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Biomedical subjects

K J Skeith

Publications and source records attributed to K J Skeith.

16 recordsLinked to original sources
PubMed1998

Use of alternative therapies by patients with rheumatic disease in Guadalajara, Mexico: prevalence, beliefs, and expectations.

OBJECTIVE: To assess the prevalence, practices, beliefs, and expectations of patients with rheumatic diseases in relation to the use of alternative therapies. METHODS: We conducted a cross-sectional survey of 300 consecutive patients with rheumatic diseases at 3 outpatient rheumatic disease clinics in Guadalajara, Mexico to evaluate the use of alternative therapies. A face-to-face structured interview was administered by a trained assistant to evaluate the prevalence of use and patient beliefs, perceptions, and expectations in relation to alternative therapies. RESULTS: Two hundred fifty patients (83%) had used a total of 1,386 alternative therapies (range 1-19); 203 (68%) patients had used alternative therapy in the previous 12 months. Sixty-one percent received at least one alternative treatment before the first rheumatology consultation, but an additional 18% initiated these therapies after their initial contact with a rheumatologist at our clinics. Only 66 (26%) of the patients using alternative therapy notified their rheumatologist about their use. Thirty-six patients (14%) discontinued formal treatment at least on one occasion in order to receive alternative therapies, and only 8 (22%) notified their rheumatologist. Alternative therapy practitioners recommended discontinuation of conventional therapy on 57% of the occasions when formal treatments were discontinued. Mean expenditures per patient for fees to alternative therapy providers were equivalent to 28 days of the official minimum daily wage, and per patient costs for the remedies themselves were equivalent to 13 days of the official minimum daily wage. Patients who used alternative therapy in the past 12 months had lower education (7 versus 10 years, P < 0.001) and were slightly more disabled (1.7 versus 1.5, modified Health Assessment Questionnaire, P < 0.01). CONCLUSIONS: In this survey most patients used alternative therapies for the treatment of their rheumatic disease. Alternative therapies were costly and appeared to decrease adherence to conventional therapy. Health care providers should openly discuss the use of alternative therapy in patients with rheumatic diseases.

Adult↗
PubMed1997

Adverse drug reactions and debrisoquine/sparteine (P450IID6) polymorphism in patients with fibromyalgia.

OBJECTIVE: To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions. METHODS: Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions. A sample of 60 patients with rheumatoid arthritis and 62 patients with localized back pain served as controls. The P450IID6 phenotype was determined for each of the fibromyalgia patients. RESULTS: Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of them reported side effects. Analgesics were used by 122 patients and 22 (18%) had experienced adverse effects. Statistical differences in the frequency of adverse effects were found with antidepressant drugs in the fibromyalgia group, compared with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35 patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52) indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log M.R. = -2.30) to 4.99 (log M.R. = 0.70). CONCLUSIONS: The problem of adverse drug reactions in fibromyalgia patients does not appear to correlate with the PM phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered xenobiotic detoxification attributable to this PM phenotype would have a significant role in the development of fibromyalgia.

Adult↗
PubMed1997

The use of standardized patients in the performance of a needs assessment and development of a CME intervention in rheumatology for primary care physicians.

OBJECTIVE: To determine the feasibility of using standardized patients in the performance of a needs assessment and subsequent development of a continuing medical education (CME) intervention in rheumatology for family physicians. METHODS: Eight family physicians and 7 rheumatologists undertook 36 encounters with standardized patients simulating 3 common rheumatologic complaints. Encounters were assessed according to a predetermined score addressing issues of communication skills, clinical diagnosis, investigations, and management. Data obtained were used to develop a small group problem based learning event. RESULTS: Mean scores differed considerably between rheumatologists and family physicians (7.2 vs 3.6; possible range -3 to +9), between individuals within the 2 groups (rheumatologists 2.5 to +9; family physicians -1 to 6.5), and between cases. Specific areas of individual and group need for the development of a subsequent CME intervention were identified and included communication skills, clinical skills in the development of a differential diagnosis, appropriate use and interpretation of investigations, and appropriate management. CONCLUSION: Standardized patients can be effectively used to undertake a needs assessment in rheumatology. Specific data can be used to develop a small group problem based learning program with objectives meeting the identified needs and using the same standardized patients.

