms and suggested pathophysiology and pathogenesis of the disorder while the latter part deals with the non-pharmacologic and pharmacologic treatment options.


[Short-term perioperative antibacterial prophylaxis using imipenem-cilastatin versus acylureide penicillins in pacemaker implantation. A 30-month follow-up]. The authors have evaluated the efficacy of short term treatment with an imipenem-cilastatin combination in a selected group of 72 patients undergoing implant or substitution of a pacemaker and with associated pathology potentially increasing the risk of infection. After 30 months' follow-up, the authors underline the efficacy and advantages of this treatment.


[Odontostomatological changes induced by drugs. I]. The purpose of the present review is to describe the unwanted effects of drugs or chemicals in the orofacial region. The authors take into consideration the alterations of salivation such as xerostomia and ptyalism, disturbances of sense of taste, halitosis and pain and swelling of the salivary glands. The dental surgeon who suspects that an oral alteration might be a drug reaction can play an important role in preventing the development of more severe toxic effects. All this points to the importance of the knowledge of pharmacology for dental practitioners.


On the evolution of language and generativity. One of the properties that most conspicuously distinguishes human language from any other form of animal communication is generativity. Language with this property therefore presumably evolved with the Homo line somewhere between H. habilis and H. sapiens sapiens. Some have suggested that it emerged relatively suddenly and completely with H. sapiens sapiens, and this view is consistent with (a) linguistic estimates as to when vocal language emerged, (b) the relatively late "explosion" of manufacture and cultural artifacts such as body ornamentation and cave drawings, and (c) evidence on changes in the vocal apparatus. However, evidence on brain size and developmental patterns of growth suggests an earlier origin and a more continuous evolution. I propose that these scenarios can be reconciled if it is supposed that generative language evolved, perhaps from H. habilis on, as a system of manual gestures, but switched to a predominantly vocal system with H. sapiens sapiens. The subsequent "cultural explosion" can then be attributed to the freeing of the hands from primary involvement in language, so that they could be exploited, along with generativity, for manufacture, art, and other activities.


Categorical perception of facial expressions. People universally recognize facial expressions of happiness, sadness, fear, anger, disgust, and perhaps, surprise, suggesting a perceptual mechanism tuned to the facial configuration displaying each emotion. Sets of drawings were generated by computer, each consisting of a series of faces differing by constant physical amounts, running from one emotional expression to another (or from one emotional expression to a neutral face). Subjects discriminated pairs of faces, then, in a separate task, categorized the emotion displayed by each. Faces within a category were discriminated more poorly than faces in different categories that differed by an equal physical amount. Thus emotional expressions, like colors and speech sounds, are perceived categorically, not as a direct reflection of their continuous physical properties.


Probing the cognitive representation of musical time: structural constraints on the perception of timing perturbations. To determine whether structural factors interact with the perception of musical time, musically literate listeners were presented repeatedly with eight-bar musical excerpts, realized with physically regular timing on an electronic piano. On each trial, one or two randomly chosen time intervals were lengthened by a small amount, and the score. The resulting detection accuracy profile across all positions in each musical excerpt showed pronounced dips in places where lengthening would typically occur in an expressive (temporally modulated) performance. False alarm percentages indicated that certain tones seemed longer a priori, and these were among the ones whose actual lengthening was easiest to detect. The detection accuracy and false alarm profiles were significantly correlated with each other and with the temporal microstructure of expert performances, as measured from sound recordings by famous artists. Thus the detection task apparently tapped into listeners' musical thought and revealed their expectations about the temporal microstructure of music performance. These expectations, like the timing patterns of actual performances, derive from the cognitive representation of musical structure, as cued by a variety of systemic factors (grouping, meter, harmonic progression) and their acoustic correlates. No simple psycho-acoustic explanation of the detection accuracy profiles was evident. The results suggest that the perception of musical time is not veridical but "warped" by the structural representation. This warping may provide a natural basis for performance evaluation: expected timing patterns sound more or less regular, unexpected ones irregular. Parallels to language performance and perception are noted.


Children's judgments in theory choice tasks: scientific rationality in childhood. The current research examined whether children could use certain metaconceptual criteria such as the range of explanation, non-ad hocness of explanation, empirical consistency, and logical consistency to choose between competing accounts of physical phenomena. The tasks were constructed so that the conceptual content of the explanations to be evaluated was either consistent, inconsistent, or neutral with regard to children's prior knowledge. It was found that even 7-year-olds could use metaconceptual criteria such as the range, empirical consistency, and logical consistency of theories when the theories did not violate their beliefs. However only older children (11-year-olds) showed a systematic preference for non-ad hoc theories over ad hoc ones. The findings are consistent with recent work in the philosophy of science showing that, in evaluating theoretical alternatives, scientists are influenced by their prior beliefs about the domain being considered. This research demonstrates that even young children share some of the cognitive underpinnings of scientific rationality that scientists do.


Lexical access in the production of noun phrases. In order to encode an event or a thought into language, the speaker has to access words from the mental lexicon and order them according to the rules of syntax. The present study taps into these components of language production as they proceed in time. The utterances investigated were Dutch noun phrases with a prenominal adjective (e.g., het groene huis--the green house). The results of two picture--word interference experiments showed interference effects from semantically related noun distractors, extending findings from production of single words to the production of phrases. In addition, the syntactic format of the noun phrase had an influence on the size and the time course of the semantic interference effect. On the basis of the results of these two experiments, a working model of the processes involved in the production of noun phrases is proposed.


