Gout Medication Research Articles

Treatment adherence in patients with gout

The treatment objectives in gout are to promptly terminate the acute flares and to prevent the long-term complications via chronic pharmacotherapy, usually with urate-lowering drugs, combined with diet and lifestyle changes. Published data indicate that adherence with pharmacotherapy is particularly poor in gout patients. In studies of pharmacy dispensing of gout medications, the percentage of patients with good adherence, defined as purchasing at least 80% of the prescribed amount of medication, ranged from 18 to 44%. In a comparative study showing a 36.8% adherence rate among gout patients, patients with hypertension or type 2 diabetes had considerably higher rates, of 72.3 and 65.4%, respectively. In addition, data are lacking on adherence to recommended dietary and lifestyle changes, whose importance has been emphasized in recent years. Poor adherence has well-documented adverse consequences on the treatment success rate and on disease progression. These data identify treatment adherence in gout as a key target of patient education.

Gout treatment and comorbidities: a retrospective cohort study in a large US managed care population

BackgroundGout prevalence increased in recent years to become one of the most common causes of inflammatory arthritis in most industrialised countries. Comorbidities may affect the disease severity and treatment patterns. We describe the main characteristics of gout patients, gout-related treatment patterns and prevalent comorbidities in a managed care population.MethodsFrom the large US PharMetrics Patient-Centric Database, patients aged 20-89 with at least 2 claims for a diagnosis of gout (ICD9 274.xx) and related prescriptions between January 1, 1996 and December 31, 2008 were included. Gout flares were ascertained during follow-up. Sex-specific multivariable Poisson regression models were used to assess factors associated with number of flares.Results177,637 gout patients were included (mean age 55.2 years; men 75.6%). Overall, more than half (58.1%) had any of the considered comorbidities; hypertension (36.1%), dyslipidemia (27.0%) and diabetes (15.1%) being the most common. Nonselective NSAIDs were the most commonly dispensed (in 38.7% of patients). Notably, 39% of patients did not receive any prescription medication for gout. Patients with comorbidities were significantly more likely to receive anti-gout prescriptions. During an acute episode the prescription of NSAIDs and colchicine increased; and 29.9% of patients received allopurinol. The risk of flares was associated with cardiometabolic comorbidities and older age in women (highest at age 60-69), while in men it decreased by age. Women with these conditions were 60% more likely to have flares (incidence rate ratio, IRR 1.60;1.48-1.74), while men were 10% (IRR 1.10; 1.06-1.13) more likely.ConclusionsComorbidities affected gout treatment patterns and the occurrence and frequency of acute attacks. Cardiometabolic comorbidities, common in this patients' population, were associated with an increased risk of flares.

Prevalence of Contraindications and Prescription of Pharmacologic Therapies for Gout

Background Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied. Methods A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease. Results The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III). Conclusion Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications.

Subconjunctival Urate Crystals: A Case Report

To report a case of localized subconjunctival urate crystals in a patient with gout. Single observational case report. Case report. An 80-year-old woman who came for cataract surgery was incidentally found to have subconjunctival crystal deposits near the superior limbus in her left eye (OS). She was taking medications for gout and hypertension. Multiple conjunctival crystals were excised from the area before cataract surgery. Light microscopy under polarization revealed crystals, and histopathological examination confirmed gouty tophi. Because subconjunctival urate crystals occur only rarely, ophthalmologists should be aware of this potential, particularly in patients with gout.

Chronic urate nephropathy with a disproportionated elevation in serum uric acid.

