Biomedical subjects

A Toledano

Publications and source records attributed to A Toledano.

At least 19 recordsLinked to original sources

PubMed1998

Synaptic immunolocalization of glyoxylate-complex molecules in the striate areas of the rat cerebral cortex: light and electron microscopic studies.

The location of glyoxylate-complex molecules has been investigated in several areas of the rat cerebral cortex using the immunohistochemical peroxidase-antiperoxidase (PAP) method. Antibodies against glyoxylate-complex molecules have been developed in the rabbit after immunization with a glyoxylate-bovine serum albumin conjugate. Observations carried out with the light microscope demonstrated positive immunostaining at the membrane level of scattered neurons located in all cortical areas, mainly in cortical layer IV. The striate areas (17, 18, 18a) had both the greatest number of immunopositive neurons and the most intense ones. At the electron microscopic level, it was observed that in the striate areas an immunopositive reaction was located mainly in the periphery of synaptic vesicles of some nerve endings, and in both pre- and postsynaptic membranes of these synaptic structures. The presence of glyoxylic acid and glyoxylate-complex molecules in such areas leads us to suggest that these substances could play an important role in selected synaptic contacts in which some pyramidal and non-pyramidal neurons are involved.

Animals↗

PubMed1998

Review of the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction.

BACKGROUND: Topical capsaicin is known to be a safe and effective pain management adjunct for rheumatoid arthritis, osteoarthritis, neuralgias, and diabetic neuropathy. However, studies and case reports in the literature have indicated that other conditions may also benefit from capsaicin: painful or itching cutaneous disorders from operations, injuries, or tumors; neural dysfunction; or inflammation of the airways and urinary tract. METHODS: To determine the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction, the authors analyzed data from 33 reports (MEDLINE search of 1966-96) on the efficacy of capsaicin. Outcome measures consisted of the response rate and degree of pain relief. Results from placebo-controlled trials were pooled when possible; effect of treatment was estimated by the method of DerSimonian and Laird. RESULTS: Pain relief for postmastectomy syndrome and cluster headache was greater with capsaicin than with placebo; also, psoriasis and pruritus responded better to capsaicin. Uncontrolled studies and case reports have indicated that pain or dysfunction was less at the end of capsaicin therapy for neck pain, loin pain/hematuria syndrome, oral mucositis, rhinopathy, reflex sympathetic dystrophy syndrome, detrusor hyperreflexia, and cutaneous pain due to tumor of the skin. CONCLUSIONS: Capsaicin is effective for psoriasis, pruritus, and cluster headache; it is often helpful for the itching and pain of postmastectomy pain syndrome, oral mucositis, cutaneous allergy, loin pain/hematuria syndrome, neck pain, amputation stump pain, and skin tumor; and it may be beneficial for neural dysfunction (detrusor hyperreflexia, reflex sympathetic dystrophy, and rhinopathy). A universal problem for many of the studies analyzed was the absence of a "burning placebo" such as camphor.

Capsaicin↗

PubMed1998

Surgical treatment of laryngotracheal stenosis: a review of 60 cases.

Management of laryngotracheal stenosis (LTS) remains one of the most challenging problems facing the otolaryngologist. The key to success is to obtain adequate rigid circular support with normal mucosal lining. Sixty patients with LTS were surgically treated in our institution over a 20-year period. Most patients were adults; the mean age was 29 years. There were 39 males and 21 females. The most frequent cause of stenosis was intubation, in 25 patients, and tracheostomy was the cause in 21. Forty-two patients (70%) were successfully decannulated following 117 procedures in this series. An average of 1.95 procedures per patient was performed. The median time between treatment and decannulation was 561 days. These results confirm the complexity of the management of LTS. Decannulation is not always possible, and to achieve this goal, more than one treatment is frequently required. It is better to prevent LTS rather than to treat it once it has occurred.

Adolescent↗

PubMed1998

Ankle fracture classification: a comparison of reliability of three X-ray views versus two.

