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E Thom

Publications and source records attributed to E Thom.

At least 37 records · Page 2Linked to original sources

Characterization of a novel eukaryotic ATP/ADP translocator located in the plastid envelope of Arabidopsis thaliana L.

Recently, we have sequenced a cDNA clone from Arabidopsis thaliana L. encoding a novel putative ATP/ADP translocator (AATP1). Here, we demonstrate that the radioactively labeled AATP1 precursor protein, synthesized in vitro, is targeted to envelope membranes of isolated spinach chloroplasts. Antibodies raised against a synthetic peptide of AATP1 recognized a single polypeptide of about 62 kDa in chloroplast inner envelope preparations. The cDNA coding for the AATP1 protein was functionally expressed in Saccharomyces cerevisiae and Escherichia coli. In both expression systems, increased rates of ATP transport were observed after reconstitution of the extracted protein into proteoliposomes. To our knowledge, this is the first report on the functional expression of an intrinsic plant membrane protein in E. coli. To yield high rates of ATP transport, proteoliposomes had to be preloaded with ADP, indicating a counter-exchange mode of transport. Carboxyatractyloside did not substantially interfere with ATP transport into proteoliposomes containing the plastidic ATP/ADP translocator. An apparent KM for ATP of 28 microM was determined which is similar to values reported for isolated plastids. The data presented here strongly support the conclusion that AATP1 represents a novel eukaryotic adenylate carrier and that it is identical with the so far unknown plastidic ATP/ADP translocator.

Adenosine Triphosphate↗

The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network.

BACKGROUND: The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation. METHODS: At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery. RESULTS: We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th percentile; P = 0.008 for values at or below the 75th percentile). For the lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52, 5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th percentile; P = 0.003 for values at the 75th percentile). CONCLUSIONS: The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.

Cervix Uteri↗

The preterm prediction study: fetal fibronectin, bacterial vaginosis, and peripartum infection. NICHD Maternal Fetal Medicine Units Network.

OBJECTIVE: To determine the relation between vaginal and upper genital tract infection and cervical-vaginal fetal fibronectin levels. METHODS: We screened 2899 women at ten centers every 2 weeks from 23-24 to 30 weeks' gestation for cervical and vaginal fetal fibronectin. A positive test was defined as a level of at least 50 ng/mL. The relation between a positive test and bacterial vaginosis at 23-24 weeks and clinical or histologic chorioamnionitis at delivery plus neonatal sepsis was determined. RESULTS: Fetal fibronectin was present in 4.0% of cervical and/or vaginal samples at 23-24 weeks and was nearly twice as common in women with bacterial vaginosis. Adjusting for the presence of bacterial vaginosis, race, and parity, women positive for fetal fibronectin were much more likely to have clinical chorioamnionitis (mean +/- standard deviation gestational age 30.6 +/- 4.1 weeks), with an odds ratio of 16.4 and 95% confidence interval of 7.1-37.8, and neonatal sepsis (6.3 and 2.0-20.0, respectively), than those who were fetal fibronectin-negative. A positive cervical fetal fibronectin test was a better predictor of clinical chorioamnionitis and neonatal sepsis than was a vaginal test or a combination of vaginal and cervical tests. Among 40 women who delivered before 32 weeks and had placental histology available for evaluation, ten had a positive cervical and/or vaginal fetal fibronectin test before delivery; all ten had histologic evidence of chorioamnionitis, compared with only 13 of 30 women (43%) who were fetal fibronectin-negative (P = .02). CONCLUSION: Women with bacterial vaginosis were more likely to have a positive fetal fibronectin test than uninfected women. Women with a positive fetal fibronectin test who delivered before 32 weeks' gestation all had evidence of histologic chorioamnionitis. Women positive for fetal fibronectin also had a 16-fold increase in clinical chorioamnionitis and a sixfold increase in neonatal sepsis. There is strong evidence that upper genital tract infection and cervical and/or vaginal fetal fibronectin are closely linked.

Adult↗

The preterm prediction study: a clinical risk assessment system.