A 38-year-old man visited our institution for evaluation of proteinuria. Prior to this, the patient was diagnosed with hypertension. One year ago, the patient was admitted to our hospital because of gout on his right knee and proteinuria. At that time, aspiration of synovial fluid revealed positive intracellular and extracellular birefringent crystals by compensated polarized light microscopy. He has been taking medications for gout and hypertension since. The urinalysis revealed 2+ proteinuria and 10–15 red blood cells per high-power field. The laboratory tests showed haemoglobin 14.7 g/dl, uric acid 11.5 mg/dl, blood urea nitrogen 29 mg/dl, creatinine 1.96 mg/dl, cholesterol 260 mg/dl and triglyceride 477 mg/dl. Ultrasonography demonstrated normal-sized kidneys with mildly increased parenchymal echogenicity in both kidneys. Microscopic study of renal biopsy showed uric acid crystals in amorphous (asterisks) or spindle shapes (arrows) deposited within the renal medulla surrounded by mononuclear inflammatory cells (Figure 1). For the pathophysiology of chronic urate nephropathy, a series of reactions initiated by hyperuricaemia or uricosuria was suggested: intra-tubular deposit of uric acid crystals, consequent local obstruction and rupture of crystals into the interstitium and, finally, an inflammatory response and interstitial fibrosis around the crystals [1]. In addition, recent studies have suggested that hyperuricaemia may induce renal injury independent of crystal formation by several mechanisms: activation of the renin–angiotensin system, stimulation of cyclooxygenase-2 and inhibition of local nitric oxide synthase with a reduction in endothelial nitric oxide [2]. Patients may present with hypertension, hyperuricaemia, mild azotaemia and mild proteinuria. We can also consider chronic urate nephropathy if there is an elevation in the serum uric acid concentration out of proportion to the degree of renal insufficiency [3]. This is a case having typical clinical manifestations with a disproportionate elevation in serum uric acid in relation to the degree of renal insufficiency. However, we also need to consider UMOD-related kidney disease (uromodulin-associated kidney disease) when the patient has renal impairment between age 15 and 40 years, precocious gout and hyperuricaemia, although urate crystals are said to be rare [4].

The Relation of Coffee Consumption to Serum Uric Acid in Japanese Men and Women Aged 49–76 Years

Objective. Few studies have suggested an inverse relation between coffee intake and serum concentrations of uric acid (UA), but none has addressed the relation in men and women separately. We examined the relation between coffee intake and serum UA levels in free-living middle-aged and elderly men and women in Fukuoka, Japan. Methods. Study subjects were derived from the baseline survey of a cohort study on lifestyle-related diseases, and included 11.662 men and women aged 49–76 years; excluded were those with medication for gout and hyperuricemia, use of diuretic drugs, and medical care for cancer or chronic kidney disease. Statistical adjustment was made for body mass index, alcohol use, hypertension, diabetes mellitus, and other factors. Results. There were inverse associations of coffee consumption with serum UA concentrations and hyperuricemia in men regardless of adjustment for covariates. Women showed a statistically significant, but weaker, inverse association between coffee and serum UA levels after allowance for the confounding factors. Conclusion. The findings add to evidence for a protective association between coffee intake and hyperuricemia.

Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI.

OBJECTIVE—High serum uric acid levels lead to gout and have been reported to be associated with an increased risk of hypertension, obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence uric acid levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms within this gene with uric acid levels and to determine whether this association is modified by obesity.RESEARCH DESIGN AND METHODS—Four single nucleotide polymorphisms within SLC2A9 (rs6855911, rs7442295, rs6449213, and rs12510549) were genotyped in the population-based prospective Bruneck Study (n = 800) and in a case-control study from Utah including 1,038 subjects recruited for severe obesity and 831 control subjects.RESULTS—We observed highly significant associations between all four polymorphisms and uric acid levels in all study groups. Each copy of the minor allele decreased age- and sex-adjusted uric acid levels by 0.30–0.35 mg/dl on average, which translates to a relative decrease of 5–6% with P values ranging from 10−9 to 10−11 in the combined analysis. An extended adjustment for BMI, creatinine, gout medication, and alcohol intake improved P values to a range of 10−14 to 10−20. The association was more pronounced in women and the population-based Bruneck Study and was significantly modified by BMI, with stronger effect sizes in individuals with high BMI.CONCLUSIONS—Genetic variants within SLC2A9 have significant effects on uric acid levels and are modified by sex and BMI.

