Effect of intrabronchial platelet rich plasma on the exercise-induced pulmonary hemorrhage endoscopic score in thoroughbred racehorses using furosemide: a preliminary study / [Efeito da instilação intrabronquial de plasma rico em plaquetas no escore endoscópico da hemorragia pulmonar induzida por exercício em cavalos Puro-Sangue Inglês de corrida e usuários de furosemida: um estudo preliminar]

The high prevalence of exercise-induced pulmonary hemorrhage (EIPH) in athletic horses constitutes to be a challenge to the racing industry and a source of major concern to animal welfare. Both experimental and clinical evidence indicate that the use of autologous platelet-rich plasma (PRP) is a promising effector of repair in a variety of pulmonary conditions. The present study evaluated the effect of intrabronchial instillation of PRP on EIPH endoscopic scores from 37 Thoroughbred racehorses. Inclusion criteria were for animals to be EIPH-positive in, at least, two consecutive post-exercise endoscopic exams and to receive 250mg of furosemide IV four hours before racing. Animals were randomly assigned into 3 groups: placebo, control, and PRP instillation. All 37 Thoroughbred racehorses included had EIPH endoscopic scores pre- and post- treatment compared by statistical analysis. The bleeding score from the group receiving PRP was significantly lower than in the control and placebo groups. No adverse effects were observed in any animal during or after the experiment. It was possible to conclude that the intrabronchial instillation of autologous PRP was effective in reducing EIPH scores in racehorses receiving furosemide and that this bioproduct can be considered as a promising coadjuvant in controlling EIPH in athletic horses.(AU)

A alta prevalência de hemorragia pulmonar induzida por exercício (HPIE) em cavalos atletas é um desafio de longa data para a indústria de corridas, além de figurar como grande preocupação sobre o bem-estar animal. As evidências experimentais e clínicas indicam que o uso do plasma rico em plaquetas (PRP) de fonte autógena é promissor na terapêutica de diversas lesões pulmonares. O presente estudo objetivou avaliar as mudanças após corrida no escore endoscópico de HPIE de 37 cavalos Puro-Sangue Inglês que receberam instilação intrabronquial de PRP autólogo. Os animais selecionados eram HPIE-positivos em, ao menos, dois exames endoscópicos consecutivos e recebiam 250mg de furosemida IV administrado quatro horas antes de cada corrida. Na comparação dos escores endoscópicos pré e pós-tratamento, verificou-se que o escore de HPIE do grupo tratado com PRP foi significantemente menor que o dos grupos controle e placebo. Nenhum efeito adverso foi observado nos animais durante ou após o experimento. Concluiu-se que a instilação intrabronquial de PRP autólogo foi efetiva na redução do escore de HPIE de cavalos de corrida usuários de furosemida e que este bioproduto pode ser considerado uma alternativa promissora no controle de HPIE em cavalos atletas.(AU)

[A protocol for the treatment of retinopathy of prematurity in Spain]. / Protocolo de tratamiento de la retinopatía del prematuro en España.

OBJECTIVE: To prepare a protocol for the treatment of retinopathy of prematurity (ROP) agreed by the majority of Spanish ophthalmologists dedicated to this topic. MATERIAL AND METHOD: A draft of the protocol was produced taking into account the experience of the participants and up to date publications. This draft was corrected by all the ophthalmologists participating in the project, and the final document was agreed by all of them. RESULTS: We present general guidelines as an aid for the treatment of ROP, including treatment criteria, treatment methods, a calendar of action, and follow-up. CONCLUSIONS: It is important to have a common working protocol for the treatment of ROP to improve care and to avoid mistakes. Although individual Hospitals may adapt the protocol to their daily activity, it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain.

Screening program for retinopathy of prematurity in Spain.

OBJECTIVE: To prepare a retinopathy of prematurity (ROP) screening program as agreed by most of Spanish ophthalmologists dedicated to this topic. MATERIALS AND METHODS: A draft of the protocol was produced taking into account the experience of the participants and current publications. This draft was corrected by all the ophthalmologists participating in the project and the final document produced was agreed by all of them. RESULTS: We present general guidelines to help in the screening of ROP, including treatment criteria, treatment methods, and a calendar of action. CONCLUSIONS: It is important to have a common working protocol in the screening of ROP to improve the action and to avoid mistakes. Although individual Hospitals may adapt the protocol to their daily activity, it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain.

