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Biomedical subjects

C Leon

Publications and source records attributed to C Leon.

At least 19 recordsLinked to original sources
PubMed2006

Decreased thrombotic tendency in mouse models of the Bernard-Soulier syndrome.

OBJECTIVE: The platelet glycoprotein (GP)Ib-V-IX complex is a receptor required for normal hemostasis deficient in the Bernard-Soulier bleeding disorder. To evaluate the consequences of GPIb-V-IX deficiency in thrombosis we generated mouse models of the disease by targeting the GPIb beta subunit. METHODS AND RESULTS: Complete deletion (GPIb beta-/-) or an intracellular truncation (GPIb beta deltaIC-/-) reproduced typical and variant forms of Bernard-Soulier, with absent and partial (20%) expression of the complex on the platelet surface. Both strains exhibited thrombocytopenia and enlarged platelets with abnormal microtubular structures but normal granule composition. They exhibited prolonged tail bleeding times, which were less pronounced in GPIb beta deltaIC-/-. Decreased thrombus formation was observed after blood perfusion over a collagen coated surface at high shear. Resistance to vascular occlusion and an abnormal thrombus composition were observed in a model of FeCl3-induced lesion of carotid arteries. In a model of laser-induced lesion of mesenteric arterioles, thrombosis was strongly reduced in GPIb beta-/- mice, while a more modest effect was observed in GPIb beta deltaIC-/- animals. Finally, the two strains were protected against death in a model of systemic thromboembolism. CONCLUSIONS: This study provides in vivo evidence of a decreased thrombotic tendency linked to defective platelet GPIb-V-IX in mouse models of Bernard-Soulier syndrome.

Animals↗
PubMed2006

Does p-glycoprotein play a role in gastrointestinal absorption and cellular transport of dietary cholesterol?

This commentary discusses the potential role of p-glycoprotein (Pgp) on the gastrointestinal absorption and cellular transport of dietary cholesterol. This is currently a controversial issue due to the conflicting evidence about the role of this ABC transporter in cholesterol transport. During the preparation of this commentary, several key publications on this topic arguing for and against this mechanism have been published. If true, this mechanism of Pgp could represent a novel role for Pgp and provide a potentially new molecular target for drug design and development.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Giant magnetoresistance in ferromagnet/superconductor superlattices.

We show magnetoresistance in excess of 1000% in trilayers containing highly spin-polarized La0.7Ca0.3MnO3 and high-Tc superconducting YBa2Cu3O7. This large magnetoresistance is reminiscent of the giant magnetoresistance (GMR) in metallic superlattices but with much larger values, and originates at spin imbalance due to the injection of spin-polarized carriers. Furthermore, in contrast to ordinary GMR, the magnetoresistance is intimately related to the superconductivity in the YBa2Cu3O7 layer and vanishes in the normal state. This result, aside from its fundamental importance, may be of interest for the design of novel spintronic devices based on ferromagnet/superconductor structures.

Journal Article↗
PubMed2005

Factors associated with poor outcomes in patients with lupus nephritis.

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 +/- 6 versus 5 +/- 5, P < 0.05), chronicity index (CI) score (4 +/- 3 versus 2 +/- 2 unit, P < 0.025), higher baseline mean arterial pressure (MAP) (111 +/- 21 versus 102 +/- 14 mmHg, P < 0.025) and serum creatinine (1.9 +/- 1.3 versus 1.3 +/- 1.0 mg/dL, P < 0.025), but lower baseline hematocrit (29 +/- 6 versus 31 + 5%, P < 0.025) and complement C3 (54 +/- 26 versus 65 + 33 mg/dL, P < 0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P < 0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.

Adult↗
PubMed2004

[Levofloxacin in patients in the ICU. Factors influencing the choice of dose and its use in combined therapy].