Risk of Multiple Myeloma following Medication Use and Medical Conditions: A Case-Control Study in Connecticut Women

Certain commonly used drugs and medical conditions characterized by chronic immune dysfunction and/or antigen stimulation have been suggested to affect important pathways in multiple myeloma tumor cell growth and survival. We conducted a population-based case-control study to investigate the role of medical history in the etiology of multiple myeloma among Connecticut women. A total of 179 incident multiple myeloma cases (21-84 years, diagnosed 1996-2002) and 691 population-based controls was included in this study. Information on medical conditions, medications, and medical radiation was obtained by in-person interviews. We calculated odds ratios (OR) as measures of relative risks using logistic regression models. A reduced multiple myeloma risk was found among women who had used antilipid statin therapy [OR, 0.4; 95% confidence interval (95% CI), 0.2-0.8] or estrogen replacement therapy (OR, 0.6; 95% CI, 0.4-0.99) or who had a medical history of allergy (OR, 0.4; 95% CI, 0.3-0.7), scarlet fever (OR, 0.5; 95% CI, 0.2-0.9), or bursitis (OR, 0.4; 95% CI, 0.2-0.7). An increased risk of multiple myeloma was found among women who used prednisone (OR, 5.1; 95% CI, 1.8-14.4), insulin (OR, 3.1; 95% CI, 1.1-9.0), or gout medication (OR, 6.7; 95% CI, 1.2-38.0). If our results are confirmed, mechanistic studies examining how prior use of insulin, prednisone, and, perhaps, gout medication might promote increased occurrence of multiple myeloma and how antilipid statins, estrogen replacement therapy, and certain medical conditions might protect against multiple myeloma may provide insights to the as yet unknown etiology of multiple myeloma.

Gout Medication Treatment Patterns and Adherence to Standards of Care From a Managed Care Perspective

To determine allopurinol treatment patterns and adherence to published standards of care for patients with gout. This retrospective claims analysis in a managed care database included patients 18 years or older, with continuous eligibility for 1 year before and after the start date and 2 or more visits during which the gout disease code (274.xx) was assigned or 1 or more pharmacy prescriptions for a gout-specific medication between January 1, 2000, and December 31, 2002 (intake period). Factors associated with compliance with allopurinol therapy were measured based on the medication possession ratio, and adherence to 2 quality-of-care indicators for gout management was assessed using multivariable logistic regression analysis. A total of 64.9% of allopurinol users had a modal daily dose or the most commonly observed daily dose of 300 mg/d, median length of therapy was 3 months, and a high proportion of patients had a medication possession ratio of 10% or less. Suggested quality-of-care Indicators for gout had low performance: 53% of patients with renal impairment received a modal daily dose of 300 mg or greater, and 83% of patients who started taking allopurinol did not have their serum urate levels measured within 180 days. Patients with gout flares were less likely to be compliant with allopurinol (odds ratio, 0.50; 95% confidence interval, 0.40-0.63). Patients with renal impairment at baseline were 3.2 times more likely to undergo serum urate testing than patients without renal impairment (odds ratio, 3.20; 95% confidence Interval, 1.25-8.23). There was low compliance with allopurinol therapy for treatment of gout. Patients potentially received suboptimal quality of care as measured by serum urate testing and appropriateness of allopurinol dosing in patients with renal impairment.

Aspirin, 1000 mg, reduced moderate to severe pain in acute migraine headache

Lipton RB, Goldstein J, Baggish JS, et al . Aspirin is efficacious for the treatment of acute migraine. Headache 2005;45:283–92.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Q Is a single dose of aspirin, 1000...

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol

Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol-SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol-SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) (P < 10(-7)). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P value = 4.7 x 10(-24)] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23-6665.26); corrected P value = 8.1 x 10(-18)]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.

Is uric acid implicated in benign paroxysmal positional vertigo?

