Pharmacokinetics of deflazacort in rabbits after intravenous and oral administration and its interaction with erythromycin.

The pharmacokinetic of deflazacort after intravenous and oral administration and the effect of erythromycin on the disposition of deflazacort in rabbits were investigated. A parallel study was carried out in twelve rabbits. The plasma concentration-time profiles of deflazacort were determined after intravenous and oral administration of single dosages of 5 mg/kg in the presence and absence (baseline) of multiple dose erythromycin regimens. Plasma concentrations of 21-desacetyldeflazacort were determined by HPLC. Plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The t½λz values following intravenous and oral administration were 3.67 and 4.96 hr, respectively. The apparent volume of distribution at steady-state (Vss ) was 4.08 ± 0.31 L/kg, this value indicates that deflazacort is widely distributed into the extravascular tissues. Moreover, bioavailability after oral administration of deflazacort (F = 87.48%) was high. Pharmacokinetic analysis after both routes of administration revealed a significant reduction in total body clearance, a significant increase in mean residence time, half-life and plasma concentrations of the steroid in the presence of multiple dose erythromycin. The results indicated the influence of the erythromycin on deflazacort disposition, which is consistent with a pharmacokinetic-type interaction in the elimination of the drug from the body. Moreover, this interaction should be considered to avoid adverse effects when using both drugs concomitantly.

Pharmacokinetics of norfloxacin after intravenous, intramuscular and subcutaneous administration to rabbits.

The disposition kinetics of norfloxacin, after intravenous, intramuscular and subcutaneous administration was determined in rabbits at a single dose of 10 mg/kg. Six New Zealand white rabbits of both sexes were treated with aqueous solution of norfloxacin (2%). A cross-over design was used in three phases (2 × 2 × 2), with two washout periods of 15 days. Plasma samples were collected up to 72 hr after treatment, snap-frozen at -45°C and analysed for norfloxacin concentrations using high-performance liquid chromatography. The terminal half-life for i.v., i.m. and s.c. routes was 3.18, 4.90 and 4.16 hr, respectively. Clearance value after i.v. dosing was 0.80 L/h·kg. After i.m. administration, the absolute bioavailability was (mean ± SD) 108.25 ± 12.98% and the Cmax was 3.68 mg/L. After s.c. administration, the absolute bioavailability was (mean ± SD) 84.08 ± 10.36% and the Cmax was 4.28 mg/L. As general adverse reactions were not observed in any rabbit and favourable pharmacokinetics were found, norfloxacin at 10 mg/kg after i.m. and s.c. dose could be effective in rabbits against micro-organisms with MIC ≤0.14 or 0.11 µg/mL, respectively.

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats.

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats. METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two-treatment, two-period study. Alfaxalone at a dose of 5 mg/kg was administered either I/V or I/M. Blood samples were collected between 2-480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5-120 minutes after drug administration using a numerical rating scale (from 0-18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded. RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5-15 minutes after I/V administration and deep sedation (scores 11-15) at 20 and 30 minutes. Deep sedation was observed from 10-45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.

TG/HDL-C RATIO AS CARDIO-METABOLIC BIOMARKER EVEN IN NORMAL WEIGHT WOMEN.

CONTEXT: Despite that the Triglycerides/High Density Lipoprotein Cholesterol (TG/HDL-C) ratio has been associated with insulin resistance and cardiovascular disease, some outcomes differ between populations. OBJECTIVE: The objective of this study was to evaluate the association between TG/HDL-C ratio and cardio-metabolic risk factors in both obese and normal weight women. DESIGN: Cross sectional, from January to December of 2015. SUBJECTS AND METHODS: Two hundred and fifty three women aged 40 to 60 years. Anthropometric and laboratory measurements were performed. Insulin resistance was measured by the homeostasis model assessment for insulin resistance (HOMA-IR). All participants underwent a Doppler ultrasound to measure intima-media thickness of carotid artery (cIMT). RESULTS: TG/HDL-C ratio correlated with body mass index (r=0.194, p=0.01), and visceral adipose tissue (r=0.193, p=0.002). Additionally, TG/HDL-C correlated with glucose (r=0.367, p=0.001), insulin (r=0.354, p=0.001) and HOMA-IR (r=0.396 p=0.001). TG/HDL-C was associated with prediabetes, Odds Ratio (OR) was 1.83 (95%CI 1.07-3.13) and insulin resistance 3.27 (95%CI 1.78-6.01), and this risk remains in normal weight women 4.7 (95%CI 1.2-17.81) for prediabetes and 4.38 (95%CI 1.42-13.84) for insulin resistance. No significant risk for cIMT. CONCLUSION: A TG/HDL-C ratio ≥ 3.0 is a potential risk factor for prediabetes and insulin resistance in women 40-60 years, even in normal weight women.

