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Biomedical subjects

A Toledo

Publications and source records attributed to A Toledo.

At least 37 records · Page 2Linked to original sources

[Respiratory failure in the Guillain Barré syndrome].

Severe involvement of the respiratory muscles is seen in 25% of patients with a diagnosis of Guillain Barré syndrome. In order to evaluate the clinical characteristics and evolution of this disorder we reviewed the clinical records of patients admitted with this diagnosis to our Hospital between January 1987 and December 1996. We identified 44 patients with respiratory failure. The age was 34.0 +/- 14.1 years, 31 patients were male and 13 female; 70.5% required mechanical ventilation (MV). The time elapsed between the beginning of symptoms and MV was 9.4 +/- 8.0 days. Total duration of MV was 1,224 +/- 1,208 hours. Patients who required ventilatory support during the first 48 hours of evolution had a significantly longer duration of MV compared to the rest of the group (2,100 +/- 2,076 vs 934 +/- 735 hours, p < 0.05). Two of the survivors needed ventilatory support for more than 6 months. All patients showed quadriparesia, 55% had cranial nerve involvement and 43% had autonomic dysregulation. Twenty-four percent had a positive serologic titer for cytomegalovirus infection. The vital capacity measured before the beginning of MV was 1,050 +/- 378 ml and at discharge 2,837 +/- 1,080 ml. Mortality was 18%, with a higher mean age among those who died (44.9 +/- 17.5 years vs 31.9 +/- 12.5, p < 0.02). Mortality was also related to sepsis, barotrauma and severe autonomic dysfunction. In our group, we identified male preponderance, a high percentage of MV with an extended duration, and a longer MV time in the group of patients with a faster evolution.

Adolescent↗

In vitro culture of Taenia crassiceps larval cells and cyst regeneration after injection into mice.

Taenia crassiceps cysticerci were disrupted through trypsinization to isolate cells which can be maintained in culture for up to 15 days. When injected intraperitoneally into susceptible BALB/cAnN mice, complete cysticerci were recovered in a number that is proportional to the quantity of injected cells. Thus, cysticerci contain cells which can reconstitute complete cysts, suggesting that individual cells play a role, independent to budding, during asexual multiplication of T. crassiceps cysticerci in the peritoneal cavity of mice. In contrast, injection of the cells into resistant C57BL/6J mice does not result in the recovery of complete cysts. These findings provide a new experimental model to identify resistance factors in the hosts, for the in vitro screening of anti-cysticerci drugs and for the genetic manipulation of cysticerci through recombinant DNA techniques.

Animals↗

Kinetic effects of trimethoprim-sulfamethoxazole in children with biliary atresia: a new dosing regimen.

Pharmacokinetics for combination trimethoprim/ sulfamethoxazole (TMP/SMX) was studied in only four patients with biliary atresia (BA): three girls, 6.2,8.0 and 8.2 years of age and one boy 8.4 years of age, as this is an uncommon obstructive anomaly of the extrahepatic biliary system and has been described as having a poor prognosis. These four patients are the survivors of 27 initial children who were operated on previously. They have been receiving 2.3 +/- 0.5 mg/kg TMP, and 11.5 +/- 2.6 mg/kg SMX every 12 h since 2 weeks after surgical treatment for biliary atresia performed at 2-2.5 months of age. The patients have suffered some episodes of cholangitis during their short lives, most of them after interrupting temporally the chemotherapy. Nevertheless, they have achieved a favorable quality of life. TMP/SMX disposition was well characterized by a one compartment open pharmacokinetic model. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for t1/2 el, ClT, and Vd of 33.2, 49.6, and 26.3%, respectively, for SMX and 108.9, 52.1, and 71.0%, respectively, for TMP. A marked difference in the pharmacokinetics of TMP and SMX was observed, for example; (ClT: mean +/- SD; 90.3 +/- 47.0 ml/kg/g for TMP and 13.7 +/- 6.8 ml/kg/h for SMX), (t1/2 el with 7.93 +/- 8.64 h for TMP and 10.51 +/- 3.49 h for SMX). In order to develop dosage schedules that would reliably achieve peak serum concentrations of TMP/SMX in the therapeutic range, we found that established dose leads to high fluctuations at steady state between C(max), ss and C(min), ss, without maintaining therapeutic levels. Recommended maintenance dose varied from 8 to 30 mg/kg for SMX with a mean of 21.9 +/- 10.89 mg/kg/12 h, and from 0.8 to 4.5 mg/kg/12 h with a mean of 3.2 +/- 1.7 mg/kg/12 h. The present study illustrates the need for pharmacokinetic studies for the individualization of drug dosing in patients with BA.

