Biomedical subjects

David Ezra

Publications and source records attributed to David Ezra.

14 recordsLinked to original sources

PubMed2006

Cytomegalovirus-associated colitis causing diarrhea in an immunocompetent patient.

Cytomegalovirus (CMV) colitis rarely occurs in immunocompetent patients. We report a case of disabling and life threatening diarrhea in an immunocompetent elderly woman due to CMV colitis. The diagnosis of CMV was based on histological examination of tissues biopsied at colonoscopy, positive CMV antigen and high CMV-IgM titer in peripheral blood samples and a good response to systemic gancyclovir treatment. We conclude that CMV should be considered in the differential diagnosis of colitis in elderly immunocompetent patients.

Age Factors↗

PubMed2006

Biologically active endophytic streptomycetes from Nothofagus spp. and other plants in Patagonia.

Endophytic streptomycetes have been isolated and characterized from several species of Nothofagus and other plants growing in the southern reaches of Patagonia. No endophytic streptomycete was obtained from any plant species studied in Northern Patagonia. However, from Southern Patagonia, biologically active Streptomyces spp. from several plant species were isolated. Each isolate, as studied by scanning electron microscopy (SEM), has small hyphae, some produce typical barrel-shaped spores in culture and each has some unique hyphal surface structures. Interestingly, although none has any detectable antibacterial killing properties, each has demonstrable killing activity against one or more pathogenic fungi including representative plant pathogenic organisms such as Phytophthora erythroseptica, Pythium ultimum, Sclerotinia sclerotiorum, Mycosphaerella fijiensis, and Rhizoctonia solani. The 16S rDNA sequences of the isolates were distinct from all other genetic accessions of Streptomyces in GenBank. However, isolate C-2 from Chiliotrichum diffusum (Compositae) is identical, in all respects, to isolate C-4 obtained from Misodendrum punctulatum (Loranthaceae). These results confirm that endophytic streptomycetes represent a novel source of biologically active microorganisms.

Antibiosis↗

PubMed2006

Cardiovascular calcifications after radiation therapy for Hodgkin lymphoma: computed tomography detection and clinical correlation.

OBJECTIVE: To study cardiovascular calcifications, detected by computed tomography, in patients following mediastinal radiation for Hodgkin lymphoma, and correlate them with clinical findings. MATERIALS AND METHODS: Fifteen patients, <or=55 years, with computed tomography detected cardiovascular calcifications after mediastinal radiotherapy for Hodgkin lymphoma were identified during a 10-year period. Calcifications were evaluated for site and extent and were correlated with clinical data including symptoms and signs of heart disease, angiographic and surgical findings. RESULTS: Accelerated calcifications were detected in the coronary arteries (n=11), in the aorta (n=11), and in the aortic valve and the mitral apparatus (n=8). Calcifications were more extensive when radiation was given at a young age. Clinical evidence of cardiovascular disease included coronary events in three patients, valvular dysfunction in two, pericarditis in two and complete atrioventricular block in one. Seven patients had no cardiac symptoms. CONCLUSION: Early cardiovascular calcifications can be radiation associated. Such calcifications may represent radiation-induced atherosclerosis and can be detected by computed tomography even in asymptomatic patients. The implication of our findings is that spiral computed tomography may serve as a non-invasive modality to detect accelerated cardiovascular calcifications in high-risk asymptomatic patients who survived Hodgkin lymphoma.

Adult↗

PubMed2005

Simultaneous deep vein thrombosis and transverse myelitis with negative serology as a first sign of antiphospholipid syndrome: a case report and review of the literature.

Transverse myelitis is a rare manifestation of antiphospholipid syndrome, usually secondary to systemic lupus erythematosus (Rheum Dis Clin North Am 20:129-158, 1994). Only about 110 reports of this complication have been reported (Lupus 10:851-856, 2001). A connection has been demonstrated between positive serology for antiphospholipid and transverse myelitis (Lupus 8:109-115, 1999). Herein, we report of a young patient admitted with deep vein thrombosis and neurological manifestations of transverse myelitis with negative serology for systemic lupus erythematosus and antiphospholipid, who developed positive anticardiolipin antibody during pulse therapy with cyclophosphamide and methylprednisolone.

Adult↗

PubMed2004

Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland.

