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Biomedical subjects

N H Shear

Publications and source records attributed to N H Shear.

At least 109 records · Page 6Linked to original sources
PubMed1996

Onychomycosis. New therapies for an old disease.

The newer generation of antifungal agents such as itraconazole and terbinafine are more effective than the older therapies, griseofulvin and ketoconazole, in the treatment of dermatophyte pedal onychomycosis. Itraconazole can be administered as continuous dosing, 200 mg per day for 3 months, or in the form of pulse therapy, 200 mg twice a day for 1 week per month for 3 consecutive months. Terbinafine is given as continuous dosing, 250 mg per day for 3 months.

Aged↗
PubMed1995

Effect of tauroursodeoxycholic and ursodeoxycholic acid on ethanol-induced cell injuries in the human Hep G2 cell line.

BACKGROUND & AIMS: Taurodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) exert a protective effect in chronic cholestasis. This study reports the effect of TUDCA and UDCA on an in vitro model for ethanol-induced liver damage. METHODS: Hep G2 cells were incubated for 24 hours with 80 mmol/L ethanol in the presence or absence of 50 mumol/L TUDCA or UDCA. Cells were also pretreated with 80 mmol/L EtOH and then exposed to 50 mumol/L bile acids. Cytotoxicity was assessed by the metabolism of formazan (3-(4,5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and sodium 3,3'-(phenylamino) carbonyl-3,4-tetrazolium-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrase and by the release into the culture medium of different enzymes (aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transferase, and lactate dehydrogenase). RESULTS: The incubation of Hep G2 with EtOH significantly (P < 0.001) increased cytotoxicity. Both TUDCA or UDCA reduced cytoxicity to a similar extent (P < 0.001). Cells pretreated with EtOH and then added with TUDCA or UDCA responded differently because TUDCA was significantly more effective (P < 0.05) than an equimolar dose of UDCA in reversing the damage. Electron microscopic examination revealed that TUDCA and UDCA were both able to prevent mitochondrial damage and to reduce steatosis induced by EtOH. CONCLUSIONS: Low doses of TUDCA and UDCA protect Hep G2 cells from EtOH-induced cytotoxicity. However, TUDCA seems to be more effective than UDCA in reversing the damage.

Cell Survival↗
PubMed1995

Lithium therapy associated with hidradenitis suppurativa: case report and a review of the dermatologic side effects of lithium.

Lithium is frequently used in the management of several psychiatric disorders including acute mania, bipolar (manic-depressive) disorder, and recurrent depression. We describe a patient in whom hidradenitis suppurativa developed while the patient was receiving lithium. The cutaneous side effects of lithium are reviewed. The most frequent are psoriasis, acneiform lesions, folliculitis, alopecia, and a maculopapular/macular eruption. Many of these side effects respond less readily to conventional therapy while the patient is receiving lithium.

Acne Vulgaris↗
PubMed1995

Azathioprine hypersensitivity-like reactions--a case report and a review of the literature.

Azathioprine is used in a variety of dermatological conditions. However, because of its side-effect profile, azathioprine is limited for use in patients with severe disease. An unpredictable, rare and potentially fatal side-effect of azathioprine is the development of a hypersensitivity reaction, often consisting of fever, hypotension and oliguria. We describe a 17-year-old patient with leucocytoclastic vasculitis who was placed on azathioprine; within 15 days of start of therapy, she developed a fever. Azathioprine was discontinued and an evaluation for sepsis was undertaken; all cultures were negative and the fever abated. Azathioprine was restarted 5 days later. After a single dose, fever, nausea and vomiting, diarrhoea, hypotension, tachycardia and oliguria developed and the patient was admitted to an intensive care unit. Azathioprine was discontinued and investigations revealed no sign of an infection. All the above signs and symptoms abated within 24 h and the patient was discharged from hospital in 7 days. A review of 28 case reports in the literature of azathioprine-induced hypersensitivity reactions suggest that most commonly a fever and gastrointestinal symptoms occurred on initial presentation. In addition, a maculopapular rash, urticaria, vasculitis, erythema multiforme or erythema nodosum may occur. Hepatotoxicity and nephritis have also been reported. The aetiology of the reaction is unknown but sudden onset of fever and hypotension suggests that this reaction may be due to cytokine or mediator release induced by azathioprine. As azathioprine is metabolized to 6-MP, rechallenges to both should be avoided in patients who experienced an azathioprine hypersensitivity-like reaction.

Adolescent↗
PubMed1995

Acetaminophen-induced toxicity to human epidermoid cell line A431 and hepatoblastoma cell line Hep G2, in vitro, is diminished by silymarin.