Biliary Atresia↗

Bupivacaine disposition and pharmacologic effects after intravenous and epidural administrations in dogs.

Pharmacokinetic variables of bupivacaine (BPV) were determined after IV and epidural administrations in the same 6 dogs. Plasma BPV concentration curves after IV administration were adjusted to biexponential kinetics: a rapid distribution phase was followed by a slower elimination phase, with half-life of 34.5 +/- 7.8 minutes. Mean plasma clearance was 20.2 +/- 7.4 ml/min/kg of body weight, and mean volume of distribution at steady state was 0.7 +/- 0.2 L/kg. After epidural administration, absorption was rapid. Peak plasma concentration, 1.4 +/- 0.4 microgram/ml, was detected approximately 5 minutes after BPV administration. The half-life corresponding to epidural administration (179 +/- 33.6 minutes) was 5 to 6 times longer than that observed after IV administration, possibly because of the slow release of BPV from the epidural space. Induction times were short (2.3 +/- 2.2 minutes); anesthesia quickly began and lasted for more than 2 hours (158 +/- 48.8 minutes). During that period, BPV plasma concentration ranged between 1.4 and 0.2 microgram/ml. Changes in systolic blood pressure and heart rate were correlated to high plasma concentration of BPV. These modifications were observed for the first 30 minutes, reaching baseline values after 60 minutes.

Anesthesia, Epidural↗

A comparative study of histamine and K+ effects on (Ca(2+)-Mg2+)-ATPase activity in synaptosomes.

Histamine (10(-4) M) and 60 mM K+, but not 60 mM Na+ or 60 mM choline+, increased the maximal synaptosomal (Ca(2+)-Mg2+)-ATPase activity by 15 and 36% respectively and decreased the extrasynaptosomal Ca2+ concentration necessary to reach it. Histamine and K+ enhanced the synaptosomal (Ca(2+)-Mg2+)-ATPase activity in a concentration-dependent manner. In synaptic plasma membranes histamine (10(-4) M) and 60 mM choline+ were not able to alter the enzymatic activity, however 60 mM K+ and 60 mM Na+ elevated (Ca(2+)-Mg2+)-ATPase activity by 20 and 15%, respectively, without altering the affinity for Ca2+. Histamine effects in synaptosomes were mediated by H2 receptor stimulation. 3-Isobutyl-1-methyl-xanthine (10(-4) M) potentiated (15%) the maximal histamine effect. The slow Ca2+ channel antagonists verapamil and diltiazem, both at 10(-6) M, completely inhibited K+ effects in synaptosomes, however histamine effects were only blocked by verapamil. The data suggest that K+ and histamine effects on synaptosomal (Ca(2+)-Mg2+)-ATPase activity are mediated by increases of intrasynaptosomal Ca2+ levels. Moreover, histamine effects on synaptosomal enzyme activity were mediated by cAMP.

1-Methyl-3-isobutylxanthine↗

Poor implantation of cryopreserved reinsemination-fertilized human embryos.

OBJECTIVE: To investigate whether a poor rate of implantation after in vitro fertilization (IVF) was due to poor embryonic/endometrial synchrony during the original IVF cycle, we have cryopreserved reinseminated-fertilized embryos for later more synchronous replacement after thawing. The chance of implantation of fresh reinseminated fertilized human oocytes is approximately one tenth that of timely fertilized embryos. STUDY DESIGN AND DATA: Retrospective study of 35 original oocyte collections in which initial normal fertilization was 47.3% (129/273 oocytes), with 49.6% fertilization (67/135) upon reinsemination. Of these, 70 initially fertilized and 67 reinsemination-fertilized embryos were cryopreserved, and 50 initially fertilized and all 67 reinsemination-fertilized embryos were subsequently thawed with 72% and 63% cryosurvival, respectively, (not significant). SETTING: Private infertility clinic. RESULTS: In 11 cycles, 23 thawed initially fertilized embryos (group A) were replaced with a 21.7% implantation rate per embryo; in 10 cycles, 13 initially fertilized and 12 reinsemination-fertilized embryos (group B) were replaced together with an 8% implantation rate; finally, in 16 cycles, 30 reinsemination-fertilized embryos (group C) were replaced with a 3.3% implantation rate (group A versus group C: P = 0.076). Comparison of clinical pregnancies between these groups was significantly different (6/11 versus 1/16; P = 0.0427). CONCLUSION: Reinsemination-fertilized embryos survive freezing as well as initially fertilized embryos, but better embryonic/endometrial synchrony does not improve chances of their implantation.