This study aimed to identify factors that influence the selection of different approaches to prescribing levofloxacin (e.g., monotherapy vs. combined therapy, 12-h vs. 24-h interval) and the effect on mortality in the ICU. An observational, prospective, multicenter study was conducted. A logistic regression analysis was performed to identify factors associated with the prescription of levofloxacin in combined therapy and at a dose of 500 mg every 12 hours. In addition, a logistic regression analysis was conducted to determine the impact of the different prescribing methods on mortality in the ICU. The most frequently administered initial dose was 500 mg/24 h (48.5%) and 500 mg/12 h (48.3%). No factors were found to influence the choice of daily dose. A total of 49.7% of levofloxacin prescriptions were in combined therapy. Factors influencing the decision to prescribe a combined regimen included diagnosis of extra-ICU nosocomial infection (OR: 1.97; 95% CI: 1.13-3.42); severe sepsis (OR: 2.56; 95% CI: 1.66-3.94); septic shock (OR: 6.22; 95% CI: 3.54-10.9); and identification of the causative pathogen (OR: 1.99: 95% CI: 1.34-2.95). The mortality rate was 21.4% and the related factors were septic shock (OR: 3.09; 95% CI: 1.38-6.91); treatment failure (OR: 23.4; 95% CI: 12.3-44.6); and combined therapy (OR: 2.36; 95% CI: 1.21-4.59). The selection of the initial dose of levofloxacin was not influenced by any factor, as long as the antibiotic was given in combined therapy in patients in whom the cause of the infection had been identified, in patients with greater systemic response, and in nosocomial infection outside the ICU. The selection of combined therapy was associated with a worse prognosis.

Anti-Infective Agents↗
PubMed1997

Grg3, a murine Groucho-related gene, is expressed in the developing nervous system and in mesenchyme-induced epithelial structures.

We have isolated cDNAs representing multiple members of murine groucho homologues, designated Grg for groucho-related genes. Among them, Grg3 appears to produce two transcripts. One of the Grg3 transcripts contains coding sequence for a complete Groucho protein homologue. The second transcript contains coding sequence for only the two amino-terminal domains of the Groucho protein, followed by a hydrophobic tail and a stop codon. We analyzed the expression of both transcripts in mouse embryos using RNase protection and in situ hybridization. Expression was detected during cell determination in the nervous system and in somitic mesoderm, overlapping Notch1 expression and adjacent to Mash1, MyoD and Myf5 expression. Thus, the expression pattern of Grg3 suggests a conserved role in the Notch signalling pathway to regulate expression of basic helix-loop-helix proteins and cell determination. Grg3 expression was also consistently detected in epithelial structures undergoing mesenchyme induction.

Alternative Splicing↗
PubMed1997

Traditional remedies and food supplements. A 5-year toxicological study (1991-1995).

Since 1991, the Medical Toxicology Unit (MTU) at Guys' Hospital, London, has been assessing the toxicological problems associated with the use of traditional and herbal remedies and dietary supplements. This assessment was carried out by evaluating reports to the National Poisons Information Service (London) [NPIS(L)] which provides emergency information to medical professionals. Relevant telephone enquiries to NPIS(L) were identified. Further case details were obtained by follow-up questionnaire, clinical consultation, toxicological analysis of samples from patients and/or products and botanical identification of plant material. Of 1297 symptomatic enquiries evaluated there was a possible/confirmed association in 785 cases. Case series have been identified which substantiate previous reports, including liver problems following the use of Chinese herbal medicine for skin disorders, allergic reactions to royal jelly and propolis and heavy metal poisoning caused by remedies from the Indian subcontinent. Although the overall risk to public health appears to be low, certain groups of traditional remedies have been associated with a number of potentially serious adverse effects. Considering the extent of use of herbal remedies and food supplements a comprehensive surveillance system for monitoring the adverse health effects of these products is essential. Surveillance of a large population is needed for the complex task of identifying the uncommon and unpredictable adverse effects which are potentially serious. In the UK, the Medicines Control Agency responded to the MTU report by recognising the need for vigilance and by incorporating adverse reactions reporting on unlicensed herbal remedies into their drug reaction monitoring function. As a further step to safeguard the patients/consumers an effective single regulatory system is required which would ensure the safety and quality of all herbal remedies and food supplements available in the UK.

Amino Acids↗
PubMed1996

Use of occlusive dressings on central venous catheter sites in hospitalized children.

Although the use of occlusive dressings in adults has been criticized in the literature, there has been little written on their use in the pediatric population. Management of dressing sites requires nursing judgement unique to this population. This study focused on the progression of microbial colonization and signs of inflammation occurring beneath repeated occlusive dressings applied to central venous catheter (CVC) insertion sites among 104 hospitalized children (neonate to 18 years). A noninvasive skin culture was obtained within 24 hours of CVC placement, 3 to 7 days later before the next routine dressing change, and at the time the CVC was discontinued or the child was discharged, whichever occurred first. Results showed a significant increase in microbial growth (p < or = .001) at the second dressing change, when serosanguinous drainage was heaviest, and continued significant growth (p < or = .001) when the dressing was discontinued. This microbial growth pattern was curious in the face of a 0.3% systemic sepsis rate. When neonates under 1,800 g were excluded from calculation, the pattern was not notable (p = .2119). Findings suggest the use of occlusive dressings during prolonged hospitalization for tunnelled CVCs does not lead to increased site infections in children over 1,800 g.

