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Biomedical subjects

R Aly

Publications and source records attributed to R Aly.

At least 19 recordsLinked to original sources
PubMed2001

Self-consistent simulations of electroporation dynamics in biological cells subjected to ultrashort electrical pulses.

The temporal dynamics of electroporation of cells subjected to ultrashort voltage pulses are studied based on a coupled scheme involving the Laplace, Nernst-Plank, and Smoluchowski equations. A pore radius dependent energy barrier for ionic transport, accounts for cellular variations. It is shown that a finite time delay exists in pore formation, and leads to a transient overshoot of the transmembrane potential V(mem) beyond 1.0 V. Pore resealing is shown to consist of an initial fast process, a 10(-4) s delay, followed by a much slower closing at a time constant of about 10(-1) s. This establishes a time-window during which the pores are mostly open, and hence, the system is most vulnerable to destruction by a second electric pulse. The existence of such a time window for effective killing by a second pulse is amply supported by our experimental data for E. coli cells. The time constant for the longer process also matches experiments. The study suggests that controlled manipulation of the pore "open times" can be achieved through multiple, ultrashort pulses.

Biological Transport↗
PubMed2001

Producing experimental lesions of cutaneous candidiasis.

Dermatophyte parasitism in normal patients, and even in most immunodeficient patients, is strictly limited to the stratum corneum. The dermatophyte fungi do not readily invade deeper body tissues. Cutaneous candidiasis, however, seems to be strictly an opportunistic infection of ecologically suitable skin by a yeast that is normally present in the gastrointestinal tract and mucosal surfaces of many healthy persons.

Arm↗
PubMed2001

Treatments for common superficial fungal infections.

Fungal infection of keratinized tissue is caused by any of the dermatophyte species. The topical allylamines and benzylamines have been especially effective in treating these infections because of their in vitro fungicidal activity and short treatment duration. With the development of new oral azoles and allylamine antifungal agents, there has been a renewed interest in treating superficial skin fungal infections. The use of topical and oral antifungal agents in treating cutaneous fungal infections is examined.

Antifungal Agents↗
PubMed2000

A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns.

BACKGROUND: Onychomycosis, a fungal infection of the nail bed, is responsible for up to 50% of nail disorders. Although several surveys have been conducted in different parts of the world, there have been no multicenter epidemiologic surveys of onychomycosis in North America. OBJECTIVE: A 12-center study was undertaken to (1) determine the frequency of onychomycosis, (2) identify organisms recovered from the nails, and (3) determine the antifungal susceptibility of isolates. METHODS: A total of 1832 subjects participated in this study and completed a comprehensive questionnaire, and nail clippings were collected for potassium hydroxide examination and culturing. RESULTS: The frequency of onychomycosis, as defined by the presence of septate hyphae on direct microscopy and/or the recovery of a dermatophyte, was found to be 13.8%. In general, the dermatophyte isolates were susceptible to the antifungals tested. CONCLUSION: Because of the limited number of large-scale studies, the baseline incidence is not firmly established. However, the higher frequency of onychomycosis in this study may confirm the suspected increase in incidence of disease in North America.

Adolescent↗
PubMed2000

Epidemiology of tinea capitis.

This paper addresses the changing epidemiology of tinea capitis in the USA and in Europe that has occurred over the last several decades. Several dermatophytes are involved in the etiology, and the primary etiological agents of tinea capitis are limited to the genera Microsporum and Trichophyton. In addition, the sources of these infections are discussed and although geophilic dermatophytes occur worldwide, anthropophilic species and some zoophilic fungi may be geographically restricted, depending on host range. For example, tinea capitis due to geophilic organisms is rare in the USA.

Animals↗
PubMed2000

Training medical myocologists in developing countries.

Although there has over recent years been a marked rise in the incidence of serious fungal infections, many of which are prevalent in developing countries, few facilities exist for diagnosis and research in medical mycology. In most countries, medical mycology is not taught adequately to medical students and consequently there is little awareness of the importance of fungal infections. Model teaching programmes need to be developed. Practical knowledge of mycoses, their diagnosis and treatment and also basic mycology can be disseminated through well-constructed courses and workshops. Formalized training in mycology research also needs to be introduced. To achieve all of this, expertise and additional resources need to be made available. In this regard, ISHAM can and should help.

Developing Countries↗
PubMed1999

Saccharomyces cerevisiae cells harboring the gene encoding sarcotoxin IA secrete a peptide that is toxic to plant pathogenic bacteria.

Sarcotoxin IA is a cecropin-type antibacterial protein produced by the flesh fly, Sarcophaga peregrina. Similar to other bactericidal small proteins produced by insects, sarcotoxin IA is released into the hemolymph of larvae and nymphs upon mechanical injury or bacterial infection. The gene (sarco) that encodes this toxin was introduced into Saccharomyces cerevisiae yeast cells and was expressed under a constitutive yeast promoter. The transformed yeast cells were grown in a liquid medium, and a peptide with a similar molecular size to that of the mature sarcotoxin IA was detected in the medium by Western blot analysis. The secreted sarcotoxin-like peptide (SLP) had a potent cytotoxic effect against several bacteria, including plant pathogenic bacteria, similar to the toxic effects of the authentic sarcotoxin IA. Erwinia carotovora was more susceptible to the toxic medium than Pseudomonas solanacearum and Pseudomonas syringae pv. lachrymans. Thus, yeast may be used in the production of such proteins for employment against various bacterial pathogens.