Many patients with cardiac arrhythmias require concomitant therapy with warfarin and amiodarone. Beyond the predictable pharmacokinetic drug-drug interaction requiring a significant warfarin dose reduction, the iodine-rich amiodarone affects the thyroid gland, causing overt hypothyroidism or thyrotoxicosis in 14%-18% of cases. In turn, thyroid disorders may affect warfarin sensitivity, with hypothyroidism and thyrotoxicosis resulting in increased or decreased warfarin requirements, respectively. We describe 3 patients on concomitant amiodarone and warfarin who developed amiodarone-induced thyrotoxicosis heralded by a significant decrease in warfarin requirements. We review the literature on the mechanisms of the complex drug-drug and drug-disease interactions within the thyroid gland, warfarin, and amiodarone triad. Given that significant thyroid disorders may be only mildly symptomatic and thus may escape clinical detection, we suggest that thyroid function should be tested in any patient with otherwise unexplained changes in warfarin dose requirements, particularly if concomitantly treated with amiodarone.

Adult↗

PubMed2004

Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp.

Coronamycin is a complex of novel peptide antibiotics with activity against pythiaceous fungi and the human fungal pathogen Cryptococcus neoformans. It is also active against the malarial parasite, Plasmodium falciparum, with an IC(50) of 9.0 ng ml(-1). Coronamycin is produced by a verticillate Streptomyces sp. isolated as an endophyte from an epiphytic vine, Monstera sp., found in the Manu region of the upper Amazon of Peru. Bioassay-guided fractionation of the fermentation broths of this endophyte on silica gel and HPLC chromatography yielded two principal, inseparable, peptides with masses of 1217.9 and 1203.8 Da. Three other minor, but related components, are also present in the preparation. Amino acid analysis of coronamycin revealed residues of component 1, component 2, methionine, tyrosine and leucine at a ratio of 2:2:1:1:3. Other compounds with antifungal activities are also produced by this endophytic streptomycete.

Animals↗

PubMed2004

New endophytic isolates of Muscodor albus, a volatile-antibiotic-producing fungus.

Muscodor albus, an endophytic fungus originally isolated from Cinnamomum zeylanicum, produces a mixture of volatile organic compounds (VOCs) in culture and its spectrum of antimicrobial activity is broad. Using the original isolate of M. albus as a selection tool, it has been possible to find other culturally and biochemically unique wild-type isolates of this organism existing as endophytes in a variety of other plant species, including Grevillea pterifolia (fern-leafed grevillea), Kennedia nigriscans (snake vine) and Terminalia prostrata (nanka bakarra) growing in the northern reaches of the Northern Territory of Australia. Interestingly, none of the new isolates had a culture morphology that was identical to the original isolate, nevertheless each possessed hyphal characteristics that resembled that isolate. Furthermore, their ITS-5.8S rDNA sequences were 96-99 % identical to that of M. albus and the isolates were considered M. albus on the basis of the DNA sequence data. However, the VOCs produced by these new isolates greatly differed in quality from the original strain by virtue of the production of naphthalene, naphthalene, 1,1'-oxybis-, and one or more other compounds. In bioassays with a range of test micro-organisms, including fungi and bacteria, each isolate possessed biological activity but the range of activity was great. Artificial mixtures of some of the VOCs mimicked the effects of the VOCs of the fungus. The value of these observations to the biology and practical uses of M. albus in agriculture and other applications is discussed.

Anti-Bacterial Agents↗

PubMed2004

Applying an artificial neural network to warfarin maintenance dose prediction.

BACKGROUND: Oral anticoagulation with warfarin can lead to life-threatening events as a result of either over-anticoagulation or undertreatment. One of the main contributors to an undesirable warfarin effect is the need to adjust its daily dose for a specific patient. The dose is adjusted empirically based on the experience of the clinician, a method that is often imprecise. There is currently no other well-accepted method for predicting the maintenance dose of warfarin. OBJECTIVE: To describe the application of an artificial neural network to the problem of warfarin maintenance dose prediction. METHODS: We designed a neural network that predicts the maintenance dose of warfarin. Data on 148 patients attending a large anticoagulant clinic were collected by file review. Using correlational analysis of the patients' data we selected the best input variables. The network was trained by using the back-propagation algorithm on a subset of our data and the results were validated against the rest of the data. We used a multivariate linear regression to create a comparable model. RESULTS: The neural network generated reasonable predictions of the maintenance dose (r = 0.823). The results of the linear regression model were similar (r = 0.800). CONCLUSION: Neural networks can be applied successfully for warfarin maintenance dose prediction. The results are promising, but further investigation is needed.

Adolescent↗

PubMed2003

Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study.

