Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial

The expression of cytokeratins (CKs) in normal cervical epithelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively n the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, as well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions.     

Effect of level of dietary energy and protein on embryo survival and progesterone production on day eight of pregnancy in Rasa Aragonesa ewes

The aim of this experiment was to investigate the effects of dietary protein and energy on ovulation rate and embryo survival to day 8 of pregnancy, and the associated concentrations of progesterone in jugular, ovarian and uterine veins, in a Spanish breed of sheep. In mid-October, three groups of ewes were fed to provide 1.5 x (H; n = 9), 0.5 x (L; n = 12) or 0.5 x plus 7.44 g CP/MJ ME (LP; n = 8) energy requirements for maintenance of live weight from day -14 relative to a synchronized mating on day 0. A significant effect of nutrition on ovulation rate was observed (H: 2.22 +/- 0.16; L: 1.50 +/- 0.16; LP: 1.88 +/- 0.12 corpora lutea; P < 0.05). Mean LH and progesterone concentrations were affected by nutrition on day 7, L ewes showing the highest mean LH level (P < 0.01), while H ewes presented the lowest mean LH concentration and the highest mean plasma progesterone concentration (P < 0.01). Laparotomies were performed on six animals of each group on day 8 to determine the effect of nutrition on embryo development. A significantly higher percentage of embryos recovered from L and LP ewes presented an earlier stage of development (morulae or early blastocysts) (P < 0.001), while 100% embryos of H ewes were expanded blastocysts. The ratio expanded blastocysts/corpora lutea was significantly higher in H ewes (0.86) when compared with L and LP groups together (0.57; P < 0.05). Mean progesterone concentration in the ovarian vein was 800-fold higher than mean jugular venous levels with no differences between groups. Samples from ovarian veins contralateral to corpus luteum-bearing ovaries showed mean progesterone concentrations significantly lower than samples opposite to corpus luteum (ipsilateral: 1037.84 +/- 138.45; contralateral: 30.4 +/- 11.22 ng/ml; P < 0.001). Mean progesterone concentration in the uterine vein was approximately 30-fold higher than in jugular and similar in both uterine horns and treatments. No effect of nutrition on pregnancy rate was observed (H: 89%; L: 92%; LP: 100%). These results suggest that neither dietary energy nor protein are able to modify pregnancy rate or progesterone concentrations in ovarian and uterine veins eight days after mating. However, the delay in embryo development observed in the embryos collected from L and LP ewes may give rise to compromised embryo growth and development some days later.     

Localization of distinct F2-isoprostanes in human atherosclerotic lesions

F2-Isoprostanes are prostaglandin (PG) isomers formed in situ in cell membranes by peroxidation of arachidonic acid. 8-epi PGF2alpha and IPF2alpha-I are F2-isoprostanes produced in humans which circulate in plasma and are excreted in urine. Measurement of F2-isoprostanes may offer a sensitive, specific, and noninvasive method for measuring oxidant stress in clinical settings where reactive oxygen species are putatively involved. We determined whether isoprostanes were present in human atherosclerotic lesions, where lipid peroxidation is thought to occur in vivo. 8-epi PGF2alpha ranged from 1.310-3.450 pmol/micromol phospholipid in atherectomy specimens compared with 0.045-0.115 pmol/micromol phospholipid (P < 0.001) in vascular tissue devoid of atherosclerosis. Corresponding values of IPF2alpha-I were 5.6-13.8 vs. 0.16-0.44 pmol/micromol phospholipid (P < 0.001). Levels of the two isoprostanes in vascular tissue were highly correlated (r = 0.80, P < 0.0001). Immunohistochemical studies confirmed that foam cells adjacent to the lipid necrotic core of the plaque were markedly positive for 8-epi PGF2alpha. These cells were also reactive with anti-CD68, an epitope specific for human monocyte/macrophages. 8-epi PGF2alpha immunoreactivity was also detected in cells positive for anti-alpha-smooth muscle actin antibody, which specifically recognizes vascular smooth muscle cells. Our results indicate that 8-epi PGF2alpha and IPF2alpha-I, two distinct F2-isoprostanes and markers of oxidative stress in vivo, are present in human atherosclerotic plaque. Quantitation of these chemically stable products of lipid peroxidation in target tissues, as well as in biological fluids, may aid in the rational development of antioxidant drugs in humans.     