The tip-of-the-tongue phenomenon: do experimenter-presented interlopers have any effect? When a person is in a tip-of-the-tongue (TOT) state, they will sometimes recall a word that is similar in sound to the word they are attempting to retrieve. Woodworth (1929) argued that these interloper words both cause and sustain TOT states, whereas Brown and McNeill (1966) suggested that they are part of the process that leads to TOT resolution. Jones and Langford (1987) and Jones (1989) explicitly presented interloper words along with definitions of words that subjects were asked to recall. They reported that interlopers that were phonologically related to the target word increased the incidence of TOTs and concluded that this supported Woodworth's position. In three experiments, we adopted the interloper paradigm, but also included a control group who heard the definitions without interloper words. In Experiment 1, the definitions that Jones used with phonological interlopers created more TOTs even when no interlopers were presented. In Experiments 2a and 2b, we matched definitions for the number of TOTs they produced in the absence of interlopers. Under these circumstances we found no effect of interloper words at all. We conclude that there is no evidence from this paradigm to support the idea that interloper words are involved in either the causation or resolution of TOTs.


What sort of innate structure is needed to "bootstrap" into syntax? The paper starts from Pinker's theory of the acquisition of phrase structure; it shows that it is possible to drop all the assumptions about innate syntactic structure from this theory. These assumptions can be replaced by assumptions about the basic structure of semantic representation available at the outset of language acquisition, without penalizing the acquisition of basic phrase structure rules. Essentially, the role played by X-bar theory in Pinker's model would be played by the (presumably innate) structure of the language of thought in the revised parallel model. Bootstrapping and semantic assimilation theories are shown to be formally very similar, though making different primitive assumptions. In their primitives, semantic assimilation theories have the advantage that they can offer an account of the origin of syntactic categories instead of postulating them as primitive. Ways of improving on the semantic assimilation version of Pinker's theory are considered, including a way of deriving the NP-VP constituent division that appears to have a better fit than Pinker's to evidence on language variation.


Evaluation of C. diff.-CUBE test for detection of Clostridium difficile-associated diarrhea. The toxin B assay was used to evaluate C. diff.-CUBE, a new dot-immunobinding assay (DIA) for the laboratory diagnosis of Clostridium difficile-associated diarrhea. The widely used latex agglutination test was also included for comparison. Stools from 100 patients suspected of having C. difficile-associated diarrhea were tested. The toxin B assay, latex agglutination, and DIA tests were positive for 12%, 9%, and 22% of the specimens, respectively. The sensitivity, specificity, and positive and negative predictive values of the DIA test were 67%, 84%, 36%, and 95%, respectively, compared with the toxin B assay. The specificity (98%) and positive predictive value (78%) for the latex agglutination test were significantly higher than those of the DIA test. Of 13 specimens solely positive by the DIA test, 11 were cultured and none were positive. Clinical assessment supported only two of the 13 positive DIA results. When clinical assessment was included in the analysis, the DIA positive predictive value rose to 45%. Although the sensitivity and negative predictive values of the DIA test are comparable to the latex agglutination test, the low specificity and positive predictive values of the DIA test make it an inappropriate method to use for screening in a population with a low prevalence of true positives.


Comparison of standard and quantitative blood cultures in the evaluation of children with suspected central venous line sepsis. We reviewed our experience with paired quantitative and standard blood cultures in the evaluation of children with suspected central-line sepsis with the hypothesis that by employing both systems we would increase our yield of pathogenic isolates. A total of 913 paired cultures were reviewed, representing 267 pathogenic isolates and 58 individual episodes of sepsis. The isolates were analyzed for recovery rates for each system and by combining both systems. The Isolator system proved to be equal to the BACTEC system for the recovery of all groups of pathogenic isolates. The combined use of both the quantitative and the standard culture systems demonstrated a statistically significant advantage (p less than 0.001) for the recovery of pathogens as compared with either system alone. The use of either system alone would have missed 15% of the total pathogenic isolates. Quantitative colony counts were helpful in identifying the line as the source of infection in 35 to 58 episodes of sepsis and were often beneficial in the clinical management central venous line infection. We recommend the use of the Isolator 1.5 ml combined with a conventional broth-bottle system in selected pediatric patients to enhance the recovery of pathogenic organisms.


Evaluation of three different STb assays and comparison of enterotoxin pattern over a five-year period in Swedish porcine Escherichia coli. The pig intestinal loop (PIL) assay, inhibition enzyme-linked immunosorbent assay (ELISA), and DNA hybridization assay were compared for analysis of Escherichia coli heat-stable enterotoxin b (STb) on 201 porcine E. coli strains. The DNA hybridization had a 95% correlation with the STb ELISA and was therefore chosen as the method for subsequent screening of enterotoxin genes: heat labile (LT), heat-stable a (STa), and/or STb. In contrast to the PIL assay, both the STb ELISA and DNA hybridization assays were more sensitive, reliable, reproducible, and showed good correlation with each other. Consequently, the STb ELISA is preferable for analysis of toxin preparations and screening of E. coli, whereas the DNA hybridization is better for large-scale epidemiologic screening. Escherichia coli strains (n = 437) associated with porcine diarrhea isolated in Sweden during 1989 were investigated. Of the strains, 135 (31%) were positive for at least one of these toxins and, therefore, designated enterotoxigenic E. coli (ETEC). Our results were compared with the enterotoxin pattern found in earlier studies of Swedish porcine strains. The only change in occurrence of toxins was found in strains isolated from piglets less than 1 week of age. LT- and STb-producing ETEC had decreased, and STa-producing ETEC had increased in prevalence. The occurrence of STb among ETEC of weaned pigs was 93%. This toxin was also found to be more common than STa when strains from all age groups were considered.