Our hypothesis was that malleolar ankle fractures could be classified with two radiographic views as reliably as with three views. Four different observers independently evaluated 99 sets of ankle radiographs. The examiners classified the ankle fractures by using both the Lauge-Hansen and Danis-Weber systems. The interobserver and intraobserver variations were analyzed by kappa statistics. With regard to intraexaminer reliability, the examiners demonstrated excellent accord in classifying the fractures in the Danis-Weber system with either three views or two views. The kappa values were comparable. In the Lauge-Hansen system, three examiners demonstrated excellent accord and one examiner demonstrated good accord in classifying the fractures. Similar kappa values were generated when examiners classified fractures with either three views or two views. With regard to interexaminer reliability, good to excellent accord was demonstrated overall among the four examiners when they used the Danis-Weber system with either three views or two views. The examiners were in good agreement when they used the Lauge-Hansen system. Similar kappa values were generated whether the examiners used three views or two views. Three radiographic views are usually ordered for evaluation of an acute ankle injury. Previous studies have shown that only two views are needed for diagnosis of a malleolar ankle fracture. This study demonstrates that malleolar ankle fractures can be classified with two views, lateral or mortise, with a reliability as good as that achieved with three views. The best agreement is achieved with lateral and mortise views.

Ankle Injuries↗

PubMed1997

Administration of H1 and H2 antagonists for chemoprophylaxis: a double-blind, placebo-controlled study in healthy volunteers.

A double-blind, placebo-controlled trial was performed to establish the duration of action of antihistamines and their ability to attenuate the adverse affects associated with histamine release. Thirty volunteers were assigned randomly to receive either placebo or a combination of the H1 blocker dimetindene maleate (0.1 mg/kg) and the H2 blocker cimetidine (5 mg/kg). A bolus dose of histamine (450 ng/kg) was given 15 minutes after antihistamine or placebo treatment and repeated after 2, 4, and 6 hours. Cardiovascular variables, plasma histamine levels, cutaneous manifestations, and objective and subjective signs and symptoms associated with histamine release were determined before and after each histamine injection. Although many of the signs of histamine release, including erythema and metallic taste, could be attenuated effectively for 6 hours with antihistamine treatment, the protection against histamine-induced flush and headache diminished after 2 hours. Statistically significant protection against histamine-mediated tachycardia persisted for only 2 hours. Antihistamine treatment significantly reduced the increase in plasma histamine levels after the first histamine injection but did not alter the levels after subsequent histamine injections. The currently recommended administration regimen for prophylaxis with antihistamines is insufficient to prevent histamine-mediated side effects, and additional doses may be required after 4 hours to achieve appropriate chemoprophylaxis.

Adult↗

PubMed1997

The safety and efficacy of oral methylnaltrexone in preventing morphine-induced delay in oral-cecal transit time.

Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier that has the potential to antagonize the peripherally mediated gastrointestinal effects of opioids. In recent trials in human volunteers, we demonstrated that intravenous methylnaltrexone prevented morphine-induced changes in gastrointestinal motility and transit, without affecting analgesia. In this study, 14 healthy volunteers were first given three ascending oral doses of methylnaltrexone to obtain safety and tolerance data (phase A study). In phase B, these subjects were then given single-blind oral placebo and intravenous placebo, followed by randomized, double-blind oral placebo and intravenous morphine (0.05 mg/kg) or oral methylnaltrexone (19.2 mg/kg, an established highest and safe dose based on previous administrations of two smaller doses of 0.64 mg/kg and 6.4 mg/kg in phase A) and intravenous morphine (0.05 mg/kg). Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique after lactulose ingestion. Morphine significantly increased oral-cecal transit time from 114.6 +/- 37.0 minutes (mean +/- SD) to 158.6 +/- 50.2 minutes (p < 0.001). Oral methylnaltrexone (19.2 mg/kg) completely prevented morphine-induced increase in oral-cecal transit time (110.4 +/- 45.0 minutes; not significant compared with baseline; p < 0.005 compared with morphine alone). These sessions were then followed by single-blind evaluations of descending doses of methylnaltrexone. We observed that 6.4 mg/kg oral methylnaltrexone significantly attenuated the morphine-induced delay in oral-cecal transit time (p < 0.005 compared with morphine alone), and a dose-dependent response was obtained. There was no correlation between oral methylnaltrexone effects on the transit time and the drug plasma concentration, suggesting direct preferential luminal effects of oral methylnaltrexone. Oral methylnaltrexone may have a clinical value in the prevention and treatment of constipation induced by long-term opioid use.

Administration, Oral↗

PubMed1997

Observer reliability in ankle radiographic measurements.

