Development, evaluation and validation of machine learning algorithms to detect atypical and asymptomatic presentations of Covid-19 in hospital practice.

BACKGROUND: Diagnostic methods for Covid-19 have improved, both in speed and availability. Because of atypical and asymptomatic carriage of the virus and nosocomial spread within institutions, timely diagnosis remains a challenge. Machine learning models trained on blood test results have shown promise in identifying cases of Covid-19. AIMS: To train and validate a machine learning model capable of differentiating Covid-19 positive from negative patients using routine blood tests and assess the model's accuracy against atypical and asymptomatic presentations. DESIGN AND METHODS: We conducted a retrospective analysis of medical admissions to our institution during March and April 2020. Participants were categorized into Covid-19 positive or negative groups based on clinical, radiological features or nasopharyngeal swab. A machine learning model was trained on laboratory parameters and validated for accuracy, sensitivity and specificity and externally validated at an unconnected establishment. RESULTS: An Ensemble Bagged Tree model was trained on data collected from 405 patients (212 Covid-19 positive) producing an accuracy of 81.79% (95% confidence interval (CI) 77.53-85.55%), the sensitivity of 85.85% (CI 80.42-90.24%) and specificity of 76.65% (CI 69.49-82.84%). Accuracy was preserved for atypical and asymptomatic subgroups. Using an external data set for 226 patients (141 Covid-19 positive) accuracy of 76.82% (CI 70.87-82.08%), sensitivity of 78.38% (CI 70.87-84.72%) and specificity of 74.12% (CI 63.48-83.01%) was achieved. CONCLUSION: A machine learning model using routine laboratory parameters can detect atypical and asymptomatic presentations of Covid-19 and might be an adjunct to existing screening measures.

Pharmacokinetics of ceftazidime administered to lactating and non-lactating goats.

The aim of this work was to determine the pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) ceftazidime administered to lactating (LTG; n=6) and non-lactating (NLTG; n=6) healthy Creole goats in 2 trials (T1 and T2). During T1 and T2, goats randomly received a single dose of i.m. or i.v. ceftazidime (10 mg/kg). Serum concentration of iv ceftazidime in NLTG and LTG goats is best described by 2 and 3 compartment models, respectively. The pharmacokinetic parameters of iv and im ceftazidime administered to LTG and NLTG showed statistically significant differences (P < 0.05) in the constants (lamda(z), T1 vs. T2 [i.v.] 0.5 +/- 0.1 vs. 0.3 +/- 0.1/h; T1 vs. T2 [i.m.] 0.5 +/- 0.2 vs. 0.3 +/- 0.1/h) and in the mean times (t(1/2), T1 vs. T2 [i.v.] 1.6 +/- 0.3 vs. 2.3 +/- 0.6 h; T1 vs. T2 [i.m.] 1.6 +/- 0.7 vs. 2.6 +/- 0.9 h) of elimination. The bioavailability of ceftazidime in LTG and NLTG was 113.0 +/- 17.8 and 96.0 +/- 18.0%, respectively. Ceftazidime concentration in milk at 2 h was: i.v. = 1.9 +/- 0.2 and i.m. = 2.4 +/- 0.5 microg/ml; the penetration in milk was i.v. = 18.3 +/- 13.5 and im = 14.3 +/- 10.6%. Ninety-six hours after i.v. and i.m. administration, residues of the drug were not found in milk. In conclusion, ceftazidime, when administered to goats, showed high concentration times in serum, good penetration into milk and a bioavailability that makes it suitable to be used by the i.m. route.

Unión de los antibióticos tilosina, tilmicosina y oxitetraciclina a proteínas presentes en abejas, larvas y productos de la colmena de Apis mellifera L / Binding of tylosin, tilmicosin and oxytetracycline to proteins from honeybees, larvae and beehive products