BACKGROUND: Treatment of patients with excessive anticoagulation is routinely done by intravenous phytonadione (vitamin K1). Oral administration of phytonadione has been shown to be an effective alternative to the intravenous route, but these methods have never been compared directly. Our objective was to compare efficacy and safety of intravenous vs oral phytonadione treatment in patients with excessive anticoagulation without bleeding. METHODS: The study was a prospective randomized controlled trial of consecutive patients presenting with excessive anticoagulation without major bleeding. Patients with a baseline international normalized ratio (INR) of 6 to 10 (n = 44, 47 episodes) received either intravenous or oral phytonadione (0.5 mg or 2.5 mg, respectively), and patients with an INR greater than 10 (n = 17, 19 episodes) received 1 mg or 5 mg, respectively. Efficacy and safety end points were sequential INR changes and the proportion of patients achieving therapeutic range (INR, 2-4), overcorrection (INR<2.0), or undercorrection (INR>4.0) INR values. RESULTS: Sixty-six episodes of excessive anticoagulation were studied. In patients with baseline INR 6-10 the response to intravenous phytonadione was more rapid than in the oral group, and the proportion of patients reaching therapeutic range INR at 6 hours (11/24 vs 0/23) and at 12 hours (16/24 vs 8/23) was significantly higher. However, mean +/- SD INR values were similar for both groups at 24 hours (2.9 +/- 0.8 vs 2.6 +/- 0.8). Patients in the intravenous group tended to be more often (7/24 vs 2/23) overcorrected (INR<2). In patients with baseline INR values greater than 10 efficacy and safety were comparable for both routes of administration. CONCLUSION: Oral administration of phytonadione had similar efficacy and safety as intravenously administered phytonadione and may be suitable for treatment of patients with excessive anticoagulation.

Administration, Oral↗

PubMed2003

Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat.

BACKGROUND: In view of the demonstrated interaction between endothelin and the renin-angiotensin system, the antihypertensive effect of combined therapy with an endothelin antagonist LU-135252 and the angiotensin converting enzyme inhibitor trandolapril, was studied in fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic male Sprague-Dawley rats. METHODS: Forty animals were fed a fructose-enriched diet (Tekled, Harlan) for 5 weeks, as follows: group A, fructose only; group B, trandolapril 0.1 mg/kg/day added during the last 2 weeks; group C, LU-135252 100 mg/kg/day added during the last 2 weeks; group D, both trandolapril and LU-135252 added the last 2 weeks. Systolic blood pressure (BP) was measured weekly in conscious rats by the indirect tail-cuff method. Blood samples from a retro-orbital sinus puncture were taken at the beginning of the experiment and after 3 and 5 weeks and examined for insulin and triglyceride concentrations. RESULTS: Systolic BP decreased in group B (trandolapril) from 148.8 +/- 9.8 at 3 weeks to 138.3 +/- 8.7 mm Hg after 5 weeks; in group C (endothelin antagonist) from 155.1 +/- 5.5 to 142.5 +/- 10.6 mm Hg; and in group D (combination) from 154.6 +/- 10.9 to 121.2 +/- 8.9 mm Hg. Triglyceride levels decreased only in the combined trandolapril/endothelin antagonist group from 167.6 +/- 55.3 in the third week to 134.9 +/- 53.7 mg/dL after 5 weeks. Insulin levels decreased only on combination therapy from 7.4 +/- 3.6 to 5.3 +/- 3.8 ng/mL during the same period. The BP decrease was additive compared with the respective individual substances. CONCLUSIONS: The trandolapril/endothelin antagonist combination appears to offer a rational antihypertensive combination that is superior to that of either drug alone. This finding applies to the specific rat model studied in which BP, insulin, and triglycerides were increased by fructose diet.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Potential dosing errors using portable prothrombin time monitoring devices.

Portable prothrombin time (PT) monitors facilitate the control of warfarin therapy. Few studies have compared the influence of using different monitors on dosage decisions. We determined the comparability of data generated by two portable PT monitors, Coaguchek S, (Roche Diagnostics Boehringer-Mannheim) and Hemochron Jr (International Technidyne Corporation Ltd.), with that of a reference laboratory. Simultaneous International Normalized Ratio (INR) measurements (portable monitor and laboratory) were performed in 193 consecutive patients receiving warfarin for at least 3 months. Agreement of measurements was assessed by both regression analysis and influence on dosage decisions in accordance with pre-defined criteria. The Coaguchek S versus laboratory INR regression line (n = 111; r2 = 0.88; P < 0.001) was close to the line of identity, while that of the Hemochron Jr (n = 82; r2 = 0.61; P < 0.001) was not. The overall proportion of dual INR measurements that fulfilled the clinical criteria of agreement was 90% for the Coaguchek S compared with 62% for the Hemochron Jr (P < 0.0001). For laboratory INRs 2.0-2.5, 2.6-4.0 and > 4.0, the proportions of portable measurements that satisfied the clinical criteria for the Coaguchek S versus the Hemochron Jr were 96 versus 63% (P < 0.001), 81 versus 45% (P < 0.04), and 67 versus 17% (P < 0.85), respectively. Warfarin dosing based solely on the portable devices would have resulted in unjustified dose increments in 22% of the patients with the Hemochron Jr device compared with 8% with the Coaguchek S monitor (chi2 = 4.43; P = 0.035). The Coaguchek S monitor provides measurements for INR values within the therapeutic range that agree well with the standard laboratory. The Hemochron Jr measurements result in different dosage adjustments even within the therapeutic range, but especially for INR values > 4.0. For both monitors, agreement of INR measurements with the standard decreases with increasing INR values.