OBJECTIVE: Our aims were to develop a risk assessment system for the prediction of spontaneous preterm delivery using clinical information available at 23 to 24 weeks' gestation and to determine the predictive value of such a system. STUDY DESIGN: A total of 2929 women were evaluated between 23 and 24 weeks' gestation at 10 centers. Demographic factors, socioeconomic status, home and work environment, drug and alcohol use, and medical history were evaluated. Information regarding symptoms, cultures, and treatments in the current pregnancy were ascertained. Anthropomorphic and cervical examinations were performed. Univariate analysis and multivariate logistic regression were performed in a random selection, constituting 85% of the study population. The derived risk assessment system was applied to the remaining 15% of the population to evaluate its validity. RESULTS: A total of 10.4% of women were delivered of preterm infants. The multivariate models for spontaneous preterm delivery were highly associated with spontaneous preterm delivery (p < 0.0001). A low body mass index (<19.8) and increasing Bishop scores were significantly associated with spontaneous preterm delivery in nulliparous and multiparous women. Black race, poor social environment, and work during pregnancy were associated with increased risk for nulliparous women. Prior obstetric outcome overshadowed socioeconomic risk factors in multiparous women with a twofold increase in the odds of spontaneous preterm delivery for each prior spontaneous preterm delivery. Current pregnancy symptoms, including vaginal bleeding, symptomatic contractions within 2 weeks, and acute or chronic lung disease were variably associated with spontaneous preterm delivery in nulliparous and multiparous women. When the system was applied to the remainder of the population, women defined to be at high risk for spontaneous preterm delivery (> or = 20% risk) carried a 3.8-fold (nulliparous women) and 3.3-fold (multiparous women) higher risk of spontaneous preterm delivery than those predicted to be at low risk. However, the risk assessment system identified a minority of women who had spontaneous preterm deliveries. The sensitivities were 24.2% and 18.2% and positive predictive values were 28.6% and 33.3%, respectively, for nulliparous and multiparous women. CONCLUSIONS: Although it is possible to develop a graded risk assessment system that includes factors that are highly associated with spontaneous preterm delivery in nulliparous and multiparous women, such a system does not identify most women who subsequently have a spontaneous preterm delivery. This system has investigational value as the basis for evaluating new technologies designed to identify at-risk subpopulations.

Black People↗

Low-dose aspirin in nulliparous women: safety of continuous epidural block and correlation between bleeding time and maternal-neonatal bleeding complications. National Institute of Child Health and Human Developmental Maternal-Fetal Medicine Network.

OBJECTIVE: Our purpose was to determine the frequency and safety of the use of epidural anesthesia and the correlation between bleeding time and maternal-neonatal bleeding complications in a group of pregnant women who participated in a multicenter trial of low-dose aspirin in pregnancy. STUDY DESIGN: Data regarding type of anesthesia used for labor and delivery were available in 1629 nulliparous women who were randomly assigned at 13 to 27 weeks to receive 60 mg/day aspirin or a placebo. A total of 891 (55%) received epidural anesthesia, and the remaining 738 did not. RESULTS: Among the 891 women known to have received epidural anesthesia, 451 were assigned to low-dose aspirin and 440 to placebo. There was no instance of bleeding related to epidural use. In addition, there were no differences in maternal and neonatal complications between those receiving or not receiving epidural anesthesia. Within the group receiving epidural anesthesia there were no differences in bleeding complications between those assigned to aspirin on placebo. One of the five centers also obtained bleeding times in 303 women (149 received aspirin and 154 received placebo). The mean +/- SD bleeding time in women assigned to low-dose aspirin was significantly higher than in women assigned to placebo (6.99 +/- 2.95 minutes vs 5.99 +/- 2.43 minutes, p = 0.004). In addition, the frequency of women having a bleeding time > 10 minutes was higher in the aspirin group (14.1% vs 5.2%, p = 0.01). Interestingly, women who received an epidural anesthetic had a lower bleeding time than those not receiving an epidural (p = 0.003), irrespective of the treatment used. CONCLUSIONS: In women assigned to low-dose aspirin there were no adverse effects related to epidural anesthesia. In spite of an increased bleeding time in a subset of pregnant women assigned to low-dose aspirin, maternal-neonatal bleeding complications were not increased.

