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Biomedical subjects

Steven H Yale

Publications and source records attributed to Steven H Yale.

At least 19 recordsLinked to original sources

Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9.

OBJECTIVE: To study the potential of three top-selling herbal products, Ginkgo biloba, Echinacea purpurea, and Serenoa repens to inhibit the in vitro enzymatic activity of three of the most important drug metabolizing enzymes, cytochrome P450 (CYP) 3A4, 2D6, and 2C9. METHODS: High throughput CYP inhibition screening was used to test the inhibitory capacity of extracts of commercially available herbal medications on the metabolism of CYP enzyme substrates. RESULTS: S. repens showed potent inhibition of the metabolic activity of all three CYPs tested. The effects of G. biloba and E. purpurea varied. E. purpurea demonstrated mild inhibition of CYP3A4 activity with 7- benzyloxy-4-trifluoromethylcoumarin (BFC) as the model substrate, but mild inducing effects in the presence of the model substrate resorufin benzyl ether (BzRes). Little effect on CYP2D6 and moderate inhibition of CYP2C9 was seen with both E. purpurea and G. biloba. G. biloba also showed mild-to-moderate inhibition of CYP3A4 depending on the model substrate. CONCLUSIONS: The inhibitory capacity of herbal products varies depending on the concentrations of the model substrate and the herbal extract, as well as the identity of the model substrate, as demonstrated by the varied effects of CYP3A4 enzymatic activity with different model substrates. The potential for strong adverse interactions exists for Serenoa repens, which was a potent inhibitor of all three CYPs examined. Physicians are encouraged to advise patients of the risks of combining herbal products with prescription medications.

Aryl Hydrocarbon Hydroxylases↗

Disorders of flushing.

Disorders of flushing encompass a broad spectrum of diverse acquired and inherited conditions. Chemical mediators involved in the flushing response are incompletely understood. Flushing episodes rarely can be associated with significant morbidity and mortality. The goal of the physician is to separate benign from potentially life-threatening conditions. Accurate diagnosis requires a thorough history and physical examination emphasizing the age of the patient, temporal association of flushing with occupation, environmental, stress, food, or drug exposure, and the duration of the episode. In some cases, despite a thorough evaluation, the etiology for flushing remains unknown. Understanding the distinct mechanisms that lead to flushing helps provide a rational approach to treatment.

Alcohol Drinking↗

Murphy's Sign.

Explore the source record for details and available documents.

Abdomen↗

A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data.

BACKGROUND: Rapid genetic screening for cytochrome P450 (CYP) 2C9 variants may play a role in improving the efficacy and safety of warfarin in individuals with CYP2C9 variants. The feasibility of prospective CYP2C9 model-based warfarin dosing has not yet been assessed. OBJECTIVES: To evaluate the feasibility of applying a CYP2C9 gene-based warfarin dosing model in clinical practice. DESIGN: Prospective, randomized, single-blinded clinical pilot trial. SETTING: Large multispecialty group practice. PATIENTS: Candidates were recruited from a list of clinic patients eligible for warfarin initiation. This included patients with newly diagnosed thromboembolic disease or atrial arrhythmia, as well as patients anticipating elective valvuloplasty or arthroplasty. Patients who previously received warfarin were excluded. INTERVENTIONS: Subjects were randomized to receive either 1) a standard initiation dose of 5 mg warfarin/day, or 2) rapid CYP2C9 genotyping and an initiation dose determined using parameters estimated from a previously published multivariate model [including age, body size, co-morbidity (e.g., diabetes), clinical indication (e.g., valvuloplasty) and CYP2C9 genotype]. MEASUREMENTS: Primary outcome measurements were patient willingness to participate, physician willingness to refer, sample processing time, ability to administer calculated dosage and adequacy of follow-up. LIMITATIONS: This pilot trial was designed to assess the feasibility of model-based warfarin dosing. Power was insufficient for statistical comparison of adverse event rates. RESULTS: Forty-three of 117 patients had no prior warfarin treatment and were eligible. Five declined to participate. Twenty patients were randomized to a standard initiation dose of 5 mg daily. Eighteen patients were randomized to model-based dosing. All but one participant received the assigned initiation dose. Blood draw to dosage calculation time (including genotyping) required approximately 4 hours. Six adverse events occurred within the standard dosing group, and two adverse events occurred within the model-based dosing group. CONCLUSIONS: Prospective application of a multivariate CYP2C9 gene-based warfarin dosing model is feasible.

Aged↗

Efficacy of the influenza vaccine in patients with malignant lymphoma.