Adolescent↗
PubMed1995

Possible association of liver damage with the use of Chinese herbal medicine for skin disease.

From January 1991 to December 1993, we received reports of 11 cases of liver damage following the use of Chinese Herbal Medicine (CHM) for skin conditions. There was strong evidence of an etological association in 2 cases in which recovery after dechallenge and recurrence of hepatitis after rechallenge were observed. The time-course relationship, recovery after ceasing CHM, and absence of alternative causes of liver damage suggested an association in 2 further symptomatic cases following a single period of exposure. Herbal material was available for analysis in 7 cases. The plant mixtures varied so no single ingredient could account for liver injury in this case series. The mechanism of toxicity is unclear; effects do not appear dose-related and are probably idiosyncratic. Liver function should be monitored in patients who use CHM for skin disorders and its use discontinued if problems occur. The complexity of these cases illustrates the requirement for continuous surveillance of CHM including pharmacognostical investigation of ingredients.

Adult↗
PubMed1994

Toxicological problems resulting from exposure to traditional remedies and food supplements.

The National Poisons Unit, London, carried out a pilot survey to investigate the frequency and severity of adverse effects/toxicity from exposure to traditional medicines and food supplements reported to the Unit. Enquiries related to suspected poisoning events were reviewed retrospectively from January 1983 to March 1989, and prospectively in 1991. Further information about cases identified by the prospective review was obtained, when appropriate, by follow-up questionnaire, clinical consultation by a consultant toxicologist, toxicological analyses of samples from patients and from products, and botanical identification of dried plant material. In total, 5536 enquiries were identified. Symptoms were reported in 657 (12%) of these. There was a large number of reports of accidental ingestion of vitamin preparations by children under 5 years. Appropriate assessment was possible in only relatively few cases, due to insufficient documentation, and poor labelling of certain products. A probable link between exposure and adverse effects was identified in 42 cases, and was highly probable in two. Heavy metal poisoning resulting from use of contaminated traditional remedies was confirmed in 5 cases. There was evidence that some patients took excessive doses of food supplements, without realising that this might result in toxic effects. The results of this pilot study suggest that there is a need for further surveillance to provide an appropriate risk assessment of food supplements and herbal remedies, improved quality control and labelling of these products, and increased awareness of their potential hazard.

Adolescent↗
PubMed1993

Osteochondral allografts for osteochondritis dissecans and osteonecrosis of the femoral condyles.

Osteochondral allografts were used in 11 patients with osteochondritis dissecans and 4 with osteonecrosis of the femoral condyles. The lesions were mainly in the medial condyle in 13 cases, and in the weightbearing area in 10. The grafts had a mean size of 6 cm2; 8 were kept in hypothermia at 4 degrees C for less than 24 h and 7 were stored at -80 degrees C with cryoprotection. After an average follow up of 3.2 years, only 2 patients needed a further operation, one for nonunion and the other for a fracture of the graft. The others had improved clinically and showed radiological union of the graft with preservation of the joint space.

Adult↗
PubMed1993

Electrophysiological evaluation of moricizine in patients with sustained ventricular tachyarrhythmias: low efficacy and high incidence of proarrhythmia.

In patients with history of sustained ventricular tachycarrhythmias, the efficacy and safety of moricizine have not been systematically evaluated by electrophysiological studies. We performed electrophysiological testing in these patients in the drug-free state and then after moricizine loading, and evaluated the safety profile of moricizine during in-hospital loading and follow-up. The study population comprised of 31 patients with clinically sustained ventricular tachyarrhythmia. The underlying heart disease was coronary in 25 patients, cardiomyopathy in 5 patients, and none in 1 patient. The left ventricular (LV) ejection fraction ranged from 15%-69% (mean 39 +/- 15%). During the baseline drug-free electrophysiological testing, sustained ventricular tachycardia was inducible in 27 patients, ventricular fibrillation in 1 patient, and reproducible, nonsustained ventricular tachycardia (15-25 sec) in 3 patients. All 31 patients received moricizine to the maximum tolerated dose (851 +/- 185 mg) over a period of 2-7 days. Six patients developed ventricular proarrhythmia within the first 4 days. Proarrhythmia required multiple cardioversions in three patients, was not associated with QT prolongation, and spontaneously resolved 6-24 hours after withdrawal of moricizine. Of the remaining 25 patients, 24 underwent electrophysiological testing on moricizine and 4 patients (16%) were rendered noninducible. The VT cycle length in the other 20 patients slowed from 243 +/- 30 msec to 299 +/- 60 msec (P < 0.09). Four noninducible patients, two patients with inducible but slowed VT and one patient who had refused further testing were discharged on moricizine.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

Cellular localization of the neural cell adhesion molecule L1 in adult rat neuroendocrine and endocrine tissues: comparisons with NCAM.