Adult↗

PubMed2003

Impact of pre-treatment INR level on the effect of intravenous low dose vitamin K in patients with excessive anticoagulation.

Administration of vitamin K is the common mode of treatment in excessively anticoagulated patients. However, patient's response to vitamin K varies, depending on the vitamin K dose and the route of administration. Another potential source of variation is the pre-treatment INR which has not been accounted for in most previous studies. In the present study the effect of baseline INR on the response to a single dose of intravenous vitamin K (0.5 mg) was studied in 95 episodes of excessively anticoagulated patients (n = 76). In 67 episodes of moderately excessive baseline INR (6-10) mean INR declined from 8.0 +/- 1.2 to 2.6 +/- 0.9 at 24 hours, 59/67 (88%) responding within the first 12 hours and not requiring a second dose. In contrast, in 28 episodes with highly excessive baseline INR (> 10) response was slower; mean INR declining from 13.6 +/- 2.7 to 4.0 +/- 2.1 at 24 hours. In 14/28 of these episodes, patients failed to respond to vitamin K in the first 12 hours and required a second vitamin K dose. We conclude that INR at presentation affects the response to vitamin K and that this INR value should be considered in determining appropriate vitamin K doses.

Acenocoumarol↗

PubMed2002

Naphthalene, an insect repellent, is produced by Muscodor vitigenus, a novel endophytic fungus.

Muscodor vitigenus is a recently described endophytic fungus of Paullinia paullinioides, a liana growing in the understorey of the rainforests of the Peruvian Amazon. This fungus produces naphthalene under certain cultural conditions. Naphthalene produced by M. vitigenus was identified by gas chromatography/mass spectrometry. Its chromatographic and mass spectral properties were identical to authentic naphthalene. Agar plugs supporting growth of the fungus and producing known amounts of naphthalene effectively repelled the adult stage of the wheat stem sawfly, Cephus cinctus, in Y-tube bioassay tests. Authentic naphthalene, at comparable concentrations to those in tests involving the fungus itself, mimicked the insect repellency of the fungus. Although other Muscodor spp. produce volatile antimicrobials, M. vitigenus is unique in its ability to produce naphthalene almost exclusively. This report also describes the potential practical implications of M. vitigenus.

Animals↗

PubMed2002

Effect of enoxaparin on homocysteine concentration in warfarin-treated patients.

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentration is an emerging independent risk factor for hypercoagulability states and cardiovascular diseases. Many disease states and various drug treatment regimens are known to affect plasma tHcy concentration. OBJECTIVE: To examine the effect of short-term treatment with the low-molecular-weight heparin enoxaparin on plasma tHcy concentrations. METHODS: A prospective study was conducted in an outpatient anticoagulation clinic set in a tertiary care referral medical center. Subjects included twenty-four consecutive patients treated with warfarin who were scheduled for short-term enoxaparin treatment. Fasting plasma tHcy concentrations were measured before and after 3 days of enoxaparin treatment in patients who began short-term therapy with enoxaparin because of temporary inadequate anticoagulation (international normalized ratio <1.5). The main outcome measures were the difference in tHcy concentration between baseline and after enoxaparin treatment. RESULTS: tHcy plasma concentrations decreased in most patients (n = 21), did not change in 2, and increased in 1 patient after 3 days of enoxaparin treatment. The decline of tHcy was statistically significant: from 9.8 +/- 3.4 to 7.6 +/- 2.6 micro mol/L (mean +/- SD; p < 0.005). This decline was more prominent in patients with baseline tHcy plasma concentrations above the normal range compared with patients with normal baseline concentrations. Six patients in whom a third sample was obtained 15-30 days after the last enoxaparin injection developed decreased mean tHcy plasma concentrations: from 9.1 +/- 3.0 micro mol/L at baseline to 6.4 +/- 2.0 micro mol/L on day 3 and further to 5.7 +/- 1.8 micro mol/L on days 15-30. No relation was found between age, gender, treatment indication, and average weekly dose of warfarin to the presence or magnitude of tHcy plasma concentration decline. CONCLUSIONS: Short-term treatment with enoxaparin reduces plasma tHcy concentrations. Further studies are needed to clarify the mechanism and the clinical significance of enoxaparin's effect.

Adult↗