Analysis of Variance↗

Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVE: We conducted a large clinical trial to evaluate the effect of low-dose aspirin on the frequency of preeclampsia in nulliparous women. A secondary objective of the trial was to identify those clinical characteristics that might be predictive for the development of preeclampsia. STUDY DESIGN: A total of 2947 healthy women with a single fetus were prospectively followed up from randomization at 13 to 27 weeks' gestation to the end of pregnancy. Of these, 1465 women were assigned to low-dose aspirin and 1482 to placebo. Baseline maternal blood pressure and demographic characteristics were examined for the prediction of preeclampsia. RESULTS: Preeclampsia developed in 156 women (5.3%). Four characteristics predicted the development of preeclampsia: in order of importance, systolic blood pressure at entry, prepregnancy obesity (weight as a percentage of desirable weight), number of previous abortions or miscarriages, and smoking history. Contrary to previous reports, black race was not a risk factor for preeclampsia. Systolic blood pressure was a better predictor of preeclampsia than either diastolic or mean arterial blood pressure. The greater the blood pressure or prepregnancy weight, the greater was the risk for preeclampsia. If the woman had never smoked or had never been previously pregnant, her risk was also higher than average. A multivariate logistic regression equation based on these four factors was able to define a tenth of the population at very high risk and another tenth at very low risk; the ratio of risk between these two groups was 12:1. The p value for each of the multivariate coefficients of the risk equation was systolic blood pressure (p < 0.001), prepregnancy weight (p < 0.01), smoking history (p < 0.01), and gravidity (p < 0.05). There were no statistically significant differences in the predictive values of these risk factors between women receiving low-dose aspirin or placebo. CONCLUSIONS: These risk factors should be of value to practitioners counseling women regarding preeclampsia. Moreover, such risk factors should be considered in the design of future studies dealing with preeclampsia.

Abortion, Induced↗

The preterm prediction study: significance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to evaluate the association of bacterial vaginosis, trichomonas vaginitis, and monilial vaginitis with spontaneous preterm birth at < 35 weeks 0 days. STUDY DESIGN: A total of 2929 women at 10 centers were studied at 24 and 28 weeks' gestation by Gram stain of vaginal smear, wet mount, and 10% potassium hydroxide preparations to detect vaginal infections. RESULTS: The rates of detected infection at 24 and 28 weeks, respectively, were bacterial vaginosis 23.4% and 19.4%, trichomonas 3.3% and 2.7%, and monilia 21.1% and 19.5%. The occurrence of bacterial vaginosis at 28 weeks was associated with an increased risk of spontaneous preterm birth, odds ratio 1.84 (95% confidence interval 1.15 to 2.95, p < 0.01). Detection of Trichomonas vaginalis (by wet mount) or monilia (by potassium hydroxide preparation) had no significant associations with preterm birth. CONCLUSION: The presence of bacterial vaginosis at 28 weeks' gestation is associated with an increased risk of spontaneous preterm birth.

Adult↗

Risk factors for the development of preterm premature rupture of the membranes after arrest of preterm labor.

OBJECTIVE: Our purpose was to determine risk factors predictive of preterm premature rupture of the membranes in women treated for preterm labor with intact membranes. STUDY DESIGN: Women with intact membranes participating in a National Institute of Child Health and Human Development multicenter randomized trial of adjunctive antibiotic therapy for preterm labor (24 to 34 weeks) were studied (n = 275). After randomization, 22 women continued to have contractions and were delivered of their infants. The remaining 253 women whose contractions had ceased composed our study population. Preterm premature rupture of the membranes was diagnosed if ruptured membranes occurred > or = 1 hour before the onset of recurrent preterm labor. As part of the study protocol, most women underwent amniocentesis on admission. RESULTS: Preterm premature rupture of the membranes developed in 44% women (17.4%). Women who had preterm premature rupture of the membranes were more likely to be black (p = 0.004), to be multiparous (p = 0.014), to have a history of abortion(s) (p = 0.001), to have had a preterm birth(s) (p = 0.036), to have early onset preterm labor (p = 0.04), to have more advanced cervical dilatation (p = 0.0001), to have one or more amniotic fluid markers suggestive of infection (p = 0.01, odds ratio 4.2), and to have positive amniotic fluid cultures (p = 0.0007, odds ratio 27). Assignment to antibiotic therapy did not prevent preterm premature rupture of the membranes in the 253 women randomized or in the 16 women with a positive amniotic fluid marker(s) of infection. CONCLUSION: Black race, multiparity, a history of abortion or preterm birth, advanced dilatation, and a positive amniotic fluid marker(s) are associated with preterm premature rupture of the membranes in women with preterm labor. Antibiotic treatment did not prevent preterm premature rupture of the membranes.