The tissue distribution and cellular localization of the neural cell adhesion molecule L1 was determined by immunocytochemistry at the optical and ultrastructural levels in adult rat neuroendocrine tissues and pancreatic endocrine cells. L1 was found to be abundant in the neurohypophysis but undetectable in the rest of the pituitary gland. It was barely detectable in the normal rat endocrine pancreas, but a rat pancreatic insulinoma cell line was found by immunofluorescence to express low levels of L1. In the adrenal medulla, it was present on a sub-population of chromaffin cells and its density appeared to be lower on surfaces exposed to the extracellular matrix. Double immunolabelling showed this sub-population to consist of noradrenergic chromaffin cells. Adrenergic chromaffin cells were found not to express L1. In addition, the tissue distribution and cellular localization of NCAM mRNAs was determined by in situ hybridization, extending our previous studies on the cellular expression of NCAM proteins in endocrine and neuroendocrine tissues. This confirmed that the NCAM message has a wider cellular distribution than L1 within the hypophysis and the adrenal gland. In addition to secretory cells, L1 immunoreactivity was detected in glial cells, in particular in the pituicytes of the neurohypophysis, which further distinguishes them from astrocytes, their counterparts in the central nervous system. These data are discussed in terms of the different embryological origins of the various endocrine tissues examined and also in terms of the specific design constraints imposed on these tissues during their development.

Adrenal Glands↗
PubMed1992

Prognostic significance of programmed ventricular stimulation in patients surviving complicated acute myocardial infarction: a prospective study.

In survivors of complicated myocardial infarction, the inducibility of sustained ventricular tachycardia may help identify a subset that is at increased risk for subsequent sudden cardiac death or spontaneous sustained ventricular tachycardia. We performed prehospital discharge programmed ventricular stimulation in 86 survivors of acute myocardial infarction complicated by heart failure, angina pectoris, or nonsustained ventricular tachycardia. These patients also underwent cardiac catheterization with coronary angiography and 24-hour ambulatory ECG recording. Programmed ventricular stimulation induced sustained ventricular tachycardia in 19 patients (22%) and ventricular fibrillation in six (7%) and did not induce these arrhythmias in 61 patients (71%). During an average follow-up of 18 +/- 13 months, 11 patients had arrhythmic events (seven sudden death and four nonfatal spontaneous sustained ventricular tachycardia) and 10 patients had nonsudden cardiac death. The total cardiac mortality rate was 20%. Arrhythmic events occurred in 32% of the 19 patients with inducible sustained ventricular tachycardia compared with 7% of the remaining 67 patients (p less than 0.003). By multivariate analysis the occurrence of arrhythmic events was independently predicted by both inducible sustained ventricular tachycardia and Killip class III or IV heart failure. The risk of arrhythmic events was 4.4% in the absence of both variables versus 38.4% (p less than 0.001) when both variables were present. The total cardiac mortality rate was best predicted by low left ventricular ejection fraction (less than 30%). Thus programmed ventricular stimulation is useful in risk stratification of survivors of complicated acute myocardial infarction. The prognostic utility appears to be particularly high in patients with infarction complicated by Killip class III or IV heart failure.

Arrhythmias, Cardiac↗
PubMed1992

Intact articular cartilage cryopreservation. In vivo evaluation.

By varying the parameters that determine the cryopreservation process (freezing rate, storage temperature, cryoprotective agents, storage time), various protocols have been designed for preservation of osteochondral allografts of rabbit femoral condyles. The grafts were implanted orthotopically for three months. After harvesting, the results were evaluated by optical microscopy, histochemistry, and electron microscopy (scanning and transmission). A quantitative study and statistical analysis was performed using a gradation scale of chondral degeneration. Synovial reaction was higher in the fresh allograft than in the cryopreservation groups. Glycerol yielded better results than DMSO as a cryoprotective agent. No cryopreservation protocols produced the results equal to the control groups of either fresh auto- or allografts. Optimal preservation was achieved with either the group with hypothermic storage at 4 degrees for no more than 48 hours or the group with slow freezing to -80 degrees and preparative exposure to 15% glycerol at 4 degrees for 60 minutes. No statistically significant differences were found in these two groups.

Animals↗