[Diode laser photocoagulation of retinopathy of prematurity]. / Fotocoagulación con láser de diodo en la retinopatía del prematuro.

OBJECTIVE: To describe diode laser photocoagulation results in retinopathy of prematurity (ROP) in our hospital. MATERIAL AND METHOD: Retrospective cross-sectional study based on clinical histories of the premature infants treated during the period from 2004 to 2008. RESULTS: In the treated group we found a predominance of pre-threshold retinopathy versus threshold retinopathy (84.35% vs 15.65%). The anatomic results were good in 96.5% of 147 eyes. None of the treated eyes in pre-threshold stage showed a poor result. Nine months after treatment, 84.85% of 132 eyes showed good functional results. A poor visual response was associated in most of the cases with neurological diseases. Infants with intraventricular haemorrhages had the worst anatomical and functional results. Strabismus (23.5%) and nystagmus (10.3%) rates were high, probably due to the increased prevalence of neurological diseases. The mortality rate in treated children was 7.3%. CONCLUSIONS: Diode laser photocoagulation in ROP offers very good anatomical results when performed at the appropriate time. Nevertheless, prematurity is still a very important cause of visual dysfunction in infancy due to the associated neurological disturbances.

Intramolecular Friedel-Crafts-type reactions involving N-acyliminium ions derived from glycine templates.

Enantiomerically pure 4-substituted 2-aralkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones (1b-m) in which the alkyl chain is (CH(2))(n), n = 1-3, behave as glycine templates giving by treatment with [hydroxy(tosyloxy)iodo]benzene in ethyl acetate cis-1-tosyloxy derivatives. When these compounds contain electron-rich aryl substituents with n = 2, they spontaneously cyclize through intramolecular Friedel-Crafts-type diastereoselective reactions to give penta- or hexacyclic compounds. Otherwise, they give by solvolysis cis-1-alkoxy derivatives, which in a second step, may be cyclized in acid if n = 2, 3. All these reactions must occur through N-acyliminium species in S(N)1-like mechanisms. 1-Alkoxy-2-arylmethyl derivatives are reluctant to cyclize, giving trans-1-hydroxy compounds as the only isolated reaction products.

Intravitreal pharmacokinetics and retinal concentrations of ganciclovir and foscarnet after intravitreal administration in rabbits.

PURPOSE: To perform a detailed pharmacokinetic study and to evaluate the drug levels reached in the retina after the intravitreal administration of ganciclovir and foscarnet to rabbits. METHODS: Retinal and vitreal levels of both drugs were measured by high-performance liquid chromatography at 1, 6, 12, 24, 36, 48, 60, and 72 hours after a single intravitreal injection of 196 microg and 800 microg of ganciclovir and 960 microg of foscarnet to three groups of 24 pigmented rabbits. A noncompartmental pharmacokinetic analysis was used. RESULTS: Both drugs incorporated rapidly into the retina, but no equilibrium was observed between the drug levels in the vitreous humor and retina. Mean ganciclovir levels in vitreous and retina were 179.6 microg/g and 131.3 microg/g (dose of 196 microg), 755.7 microg/g and 381.6 microg/g (dose of 800 microg) at 1 hour after administration, decreasing to 0.1 microg/g, 0.6 microg/g, 0.8 microg/g, and 0.7 microg/g, respectively, by 72 hours. Mean foscarnet levels in vitreous and retina were 944 microg/g and 217.1 microg/g at 1 hour after administration, decreasing to 74 microg/g and 17.1 microg/g, respectively, by 72 hours. Whereas both doses of ganciclovir yielded retinal levels above the mean inhibitory concentration (IC50) of most human cytomegalovirus (CMV) isolates for more than 60 hours, foscarnet retinal levels were lower than the CMV IC50 before 36 hours had elapsed after administration. CONCLUSIONS: The results suggest that the intravitreal administration of ganciclovir has a better pharmacokinetic profile than foscarnet for the treatment of retinitis caused by CMV and other herpes viruses and support the administration of intravitreal ganciclovir twice a week as a treatment for CMV retinitis.

Intravitreal, retinal, and central nervous system foscarnet concentrations after rapid intravenous administration to rabbits.