Abortion, Spontaneous↗

Body fat as a predictor of the antihypertensive effect of nifedipine.

OBJECTIVE: The aim of this study was to investigate the relationship between the blood pressure response and body fat in patients treated with the calcium entry blocker nifedipine. SUBJECTS: Forty untreated subjects with moderate hypertension completed the study. INTERVENTIONS: Height, weight, body mass index (BMI) and body fat (measured by near infrared spectrophotometry using Futrex 5000) were measured before the start of the study. Based on blood pressure measurements before and 30 min after one capsule of 10 mg nifedipine, the patients were allocated to treatment with 10 mg nifedipine daily in the responder group (reduction in diastolic blood pressure > or = 10 mmHg) and with 20 mg nifedipine daily in the non-responder group. Finally, the blood pressure was measured after 1 week. RESULTS: Twelve patients were classified as responders and 28 patients as non-responders. The responder/non-responder groups were comparable with respect to the blood pressure readings initially and to age, whereas the non-responders had higher weight (P < 0.01) and BMI (P < 0.01), more body fat (P < 0.01) and were smaller in height (P < 0.01). After 1 week no additional antihypertensive effect was observed in either group. The blood pressure reduction was negatively correlated to the body fat mass in kilogrammes (P < 0.05 for systolic and P < 0.01 for diastolic blood pressure) in the responder group but not in the non-responder group, whereas no significant correlations were found to BMI in either group. CONCLUSION: Our data indicate that the body fat can be used to predict the antihypertensive effect of nifedipine.

Adipose Tissue↗

Purification of highly intact plastids from various heterotrophic plant tissues: analysis of enzymic equipment and precursor dependency for starch biosynthesis.

Starting with a protocol originally developed for the purification of intact plastids from cauliflower buds [Journet and Douce (1985) Plant Physiol. 79, 458-467] we have modified this method to obtain intact heterotrophic plastids from etiolated barley leaves (Hordeum vulgare) and pea (Pisum sativum) and maize (Zea mays) endosperm. Two subsequent centrifugation steps on Percoll gradients were performed, the first as an isopycnic, the second as zonal, centrifugation step in a swing-out rotor. Percoll density and centrifugation time were adjusted for the various tissues. The obtained plastid preparations are characterized by a low degree of contamination with other cellular components and an intactness of at least 90%. In isolated maize endosperm amyloplasts, starch synthesis is driven by exogenously applied hexose phosphates (glucose 6-phosphate and glucose 1-phosphate) rather than by dihydroxyacetone phosphate. The hexose-phosphate-dependent starch synthesis is strictly dependent upon the intactness of the plastids and is increased up to 9-fold when ATP and 3-phosphoglyceric acid are added to the incubation medium. The occurrence of fructose-1,6-bisphosphatase and malate dehydrogenases in some plastid types is discussed in relation to their possible role in starch synthesis.

Brassica↗

Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

BACKGROUND: Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication, its efficacy and safety in healthy, nulliparous pregnant women are not known. METHODS: We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia. Of this group, 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies. We also evaluated the effect of aspirin on maternal and neonatal morbidity. RESULTS: Of the original group of 3135 women, 2985 (95 percent) were followed throughout pregnancy and the immediate puerperium. The incidence of preeclampsia was lower in the aspirin group (69 of 1485 women [4.6 percent]) than in the placebo group (94 of 1500 women [6.3 percent]) (relative risk, 0.7; 95 percent confidence interval, 0.6 to 1.0; P = 0.05), whereas the incidence of gestational hypertension was 6.7 and 5.9 percent, respectively. There were no significant differences in the infants' birth weight or in the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between the two groups. Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg (incidence among such women, 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group; P = 0.01). The incidence of abruptio placentae was greater among the women who received aspirin (11 women, vs. 2 in the placebo group; P = 0.01). CONCLUSIONS: Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women, primarily through its effect in those who have elevated systolic blood pressure initially. This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae.