The skin and liver may be targets for cytotoxicity induced by oxidative drug metabolites. We used human epidermoid A431 cells and human hepatoblastoma Hep G2 cells as the experimental model. The aim of the study was to investigate and evaluate the effect of silymarin on acetaminophen (APAP)-induced toxicity under controlled conditions. Silymarin is known to be a potent antioxidant that diminishes toxicity induced by a variety of other hepatotoxins (e.g. Amanita phaloides, algae's toxins, carbon tetrachloride). Glutathione (GSH) depletion was enhanced by adding to the medium buthionine sulfoximine [L-buthionine-(S,R)-sulfoximine, BSO]. Cells were incubated with high-concentration 5-20 mM APAP or alpha-(minimum essential medium for 2-24 h to evaluate the drug's ability to reduce cytoviability. Viability was then quantitated by metabolism of the tetrazolium dyes (MTT) and neutral red (NR). Cytoviability was 100% for controls. For Hep G2 treated for 24 h with 20 mM, APAP viability was 56.0% by MTT and 62.5% by NR. BSO-treated cells showed an enhanced cytotoxicity, determined by both assays. Administration of 0.5 mM silymarin reduced cytotoxicity significantly. In A431 cells, treatment with 20 mM APAP reduced viability by 57% (MTT) and 69% (NR) versus control (100%). BSO further decreased viability. Since incubation with silymarin showed significant protection against APAP toxicity, it can be considered a cytoprotective agent in this in vitro model of drug toxicity. GSH concentrations in both cell lines decrease significantly after exposure to 20 mM APAP, or 0.5 mM versus control (p < 0.05), and increased (p < 0.001) if incubated with APAP and silymarin. The protective effect could be through mitochondrial membrane stabilization and/or an increase in available GSH.

Acetaminophen↗
PubMed1995

Pharmacoeconomic analysis of topical treatments for tinea infections.

The purpose of this study was to perform a government-perspective economic analysis of the most widely used topical creams [namely, ciclopirox (CIC), clotrimazole (CLO), ketoconazole (KET), miconazole (MIC), and terbinafine (TER)], for the treatment of 2 types of dermatophyte skin infections: dermatophytosis major (excluding onychomycosis) and dermatophytosis minor. A 3-phase approach was used. In phase I, experts were assembled to identify the standard approach for management of fungal infections and a decision tree was constructed to model the process; in phase II, meta-analysis was used to determine success, failure, and relapse rates; and in phase III, economic analyses were performed including cost of regimen, total expected cost and cost-effectiveness analysis. Sensitivity analyses (robustness analyses) were also performed in phase III. It was found that while TER was successful following 1 week of administration for minor infections and after 2 weeks for major infections, duration of drug treatment was usually twice that time. Other comparators (CIC, CLO, KET and MIC) took 4 weeks to achieve a successful outcome. In addition, an extra 2 weeks were often needed to clear both types of infections because the comparators are fungistatic, whereas TER is fungicidal. In the total expected cost analysis, TER had the lowest overall cost of treating patients for both infection categories. It was also responsible for the highest number of disease-free days and, consequently, the lowest cost per disease-free day. Sensitivity analyses confirmed that TER was the most cost-effective topical agent for treating dermatophytosis major (excluding onychomycosis) and dermatophytosis minor.

Administration, Topical↗
PubMed1995

Terbinafine for the treatment of pedal onychomycosis. A foot closer to the promised land of cured nails?

Onychomycosis of the nails includes fungal infection caused by primary nail pathogens that invade the healthy nail plate and secondary invasion in nails with preexisting disease. Onychomycosis may be due to secondary infection from tinea pedis and is the most common nail disease, accounting for roughly 30% of all cutaneous fungal infections. In a survey of 9332 British adults, 16 years of age and older, the prevalence of dermatophyte infection was 2.6% to 2.8%. In subjects 55 years of age or older, the prevalence was 4.7%. In the United States, a similar prevalence has been reported. Onychomycosis can have a significant psychological effect on the subject. In a North American study, the relative composition of isolates from nails was dermatophytes (91%), yeasts (5%), and molds (4%). Candida is isolated predominantly from fingernails. Uncommonly, there are mixed infections. In other parts of the world, the frequency of these agents may vary.

Adult↗
PubMed1994

Improving the diagnosis of hypersensitivity reactions associated with sulfonamides.

