Pseudotumor cerebri syndrome with different types of hormonal contraceptives in women of child-bearing age.

BACKGROUND AND PURPOSE: There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel. METHODS: We conducted a retrospective cohort study, with a case-control analysis of 4 871 504 women aged 15-45 years in the period 2008-2015, using IQVIA Ambulatory Electronic Medical Records data in the USA. Patients who used nine different contraceptive agents including intrauterine levonorgestrel, medroxyprogesterone injection, etonogestrel/ethinyl estradiol vaginal ring and combination oral contraceptives (COCs) that contained ethinyl estradiol and the progestins levonorgestrel, norgestimate, desogestrel, norethindrone and drospirenone, were included. Diagnosis of PTCS was defined using the first International Classification of Diseases, 9th or 10th revision, code for intracranial hypertension in patients who had also received an imaging code in the 30 days prior to the index date. RESULTS: A total of 3323 PTCS cases and 13 292 matched controls were identified. No increase in risk was found when analysing intrauterine levonorgestrel or COCs containing desogestrel, norethindrone, drospirenone, norgestimate or norgestrel versus COC levonorgestrel. The adjusted incidence rate ratio for etonogestrel/etonogestrel/ethinyl estradiol vaginal ring and medroxyprogesterone suspension compared with levonorgestrel COC was 4.45 [95% confidence interval (CI) 1.98-9.96] and 2.20 (95% CI 1.33-3.64), respectively. CONCLUSIONS: This study found an elevated risk for PTCS among users of etonogestrel vaginal ring and medroxyprogesterone suspension when compared with oral levonorgestrel. Future studies are needed to confirm these findings.

Concurrent of blaCTX-M and blaNDM-1 genes in clinical isolates of Escherichia coli from northern Iran.

The emergence of E. coli producing extended-spectrum ß-lactamases and metallo ß-lactamases has been reported as an important cause of treatment failure. The present study aimed to evaluate the existence of blaCTX-M, blaTEM, blaSHV, blaNDM-1 and blaIMP1 genes among E. coli isolated from patients in Babol, Northern Iran. The pattern of antibiotic resistance and the prevalence of multidrug-resistant (MDR) E. coli isolates were determined. E. coli isolates were separated from clinical specimens and antimicrobial susceptibility test (AST) was performed using the disk diffusion method. These isolates were further evaluated for the production of ESBLs and MBLs enzymes using cefotaxime (CTX), ceftazidime (CAZ) disks with and without clavulanic acid, and two CAZ with 2 mercaptopropionic acid disks, respectively. The ESBLs and MBLs positive isolates were analysed for the existence of blaCTX-M, blaTEM, blaSHV, blaNDM-1 and blaIMP-1 genes with the conventional PCR method. Of 259 isolates, 117 ß-lactamase producing E.coli were detected. MDR isolates were observed in 110/117 (94.9%) E. coli. Among 117 isolates, ESBLs, MBLs and coproduction of ESBL and MBL enzymes were observed in 45, 7 and 65 isolates, respectively. PCR analysis showed that the predominant genes were blaCTX-M15(95.5%) and blaNDM-1 (31.9%) among ESBL and MBL producing E. coli, respectively. Also, the concurrent occurance of the blaCTX-M with blaTEM, blaSHV, blaNDM-1 and blaIMP-1 genes were demonstrated. In conclusion, high prevalence rate of MDR isolates, particularly ESBL and MBL producing E. coli, observed in the current study shows the necessity of control and management strategies for the aforementioned isolates. Also, the early detection of concurrent ESBLs and MBLs producing E. coli is necessary to avoid treatment failure and prevent the distribution of such bacteria.

Concurrent of blaCTX-M and blaNDM-1 genes in clinical isolates of Escherichia coli from northern Iran