Education, Medical, Continuing↗
PubMed1996

Nonsteroidal antiinflammatory drug-induced enteropathy and severe chronic anemia in a patient with rheumatoid arthritis.

This report describes the case of a woman who was admitted to the hospital with severe anemia and refractory rheumatoid arthritis. She had been transfusion dependent for 8 years and was receiving a combination of indomethacin and naproxen. An indium-111 white blood cell scan revealed small bowel inflammation. Salsalate was substituted for her previous nonsteroidal antiinflammatory drugs (NSAIDs), and metronidazole was initiated. This resulted in maintenance of a normal hemoglobin level for at least 1 year after discharge. Small intestine inflammation and bleeding (enteropathy) due to NSAIDs must be considered in the evaluation of anemia in patients with arthritis.

Aged↗
PubMed1996

The influence of renal function on the pharmacokinetics of unchanged and acyl-glucuroconjugated ketoprofen enantiomers after 50 and 100 mg racemic ketoprofen.

1. To study the effect of renal dysfunction on the pharmacokinetics of ketoprofen (KT), and the possibility of saturation of clearance with elevation of dose, single 50 and 100 mg doses of racemic ketoprofen were administered in a cross-over fashion to seven patients (creatinine clearance, CLCR, 6-72 ml min-1). 2. The stereospecific disposition kinetics of KT enantiomers and their acyl-glucuronide conjugates (KTconj) were determined in plasma and urine for 24 h post-dose. 3. Decreased renal function was associated with a reduced KT oral clearance (CLO) and terminal elimination rate constant (lambda z). Renal clearance of KT conj (CLrconj) was reduced with diminished renal function. 4. Following both 50 and 100 mg doses, there was significant stereoselectivity in the AUC of KT (mean S/R, 0.87 and 0.83, respectively), the AUC of KTconj (mean S/R, 3.4 and 5.2, respectively) and the cumulative urinary excretion of KTconj (mean S/R, 2.1 and 2.2, respectively). The stereoselectivity in renal dysfunction in contrast with the observations previously made in healthy subjects may suggest a disease-related process. 5. CLO remained constant after increasing the dose, indicating linearity in the pharmacokinetics of KT despite reduced CLCR. CLrconj, however, was significantly reduced after the 100 mg dose suggestive of saturation of the urinary clearance and existence of a compensatory pathway. 6. Renal impairment reduces CLrconj and this appears to be the rate-limiting step for clearance of KT due to the observed stronger correlations of CLO with CLrconj than with CLCR. 7. Dose reduction of ketoprofen is indicated only for patients with CLCR < 20 ml min-1.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Hematologic disposition of hydroxychloroquine enantiomers.

Hydroxychloroquine (HCQ) is a racemic antiarthritic agent that has a long half-life (t1/2) in plasma and accumulates in blood cells. To study the relationships between HCQ concentrations in plasma, serum, and whole blood and to determine the optimal blood fraction to use for therapeutic drug monitoring of the drug, we studied the relative distribution of the HCQ enantiomers in various fractions of human blood under in vivo and in vitro conditions. Substantially greater concentrations of both enantiomers were found in serum as compared with plasma because of release via platelet activation. After in vitro incubations of the separated blood cells with HCQ, high concentrations of both enantiomers were found in leukocytes, and low concentrations in erythrocytes and platelets; the R:S ratio in vitro was near unity in all of the cells examined. Unlike the in vitro cellular uptake, the concentrations of HCQ in vivo were significantly lower and stereoselective (R:S ratio = 2). There was almost no drug in the polymorphonuclear cells (PMN) in vivo, despite a substantial uptake in vitro after incubation of separated cells. The enantiomeric (R:S) ratio in the urinary excretion of the enantiomers was significantly correlated with that in plasma. The plasma-protein binding of the enantiomers was stereoselective and complimented the cellular uptake findings; the unbound fraction was dependent on the plasma concentrations of alpha 1-acid glycoprotein, but not albumin. Although concentrations in whole blood correlated well with those in lymphocytes and monocytes (the proposed site of HCQ action), stronger correlations were found between concentrations in serum and in the mononuclear cells.

Adult↗
PubMed1994

Pharmacokinetic optimisation of the treatment of osteoarthritis.