The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is difficult because symptoms are seldom pathognomonic. The authors compared the performance of two new diagnostic aids in the differential diagnosis of 27 cases of skin reactions associated with sulfonamide therapy. One test, the Bayesian Adverse Reaction Diagnostic Instrument (BARDI), calculates the posterior probability (PsP) of a drug being the etiology of an idiosyncratic ADR. The other, the lymphocyte toxicity assay (LTA), is a biochemical test that determines the percent of cell death because of toxic metabolites of a drug. Cases were assessed independently and blindly by BARDI and then the LTA. Skin reactions consisted of 19 exanthematous eruptions, 2 vasculitis, 1 erythema multiforme, and 5 urticarial rashes. BARDI indicated that the drug was very likely associated with 20 adverse events (PsP = 0.59 to 0.99); and unlikely to have caused 7 (PsP = 0.02 to 0.38). The LTA showed that 19 patients (70%) were test positive, and 8 were test negative. Comparing BARDI to LTA showed that BARDI had 79% sensitivity and 67% accuracy, but only 38% specificity. However, when the results of the LTA were incorporated into the calculation of the PsP based on this comparison, BARDI indicated that the drug was very likely associated with 18 reactions (PsP = 0.61 to 0.99) and unlikely to have caused 9 reactions (PsP = 0.003 to 0.47). The agreement increased from 67% to 96%. These findings indicate that the accuracy of diagnosis of idiosyncratic ADRs improved when the results of BARDI and LTA were combined. These findings also crossvalidate the results obtained by using BARDI.

Adolescent↗
PubMed1994

Antifungal agents: an overview. Part II.

The recent introduction of a new generation of antifungal drugs promises to alter significantly therapy for both systemic and superficial mycoses, in particular, onychomycosis. This article presents an in-depth review of the azoles (the triazoles itraconazole and fluconazole), the allylamines (naftifine and terbinafine), and the morpholine derivative amorolfine.

Allylamine↗
PubMed1994

Enhanced differential diagnosis of anticonvulsant hypersensitivity reactions by an integrated Bayesian and biochemical approach.

OBJECTIVE: The differential diagnosis of hypersensitivity reactions associated with anticonvulsants requires accuracy because of the many implications for patient management. We tested an integrated Bayesian and biochemical diagnostic approach. METHODS: The patients were analyzed clinically by two tests. One test, the Bayesian Adverse Reaction Diagnostic Instrument (BARDI), calculates the posterior probability of a drug being the cause based on epidemiologic and case data. The other, the lymphocyte toxicity assay, is an in vitro rechallenge that determines the percentage of cell death attributable to a drug's toxic metabolites. The setting for the study was an adverse drug reaction clinic at Sunnybrook Health Science Centre and the Hospital for Sick Children, Toronto, Ontario, Canada. Fifty-one patients who had hypersensitivity reactions after receiving aromatic anticonvulsants were tested. Four of these patients had more than one reaction reported, with different anticonvulsants generating 56 distinct events. RESULTS: Compared to the lymphocyte toxicity assay, BARDI had 94% sensitivity, 93% accuracy, and 50% specificity. When lymphocyte toxicity assay data were incorporated into BARDI, agreement rose from 93% to 100%. BARDI also identified which drug was a more likely cause for 11 patients receiving multiple anticonvulsants. CONCLUSION: These findings show that BARDI and the lymphocyte toxicity assay have high concordance and, when used in an integrated approach, these tests can improve the diagnostic accuracy and enhance the management of patients with hypersensitivity reactions.

Adolescent↗
PubMed1994

Cost-effectiveness analysis for onychomycosis therapy in Canada from a government perspective.

An economic analysis of the oral antifungal drugs griseofulvin (GRI), ketoconazole (KET), and terbinafine (TER), currently registered and used in treating onychomycosis of fingernails and toenails, was performed using a model that incorporates elements of both meta-analysis and pharmacoeconomics. The meta-analysis of published studies determined rates of success, relapse and side-effects. The perspective taken for the analysis was that of the government payer, with expected total cost and cost-effectiveness being calculated. A multiphase approach was used. The studies of onychomycosis of the fingernails showed that TER had a 95.0% success rate, KET 80.9%, and GRI 59.6%. GRI had the lowest acquisition costs. The success rates for onychomycosis of the toenails were: TER 78.3%, KET 40.8%, and GRI 17.5%. GRI had the lowest acquisition costs. However, expected cost comparison showed TER had the lowest cost because of shorter treatment duration. The expected cost of therapy with a 100% government payer perspective for fingernail onychomycosis was the lowest for TER ($439.83), followed by GRI ($480.80), then KET ($755.46). Toenail onychomycosis showed the same order for the comparators, with TER $1049.77, GRI $1388.54 and KET $1936.48. When compared with TER, fingernail cost-effectiveness ratios for GRI and KET were 1.51 and 2.00. Toenail cost-effectiveness ratios were 2.49 and 2.48, respectively. For both fingernail and toenail onychomycosis, TER had the greatest number of disease-free days (973 for fingernails; 1073 for toenails), followed by KET (837; 798), then GRI (702; 569).(ABSTRACT TRUNCATED AT 250 WORDS)

Antifungal Agents↗