[Evaluation of visceral adipose tissue and lipid level in premenopausal and postmenopausal women's]. / Evaluación del tejido adiposo visceral y de la concentración de lípidos en mujeres pre y posmenopáusicas.

BACKGROUND: Postmenopausal women present weight gain and intensification of obesity, especially visceral adipose tissue (VAT) increases in postmenopausal women. But it is still not clear whether abdominal fat increases during this stage independently of body weight. OBJECTIVE: compare the VAT and lipid profile between postmenopausal and premenopausal Mexican women. METHODS: A case control study in postmenopausal women matched for BMI with premenopausal women. Anthropometric and laboratory measurements as well as body composition analysis were performed. RESULTS: VAT was increased in postmenopausal women in contrast with premenopausal women (114.8 ± 39.5 vs 97.3 ± 29.0, p<0.05). Compared with premenopausal women, postmenopausal women showed higher total cholesterol (231 .6 ± 56.1 vs 206.8 ± 29.5 p <0.05), and LDL-cholesterol levels (145.9 ± 48.3 vs 121.7 ± 34.1, p < 0.05), whereas H DL-cholesterol remained unchanged. CONCLUSION: The results of the present study have demonstrated that Mexican postmenopausal women had a significant increment in visceral adipose tissue and in other metabolic risk factors, independent of the body mass index.

Pharmacokinetics of tildipirosin in estuarine (Crocodylus porosus) and freshwater (Crocodylus siamensis) crocodiles.

Tildipirosin is a macrolide antimicrobial. It is authorised for the treatment and prevention of respiratory disease in cattle and pigs. There are no data on its administration in crocodiles. Therefore, this study evaluated the disposition kinetics of tildipirosin after intravenous (dose: 2 mg/kg) and intramuscular (doses: 2 and 4 mg/kg) administration in two crocodilian species (estuarine and freshwater; n = 5). Tildipirosin plasma concentrations were quantified by a validated HPLC method. Plasma concentrations obtained at each extraction time were analysed by non-compartmental methods. In the estuarine and freshwater crocodiles, the apparent volumes of distribution of tildipirosin after intravenous administration were 0.36 ± 0.10 and 1.48 ± 0.26 L/kg, respectively. These values, suggesting poorer tissue distribution, were much lower than those obtained in mammals. There was complete bioavailability of tildipirosin after intramuscular route at a dose of 2 mg/kg; however, at a dose of 4 mg/kg the bioavailability decreased by about 20-25 %. Furthermore, the pharmacokinetics of tildipirosin were markedly different in the two crocodilian species. Considering a MIC of 0.5 µg/mL, the surrogate marker AUC0-24/MIC indicates that tildipirosin would greatly exceed the value of 65 h for both crocodile species and dose levels tested. This suggests that both doses (2 and 4 mg/kg) may provide a bactericidal effect. Therefore, based on the absence of adverse reactions following the administration of tildipirosin in both crocodilian species, and considering its favourable pharmacokinetic properties, tildipirosin may be useful in treating infections in these reptiles.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist.

High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/1 on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.

[Pneumonia in patients with SARS-CoV-2 infection: series of 17 cases in the region of Murcia]. / Neumonía neumocócica en pacientes con infección por SARS-CoV-2: serie de 17 casos en la Región de Murcia.

OBJECTIVE: Currently the prevalence of pneumococcal coinfection in patients with COVID-19 is unknown. In this work we present its clinical characteristics, evolution and treatment. METHODS: Retrospective data collection from August to October 2020 in two hospitals in the Murcia region. RESULTS: Eighteen patients had COVID-19 diagnosed by PCR and pneumococcal infection confirmed by antigenuria, which represented a prevalence of 2%. A total of 88% had radiological alterations upon admission (two patients had an X-ray within normality) and 29% had elevated procalcitonin. Mortality in our series was 12%. CONCLUSIONS: It could be reasonable to consider the start of antimicrobial therapy in those cases in which there is a moderate or high suspicion of bacterial coinfection, being essential the early suspension of antibiotic treatment if it is not confirmed.

Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.

PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.

Latin American Dialysis and Renal Transplant Registry: 2008 report (data 2006).