Osteoarthritis is the most frequently encountered form of arthritis worldwide. Pharmacological therapies consisting of nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics such as paracetamol (acetaminophen), codeine and dextropropoxyphene are the principal means of symptom control. Osteoarthritis appears to have little impact on the pharmacokinetics of these drugs per se. However, other clinical features commonly associated with patients with osteoarthritis, such as advanced age, obesity or concurrent diseases and medications, may be important. A limited number of concentration-response studies have demonstrated the existence of a pharmacokinetic/pharmacodynamic relationship for these drugs. However, the information derived from patients with osteoarthritis is very limited. Simple analgesics have been shown to be as effective as NSAIDs in some studies. Furthermore, the response does not appear to be able to be predicted on the basis of clinical features of inflammation. It appears that a defined concentration-toxicity relationship exists and should be considered when dosage regimens for patients are formulated. Symptoms occur with a circadian rhythm, and similarly, there is circadian variation in the pharmacokinetic/pharmacodynamic response of a number of NSAIDs in patients with osteoarthritis. Selection of the optimal drug formulation will also be influenced by the need for continuous or intermittent therapy in these patients.

Aged↗
PubMed1994

Comparative efficacy and toxicity of 10-ethyl-10-deazaaminopterin and methotrexate in a mycobacterial rat arthritis model.

OBJECTIVE: To compare the efficacy and toxicity of the newer antifolate 10-ethyl-10-deazaaminopterin (10-EDAM) with methotrexate (MTX) in an animal model of inflammatory arthritis. METHODS: Groups of 8 or 9 female Lewis rats received intraperitoneal (ip) Mycobacterium butyricum to induce arthritis, and then one of the antifolates at either 1.0 mg/kg/day by oral gavage or 0.2 mg/kg/2 days ip until 25 days post-induction. Treatment groups were compared with control arthritic and non-arthritic animals. Efficacy was assessed by changes in weight, paw volume, and paw diameter, as well as maximum arthritis index, plasma albumin and plasma iron levels. Toxicity was documented for all groups. RESULTS: 10-EDAM was as effective as MTX at identical doses in preventing arthritis. 10-EDAM produced less toxicity than MTX at the higher dose used but similar toxicity at the lower dose. CONCLUSIONS: 10-EDAM may provide an alternative antifolate therapy in the clinical management of inflammatory arthritis, and appears to be less toxic than MTX.

Aminopterin↗
PubMed1993

Ketoprofen pharmacokinetics in the elderly: influence of rheumatic disease, renal function, and dose.

An age-related accumulation of ketoprofen due to a reduced clearance has been reported in the elderly. Other studies have not observed these changes in the kinetics of unchanged ketoprofen, but have reported increased plasma levels and reduced urinary excretion of conjugated ketoprofen. The authors examined the effects of dose, renal function, and the presence of arthritis on the stereoselective kinetics of ketoprofen in five nonarthritic and six arthritic elderly subjects. There was a significant difference in renal function (CLCr, mL/min; arthritic, 71.8 +/- 12.3, nonarthritic, 91.4 +/- 11.1), but not in age or weight between the two groups. Subjects received 50 mg and then 150 mg enteric-coated racemic ketoprofen, and plasma and urine samples were collected for 24 hours. No significant differences in CL/F, area under the curve (AUC), half-life (t1/2), time to reach peak concentration (tmax), or maximum peak plasma concentration (Cmax) were found between groups or between doses, and values were similar to those previously reported in young adults. Urinary ketoprofen conjugate (S:R) ratio was 1.6 +/- .25 and 1.65 +/- .27 for arthritic and nonarthritic subjects. Greater amounts of conjugated ketoprofen enantiomers were present in the plasma of the arthritic compared with nonarthritic subjects. Renal clearance of ketoprofen conjugates exhibited stereoselectivity (R > S), and was decreased in the arthritic group. Significant changes in the kinetics of unchanged ketoprofen was not found to occur in elderly subjects in the presence or absence of rheumatic disease or moderate renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Serum cytidine deaminase as a measure of disease activity in rheumatoid arthritis and systemic lupus erythematosus.

Serum cytidine deaminase (CD) as a marker of disease activity was assessed in 100 patients with rheumatoid arthritis (RA) and in 102 assessments of 85 patients with systemic lupus erythematosus (SLE). In RA CD levels correlated well with clinical assessment of disease activity, but were not influenced by varying dosages of ibuprofen as therapy. In SLE significant correlations were found between CD and anti-DNA antibody titers, as well as C3 complement levels. A subset of clinically active patients with SLE with elevated CD levels but normal anti-DNA titers was identified. Serum CD levels may be a clinically useful marker in RA and in certain subgroups of patients with SLE.