Sirs: A recent publication implicated raised uric acid levels in the aetiology of benign paroxysmal positional vertigo (BPPV) [1]. It is now accepted that BPPV is due to the presence of otoconial debris in the lumen of the semicircular canals [2] but, to date, no reliable information about the chemical composition of the particles has been available [5]. The possibility that raised levels of uric acid could contribute to precipitating crystals in the canals was an attractive hypothesis with potential treatment developments. We measured uric acid, as part of routine blood tests, in 20 consecutive patients with BPPV, 18 idiopathic and 2 with a possible posttraumatic aetiology. BPPV was diagnosed on the basis of a typical history of brief attacks of positional vertigo and confirmed in all cases by a positive Hallpike positional manoeuvre for posterior canal BPPV (17 unilateral and 3 bilateral). The results were compared with an age and sex matched group of patients with a variety of neurological or otological conditions (BPPV group, 6 male, 14 female, mean age 53.25, range 23–79, SD 14.51; control group, 5 male 15 female, mean age 53.65, range [30–77], SD 12.01). No subjects with a history of gout or diseases or medication interfering with uric acid levels were included. Uric acid uric levels in the BPPV group were, mean value 290.35, range from 150 to 475μmol/L, SD 96.11. Two males had borderline levels (440μmol/L, and 475μmol/L), normal values are from 120 to 440μmol/L. In the control group, uric acid was, mean 273.4, range 134 to 470μmol/L, SD 88.27. Two males in the control group also had borderline increases (440 and 470μmol/L). There was no significant difference in uric acid levels between these two groups (t-test, p: 0.565). Our study failed to confirm the previously reported increase in uric acid in patients with BPPV [1]. We cannot explain this discrepancy but there are two major differences in the two BPPV populations studied. In the study by Adam, conducted in Nairobi, the vast majority of patients were male Africans. In our study, the majority of patients were European females. BPPV has a clear sex preference, normally favouring females as in our own unselected sample [2], and this may be of significance since uric acid, calcium metabolism and urolithiasis are estrogen modulated [3]. We are, however, unaware of any environmental or ethnic influences on uric acid metabolism, except for inter-tribal differences in Taiwan aboriginals [4]. The measurement technique used or influences such as nutritional and physical exercise habits, could have an influence on uric acid levels. However, they would be unlikely to explain the discrepancy between the two studies because the control subjects and techniques used were local in both studies. In conclusion, although larger sample studies might be helpful, including a search for BPPV in patients with gout or hyperuricaemia, our data do not support a role for uric acid in the origin of BPPV.

Prescription drug use and costs among diabetic patients in primary health care practices in Germany.

To evaluate drug prescriptions and costs among diabetic patients in primary care practices in Germany. Computerized data on prescriptions and costs (drug company sales prices) were analyzed in 30,604 diabetic and 17,723 (5% random sample) nondiabetic patients from 362 primary care practices during 1994. Relative use ratios for drug groups were obtained from logistic regression models (odds ratio [OR] for diabetes) controlling for age, sex, and other covariates. Relative costs (diabetic:nondiabetic) were estimated by direct age and sex standardization. Diabetic patients had an increased prescription use for most drugs. A substantial increased use (OR > or = 1.4) was found for cardiovascular drugs, fibrates, gout medication, laxatives, and wound care products. Diabetic subjects (7.9% of all patients) accounted for 21% of total annual prescription costs in the practices. Total costs (U.S. dollars) per patient-year were threefold higher (diabetic patients $384; control subjects $123). After excluding antidiabetic agents and age- and sex-standardization, relative costs were still 1.5 times higher (P < 0.05). Diabetes treatment accounted for 24% of total costs in diabetic patients (insulin 12%; oral antidiabetics 6%). The most important cost factor was cardiovascular drugs (CVDs) (39%). Three CVD groups accounted for about 50% of total CVD costs in diabetic patients (ACE inhibitors 25%; Ca-antagonists 16%; nitrates 10%). Prescription use among diabetic patients in primary health care practices was predominantly increased for cardiovascular drugs and for treatment of diabetes-associated disorders. Diabetic patients accounted for over one-fifth of the total pharmacy costs in primary practices, indicating that diabetes is a major economic factor in drug use.