Retinal, vitreous humor, brain, and cerebrospinal fluid (CSF) foscarnet levels were measured by high-performance liquid chromatography after administration of an intravenous dose of 120 mg/kg of body weight to 32 pigmented rabbits. A pharmacokinetic analysis was done using a two-compartment model. The penetration ratios, defined as ratios of retinal, vitreous humor, brain, and CSF areas under the concentration-time curve from 0 to 2 h were 110% +/- 1%, 12.3% +/- 0.7%, 118% +/- 1%, and 20.2% +/- 2.2%, respectively. These results suggest a good penetration of foscarnet into the retinal and brain tissues, reaching higher concentrations than those estimated from vitreous humor and CSF levels.

Molecular bureaucracy: who controls the delays? Transient times in branched pathways and their control.

Analysis of metabolic control has until now been mainly confined to systems at steady state. This includes studies of the control of "transition time", which is actually a steady-state transit time that does not refer to the transient state. In this paper we examine the control of the transition state of a metabolic pathway in the approach to a stable steady state, showing that the time needed to attain it can be decreased or increased in different branches. Our analysis only applies to branched pathways, and we discuss why similar deviations cannot occur in unbranched pathways. In systems with several branches the acceleration of some branches during the transient phase, so that they reach their steady states more quickly, occurs at the expense of others, which are thus delayed. We present theorems that describe properties of the transient variables and their control.

Synthesis and antitumour activity of fluorinated 1-aza and 1,8-diazaanthraquinones.

A series of 3-fluoro-1-aza- and 1,8-diazaanthraquinones, structurally related to the antitumour antibiotic diazaquinomycin A, have been prepared by Diels-Alder reactions of 2-fluoro-2-propenal N, N-dimethylhydrazone and the corresponding quinones. These compounds showed potent in vitro activity against different tumour cell lines. They also showed some selectivity towards rapid-growth tumours when compared to other non-fluorinated analogues. In contrast with diazaquinomycin A, the azaanthraquinones studied here have not shown significant activity as thymidylate synthase inhibitors. Some compounds showed a high activity as inhibitors of protein, DNA and RNA biosynthesis.

Cerebrospinal fluid beta 2-microglobulin in neonates with central nervous system infections.

Beta 2-microglobulin (beta 2m) determination in CSF of 72 neonates who underwent a spinal tap as part of a sepsis or meningo-encephalitis workup was performed to evaluate the usefulness of this test in the diagnosis of CNS infections. Beta 2m was measured by enzyme immunoassay. Sixty neonates had sterile culture and normal neurological status at discharge. Twelve infants had CNS infections: 8 bacterial meningitis, 3 TORCH infections (T = toxoplasmosis, O = others, R = rubella, C = cytomegalovirus and H = herpes simplex) and 1 viral meningitis. Neonates with CNS infection exhibited significantly higher CSF beta 2m levels compared to neonates with sterile culture (6.24 +/- 2.66 vs 1.74 +/- 0.5 mg/l; P < 0.0001). CSF beta 2m levels did not correlate with the white cell count, total protein concentration or glucose level in CSF. When serum and CSF levels were measured simultaneously, the CSF beta 2m level was significantly higher than the corresponding serum level in patients with CNS infection (6.98 +/- 2.5 vs 3.2 +/- 0.25 mg/l; P < 0.01). Sensitivity, specificity, and predictive values were estimated for different cut-off points. The best operational diagnostic cut-off value was 2.25 mg/l. Receiver operating characteristic curve analysis showed an appropriate trade-off between specificity and sensitivity and indicated that CSF beta 2m was accurate in distinguishing between neonates with and without CNS infection. Conclusion. CSF beta 2m may be a useful ancillary tool in neonates when CNS infection is suspected.

[An analysis of the referrals to specialist consultations made in a health center]. / Análisis de las derivaciones a las consultas de especialistas realizadas en un centro de salud.

The study of referrals from primary care areas permits the evaluation of health care in this level and reveals the educational requirements of the specialists in family medicine. Between January and April 1988 a prospective study was carried out to evaluate the referrals to the second level of care in the health center V Centenario. In 27,657 visits 1,906 referrals to the different specialties were ordered, which represents a rate of 6.89%. The most commonly consulted specialties were gynecology (18.94% of the overall referrals), ophthalmology (18.04%) and traumatology (16.10%). Psychiatry (1.41%), neurology (1.31%) and endocrinology (1.41%) were the specialties with the lowest referral rates. We compared our results with those from other authors and we have calculated what influence would be exerted on the second level of care if all primary care physicians had similar referral rates to those obtained in our center.