Adult↗
PubMed1992

The stereoselective pharmacokinetics of etodolac in young and elderly subjects, and after cholecystectomy.

The pharmacokinetics of the enantiomers of etodolac were studied in six young subjects (ages 28 +/- 3.3 years), 6 nonarthritic elderly subjects (ages 73 +/- 6.0 years), and in three cholecystectomy patients after single oral doses of the racemate (200 mg). In all subjects, the plasma concentrations of R-etodolac, which is pharmacologically inactive, greatly exceeded those of the pharmacologically active S-enantiomer. Stereoselectivity was reflected in the pharmacokinetics, with R > S for maximum peak plasma concentration and area under the concentration versus time curve, and S > R for apparent oral clearance and apparent volume of distribution. On average, less than 25% of the dose of each enantiomer was excreted in the urine within 24 hours as alkali-labile conjugates; little or no unchanged drug was recovered. Bile constituted a minor route of elimination of etodolac as conjugated enantiomers. There were no significant differences in the pharmacokinetics of etodolac enantiomers between the young and elderly subjects. The results reflect the importance of considering stereoselectivity in evaluating the pharmacokinetics of etodolac.

Administration, Oral↗
PubMed1992

New horizons in the medical treatment of rheumatoid arthritis.

To date, the medical management of rheumatoid arthritis has been less than optimal for a significant number of patients. This has been manifested by progressive deformity, functional disability, and increased mortality in these patients. Alternative treatment schedules of currently available drugs, as recently advocated by some investigators and the results of both the preclinical and the applied clinical evaluations of a number of novel pharmacologic therapies are reviewed. Several effective nonpharmacologic treatments have been reported in the last year, and their significance in the treatment of rheumatoid arthritis are also discussed.

Arthritis, Rheumatoid↗
PubMed1991

Clinical pharmacokinetics of drugs used in juvenile arthritis.

Juvenile arthritis is defined as the occurrence of objective evidence of arthritis for a minimum of 6 weeks, in a child 16 years of age or younger. With a reported incidence of 9 to 19.6 per 100,000 children, juvenile arthritis is considered to be a rare disease. There is no known cure; however, up to 75% of patients will undergo remission by late adolescence. Drugs used in the treatment of juvenile arthritis are divided into 2 major classes: (a) the nonsteroidal anti-inflammatory drugs (NSAIDs) including salicylates, naproxen, ibuprofen, fenoprofen, ketoprofen, flurbiprofen, indomethacin, sulindac, tolmetin and diclofenac, and (b) disease modifying agents which encompass drugs such as antimalarial agents, gold, methotrexate, penicillamine and sulfasalazine. In almost all the reports dealing with the pharmacokinetics of NSAIDs, the level of disease activity has not been noted. The level of activity is important since, during a flare, the plasma albumin may fall to the point that it causes a substantial and clinically significant increase in the unbound serum concentration of highly bound drugs. The relationship between the concentration of these drugs in the systemic circulation and their efficacy is not clear. However, for many of them, therapeutic drug monitoring is recommended as a means of reducing the possibility of toxic reactions. Further pharmacokinetic and -dynamic evaluations are needed for many of these drugs in juvenile arthritis.

Adolescent↗
PubMed1990

Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis.

Low dose methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis. Current product recommendations accompanying MTX preparations advise against concurrent usage of nonsteroidal antiinflammatory drugs (NSAID), and adverse pharmacokinetic interactions have been reported with this combination. Six patients who were receiving MTX were studied with both oral and parenteral MTX, 10-25 mg/dose, without NSAID and with ibuprofen (2400 mg/day) and flurbiprofen (300 mg/day) for 6 weekly doses. Serum MTX levels were obtained at frequent intervals. Serum was separated and MTX analyzed using a radioimmunoassay (RIA). There was no observable interaction between MTX and either ibuprofen or flurbiprofen, with respect to the area under the curve per unit dose, Cmax, Cmax/dose, Tmax, and serum half-life. The pharmacokinetic indices were not significantly influenced by the route of administration.

Administration, Oral↗