Las abejas melíferas son afectadas por gran cantidad de enfermedades infecciosas principalmente producidas por bacterias, hongos, virus y parásitos eucariotas. Dentro de las ocasionadas por procariotas, la loque americana es una enfermedad extremadamente grave que afecta a larvas y pupas de abejas; su agente causal es la bacteria esporulada Paenibacillus larvae. La administración de antibióticos es la principal alternativa para el control de esta enfermedad en colmenares con altos niveles de infección. El objetivo del presente trabajo fue determinar, mediante un método biológico, la unión de los antibióticos tilosina, tilmicosina y oxitetraciclina a las proteínas presentes en abejas adultas, larvas menores de 72 horas, larvas mayores de 72 horas, jalea de obreras, miel y polen, con la finalidad de diseñar un modelo de ruta cinética de los antibióticos. Los límites de sensibilidad de la técnica de valoración de estos antibióticos fueron 0,05 μg/ml para tilosina y tilmicosina, y 0,01 μg/ml para oxitetraciclina. Los coeficientes de correlación fueron superiores a 0,90 y los coeficientes de variación intra e inter-ensayo inferiores al 5%. Tanto tilosina como oxitetraciclina presentaron un porcentaje de unión a proteínas de un 15% en promedio en tejidos y subproductos de la colmena, lo cual resultó inferior a lo observado con tilmicosina (29% en promedio). En conclusión, por sus características químicas, su actividad antimicrobiana y su baja tasa de unión a las abejas, larvas y subproductos de la colmena, la tilosina presenta propiedades farmacocinéticas que podrían representar una ventaja terapéutica para el tratamiento de la loque americana en colmenas.

American Foulbrood (AFB) caused by the spore-forming bacterium Paenibacillus larvae is the most serious disease of bacterial origin affecting larvae and pupae of honeybees. Antibiotics are used in many countries for the control of AFB in high incidence areas, but their misuse may lead to antibiotic resistance of bacterial strains and honey contamination. The objective of the present work was to determine, through a biological method, the protein binding of tylosin, tilmicosin and oxytetracycline to worker jelly; honey; pollen; adult bees and larvae in order to propose their kinetic routes. The sensitivity limit of the technique used was 0.05 μg/ml for tylosin and tilmicosin and 0.01 μg/ml for oxytetracycline, respectively. The method had intra and inter-assay correlation coefficients over 0.90, respectively and a coefficient variation of intra-and inter-assay for all antibiotics and processed samples under 5%. Tylosin and oxytetracycline presented lower percentages of protein binding in tissues and hive products (average 15%) in relation to those observed for tilmicosin (29%). In conclusion, tylosin is useful for AFB control in honey bee colonies due to its chemical characteristics, antimicrobial activity and levels of protein binding in bees, larvae, and beehive products.

[Binding of tylosin, tilmicosin and oxytetracycline to proteins from honeybees, larvae and beehive products]. / Unión de los antibióticos tilosina, tilmicosina y oxitetraciclina a proteínas presentes en abejas, larvas y productos de la colmena de Apis mellifera L.

American Foulbrood (AFB) caused by the spore-forming bacterium Paenibacillus larvae is the most serious disease of bacterial origin affecting larvae and pupae of honeybees. Antibiotics are used in many countries for the control of AFB in high incidence areas, but their misuse may lead to antibiotic resistance of bacterial strains and honey contamination. The objective of the present work was to determine, through a biological method, the protein binding of tylosin, tilmicosin and oxytetracycline to worker jelly; honey; pollen; adult bees and larvae in order to propose their kinetic routes. The sensitivity limit of the technique used was 0.05 µg/ml for tylosin and tilmicosin and 0.01 µg/ml for oxytetracycline, respectively. The method had intra and inter-assay correlation coefficients over 0.90, respectively and a coefficient variation of intra-and inter-assay for all antibiotics and processed samples under 5%. Tylosin and oxytetracycline presented lower percentages of protein binding in tissues and hive products (average 15%) in relation to those observed for tilmicosin (29%). In conclusion, tylosin is useful for AFB control in honey bee colonies due to its chemical characteristics, antimicrobial activity and levels of protein binding in bees, larvae, and beehive products.

Pharmacokinetics of trifluralin in blood and heart tissue of mice.