INTRODUCTION: Between 1991 and 2006, the Latin American Dialysis and Renal Transplantation Registry collected data from 20 countries (Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Dominican Republic, Venezuela and Uruguay). Access to RRT was universal in Argentina, Brazil, Chile, Cuba, Puerto Rico, Venezuela and Uruguay, all countries belonging to the medium-high or high income group. METHODS: Data about patients on renal replacement therapy (RRT) were supplied by national affiliates or the Registry's Coordination Committee. Transplant data were gathered and shared with the Latin American and Caribbean Society of Transplantation. RESULTS: RRT prevalence increased from 162 patients per million population (pmp) in 1991 to 478 pmp in 2005 and 473 pmp in 2006 (59.2% hemodialysis, 20.4% peritoneal dialysis and 20.4% with a functioning kidney allograft). Countries with the highest prevalence were Puerto Rico (1,148.9 pmp), Uruguay (924.5 pmp) and Chile (907.6 pmp). Latin America's (LA) incidence increased from 27.8 pmp in 1992 to 188 pmp in 2006. The LA Kidney transplant rate increased from 3.7 pmp in 1987 to 15,4 pmp in 2006, and 166 combined transplants - kidney and another organ, mainly pancreas - were performed. In the medium-high income group 2006, (Argentina, Brazil, Chile, Costa Rica, Cuba, Mexico, Panama, Uruguay, Venezuela) the prevalence rate was 534.8 pmp vs. 289.5 pmp in the middle-low income group. The transplant rate was 18.4 pmp in the medium-high income group vs. 7 pmp in the middle-low group (p < 0.01). CONCLUSIONS: RRT incidence and prevalence continue to grow steadily. Access to RRT is universal only in some countries included in the medium-high or high income group. It is imperative to accomplish the goal of making RRT available to all who need it.

Pharmacokinetics and milk penetration of difloxacin after a long-acting formulation for subcutaneous administration to lactating goats.

The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n=6) after intravenous (IV) and subcutaneous (SC) administration and subcutaneous administration of a long-acting poloxamer 407 gel formulation (P407). Difloxacin concentrations were determined by HPLC with fluorescence detection. Minimum inhibitory concentrations of difloxacin against 14 strains of Staphylococcus aureus isolated from mastitic goats' milk in Spain were determined to compute pharmacodynamic surrogate markers. The concentration-time data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Following SC and P407 administration, difloxacin achieved maximum milk concentrations of 1.34+/-0.12 and 2.97+/-1.18 mg/L, respectively, at 4.00+/-0.00 h (SC) and 3.60+/-0.89 h (P407) after administration. The absolute bioavailabilities after SC and P407 administration were 81.74+/-15.60% and 72.58+/-20.45%, respectively. Difloxacin penetration from the blood into the milk was good and high concentrations were found in milk secretions. From these data, a 15 mg/kg dose of difloxacin P407 would appear to be effective against Staphylococcus aureus isolated from mastitic goats' milk with minimum inhibitory concentrations

Short communication: Fluoroquinolone susceptibility of Staphylococcus aureus strains isolated from caprine clinical mastitis in southeast Spain.

The antibiotic susceptibility of 32 strains of Staphylococcus aureus isolated from the mastitic milk of dairy goats was evaluated. The antibiotics tested were 3 fluoroquinolones that have been developed especially for use in veterinary medicine: danofloxacin, marbofloxacin, and orbifloxacin. Minimum inhibitory concentration (MIC) tests were performed according to the microdilution broth method. The MIC(90) (concentration at which 90% inhibition is achieved) values obtained were 0.5, 1, and 1 mg/L for danofloxacin, marbofloxacin, and orbifloxacin, respectively. Danofloxacin was the most active fluoroquinolone tested against Staph. aureus strains isolated from milk; however, specific testing is required before using these drugs as therapy for the control of clinical mammary infections in goats.

Anal cytology in women: Experience from a single tertiary center.

INTRODUCTION: Anal cytology (AC) can be used as a screening tool for detection of anal HPV associated lesions, mainly in men who have sex with men and in immunosuppressed patients. Our aim is to review our experience with AC in women. MATERIAL & METHODS: We have retrospectively reviewed all AC diagnosed between 2010-2017 in a single tertiary hospital (n = 644) and selected those performed in women (n = 158). RESULTS: 24.53% of AC were performed in women. 14.7% of all women were HIV positive and 56.7% referred anal intercourse. Squamous lesions were found in 27.2% of women, most of them ASCUS and LSIL (14% and 11.5%). HPV DNA was detected in 38.6% of patients, and 63.9% of them showed positivity for multiple high-risk types. Anal biopsy showed high grade lesions in 20% of biopsied patients. We observed a significant relationship between HPV status and receptive anal sex, and the association between HPV status and anal histological diagnosis tended to significance. Sensitivity, specificity, negative predictive value and positive predictive value for anal cytology were 57%; 83%; 28% and 94%, respectively. 70.9% of women had synchronous cervical cytology, and squamous cervical lesions were detected in 46.4% of the cases, most of them LSIL or ASCUS (21.4% and 15.2%). We did not confirm a significant association between cytological diagnosis of cervical and anal samples. CONCLUSIONS: AC is less widely used in women than in homosexual men. However, women show important rates of anal lesions, regardless of their HIV status. More studies should be performed to assess the potential impact of screening protocols in this population.