@#The emergence of E. coli producing extended-spectrum β-lactamases and metallo β-lactamases has been reported as an important cause of treatment failure. The present study aimed to evaluate the existence of blaCTX-M, blaTEM, blaSHV, blaNDM-1 and blaIMP- 1 genes among E. coli isolated from patients in Babol, Northern Iran. The pattern of antibiotic resistance and the prevalence of multidrug-resistant (MDR) E. coli isolates were determined. E. coli isolates were separated from clinical specimens and antimicrobial susceptibility test (AST) was performed using the disk diffusion method. These isolates were further evaluated for the production of ESBLs and MBLs enzymes using cefotaxime (CTX), ceftazidime (CAZ) disks with and without clavulanic acid, and two CAZ with 2 mercaptopropionic acid disks, respectively. The ESBLs and MBLs positive isolates were analysed for the existence of blaCTX-M, blaTEM, blaSHV, blaNDM-1 and blaIMP-1 genes with the conventional PCR method. Of 259 isolates, 117 β-lactamase producing E.coli were detected. MDR isolates were observed in 110/117 (94.9%) E. coli. Among 117 isolates, ESBLs, MBLs and coproduction of ESBL and MBL enzymes were observed in 45, 7 and 65 isolates, respectively. PCR analysis showed that the predominant genes were blaCTX-M- 15(95.5%) and blaNDM-1 (31.9%) among ESBL and MBL producing E. coli, respectively. Also, the concurrent occurance of the blaCTX-M with blaTEM, blaSHV, blaNDM-1 and blaIMP-1 genes were demonstrated. In conclusion, high prevalence rate of MDR isolates, particularly ESBL and MBL producing E. coli, observed in the current study shows the necessity of control and management strategies for the aforementioned isolates. Also, the early detection of concurrent ESBLs and MBLs producing E. coli is necessary to avoid treatment failure and prevent the distribution of such bacteria.

Risk of intraocular hemorrhage with new oral anticoagulants.

PurposeTo assess the risk of intraocular hemorrhage with warfarin and new oral anticoagulants (NOACs).MethodsWe ascertained all reported cases of intraocular hemorrhage (vitreous, choroidal, or retinal) with warfarin and NOACs (including dabigatran, rivaroxaban, apixaban) from the World Health Organizations's Vigibase database from 1968-2015. We used a disproportionality analysis to compute reported odds ratios (RORs) and corresponding 95% confidence by comparing the number of events with the study outcomes and study drugs compared with all other drugs reported to Vigibase. A harmful signal was deemed for a lower limit of the 95% confidence interval above 1.ResultsWe identified 80 cases of intraocular hemorrhage (vitreous, choroidal, or retinal) with warfarin in the World Health Organizations's Vigibase database from 1968-2015. A total of 156 cases of intraocular hemorrhage with NOACs (82 with rivaroxaban, 65 with dabigatran, 9 with apixaban). Warfarin had the highest signal of association with choroidal hemorrhage (ROR= 65.40 (33.86-126.30)). Rivaroxaban had the highest signal of association with both retinal and vitreous hemorrhage (ROR=7.41 (5.73-9.59) and ROR= 11.14 (7.37-16.86), respectively). Dabigatran was also significantly associated with retinal and vitreous hemorrhage (ROR= 3.78 (2.82-5.08) and ROR= 5.83 (3.66-9.30), respectively). The number of reports of retinal and vitreous hemorrhage were also significantly higher with apixaban, but the number of cases may be too little to make a meaningful evaluation.ConclusionA signal for risk of intraocular hemorrhage was detected for warfarin, dabigatran, and rivaroxaban. Large epidemiologic studies are needed to further confirm these findings.

Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

BACKGROUND: Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage. OBJECTIVES: To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 µg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 µg (DRSP/EE30). METHODS: Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current). RESULTS: The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41). CONCLUSIONS: We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected.

A meta-analysis on wood dust exposure and risk of asthma.

Work-related asthma is the most common occupational respiratory disorder in the industrialized countries. It has been postulated that wood dust exposure may increase the risk of work-related asthma. The objective of this study was to assess, through a meta-analysis, the risk of developing work-related asthma associated with wood dust exposure. A systematic search of the literature was performed. Inclusion and exclusion criteria were applied and a quality scale used to measure the quality of the included studies was developed. Using standard meta-analysis techniques, studies were pooled using both random and fixed effects models. Nineteen studies were included which consisted of three cohort studies, twelve case-control studies and four mortality studies. The pooled relative risk (RR) of asthma among workers exposed to wood dust was 1.53 (95% CI 1.25-1.87). When the analysis was restricted to studies carried out on Caucasian populations, the pooled RR was 1.59 (95% CI 1.26-2.00) while the pooled RR of studies on Asian populations was 1.15 (95% CI 0.92-1.44). Wood workers present a higher risk of asthma. Future research should include careful evaluation of ethnicity and nativity as risk modifiers.