BACKGROUND: Trifluralin displays anti-Trypanosoma cruzi activity and a potential therapeutic effect for the treatment of Chagas disease. We assessed peroral and intramuscular trifluralin pharmacokinetics in mouse blood and heart tissue. METHODS: A parallel experimental design was used. Healthy adult male CF1 albino mice (n = 108, 25-35 g bw) received a single peroral or intramuscular trifluralin dose (50 mg/kg in peanut oil). Blood and heart tissue samples were taken at set times after intramuscular and peroral trifluralin administration. Feces and tissue samples were taken 12 h after intramuscular trifluralin administration. Trifluralin concentrations in whole blood, feces and tissues were determined by HPLC. RESULTS: After intramuscular and peroral administration, maximum whole blood concentration (C(max)) was attained at 30 min and 2.0 h (t(max)) (28.2 +/- 0.7 and 7.8 +/- 0.033 microg/ml; p < 0.05). C(max) in heart tissue was attained at 1.0 and 2.0 h (0.6 +/- 0.004 and 0.2 +/- 0.002 microg/g; p < 0.05). Liver, perirenal and subcutaneous fat concentrations were 55.1, 66.3 and 59.7 ng/mg tissue protein. Peroral and intramuscular penetration ratios determined by comparing heart tissue areas under the curve were 6.3 and 4.0%, respectively. CONCLUSION: Intramuscular trifluralin could be a new alternative for the treatment of Chagas disease.

Phosphorus removal from municipal wastewater by hydrous ferric oxide reactive filtration and coupled chemically enhanced secondary treatment: part I--performance.

This work examines the performance of a hydrous ferric oxide (HFO) reactive filtration (RF) process with coupled chemically enhanced secondary treatment (RECYCLE) for phosphorus removal from municipal wastewater (HFO-RF-RECYCLE). A 3-month, 0.95-ML/d (0.25-mgd) demonstration of HFO-RF-RECYCLE was performed at a municipal wastewater treatment plant equipped with oxidation ditches and secondary clarifiers. Influent to the plant averaged 6.0 mg/L phosphorus, with a tertiary effluent average of 0.011 mg/L phosphorus. Iron doses to the plant were low, at 5 mg/L. Inline recycling of HFO solution rejects to the plant influent resulted in a maximum 90.3%, dose-dependent reduction of phosphorus in the secondary effluent at 4.5 ML/d (1.2 mgd). Other results included reduction of total suspended solids and turbidity. A mass balance analysis was performed. We conclude that HFO-RF-RECYCLE may allow very low levels of phosphorus discharge from municipal wastewater treatment plants with a ferric-iron-based tertiary filtration process and residual recycling.

Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.

OBJECTIVES: After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. METHODS: Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain. RESULTS: In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (P<0.005) and at nine months outside the motor cortex of probable/definite patients (P<0.005). However, there was no clear pattern of progressive change over time. CONCLUSIONS: NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.

Evaluation of cefepime kinetic variables and milk production volume in goats

Avaliaram-se as variáveis cinéticas da cefepime e a produção de leite de cabras após a administração parenteral (intravenosa e intramuscular) de cefepime, com e sem reação inflamatória na região implantada. Dez cabras em lactação, implantadas com caixas de material sem reação imunológica para colher o fluido de tecido (FT) foram usadas em dois experimentos. No primeiro a aplicação de cefepime foi feita na primeira semana após a implantação e no segundo na oitava semana. Na primeira semana após a implantação observou-se elevação dos níveis de proteína no fluido do tecido após uma simples dose de 20mg/kg de cefepime via endovenosa ou intramuscular. Amostras do sangue e do leite foram obtidas e as variáveis cinéticas foram avaliadas.

Effect of physical activity on the pharmacokinetics of ceftazidime in mice.

BACKGROUND: The aim of the present work was to assess comparatively the pharmacokinetic profile of ceftazidime (CAZ) in trained and non-trained mice. METHODS: The study was performed on 256 mice divided at random into four groups: long-term physically trained mice with (E1a) and without (E1b) physical activity prior to the administration of CAZ, and untrained mice with (E2a) and without (E2b) physical activity prior to the administration of the antibiotic. CAZ was administered intramuscularly (25 mg/kg) to all mice, and blood samples were obtained at different time points. The plasma concentrations of CAZ were determined by HPLC and analyzed by non-compartmental models. RESULTS: The area under the curves in groups E1a and E2a (27.3 and 22.9 microg x ml(-1) x h, respectively) were different compared to the other groups [(E1b) = 11.1 and (E2b) = 15.6 microg x ml(-1) x h; p < 0.05]. Differences were observed between the concentration-time of CAZ in E1a compared to E1b, E1a versus E2a, E1a versus E2b, E1b versus E2a and E1b versus E2b (p < 0.05). CONCLUSION: Physical activity performed prior to CAZ administration modified the pharmacokinetic profile of the drug administered to mice.

Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI.