Abruptio Placentae↗

Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.

OBJECTIVE: Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos. RESULTS: Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization. CONCLUSION: The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.

Administration, Oral↗

Synthesis and biodistribution of 18F-labeled fleroxacin.

[18F]Fleroxacin (6,8-difluoro-1,4-dihydro-1-(2-[18F]fluoroethyl)-4- oxo-7-(4-methyl-1-piperazinyl)-3-quinolinecarboxylic acid) was synthesized from its methylsulfonyl ester precursor. 6,7,8-Trifluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester (Ro 19-7423) was alkylated with 2-bromoethanol to produce 6,7,8-trifluoro-1,4-dihydro-1-(2-hydroxyethyl)-4-oxo-3-quinolinecarboxyl ic acid ethyl ester in 76% yield which was then condensed with 1-methyl-piperazine to produce 6,8-difluoro-1,4-dihydro-1-(2-hydroxyethyl)-7-(4-methyl-1-piperazinyl)4- oxo-3- quinolinecarboxylic acid ethyl ester in 67% yield. This product was reacted with methanesulfonyl chloride to produce the mesylate precursor of fleroxacin in 66% yield. Nucleophilic substitution of the mesylate with 18F- in the presence of Kryptofix 2.2.2 followed by basic hydrolysis produced [18F]fleroxacin with a radiochemical yield of 5-8% [EOS] within 90 min. The pattern of biodistribution of [18F]fleroxacin was similar to the 14C-labeled drug.

Animals↗

Blinking, alpha brain waves and smoking in schizophrenia.

Blink rates (BR) and alpha brain waves were studied in 13 schizophrenic and 13 healthy smokers under conditions of smoking deprivation as well as smoking saturation and under different task conditions of smooth pursuit eye movements. Task conditions significantly changed BR and alpha power; smoking enhanced BR and alpha frequency, the latter effect being especially pronounced in schizophrenics for F3-F4 leadings. Concerning BR, groups differed significantly as long as smoking quantity was not statistically controlled. BR, alpha power and smoking quantity were consistently correlated above chance levels. Results are discussed with respect to the blink alpha neurocircuit model.

Adult↗

Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography.

Positron emission tomography (PET) with [18F]fleroxacin was used to study the pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.

Adult↗

Reduction of body mass and change in body composition on a very low calorie diet.

The quality of weight loss was estimated during a very low calorie diet (VLCD) weight-reducing regime by determining the body composition every second week using near-infra-red interactance (NII). The study was performed on 127 overweight volunteers, aged 18-72 years, who, for eight consecutive weeks, used a VLCD to lose weight. Mean weight reduction was 12.7 kg (12.6% of initial weight). Mean body fat (BF) loss was 9.5 kg (23.8% of initial BF), which constitutes 75% of the weight loss. Mean reduction in lean body mass (LBM) was 3.2 kg (5.2% of initial LBM). We found no correlation between initial body mass index (BMI) and loss of LBM, or between initial body composition and weight loss. Weight reduction observed in this study is mainly due to reduction in body fat, and the loss of LBM is considered not to be larger than acceptable.

Adolescent↗

[The effect of moderate physical exercise in the treatment of overweight. Quantitative and qualitative evaluation of weight loss by weighing and body composition measurements].

The present study includes 413 persons with overweight or obesity problems, with Body Mass Index (BMI) ranging from 26.7 to 40.2 kg/m2, who participated in a seven weeks weight reduction programme. All persons were given the opportunity either to follow a low-fat diet (1,200 kcal/d) alone or a low-fat diet combined with an exercise programme (1/2 hour walk every day). 240 persons decided to follow the full programme (diet and exercise) (group I), while 173 persons only dieted (group II). The results indicate that a combination of diet and modest exercise is superior to dieting alone when trying to achieve a reduction in weight where the major part of the weight loss is due to reduction of the fat deposits. Whether this will have an essential influence on the long-term results of different weight reduction programmes needs to be investigated in more detail.

Adult↗

Pharmacokinetics of 18F-labeled fleroxacin in rabbits with Escherichia coli infections, studied with positron emission tomography.

18F-labeled fleroxacin was used to measure the pharmacokinetics of fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g). Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system.

Animals↗