The effects of anesthesia on the biodistribution of drugs in rats: a carboplatin study

PURPOSE: Anesthetics can alter the biodistribution profile of drugs and, consequently, the regional pharmacokinetics of antineoplastic drugs at the tumor site. The effect of coadministered anesthetics on the biodistribution profile of carboplatin was studied in rats. METHODS: Female Wistar rats were used to compare the effects of ketamine/xylazine, thiopental and pentobarbital on the biodistribution of 30 mg/kg radiolabelled 195mPt-carboplatin administered intravenously, with conscious rats as the control group. Blood and urine samples were collected between 5 and 120 min. RESULTS: The percentage values of the injected dose of platinum per ml (%ID/ml) in plasma at the final time-point were respectively, 0.557%, 0.156%, 0.115% and 0.086%, in pentobarbital-, ketamine/xylazine- and thiopental-injected rats, and in conscious animals. Following the same sequence of groups, the %ID/ml values of platinum in the cumulative urine were 0.001%, 0.619%, 0.184% and 0.118%, respectively. Urine output varied from very little in the pentobarbital group, to several milliliters in the other groups. CONCLUSIONS: There was an increase of almost 100-fold in total platinum uptake in the kidneys, cerebrum and cerebellum of rats receiving pentobarbital over the uptake in the control rats, whereas the biodistribution profile of the thiopental group had the least variance. These results demonstrate the importance of anesthetic selection in animal pharmacokinetic studies, as it influences the biodistribution and pharmacokinetic profile of the drug being studied.     

Preoperative pulmonary evaluation of the thoracic surgical patient

A test designed to separate those undergoing thoracic surgery without complications and those with complications must be both highly specific and sensitive. Clearly, the difference between patients at opposite ends of the population curves is easy to identify. Spirometry can be helpful for screening, although it is not a very discriminating test. If patients fall in the overlap region between the populations, however, it is impossible to discern the risks with any certainty using low-yield tests. A test with higher sensitivity, specificity, and predictive values is necessary to ascertain such marginal differences. With this kind of analysis at hand, preoperative testing can be divided into three predictive value groups. Calculating the predictive value of each preoperative test can provide a comparative measure of usefulness of discriminative power (Table 1). In this way, spirometry, blood gas analysis, and stair climbing tolerance are shown to be poor predictors of outcome. An intermediate predictive value can be achieved using diffusion capacity, exercise-induced decreases in O2 saturation, and exercise PVR. High predictive value can be accomplished with combination indexes (PPP, possibly PRQ), measurement of VO2 at 40 watts of exercise, or VO2max. Logic dictates a step-wise preoperative evaluation using prediction value analysis (Fig.4). A flow decision chart for the preoperative evaluation of patients for pulmonary resection begins with exercise oximetry, spirometry, and blood gas analysis as general screening tests to separate those patients at minimal or no risks for complications from those patients that require further evaluation. Functional indexes (PPP, PRQ) or exercise testing can aid further in the selection of those patients in whom a nonsurgical option should be considered. Flow decision chart for the preoperative evaluation of patients for pulmonary resection should continue to evolve as new information about outcome studies is gathered. Examination of outcome data will provide us with reduction of the size of the nonoperable population, so that we can deny only those patients who truly pose a prohibitive risk.     