[Diagnostic protocol for imported febrile syndrome]. / Protocolo diagnóstico del síndrome febril importado.

In this protocol we shall set out the steps to follow in the clinical assessment of the patient with fever and where there is an epidemiological history of travel to tropical or subtropical areas. This is not intended to be exhaustive, but as a guide to doctors in their initial diagnostic approach to the patient who has come from the tropics consulting with a fever in the Emergency Department or the hospital ward. Differential diagnosis should be approached first and foremost on the basis of excluding malaria, but haemorrhagic fevers, rickettsiosis, typhoid fever and many other infections, some that are unique to tropical areas, and others that are cosmopolitan but more prevalent in such areas should also be taken into account.

Pharmacokinetics and milk penetration of orbifloxacin after intravenous, subcutaneous, and intramuscular administration to lactating goats.

The single-dose disposition kinetics of orbifloxacin were determined in clinically normal lactating goats (n = 6) after intravenous, subcutaneous, and intramuscular administration of 2.5 mg of orbifloxacin/kg of body weight. Orbifloxacin concentrations were determined by HPLC with fluorescence detection. The concentration-time data were analyzed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution and clearance of orbifloxacin after intravenous administration were 1.13 +/- 0.08 L/kg and 0.40 +/- 0.11 L/h x kg, respectively. Following subcutaneous and intramuscular administration, orbifloxacin achieved maximum plasma concentrations of 1.85 +/- 0.20 and 1.66 +/- 0.14 mg/L at 1.25 +/- 0.22 and 0.87 +/- 0.38 h, respectively. The absolute bioavailabilities after subcutaneous and intramuscular routes were 108.96 +/- 17.61% and 105.01 +/- 15.61%, respectively. Orbifloxacin penetration from the blood into the milk was rapid and showed high levels of concentrations in milk secretion. From this data, orbifloxacin could have success against susceptible mastitis pathogens in goats.

Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of difloxacin in sheep.

The disposition kinetics of difloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration were determined in sheep at a single dose of 5mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental pharmacokinetics method (after IV, IM and SC administration). Plasma concentrations of difloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V(ss)) and clearance (Cl) of difloxacin after IV administration were 1.68+/-0.21L/kg and 0.21+/-0.03L/hkg, respectively. Following IM and SC administration difloxacin achieved maximum plasma concentration of 1.89+/-0.55 and 1.39+/-0.14mg/L at 2.42+/-1.28 and 5.33+/-1.03h, respectively. The absolute bioavailabilities after IM and SC routes were 99.92+/-26.50 and 82.35+/-25.65%, respectively. Based on these kinetic parameters, difloxacin is likely to be effective in sheep.

Multidrug-resistant tuberculosis without HIV infection: success with individualised therapy.

OBJECTIVE: To evaluate the results of the treatment of non-HIV-infected multidrug-resistant tuberculosis (MDR-TB) patients admitted to a tuberculosis unit in a reference centre between June 1998 and December 2000. RESULTS: Twenty-five patients were studied (23 men). Empirical treatment was selected according to drugs previously used and adjusted according to in vitro test results. Patients had previously received an average of 5.5 drugs and were resistant to an average of 4.7 drugs. They were treated with a median number of four drugs (an injectable drug plus three oral drugs) for a median of 18 months. Ofloxacin and cycloserine was used in 17 cases (68%), ethionamide/prothionamide in 18 (72%) and para-aminosalicylic acid in 12 patients (48%). Psychological support and counselling was provided. Two patients required surgery. Globally, 21 patients (84%) met cure criteria. After a 24-month follow-up, none of the 21 patients who successfully completed treatment presented relapse or death. CONCLUSION: MDR-TB is a curable disease in non-HIV-infected patients. Individualised treatment regimens should be based on treatment history and the study of in vitro susceptibility and by promoting a relationship with the patient that makes adherence to treatment easier and minimises side effects.