OBJECTIVE: To determine 1) the reproducibility of metabolite measurements by (1)H MRS in the motor cortex; 2) the extent to which (1)H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS. METHODS: Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice (1)H MRSI. (1)H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain. RESULTS: The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS. CONCLUSION: Metabolite changes measured by (1)H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.

Pharmacokinetics and residues in milk of oxytetracyclines administered parenterally to dairy goats.

OBJECTIVE: To determine for two commercial preparations of oxytetracycline (OTC) the pharmacokinetic behaviour, the presence of detectable milk residues and the penetration in milk of OTC administered by intravenous (IV) (conventional formulation [CF]) and intramuscular (IM) routes (CF and long-acting [LA] formulations) in goats producing milk. The effects of these formulations on plasma activity values of creatine kinase (CK) and lactate dehydrogenase (LDH) were also determined as indicators of tissue damage. PROCEDURE: Five healthy lactating goats producing 1.5+/-0.5 L/d milk and weighing 56.0+/-4.8 kg were used. Single doses of OTC chlorhydrate (CF) were administered (20 mg OTC/kg) by IV (Trial 1 IV) and IM (Trial 1 IM) routes and OTC dehydrate (LA) by the IM route. The same goats were first given IV CF, then IM CF followed by IM LA with 3 weeks between each treatment. Blood and milk samples were taken. The quantification of OTC was performed by HPLC and the plasma activities of CK and LDH enzymes were determined by spectrophotometry. The presence of OTC residues in milk was determined by a commercial reagent. The plasma pharmacokinetic parameters were calculated using a two-compartment model. RESULTS: Estimates of kinetic variables following IV administration were: Vss= 400.0+/-120.0 mL/kg and CL= 110.0+/-14.0 (mL/h)/kg. The t(fi) for IV= 3.0+/-0.3 h; IM, CF = 10.5+/-2.1 h and IM, LA = 15.1+/-3.1 h. The concentration of OTC in milk at 48 h was: IV= 0.6+/-0.4; IM CF= 1.1+/-0.2 and at 72 h (IM LA)= 0.6+/-0.1 microg/mL and the penetration in milk of OTC was: IV= 70.0+/-18.0; IM CF= 79.0+/-14.0 and IM LA= 66.0+/-6.0%. The areas under the curve of CK and LDH activities in plasma were calculated by the trapezoidal method. Values of CK and LDH IM, LA were greater (P < 0.05) than those observed for IM, CF at 2 and 3 days after administration of the antibiotic. Finally, the bioavailability of OTC CF = 92.0+/-22.0 and LA= 78.0+/-23.0% was suitable for its usage by the IM route in lactating goats. CONCLUSION: Plasma concentration-time values of OTC administered parenterally in production dairy goats showed similar bioavailability for the two pharmaceutical preaprations. The presence of detectable residues in milk indicates that milk should not be used for human consumption for 2 and 3 days after administration of conventional and long-acting formulations, respectively. The increments in CK and LDH activities after the IM administration of LA are consistent with the presence of tissue damage provoked by the pharmaceutical preparations at the injection site.

Pharmacokinetics and penetration into tissue fluid of ceftizoxime in normal and hyperthermic sheep.