In vivo and in vitro developmental toxicity in LPS-induced zinc-deficient rabbits

Adenosine, produced from the decomposition of adenosine triphosphate, is believed to provide protective effects during ischemia. On the other hand, adenosine metabolites may serve as precursors for oxygen free radical formation. The time course of formation of adenosine and its purine metabolites was studied during retinal ischemia in rats. Concentrations of adenosine and its purine nucleoside metabolites inosine, hypoxanthine, and xanthine in the retina-choroid of ketamine/xylazine-anesthetized rats were measured during retinal ischemia using high performance liquid chromatography. Quantitative measurements were made possible in the small tissue mass through the use of internal standards. Ischemia was induced by ligation of the central retinal artery. In each rat, one eye was ischemic while the other served as a non-ischemic control. Eyes were frozen in situ at 1, 5, 10, 20, 30, 60, and 120 min of ischemia. The retina-choroid was then removed from the frozen eyes and analysed. Significant increases in the concentrations of adenosine, inosine, and hypoxanthine in ischemic compared to control retina-choroid were detectable within 1 to 5 min of the onset of ischemia, and within 10 min for xanthine. Increase in adenosine concentration in ischemic relative to control retina-choroid plateaued at 30 min of ischemia, while inosine and hypoxanthine concentrations increased continuously. The increase in xanthine concentration was exponential throughout the measurement period. This study documented the time-related changes in purine nucleoside concentration during ischemia. Prolonged ischemia results in ongoing production of xanthine, which by serving as a precursor for oxygen free radical formation, could be a pathogenic factor in prolonged retinal ischemia.     

Hearing, speech, language, and vestibular disorders in the fetal alcohol syndrome: a literature review

Fetal alcohol syndrome (FAS) is characterized in part by mental impairment, as well as craniofacial and ocular anomalies. These conditions are traditionally associated with childhood hearing disorders, because they all have a common embryonic origin in malformations of the first and second branchial arches, and have similar critical periods of vulnerability to toxic insult. A review of human and animal research indicates that there are four types of hearing disorders associated with FAS. These are: (1) a developmental delay in auditory maturation, (2) sensorineural hearing loss, (3) intermittent conductive hearing loss due to recurrent serous otitis media, and (4) central hearing loss. The auditory and vestibular systems share the same peripheral apparatuses (the inner ear and eighth cranial nerve) and are embryologically and structurally similar. Consequently, vestibular disorders in FAS children might be expected. The evidence for vestibular dysfunction in FAS is ambiguous, however. Like other syndromes associated with craniofacial anomalies, hearing disorders, and mental impairment, FAS is also characterized by a high prevalence of speech and language pathology. Hearing disorders are a form of sensory deprivation. If present during early childhood, they can result in permanent hearing, language, and mental impairment. Early identification and intervention to treat hearing, language, and speech disorders could therefore result in improved outcome for the FAS child. Specific recommendations are made for intervention and future research.     

Severe neonatal echovirus 20 infection characterized by hepatic failure

Genitourinary involvement by the Echinococcus granulosus larvae (urinary hydatidosis) ranks third in order of frequency after liver and lung involvement. The finding of a primary hydatidic cyst with retroperitoneal location is an uncommon fact. This paper presents once case of this infrequent disease. A revision of the different etiopathogenic mechanisms, as well as diagnostic and therapeutic approaches is made.     

A role for oestrogens in the male reproductive system

Oestrogen is considered to be the 'female' hormone, whereas testosterone is considered the 'male' hormone. However, both hormones are present in both sexes. Thus sexual distinctions are not qualitative differences, but rather result from quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males, oestrogen is present in low concentrations in blood, but can be extraordinarily high in semen, and as high as 250 pg ml(-1) in rete testis fluids, which is higher than serum oestradiol in the female. It is well known that male reproductive tissues express oestrogen receptors, but the role of oestrogen in male reproduction has remained unclear. Here we provide evidence of a physiological role for oestrogen in male reproductive organs. We show that oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis. Disruption of this essential function causes sperm to enter the epididymis diluted, rather than concentrated, resulting in infertility. This finding raises further concern over the potential direct effects of environmental oestrogens on male reproduction and reported declines in human sperm counts.