Risk factors for nuclear opalescence in a longitudinal study. LSC Group. Longitudinal Study of Cataract.

This study evaluated risk factors for increases in nuclear opacification of the lens in the Longitudinal Study of Cataract (1989-1993; Boston, Massachusetts), which included 764 participants. Baseline data on demographic, medical, and other risk factors were available from an earlier case-control study; follow-up visits were completed yearly over a 4-year period. The lens photographs taken at baseline and at each follow-up visit were graded using the Lens Opacities Classification System III protocol. Analyses evaluated which risk factors collected at baseline were related to increased nuclear opacification at follow-up. The MULCOX2 method, an extension of Cox regression for nested event-time data, was used to estimate the effects of the risk factors. This method accounted for the correlation between fellow eyes. Results showed that the risk of nuclear opacification increased with each year of age (relative risk (RR) = 1.07), white race (RR = 2.94), lower education (RR = 1.50), use of gout medications (RR = 2.32), current smoking (RR = 1.58), family history of cataract (RR = 1.39), and preexisting posterior subcapsular opacities (RR = 6.67). An association with early use of eyeglasses was also suggested (RR = 1.37). In conclusion, nuclear opacification was related to demographic and other variables, including potentially modifiable factors such as current smoking and use of gout medications. Most risk factors identified by this longitudinal study confirm those found by the original case-control study. The increased risk of nuclear opacities in whites appears to be a new finding.

Dietary effects of allopurinol and sulfinpyrazone on development, survival, and reproduction of German cockroaches (Dictyoptera: Blattellidae).

Diets containing two gout medications, allopurinol and sulfinpyrazone, were fed ad libitum to first- or second-instar German cockroaches for 15 wk or until 100% mortality was reached. Cockroaches fed greater than or equal to 0.10% allopurinol diets weighed significantly less than those fed the control diet. Mortality of cockroaches fed diets containing greater than or equal to 0.05% allopurinol was significantly greater than those fed the control diet. The LT50 (6.1 wk) of cockroaches fed diets containing 0.10% allopurinol was significantly less than those fed any other diet containing allopurinol. LT50s and slopes were proportional and inversely related, respectively, to percentage of allopurinol in the diet. The addition of sulfinpyrazone to allopurinol diets minimally enhanced the blatticidal nature of the diets. Nymphs fed diets containing greater than or equal to 0.05% allopurinol experienced significant delays in adult emergence. Cockroaches fed greater than or equal to 0.01% allopurinol diets aborted a significantly greater percentage of their oothecae than those fed the 0.001% allopurinol or control diets. Hatched oothecae from cockroaches fed the 0.01% allopurinol diet had significantly fewer nymphs than those fed the 0.001% allopurinol or control diets. Percentage of oothecae aborted and number of nymphs per hatched ootheca from cockroaches fed a 2% sulfinpyrazone diet did not differ significantly from the control.

Myopia and Cataract-Reply

In Reply. —We appreciate the interest raised by our article. Liu et al cite our findings of an association between gout medications and mixed cataract, and summarize their previously reported findings among 53 patients using allopurinol. In our study, the use of any type of gout medication was investigated. Such use was found to be related to mixed cataract, our largest case group, but our results do not exclude associations of gout medications with individual cataract types. Dr Johnson comments on possible mechanisms to explain our finding of an association between use of eyeglasses before age 20 years and mixed cataract. Although our study obtained data on use of sunglasses, as suggested by Dr Johnson, no significant relationships with cataract were found. We agree with him that analyses exploring associations of risk factors with mixed cataract subgroups are of interest. Such analyses are ongoing and will be included in a