The pharmacokinetics of ceftizoxime was studied in six sheep before and after inducing hyperthermia using Escherichia coli endotoxin. Sheep implanted subcutaneously with cages of non-reactive material for collecting tissue cage fluid (TCF) were used to conduct two trials. In Trial 1 animals with normal basal temperature (normal sheep (NS)) were given intravenous (i.v.) and intramuscular (i.m.) monodoses of ceftizoxime (20mg/kg BW) at 1 week interval. One and 5 weeks later (Trial 2) each sheep were injected 1µg/kg BW of endotoxin to produce hyperthermia (hyperthermic sheep (HS)) previously to i.v. administration (HSi.v.) and i.m. (HSi.m.) of ceftizoxime (20mg/kg BW), respectively. Serum and TCF samples were collected over 6h post-administration. Ceftizoxime concentrations in serum and TCF were determined by a microbiological assay. The concentrations in serum and TCF of ceftizoxime were analyzed through compartmental and non-compartmental models.Rectal temperature were significantly incremented in all animals during Trial 2. The half-time and constant of elimination in serum of ceftizoxime in NSi.v. (t(1/2)=1.1+/-0.4h; lambda(z)=0.7+/-0.2h(-1)) were statistically different those observed in HSi.v. (t(1/2)=1.4+/-0.4h; lambda(z)=0.5+/-0.2h(-1)). The constants of distribution in NSi.v. and HSIV were 5.1+/-4.6 and 4.1+/-3.4h(-1), respectively. The time to reach the maximum concentrations in TCF was latter (p<0.05) in NS (t(max)=2.3+/-0.7h) than in HS (t(max)=1.3+/-0.6 h). After i.m. administration in NS the absorption half-life (0.12+/-0.19h) was latter (p<0.05) than in HS (0.06+/-0.007h) with greater areas under the curve (AUC in NS=65.4+/-20.8 and AUC in HS=34.7+/-7.5 (µg/ml) h). The maximum value of concentration in serum (C(max)) and AUC in TCF were greater (p<0.05) in NS (C(max)=46.1+/-10.6µg/ml and AUC=84.4+/-17.4 (µg/ml) h) as compared to same HS (C(max)=27.0+/-12.9µg/ml and AUC=47.9+/-3.9 (µg/ml) h). The concentrations of ceftizoxime in TCF after i.v. and i.m. in NS and HS were elevated during a 6h period after administration. The bioavailability of ceftizoxime in NS (101.6+/-59.9%) and HS (87.4+/-63.3%) was suitable for its use by the i.m. route.

Rapid decay of cocaine-induced behavioral sensitization of locomotor behavior.

Sprague Dawley rats received three daily intraperitoneal (i.p.) injections of saline or 15 mg/kg cocaine. Following an interval of 2, 5 or 8 days, the behavioral response of separate groups of rats to a challenge injection of cocaine (15 mg/kg) was tested in an open field. After repeated cocaine (15 mg/kg) injection, movement in both the vertical and horizontal plane was increased in cocaine-treated rats 2, but not 5 or 8, days after treatment as compared to saline-treated subjects. In addition, behavioral ratings along an ordinal scale designed to reflect increases in behavioral activation were increased in cocaine-treated rats 2, but not 5 or 8, days after treatment. These results stand in contrast to other reports demonstrating long-lasting neural and behavioral changes after similar treatment regimens. Taken together, the results suggest that a treatment regimen of 15 mg/kg per day of cocaine for 3 days produces behavioral sensitization of locomotor behavior; however, this cocaine-induced behavioral sensitization does not persist beyond a few (< 5) days after repeated cocaine treatment, using the current experimental parameters.

Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract.

BACKGROUND: Immediate hypersensitivity to peanuts is a frequent cause of anaphylactic reactions and deaths in children and adults. Currently, preventive treatment consists of avoidance, which is difficult because of the widespread and often disguised use of peanuts in the food industry. METHODS: Twelve patients with immediate hypersensitivity to ingestion of peanuts were recruited. Half were treated with injections of peanut extract: a maintenance level of tolerance was first achieved by a rush protocol, then maintained with weekly injections for at least 1 year. The other six were untreated control subjects. All patients underwent double-blind, placebo-controlled, oral peanut challenges initially, after approximately 6 weeks, and after 1 year. RESULTS: All treated patients achieved the maintenance dose of 0.5 ml of 1:100 wt/vol peanut extract by the rush injection protocol. All experienced increased tolerance to double-blind, placebo-controlled peanut challenge and decreased sensitivity on titrated skin prick testing with peanut extract, whereas the threshold to oral peanut challenge and cutaneous reactivity to peanut extract were unchanged in the untreated control subjects. Systemic reactions were common in the treated group both during rush immunotherapy and with maintenance injections. Only three patients remained tolerant of the full maintenance dose. The increased tolerance to oral peanut challenge was maintained in the three subjects who received full maintenance doses, but there was partial (n = 2) or complete (n = 1) loss of protection in the patients who required dose reduction because of systemic reactions. CONCLUSIONS: Injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts. Injections result in repeated systemic reactions in most patients, even during maintenance injections. For clinical application of this method of treatment, a modified peanut extract is needed.

The pharmacokinetics of ceftazidime in lactating and non-lactating cows.