Adult↗

Calcium effects on the solubilization of membrane-bound histidine decarboxylase in the rat brain.

In a previous work we have shown that histidine decarboxylase (HD) activity is found in a soluble and a membrane-bound form. A major part (82%) of the membrane-bound HD activity in the crude mitochondrial fraction (P2) was present in the synaptic plasma membrane-containing subfraction. Physiological concentrations of Ca2+ had no direct effect on HD activity but caused a solubilization of approximately 50% of membrane-bound HD in the P2 fraction. Mg2+ had similar but lower effects (20% solubilization) than Ca2+. Incubation with depolarizing concentrations of K+ in the presence of 1 mM CaCl2 caused a significant (30%) solubilization of HD.

Animals↗

Observations on the morphology of pronuclei and nucleoli in human zygotes and implications for cryopreservation.

The effects of cryopreservation on human zygotes at various stages between the appearance of pronuclei and their close association were investigated. Pronuclear zygotes (n = 233) from 101 patients were frozen using propanediol 21-35 h following egg collection. The incidence of implantation of thawed pronuclear zygotes frozen 29-35 h following oocyte collection was significantly higher than that of younger pronuclear zygotes (28 versus 10%, respectively). Zygote age did not affect cell survival following cryostorage. The diameter and association of pronuclei and the number and distribution of nucleoli were determined from video tape recordings of 140 fresh zygotes. Pronuclear migration continued after pronuclear enlargement. The number of nucleoli remained constant during pronuclear migration, but their random distribution within the pronucleus diminished. Strongly adhered pronuclei had significantly more aligned nucleoli on adjacent sides than pronuclei which were still visually separated by ooplasm. This equatorial distribution of nucleoli was noted in the majority of zygotes older than 26 h. The findings suggest that zygote cryopreservation should be initiated when pronuclear migration is completed. This moment can be determined accurately by studying pronuclear association and nucleolar alignment.

Cell Nucleolus↗

Synaptosomal (Ca2+-Mg2+)-ATPASE activity modulation by cyclic AMP.

Dibutyryl cyclic AMP, in a concentration-dependent manner, increased synaptosomal (Ca2+-Mg2+)-ATPase activity, but in synaptic plasma membranes lacked any effect. The maximal enzyme activity in synaptosomes was increased by 38%, leaving unaltered the extrasynaptosomal Ca2+ concentration necessary to reach it. In the presence of 5 microM cyclic AMP, cyclic AMP-dependent protein kinase increased (30%) maximal (Ca2+-Mg2+)-ATPase activity in synaptic plasma membranes, but the apparent affinity for Ca2+ was not modified. This effect was partially inhibited (60%) by a cyclic AMP-dependent protein kinase inhibitor. The data suggest that synaptosomal (Ca2+-Mg2+)-ATPase activity is modulated by a cyclic AMP-dependent phosphorylation reaction.

Animals↗

Histamine stimulated synaptosomal Ca2+ uptake through activation of calcium channels.

Histamine stimulated Ca2+ uptake in synaptosomes was completely inhibited by the slow Ca2+ channel antagonists verapamil, cinnarizine and flunarizine, and slightly inhibited by nifedipine and diltiazem. Ca2+ uptake in synaptosomes depolarized or predepolarized with varying K+ concentrations was increased by histamine, in both conditions, until 30mM K+. At higher K+ concentrations histamine was not able to alter K+ effects in either conditions. 30mM K+ stimulated uptake of Ca2+ in the absence or presence of histamine was not inhibited by verapamil and diltiazem. However nifedipine slightly inhibited K+ and K+ +histamine effects. 3-Isobutyl-1-methyl-xanthine and dibutyryl cyclicAMP potentiated (10%) the uptake of Ca2+ in synaptosomes induced by histamine. Dibutyryl cyclicAMP alone however decreased the basal Ca2+ uptake in a concentration-dependent manner. Verapamil, but not diltiazem, antagonized the effects elicited by 3-isobutyl-1-methyl-xanthine and dibutyryl cyclicAMP in the presence of histamine. The data suggest that the increase in synaptosomal Ca2+ uptake induced by histamine is mediated by the activation of the voltage sensitive calcium channels, and possibly a cyclicAMP-dependent protein kinase phosphorylation can modulate the opening of Ca2+ channels.

1-Methyl-3-isobutylxanthine↗

Histamine H2-receptor mediated activation of neonatal rat brain ornithine decarboxylase in vivo.