We analyzed 50 sets of ankle radiographs to determine the interobserver and intraobserver reliability when obtaining common linear and angular measurements. The radiographs were divided into two groups: one group included 25 normal ankles, and the second group included 25 fractured ankles. Each set of radiographs was evaluated independently by four different observers on two separate occasions under controlled conditions. Six radiographic parameters were measured on all 50 sets of films: syndesmosis A, syndesmosis B, syndesmosis C, the medial clear space, and the talocrural and bimalleolar angles. On the 25 sets of fracture films, four additional measurements of fracture displacement were included: displacement of the medial malleolus (mortise), displacement of the lateral malleolus (AP and lateral), and displacement of the posterior malleolus. Reliability was evaluated with an analysis of variance intraclass correlation coefficient. Among the examiners, 9 of the 10 parameters could be measured reliably. Intraobserver reliability was found to increase with the experience of the examiner.

Analysis of Variance↗

PubMed1997

[Growth and aging factors in physiological senility and Alzheimer's disease].

INTRODUCTION: Both the normal and pathological development and involution of the CNS are regulated by an important set of both, 'growth factors' (inducing growth, differentiation, survival, adaptation or plasticity in neurons) and 'ageing factors' (inducing involution, atrophy, necrosis or apoptosis). In neurodegenerative diseases, significant deficits of growth factors and important presence of ageing factors are being detected, mainly in Alzheimer's disease (AD). DEVELOPMENT: In this review, the most important growth factors (NGF, BDNF, neuromodulators, glial factors, etc.) and ageing factors (amyloid, tanatins, calcium, mitochondrial factors, etc.) in the pathogenesis of the AD are discussed. CONCLUSIONS: The knowledge and assessment of these endogenous factors must have an important role in the diagnosis and treatment of the cognitive impairment that characterizes senility and AD.

Aged↗

PubMed1997

[Results of surgery for hyperparathyroidism].

Since 1983, we have performed 110 parathyroidectomies in 109 patients. The hyperparathyroidism was diagnosed as primary in 102 (93.6%) patients, secondary in 6 (5.5%), and tertiary in 1 (0.9%). Sixty-one patients (55.9%) had single adenomas, 2 (1.8%) had double adenomas, 44 (40.3%) had hyperplasia and 1 (0.9%) had parathyroid cancer. Sixty-five adenomas were resected (59.6%). Subtotal parathyroidectomy was performed in 34 cases (31.2%) and total parathyroidectomy with autotransplant in 10 cases (9.2%). In two cases, primary surgery did not solve hypercalcemia; one underwent successful surgery several months later. Twenty-two patients (20.2%) developed transient hypocalcemia. Persistent hypoparathyroidism was detected in 8 patients (7.3%). After exposure of 220 nerves, 2 patients (0.9%) developed permanent unilateral recurrent paralysis. Our results were similar to those of other series.

Adenoma↗

PubMed1996

Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without affecting analgesia: a double-blind randomized placebo-controlled trial.

Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier and the potential to antagonize the peripherally mediated effects of opioids. The effectiveness of methylnaltrexone in preventing morphine-induced changes in gastrointestinal motility and transit without affecting analgesia was evaluated in humans. Twelve healthy volunteers were given intravenous placebo, placebo plus 0.05 mg/kg morphine, or 0.45 mg/kg methylnaltrexone plus 0.05 mg/kg morphine. Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique, and analgesia was measured with use of the cold-pressor test. Morphine significantly increased oral-cecal transit time from 104.6 +/- 31.1 minutes (mean +/- SD) to 163.3 +/- 39.8 minutes (p < 0.01). Methylnaltrexone prevented 97% of morphine-induced increase in oral-cecal transit time (106.3 +/- 39.8 minutes; not significant compared with baseline; p < 0.01 compared with morphine alone). Methylnaltrexone did not affect the analgesic effect of morphine on both pain intensity and pain bothersomeness ratings. At a higher dose of morphine (0.1 mg/kg), our preliminary results indicated that 0.45 mg/kg methylnaltrexone also prevented the morphine-induced delay in oral-cecal transit time, with no effect on analgesia. Methylnaltrexone may be a useful adjunct to opioids for the relief of opioid-induced constipation.

Adolescent↗

PubMed1996

Assessing myocardial perfusion with Albunex during coronary artery bypass surgery: technical considerations and safety of aortic root injections.