BACKGROUND: The benefits and efficacy of the influenza vaccine have been controversial and have had mixed reviews in the recent literature. Immunosuppressed patients and those receiving chemotherapy are particularly at risk for infectious complications and are therefore given high priority to receiving prophylactic vaccines. METHOD: We administered the influenza vaccine to 29 patients with malignant lymphoma who were receiving chemotherapy or had recently completed therapy during the flu season of 2003-2004. An aged-matched control group received the same vaccine during the same period. The ability of both groups to mount a protective titer of antibodies to the antigens in the vaccine was measured. RESULTS: Three of 29 patients (10%) in the lymphoma group were able to mount a 4-fold titer to at least one of the influenza A antigens. One patient developed a protective titer to both influenza A and B antigens and 3 of 29 responded to the influenza B antigen. In the control group 13 of 29 (45%) responded to an influenza A antigen and 14 of 29 (48%) had a 4-fold response to the B antigen. Seven of 29 controls (24%) had a 4-fold increase in their titers to both the A and B antigens. CONCLUSIONS: This study confirmed the low incidence of response or efficacy to the influenza vaccine reported in previous studies. Only a small percentage (10%) of immunosuppressed patients with malignant lymphoma responded with a 4-fold increase in their antibody titer to the major antigens of the 2003 influenza vaccine. Most interestingly, less than 50% of the aged-matched control population studied responded with a 4-fold increase in their antibody titer. Additional studies are needed to determine methods for improving the efficacy of the vaccine and the effectiveness of the influenza vaccination program in preventing influenza infections in the United States.

Adult↗

Central pontine myelinolysis: case series and review.

OBJECTIVE: To review central pontine myelinolysis (CPM) and osmotic demyelination syndrome (ODS) and describe the clinical features, etiologic factors, and clinical outcomes of 6 patients diagnosed with CPM or ODS. STUDY DESIGN: A retrospective case series. METHODS: Medical records of patients diagnosed with CPM or ODS at Marshfield Clinic/St. Joseph's Hospital from 1986 to 2003 were reviewed. Chart abstraction was completed with a standardized data abstraction form. RESULTS: Six patients were identified, ranging in age from 31-73 years (mean age = 51.5 years). Clinical presentations were nonspecific. Common symptoms included lethargy and dysarthria. Five of the 6 patients had chronic alcoholism. All had improvements in their clinical conditions upon hospital discharge. CONCLUSIONS: CPM and ODS are rare demyelinating diseases of the pons and extrapontine sites. Prompt diagnosis and management of associated complications are essential for favorable clinical outcomes.

Adult↗

Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Echinacea purpurea stimulates the immune response and is promoted to reduce symptom severity and the duration of upper respiratory tract infections. We sought to determine the efficacy of a standardized preparation of E purpurea in reducing symptom severity and duration of the common cold. METHODS: A randomized, double-blind, placebo-controlled design was used. Patients received either 100 mg of E purpurea (freeze-dried pressed juice from the aerial portion of the plant) or a lactose placebo 3 times daily until cold symptoms were relieved or until the end of 14 days, whichever came first. Symptoms (sneezing, nasal discharge, nasal congestion, headache, sore or scratchy throat, hoarseness, muscle aches, and cough) were scored subjectively by the patient and recorded daily in a diary. Kaplan-Meier curves were used to estimate the survival function of time to resolution in each group. The Wilcoxon rank sum test was used to compare time to resolution between the 2 groups. RESULTS: One hundred twenty-eight patients were enrolled within 24 hours of cold symptom onset. Group demographic distribution was comparable for sex, age, time from symptom onset to enrollment in the study, average number of colds per year, and smoking history. No statistically significant difference was observed between treatment groups for either total symptom scores (P range,.29-.90) or mean individual symptom scores (P range,.09-.93). The time to resolution of symptoms was not statistically different (P =.73). CONCLUSIONS: Some studies have concluded that Echinacea effectively reduces the symptoms and duration of the common cold. We were unable to replicate such findings. Further studies using different preparations and dosages of E purpurea are necessary to validate previous claims.

Adolescent↗

Successful endoscopic treatment of mediastinal pseudocysts.

Mediastinal pseudocysts can pose a diagnostic and therapeutic challenge to the clinician and surgeon. Recognizing their presence and instituting appropriate therapy can reduce morbidity and mortality. This report describes unusual clinical features in a patient presenting with multiple mediastinal pseudocysts due to pancreatic duct leak secondary to pancreatic duct stenosis and an entrapment of a pancreatic duct stone. Successful endoscopic therapy averted the need for surgery.

Aged↗

Hematologic and metabolic abnormalities in a patient with anorexia nervosa.

Anorexia nervosa is a common problem in young adults that may present with a variety of metabolic and hematologic abnormalities, as well as weight loss and psychological disturbances. We present a young man with a long history of anorexia nervosa who developed pancytopenia associated with decreased bone marrow cellularity and abnormal architecture and marrow infiltration with an amorphous, gelatinous substance characteristic of anorexia nervosa. The patient also developed osteopenia with evidence of excessive calcium excretion. The pancytopenia and marrow function reverted to normal with therapeutic and dietary intervention. The effects of eating disorders can result in serious consequences with respect to an individual's health and well-being. A host of hematologic abnormalities that are associated with anorexia nervosa have the potential of increasing the risk of infection and bleeding. Additionally, because of the insidious development of anemia in some patients, decreased performance status and chronic fatigue can pose significant compromises in one's daily activities and work effort. Anorexia nervosa is a chronic illness that is distinctly more common in females than in males (ratio of 10 to 1), but can affect males in an equally debilitating manner, requiring multiple modalities of therapeutic intervention and consultation. We present the case of a male referred to the hematology department because of pancytopenia, chronic fatigue, and back pain. A diagnosis of anorexia nervosa had been made 10 years prior at the age of 18 years.

Adult↗