The effect of histamine (HA) administered via intracerebroventricular injection on ornithine decarboxylase (ODC) activity was studied in neonatal rat brain. The HA effect was dose and time dependent. Maximal increase in ODC activity was achieved 2 hr after administration of 10 micrograms HA (38% over control levels). Impromidine (HA H2-agonist) mimicked the effect of HA on ODC and ranitidine (HA H2-antagonist) inhibited the response to HA. Neither 2-thiazolylethylamine (HA H1-agonist) nor mepyramine (HA H1-antagonist) modified control ODC activity. The HA-releasers, compound 48/80 and polymixin B sulfate, elicited an increase in brain ODC activity of 35% and 32%, respectively, over the control value.

Animals↗

Properties and ontogenic development of membrane-bound histidine decarboxylase from rat brain.

Histidine decarboxylase (HD) activity was determined in high-speed fractions (100,000 g for 60 min) obtained from whole rat brain homogenates. Twenty-eight percent of the HD activity was associated with membranes, and the remaining was soluble. Several properties of the soluble and membrane-bound HD were compared. No significant differences in the values of Km for histidine and pyridoxal 5'-phosphate were observed. The solubilization of membrane-bound HD with Triton X-100 resulted in an increase of 60% over the nonsolubilized activity with no changes in the Km for substrate and cofactor. The proportion of free pyridoxal 5'-phosphate-independent activity was identical in both fractions. The soluble and membrane-bound forms of the enzyme differ slightly in their pH-activity profiles, although both enzymes showed an optimum pH near 6.5. The HD activities present in soluble and membrane fractions were determined at different postnatal ages. The soluble activity increased until day 90, whereas the membrane-bound activity became stabilized from day 20.

Aging↗

Direct stimulation of nucleoside triphosphatase activity in human ovarian nuclear membranes by human chorionic gonadotropin.

We previously reported that nuclei isolated from ovaries of premenopausal women contain binding sites for hCG/human LH (hLH). This study was undertaken to determine the possible functional significance of these nuclear binding sites. Upon addition to isolated ovarian (mostly luteal cells) nuclear membranes, hCG and hLH stimulated nucleoside triphosphatase (NTPase), an enzyme involved in nucleocytoplasmic transfer of mRNA, but not Mg2+-ATPase or NADH cytochrome c reductase activities, in a concentration-dependent manner. Heat-denatured hCG, isolated alpha- and beta-subunits of hCG, human FSH, PRL, and porcine relaxin had no effect on the enzyme. Addition of hCG antiserum blocked hCG's ability to stimulate NTPase activity. cAMP, which is a second messenger in hCG- and hLH-stimulated steroidogenesis, had no effect on NTPase activity. These results, which demonstrate that hCG acts on human ovarian nuclei directly, raise the possibility that internalized hCG might influence nuclear function(s) before it is eventually degraded in the lysosomes of ovarian cells.

Animals↗

Effects of altered thyroid function on histamine levels and mast cell number in neonatal rat brain.

The effects of altered thyroid function on the levels of histamine, histidine decarboxylase activity and the number of mast cells were studied in the brain of 5-day-old rats. At this age both brain histamine levels and mast cells number are at a maximum. In addition the major portion of the amine is stored in mast cells and upon subcellular fractionation it sediments in the crude nuclear fraction (P1). Treatments with thyroid hormones or thyrotropic hormone up to 5 days of age leads to a decrease in the histamine levels and mast cells number in the brain, whereas administration of the antithyroid agent 6-n-propyl-2-thiouracil increases both parameters. All treatments affected only the histamine in the P1 fraction and failed to alter the levels of neuronal histamine which is located in the supernatant of P1 (S1). These facts suggest that in neonatal rat thyroid hormones could be involved in the regulation of the levels of brain histamine by regulating the number of brain mast cells.

Animals↗

Colorectal cancer in rural Nebraska.

A case-control interview study of colorectal cancer was conducted in two rural counties of eastern Nebraska to determine reasons for the elevated colon cancer mortality rates during 1950 to 1969. Comparison of the information provided by 86 colorectal cancer cases and 176 matched controls (or their next of kin) revealed an increased risk among persons of Czech background, with persons of Bohemian and Moravian extraction predominating in this area. The data suggest an interaction between Bohemian ancestry and certain dietary patterns in the pathogenesis of colon cancer in this region. Colon cancer risk was elevated among commercial beer drinkers regardless of their ethnic background, although Bohemians reported heavier consumption. An excess risk was also associated with intestinal polyps, reported more often by Moravians, and with familial occurrence of gastrointestinal and other cancers. Since 1969, the mortality and incidence rates for colon cancer in this area have declined, possibly as a consequence of acculturation of the American-born descendants of Czech immigrants.

Age Factors↗