OBJECTIVE: To test the safety and report on limiting technical considerations, including optimal dosing of Albunex (Molecular Biosystems, Inc, Mallinckrodt Medical, St. Louis, MO) for myocardial opacification after intra-aortic root injections during cardiac surgery. DESIGN: This was a prospective randomized study with a control group who did not receive Albunex and a group who received intra-aortic root injections of Albunex. SETTING: Multicenter (two) independent university hospitals. PARTICIPANTS: 32 patients scheduled for elective coronary artery bypass surgery were evaluated after individual informed consent was obtained. INTERVENTIONS: 2 to 8 mL of Albunex were injected before and after coronary revascularization. MEASUREMENTS AND MAIN RESULTS: Quality of enhancement in each of four regions of the left ventricle was assessed from a short-axis mid-papillary ultrasound image by three experienced observers blinded to dose. Electrocardiogram (ECG), creatine phosphokinase (CPK) (MB fraction), and hemodynamics were evaluated at baseline and throughout the study period for up to 72 hours. No differences were noted between groups with respect to preoperative and postoperative CPK enzymes (CPK-MB fraction), ECG changes, hemodynamics, requirements for separation from CPB, need for postoperative inotropes, time to extubation, and time to discharge from the intensive care unit. The average total dose of Albunex injected was 19 mL +/- 4 (0.25 mL/kg). A single dose of 4.2 +/- 1.2 mL (0.05 mL/kg) appeared to offer optimal enhancement of contrast effect for myocardial perfusion assessment. CONCLUSION: Albunex is safe and easy to use for myocardial opacification when administered via an antegrade cardioplegia catheter into the aortic root during CPB.

Aged↗

PubMed1996

Aged murine T-lymphocytes are more resistant to oxidative damage due to the predominance of the cells possessing the memory phenotype.

Glutathione (GSH) is the most important cytosolic antioxidant. Since GSH levels are decreased with age, we hypothesized that T-lymphocytes from old mice would be more sensitive to oxidative stress. T-lymphocytes from young and old mice were exposed to hypoxanthine/xanthine oxidase, and lymphocyte viability, proliferation, GSH content, and calcium signaling were measured. Before exposure, proliferation of T-lymphocytes from young mice was greater than that of old; following exposure, the converse was true. This was in spite of the fact that old mice had lower total GSH levels and greater levels of glutathione disulfide. After oxidative challenge, intracellular calcium responses to anti-CD3 were decreased in naive T-lymphocytes from all mice, while memory lymphocytes were less affected. Higher proportions of memory lymphocytes in old mice resulted in their greater overall preservation of lymphocyte function following oxidative injury, contrary to expectations that lower lymphocyte GSH content with age would increase susceptibility to oxidative stress.

Aging↗

PubMed1996

Sedation of critically ill patients during mechanical ventilation. A comparison of propofol and midazolam.

Propofol (P) and midazolam (M) are frequently given by continuous infusion for sedation in critically ill, mechanically ventilated patients. We compared these drugs with regard to: (1) time-to-awaken; (2) reproducibility of bedside assessments of level of sedation; (3) time-to-sedation; and (4) change in oxygen consumption (V O2) from awake to sedated state. Seventy-three patients were prospectively randomized to receive either P (n=37) or M (n=36). Wake-up times after stopping the drug were assessed by blinded and unblinded observers, by asking patients to perform simple tasks. Times to sedate were assessed by consensus agreement among nurses and investigators. Demographics and APACHE II scores were not different between P and M. The P group had a significantly narrower range of wake-up times with a higher likelihood of waking in less than 60 min. Blinded versus unblinded observations had excellent correlation. Average time to sedate and decrease in V O2 were not different. We conclude that in this patient population: (1) both P and M achieved optimal sedation in a large fraction of patients when administered by specified dosing protocols; (2) P had a faster, more reliable, wake-up time; (3) assessments of time-to-awaken were objective and reproducible; (4) time to sedation was not significantly different; (5) V O2 decreased similarly with both.

APACHE↗

PubMed1996

Distribution of glyoxylate dehydrogenase activity in cortical and subcortical regions of the rat brain. A light microscopic histoenzymological study.

The distribution of the glyoxylate dehydrogenase (GLYO-DH) (Glyoxylate oxidoreductase) activity has been investigated in rat brain using the corresponding histochemical method. The results have demonstrated a positive histochemical reaction in neurons of several cortical and subcortical areas. These neurons are located in the same regions in which operate monoaminergic neurotransmitters. These facts suggest a possible interaction between glyoxylic acid and monoaminergic neurotransmission.

