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Biomedical subjects

P Rich

Publications and source records attributed to P Rich.

At least 37 records · Page 2Linked to original sources
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

Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail.

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Adult↗
PubMed1998

Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey.

The number of individuals diagnosed with diabetes mellitus is increasing. The diabetic may present with complications involving all systems of the body. While onychomycosis is often observed in diabetics, there have been no large studies on the prevalence of the condition in this patient group. We examined the prevalence of onychomycosis in diabetics attending diabetes and dermatology clinics in London, Ontario, Canada and Boston, MA, U.S.A. Diabetic subjects seen in dermatology offices were for unrelated dermatoses; those referred specifically for the management of onychomycosis were excluded from the sample. A total of 550 diabetic subjects was evaluated (283 males and 267 females), age 56.1 +/- 0.7 years (mean +/- SEM). Patients with type I diabetes constituted 34% of the sample. The racial origin was: 531 Caucasians, 17 Asians, one African-American and one American-Indian. Abnormal-appearing nails and mycological evidence of onychomycosis (mostly due to dermatophytes) were present in 253 (46%) and 144 (26%), respectively, of 550 subjects. The development of onychomycosis was significantly correlated with age (P < 0.0001) and male gender (P < 0.0001). Males were 2.99 times more likely to have onychomycosis compared with females (95% confidence interval, CI 1.94-4 61). After controlling for age and sex, the risk odds ratio for diabetic subjects to have toenail onychomycosis was 2.77 times compared with normal individuals (95% CI 2.15-3.57). After controlling for age and sex, a stepwise logistic regression demonstrated that significant predictors for onychomycosis included a family history of onychomycosis (P = 0.0001), concurrent intake of immunosuppressive therapy (P = 0.035) and peripheral vascular disease (P = 0.023). Toenail onychomycosis was present in 26% of the sample and is projected to affect approximately one-third of subjects with diabetes. Predisposing factors include increasing age, male gender, family history of onychomycosis, concurrent intake of immunosuppressive agents and peripheral vascular disease.

Adolescent↗
PubMed1996

Special patient populations: onychomycosis in the diabetic patient.

There are approximately 14 million persons with diabetes in the United States. These patients must cope with the serious complications of this disease, including neuropathy and impaired circulation (leading to the "diabetic foot" and possible amputation), renal disease, cardiovascular disease, and retinopathy (possibly leading to blindness). Although onychomycosis is no more common in diabetics than in the general population, it poses a greater risk because of the possible sequelae. Most notably, impaired sensation can make many diabetics less aware of minor abrasions and ulcerations on their feet that may be caused by trauma from poor nail grooming or by the nail changes characteristic of onychomycosis. These lesions, in turn, may develop into serious bacterial infections and contribute to the severity of the diabetic foot. Thus there is an important clinical rationale for treating diabetic patients with fungal nail infections. A secondary benefit is the improved self-esteem and enhanced quality of life.

Diabetes Complications↗
PubMed1996

A comparison of 4.5% human albumin solution and Haemaccel in neonates undergoing major surgery.

In a randomized blinded study we compared two colloid solutions in 30 neonates undergoing major surgery. Fifteen neonates received 4.5% Human albumin solution (HAS) (mean volume 25.6 ml.kg-1, SD 9.5) and the others received Haemaccel (Hoechst) (24.9 ml.kg-1, SD 10). Pre and postoperative plasma albumin and haemoglobin concentrations and plasma colloid osmotic pressure (COP) were compared. In the group given Haemaccel there was an appreciable and statistically significant decrease in the mean plasma albumin concentration from 34.27 to 28.27 g.1(-1) (mean difference 6, CI 3.38 to 8.62) and the mean COP decreased significantly from 22.2 to 19.9 mmHg (mean difference 2.3, CI 0.3 to 4.5). In the HAS group there was no significant change in either the plasma albumin concentration or COP. There was a small but significant decrease in the mean haemoglobin concentration from 15.92 to 14.35 g.dl-1 (mean difference 1.56, CI 0.57 to 2.55) after HAS. We conclude that HAS is the superior colloid for volume replacement in neonates undergoing surgery.

Hemoglobins↗
PubMed1996

Curriculum goals for the training of osteopathic family practice residents for the year 2000.

The osteopathic family practitioner of the future will play a larger role in the delivery of healthcare under managed care. To prepare for this role, osteopathic family practice residents must develop skills in direct medical care, medical education, and healthcare administration. Likewise, these residents need to become familiar with the clinical setting in which these skills are needed, specifically, ambulatory, rural, hospital, and minor emergency care environments. We propose the development of a curriculum designed to promote these skills and clinical experiences. This curriculum would expand family practice experiences; replace the current required rotations in specialty medicine with longitudinal rotations designed to develop specific family practice skills; include block rotations in hospital care, minor emergency care, and rural medicine; develop model case assignments to teach residents to integrate their roles as provider, educator, and administrator; and entail clinical experiences in medical administration and education. An evaluation process that reflects the goals of the family practice curriculum is key to the success of such a program.

Clinical Competence↗
PubMed1992

Nail biopsy. Indications and methods.

Nail biopsy is a safe and useful diagnostic procedure for many nail disorders when routine clinical and laboratory methods fail to produce a diagnosis. Prerequisites for nail biopsy are an understanding of the surgical anatomy of the nail, adequate anesthesia and hemostasis, and a nail abnormality for which histopathology can provide the diagnosis. Indications and methods for nail biopsy vary according to the site and type of pathology in the nail unit. Nail bed and perionychial biopsies can be performed easily and with minimal scarring. They are most commonly used to diagnose tumors as well as infectious and inflammatory disorders of the nail. The most important reason to biopsy the nail matrix is to make or exclude the diagnosis of melanoma in a patient with longitudinal melanonychia. Great care must be taken in nail matrix biopsy to minimize the risk of permanent nail dystrophy.