The Lens Opacities Case-Control Study

To the Editor. —We read with interest the article by Leske et al 1 in the February 1991 issue of theArchives. The authors identified ingestion of gout medications as a risk factor for the development of a mixed cataract (odds ratio, 2.48), but not of a pure posterior subcapsular, cortical, or nuclear cataract in the Final Polychotomous Logistic Regression Model (Table 5 in the article). We assume that the gout medication in question is allopurinol because the authors cited five studies on cataracts and allopurinol therapy, but omitted our findings published in 1988. 2 We examined 53 patients who attended the gout clinic at Charing Cross Hospital, London, England. All the patients, except three, had been receiving regular allopurinol therapy for at least 18 months, in the usual dose of 300 mg daily. Twenty-five of these patients had been receiving treatment for more than 6 years. We found an

The Lens Opacities Case-Control Study

The Lens Opacities Case-Control Study evaluated risk factors for age-related nuclear, cortical, posterior subcapsular, and mixed cataracts. The 1380 participants were ophthalmology outpatients, aged 40 to 79 years, classified into the following groups: posterior subcapsular only, 72 patients; nuclear only, 137 patients; cortical only, 290 patients; mixed cataract, 446 patients; and controls, 435 patients. In polychotomous logistic regression analyses, low education increased risk (odds ratio [OR] = 1.46) and regular use of multivitamin supplements decreased risk (OR = 0.63) for all cataract types. Dietary intake of riboflavin, vitamins C, E, and carotene, which have antioxidant potential, was protective for cortical, nuclear, and mixed cataract; intake of niacin, thiamine, and iron also decreased risk. Similar results were found in analyses that combined the antioxidant vitamins (OR = 0.40) or considered the individual nutrients (OR = 0.48 to 0.56). Diabetes increased risk of posterior subcapsular, cortical, and mixed cataracts (OR = 1.56). Oral steroid therapy increased posterior subcapsular cataract risk (OR = 5.83). Females (OR = 1.51) and nonwhites (OR = 2.03) were at increased risk only for cortical cataract. Risk factors for nuclear cataract were a nonprofessional occupation (OR = 1.96), current smoking (OR = 1.68), body mass index (OR = 0.76), and occupational exposure to sunlight (OR = 0.61). Gout medications (OR = 2.48), family history (OR = 1.52), and use of eyeglasses by age 20 years, which is an indicator of myopia (OR = 1.44), increased risk of mixed cataract. The results support a role for the nutritional, medical, personal, and other factors in cataractogenesis. The potentially modifiable factors suggested by this study merit further evaluation.

Metabolics and Biologicals in the Workplace

Potential decrements in job performance are associated with a wide variety of pharmaceutical agents, including antimetabolites, antineoplastics, gout medications, biologicals, hormones, plasma fractions, and antibiotics. The number of potential employees taking these medications ranges from less than 1 in 1000 for the antineoplastics in 1 in 10 for some biologicals. Whether a particular employee will experience a medication-induced performance decrement with these medications, as well as the extent of such a decrement, is in large part a function of factors such as individuality in drug response, the employee's age and diet, and drug interactions.

Augmentation of skin flap survival with allopurinol.

Although allopurinol is primarily known as an effective medication for gout, it has been shown to enhance tissue survival in a wide range of ischemic conditions. The study reported here investigated the effects of allopurinol on flap survival in a dorsal rat model. In a preliminary study, animals were given varying doses of allopurinol (0 to 400 mg per kilogram). A clinically efficacious dose was established upon conclusion of the test period by laboratory determinations and necropsy data. Other animals were divided into 3 groups: 1 (saline control), N = 11; 2 (50 mg per kilogram of allopurinol daily), N = 10; 3 (100 mg per kilogram of allopurinol qd), N = 11. Flaps were raised and necrosis assessed at 8 days. Flaps treated with allopurinol 100 mg per kilogram had significantly better survival than the controls (p less than 0.001) and 50 mg per kilogram (p less than 0.01). Allopurinol 50 mg per kilogram had no effect on flap survival.