Aldehyde Oxidoreductases↗

PubMed1996

Radiation can inhibit tumor growth indirectly while depleting circulating leukocytes.

The growth of certain UV-radiation-induced tumors is suppressed by T lymphocytes, but it has been proposed that non-T lymphocytes stimulate the growth of several of these tumors. In this study, the indirect effects of X irradiation on the growth of one such tumor in T-cell-deficient nude mice was tested. Even when the site of tumor cell injection was shielded, whole-body irradiation with 6 Gy before tumor challenge inhibited subsequent tumor growth significantly. The interval during which this indirect inhibition was observed correlated with the depletion of circulating leukocytes, which did not return to normal levels until 12-21 days after irradiation. These data are consistent with earlier results using an antibody to deplete Gr-1+ leukocytes and indicate that radiation can inhibit the growth of certain tumors indirectly without direct effects on the tumor cells or the tumor bed.

Animals↗

PubMed1996

Neuronal and non-neuronal localization of acid sulfated glycosaminoglycans (sGAG) and chondroitin proteoglycans in the rat medulla oblongata.

Acid sulfated glycosaminoglycans (sGAG) and chondroitin proteoglycans have been biochemically and immunohistochemically demonstrated in certain cortical areas of the CNS. Such molecules display an important role in cerebral function, modulating cell adhesion, migration and signal neuromediation. In the present study we have evidenced the presence of sGAG using the colloidal iron method and C0S, C4S- and C6S-proteoglycans by the immunohistochemical pre-embedding PAP method. Our results have demonstrated the presence of such molecules in several structures of nervous (axon terminals, neuronal bodies, dendrites) and non-nervous nature (glial processes, capillaries). This fact led us to suggest that the chondroitin localizations advocate for their different functions. In their various localization exist distinct proteoglycans constituted by chondroitins with diverse concentrations and other attached radicals.

Animals↗

PubMed1996

Bowel resection and neurotensin treatment. Histochemical study of neurotensin-like and somatostatin-like immunoreactivities and receptors.

The influence of a bowel-trophic neurotensin (NT) treatment (13 days, 300 micrograms/kg/every 12 hrs.) on neurotensin-like immunopositive structures (neurons, fibres and epithelial-N-cells) and the neurotensin receptors (NTr) in the residual bowel after resection (90% small bowel or 75% colon) in the rat was studied using histochemical methods. Somatostatin-like (ST) immunopositive structures (neurons, fibres and epithelial-D-cells) and somatostatin receptors (STr) were also studied, comparatively. The results displayed a general increase of N-cells (11-17%) but not of D-cells, and a higher degree of variability section-to-section in the NT and ST immunopositive nervous structures (without increased density) after both resections, both with or without NT treatment. Receptors did not change after the small bowel resection but the colon resection and/or the NT treatment produced variations in the NT binding (from -24.3 to +16.85) in different intestinal regions. In a general sense, the variations among 1) the controls, 2) the resected animals, and 3) the resected and NT-treated animals, were of less extent (< or = 24%) than previously supposed for explaining the trophic effect of NT. Our results: a) confirm the autonomy, injury-resistance and tendency to maintain the physiological features of the bowel in very diverse situations; b) open new questions on both, the neurotensinergic changes after bowel resection and the mechanisms of the trophic effect of NT treatment, and c) suggest that, when neurotensin was applied as a trophic treatment in the cases of the need of a bowel resection, no important neurotensinergic or somatostatinergic side effects should be expected in the remaining bowel. However, the higher degree of variability section-to-section after surgery in the nervous structures was not modified by the NT treatment. This fact, and the different response of various intestinal regions to the NT treatment, suggest that functional problems in the remaining bowel could be maintained despite the growth of the mucosa induced by the NT treatment.

Animals↗

PubMed1995

Spatial and temporal control of gene therapy using ionizing radiation.

Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal cytokine, tumour necrosis factor-alpha (TNF-alpha) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment with Ad5.Egr-TNF and 5,000 cGy (rad) resulted in increased intratumoral TNF-alpha production and increased tumour control compared with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transcription by ionizing radiation in vivo represents a novel method of spatial and temporal regulation of gene-based medical treatments.

Animals↗