Biopsy↗
PubMed1991

Allergic contact dermatitis to two antioxidants in latex gloves: 4,4'-thiobis(6-tert-butyl-meta-cresol) (Lowinox 44S36) and butylhydroxyanisole. Allergen alternatives for glove-allergic patients.

Allergic contact dermatitis developed on the hands and/or face of two patients after exposure to latex examination gloves. Both patients were patch test negative to the usual rubber allergens, but both had a positive patch test reaction to 4,4'-thiobis(6-tert-butyl-m-cresol) (Lowinox 44S36). Patient 2 was also patch test positive to butylhydroxyanisole. The patients were tested with other gloves, to find gloves that they could safely use. Glove manufacturers were queried to ascertain the occurrence of Lowinox 44S36 and butylhydroxyanisole in different brands of latex and vinyl examination gloves. A list of gloves and their associated allergens was generated and is provided to assist dermatologists in helping patients choose gloves free of specific allergens.

Allergens↗
PubMed1983

The ultrasound diagnosis of testicular leukemia.

The sonographic findings present in three surgically-proven cases of testicular leukemic infiltration are discussed. The diagnosis is strongly suggested when an enlarged testis with focal or diffuse internal sonolucency is encountered in the leukemic patient in bone marrow remission.

Adult↗
PubMed1982

Ketoconazole in griseofulvin-resistant dermatophytosis.

The efficacy of ketoconazole was evaluated in twenty patients with chronic dermatophyte infections who had failed to clear with griseofulvin therapy. Trichophyton rubrum was the causative organism in nineteen of the patients, and Trichophyton mentagrophytes in one patient. Three of twelve organisms tested showed in vitro resistance to griseofulvin. Duration of infection ranged from 2 to 28 years. Patients received 200 to 400 mg of ketoconazole daily for periods up to 8 months. In addition, patients were followed for 5 months post-therapy to monitor recurrences. Clearing was seen clinically as early as 2 weeks, and by 18 weeks all patients showed marked improvement or clinical clearing, though only six achieved complete mycologic cure. Improvement followed a predictable sequence of sites, with lesions of the trunk healing first, followed by hands, feet, and finally, nails. After 8 months, though all patients showed proximal nail clearing, onychomycosis persisted in thirteen of twenty affected sites. By 5 months post-therapy, four of six patients who had achieved clearing of skin and nails showed recurrences. No significant side effects were observed during therapy, though rare, apparently idiosyncratic cases of hepatotoxicity have been reported. Ketoconazole is an affective therapeutic agent for griseofulvin-resistant dermatophytosis. Apparent cures may subsequently recur after discontinuation of therapy.

Adult↗
PubMed1982

The juvenile justice system and its treatment of the juvenile: an overview.

This article examines the juvenile court system in the United States and traces its history and philosophy. It goes on to question the concept of "juvenile delinquency" and the validity of such a concept, and looks at the "status" offender. The article presents figures and statistics which pose questions involving the efficacy of the juvenile justice system and its treatment of the young and concludes by presenting some measures which have been suggested by studies set up to establish uniform standards relating to treatment of the young.

Adolescent↗
PubMed1978

Light and electron microscopic study of the livers of pregnant mice infected with Listeria monocytogenes.

Listeria monocytogenes cells were observed in the hepatic cell cytoplasm or in the phagosome at 24 and 48 hours but not at 72 hours after inoculation in pregnant mice. The presence of bacteria initially in a membrane-bound vesicle indicates that the bacteria enter the hepatic cells by endocytosis, resulting in eventual destruction of hepatic cells. Characteristic lesions of the liver at 24 and 48 hours after inoculation consist of multiple focal areas of necrosis. The initial neutrophilic reaction seems to give way to a mononuclear reaction (listeriomas) at 72 hours after inoculation. Dilation of rough endoplasmic reticulum and release of many of the bound ribosomes with a relative increase in the number of free ribosomes was observed. Hepatic lesions were not observed in control (nonpregnant) mice.

Animals↗
PubMed1976

Dehydrogenation of the phosphonate analogue of glucose 6-phosphate by glucose 6-phosphate dehydrogenase.

6,7 -Dideoxy-alpha-D-gluco-heptose 7-phosphonic acid, the isosteric phosphonate analogue of glucose 6-phosphate, was synthesized in six steps from the readily available precursor benzyl 4,6-O-benzylidene-alpha-D-glucopyranoside. The analogue is a substrate for yeast glucose 6-phosphate dehydrogenase, showing Michaelis-Menten kinetics at pH7.5 and 8.0. At both pH values the Km values of the analogue are 4-5 fold higher and the values approx. 50% lower than those of the natural substrate. The product of enzymic dehydrogenation of the phosphonate analogue at pH8.5 is itself a substrate for gluconate 6-phosphate dehydrogenase.

Deoxy Sugars↗
PubMed1976

Role of intravenous urography in clinical assessment of polycystic kidney disease.

This study is a retrospective review of 30 patients with polycystic kidney disease analyzing the quantitative measurements of renomegaly reported in the literature and the correlation of radiographic findings with the clinical complications of uremia, hypertension, infection, and the need for dialysis. The only significant correlation noted was between renal size and the presence of infection. There was no significant correlation between renomegaly and the presence or development of hypertension, uremia, and the need for chronic dialysis.

Humans↗