The pharmacokinetics of ceftazidime (CAZ) were studied in lactating (LTG) and non-lactating (NLTG) cows. Two groups (LTG and NLTG) of 5 healthy dairy cows were given ceftazidime (10 mg/ kg body weight) intravenously (i.v.) and intramuscularly (i.m.). Serum and milk (LTG) and serum samples (NLTG) were collected over a 24-h period post-administration. CAZ concentrations in serum and milk were determined by high-performance liquid chromatography, and an interactive and weighted-non-linear least-squares regression analysis was used to perform the pharmacokinetic analysis. The pharmacokinetic profiles in LTG and NLTG cows which had received CAZ i.v. fitted a three-compartment model and a two-compartment model, respectively. The CAZ concentration-time curves in serum and the area under the curve were greater and more sustained (p < 0.05) in the LTG cows by both routes, while the serum clearance (Cls = 72.5 +/- 18.1 ml/h per kg) was lower (p < 0.05) than that in the NLTG cows (Cls = 185.9 +/- 44.2 ml/h per kg). CAZ given i.v. exhibited a relatively long half-life of elimination (t1/2 beta (LTG) = 1.1 +/- 0.2 h; t1/2 beta (NLTG) = 1.4 +/- 0.3 h). Compared with other cephalosporins, CAZ had good penetration into the mammary gland (47.7 +/- 38.2% for CAZ i.v.; 51.1 +/- 39.0% for CAZ i.m.). Finally, the bioavailability of CAZ (F(LTG) = 98.9 +/- 36.8%; F(NLTG) = 77.1 +/- 25.3%) was suitable for its used by the i.m. route in lactating and non-lactating cows.

Microfocus X-ray Diffraction of Spherulites of Poly-3-hydroxybutyrate.

The microfocus X-ray beamline at the European Synchrotron Radiation Facility has been used to investigate the variation in molecular orientation and crystallinity in spherulites of the organic polymer poly-3-hydroxybutyrate (PHB). This is the first report of the correlation of optical and X-ray measurements on spherulitic polymer films where X-ray diffraction patterns have been recorded and displayed continuously in real time while the specimen was tracked in steps of 10 mum across an incident X-ray beam with a diameter as small as 10 mum.

Pharmacokinetics and penetration into tissue fluid of cefotaxime in bovines.

Concentrations of cefotaxime in serum and tissue fluid were studied in the bovine after intravenous and intramuscular administration at a dosage of 10 mg.kg-1 body weight. Steers implanted subcutaneously with tissue cages were used. After intravenous bolus administration, profiles of mean concentrations in serum over time were described by a two-compartment open model. The rate constant of elimination was 1.4 +/- 0.3 h-1 and the half-life 0.6 +/- 0.1 h. The rate constant of distribution was 11.5 +/- 1.9 h-1, and the half-life was 0.06 +/- 0.01 h. The volume of distribution at steady state was 250.6 +/- 37.3 ml.kg-1. The area under the curve was 31.8 +/- 7.4 micrograms.ml-1.h. The penetration ratio into tissue fluid was 36.5 +/- 15.4%. After intramuscular injection, the half-life was 1.1 +/- 0.3 h, the area under the curve was 27.5 +/- 6.8 micrograms.ml-1.h, and the penetration ratio into tissue fluid was 47.1 +/- 15.8%. The concentrations in tissue fluid after intravenous and intramuscular administration of cefotaxime were elevated during a 6-hour period after administration.

Farmacocinética de ceftazidima en neonatos / Pharmacokinetics of ceftazidime in newborn infants

A pharmacokinetic study of ceftazidime was performed in newborn children. Six premature infants with a body weight up to 2000 g and with symptoms of pneumonia (Table 1) were treated with ceftazidime (50 mg/kg body weight) by endovenous route. Plasma concentrations of the antibiotic (Fig. 1) were determined by HPLC. A kinetic behavior was described through a compartment model independent analysis. The calculated parameters were as follows: half-life (T1/2z = 4.05 +/- 0.81 h) apparent volume of distribution (Vz = 686.0 +/- 258.6 ml/kg), elimination rate constant (lambda z = 0.18 +/- 0.04h-1), area under curve (AUC = 464.4 +/- 139.1 mu gh/ml, mean residence time (MRT = 5.2 +/- 1.3 h), and total clearance (CI = 114.9 +/- 30.0 ml/h. kg) (Table 2). Good correlation was observed (r = 0.83, p < 0.05 between lambda z = and Vz). The loading and maintenance doses calculated for enterobacteria and P. aeruginosa were 15 and 13 mg/kg i.v. respectively each 12 h.