Animals↗
PubMed1999

Safety of itraconazole pulse therapy for onychomycosis. An update.

After experience with more than 34 million patients over 10 years, the safety of itraconazole and its potential drug-drug interactions are well known. In clinical trials, the average incidence of adverse events with a 1-week pulse regimen was 18% in pooled safety data (n = 2,867); only 2.2% of patients dropped out. In direct comparative trials, the incidence of mild and reversible adverse effects was comparable for itraconazole and terbinafine (31% and 28%, respectively) during treatment. The rate of permanent withdrawal because of adverse events was 3.6% for itraconazole and 7.5% for terbinafine (P < .05). Itraconazole was significantly better tolerated as evaluated by the investigator and patients. The analysis of the elderly subpopulation showed that patients 65 and older tolerated itraconazole pulse well, with only 20% experiencing mild and reversible side effects (total group). In direct comparative trials, itraconazole also produced fewer adverse effects than terbinafine (13% vs 32%, respectively). As newer oral antifungal agents gain widespread use, clinicians need to be aware of their potential drug-drug interactions and their possibly serious adverse events. However, pooled data from the 1-week itraconazole pulse regimen indicated a favorable safety profile, and a dose increase to 400 mg had no impact on safety.

Aged↗
PubMed1999

Itraconazole oral solution for the treatment of tinea capitis using the pulse regimen.

A 7-year-old boy with Trichophyton tonsurans tinea capitis was cured following the administration of itraconazole oral solution. He had difficulty swallowing tablets or capsules, so the availability of the oral solution was particularly advantageous. The itraconazole was given once daily in a fasting state at a dosage of 3 mg/kg/day as a pulse lasting 1 week. The first two pulses were separated by 2 weeks and the second and third pulse by 3 weeks. The decision whether or not to administer the third pulse was guided by the presence of clinical symptoms and signs of tinea capitis just prior to the scheduled administration. The availability of the oral solution will enable more young children to be considered for treatment of tinea capitis with itraconazole than was possible when only tablets or capsules were available.

Administration, Oral↗
PubMed1998

Topical metronidazole maintains remissions of rosacea.

BACKGROUND: Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred. OBJECTIVE: To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea. DESIGN: A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study). SETTING: Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers. SUBJECTS: One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel. INTERVENTIONS: Subjects were evaluated monthly for up to 6 months to determine relapse rates. MAIN OUTCOME MEASURES: Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed. RESULTS: In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P<.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%). CONCLUSION: In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel.

Administration, Cutaneous↗
PubMed1998

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS: In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION: The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Adolescent↗
PubMed1998

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail.

BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Antifungal Agents↗
PubMed1998

Clinical efficacy of a chlorous acid preoperative skin antiseptic.

BACKGROUND: Among the ways to reduce the incidence of iatrogenic infectious disease is the use of efficacious preoperative antiseptics. Iodophors and chlorhexidines, the chief presurgical disinfectants today, have various problems with practicality. A new preoperative skin antiseptic has been developed (Alcide Corporation, Redmond, Wash) that involves the mixture of a 0.1% sodium chlorite formulation and an activating preparation of 0.5% mandelic acid to produce chlorous acid and other antimicrobial degradation products. METHODS: Under clinical conditions, the antimicrobial effectiveness of this blended preparation was compared with a chlorhexidine gluconate scrub solution. Using a Latin-square randomization scheme, we treated 2 contralateral abdominal sites and 2 contralateral inguinal sites of healthy male and female volunteers with these antiseptics or the controls of vehicle or activator alone. Microorganisms were harvested and quantified by a standard cylinder-scrub technique. RESULTS: Of 85 volunteers (170 possible sites per test region) screened to meet the USA Food and Drug Administration baseline criteria on population densities of normal flora, 61 abnormal sites and 107 inguinal sites provided suitable data. Against chlorhexidine, the chlorous acid presurgical skin preparation produced superior but statistically equivalent reductions (P > .05) of each volunteer's normal flora at 10 minutes, 30 minutes, and 6 hours after treatment. As many as 4 log reductions were achieved, and activity persisted as long as 6 hours. Compared with chlorhexidine, the chlorous acid product has the practical advantages of a shorter scrub time, less foam, air drying (instead of wiping), and no perceivable residue. CONCLUSIONS: An activated chlorous acid product statistically matched the performance of chlorhexidine gluconate in reducing populations of resident flora on treated skin sites. With an easier and shorter application procedure and strong, long-term antimicrobial activity, the new halogenated antiseptic seems to be a useful and possible efficacious preoperative skin disinfectant.

Adolescent↗
PubMed1998

Skin, hair and nail fungal infections.

Fungal infections of the skin, hair and nails are among the most common skin diseases. The increased incidence of these infections in recent years has been attributed to the large number of immunocompromised patients, life-style changes (greater attendance at gymnasiums, public baths, etc.), the use of chemotherapeutic agents, and the greater presence of elderly people in the general population. Superficial fungal infections were also the most frequent and troublesome dermatological condition occurring among US forces during the war in Vietnam.

Journal Article↗