Risk of upper gastrointestinal bleeding with oral bisphosphonates and non steroidal anti-inflammatory drugs: a case-control study.

BACKGROUND: Gastrointestinal injuries including gastric ulcers have been reported with oral bisphosphonate therapy. However, the risk of the more serious upper gastrointestinal bleeding (UGB) especially in the community setting with these drugs remains unknown. Similarly, the risk of UGB among users of both bisphosphonates and non steroidal anti-inflammatory drugs (NSAIDs) in the community is also unknown. AIM: To explore the risk of more serious UGB among users of bisphosphonates and the risk of UGB among users of both bisphosphonates and NSAIDs in the community. METHODS: We conducted a case-control study within a cohort of Quebec residents who had received a revascularization procedure from 1995 to 2004. Cohort members were followed up from the date of their first procedure until the earliest of: (1) study outcome, (2) date of death or (3) end of health care coverage. Cases were defined as those with the first diagnosis of a UGB. For each case, 20 controls were selected and matched to the cases by index date, age and cohort entry. Adjusted odds ratios for current use of bisphosphonates, NSAIDs and co-therapy of both drugs were computed. RESULTS: Within the initial cohort, 3253 incident cases of UGBs and corresponding 65 060 matched controls were identified. The adjusted odds ratio (OR) for UGB by current users of bisphosphonates was 1.01 (95% CI, 0.72-1.43). Current NSAID use was associated with an increased risk of UGB OR = 1.75; 95% CI, 1.53-1.99. The OR for use of bisphosphonates and NSAIDs was elevated OR = 2.00; 95% CI, 1.12-3.57. This risk was still elevated for users of bisphosphonates and COX-2 inhibitors [OR = 2.38 (95% CI, 1.26-4.50)]. CONCLUSION: We found no evidence of an increase in the risk of UGB among current users of bisphosphonates. The risk of combined NSAID and bisphosphonate therapy was increased, but this risk was not higher than the risk for NSAID users alone.

A novel polymorphic purine complex at the 1.5 kb upstream region of the human caveolin-1 gene and risk of Alzheimer's disease; extra-short alleles and accumulated allele homozygosity.

Crucial interaction of caveolin-1 (CAV1) with beta- and gamma-secretases, and aberrant expression of the gene encoding this protein in Alzheimer's disease (AD) support a role for CAV1 in the pathophysiology of this disease. We report a novel polymorphic purine complex stretching approximately 150 bp of genomic DNA at the 1.5 kb upstream region of the human CAV1 gene, alleles and genotypes of which are associated with sporadic late-onset AD. Extra-short alleles were observed in the case group that were absent in the control subjects. Remarkably, 63% of these alleles were observed to be homozygous in length, forming 23.7% of the homozygote length compartment in the AD cases (chi(2) = 19.08, df = 1, P < 0.000007). Increased homozygosity for length was also observed at this region in the Alzheimer's cases, for the allele lengths shared by the case and control groups [(chi(2) = 30.75, df = 1, P < 0.0000000, OR = 4.54, CI 95% (2.56-8.3)]. This region contains GGAA and GAAA motifs, the consensus binding sites for the Ets and IRF family transcription factors, respectively, and is highly conserved in distantly related non-human primates in respect with location and motif sequence. The effect of this complex sequence on the expression of CAV1, and the related mechanisms in the pathophysiology of AD remain to be clarified.

Exposure to furry pets and the risk of asthma and allergic rhinitis: a meta-analysis.

BACKGROUND: Exposure to pets has been implicated as a risk factor for asthma. However, this relation has been difficult to assess in individual studies because of the large potential of selection bias. We sought to examine the association between exposure to furry pets and asthma and allergic rhinitis by means of a meta-analysis. METHODS: We retrieved studies published in any language by searching systematically Medline (1966-March 2007), Embase, LILACS and ISI Proceedings computerized databases, and by examining manually the references of the original articles and reviews retrieved. We included cohort and case-control studies reporting relative risk estimates and confidence intervals of exposure to cats, dogs and unspecified furry animals and subsequent asthma and allergic rhinitis. We excluded cross-sectional studies and those studies that did not measure exposure but rather sensitization to pets. RESULTS: Thirty-two studies were included. For asthma, the pooled relative risk related to dog exposure was 1.14 (95% CI 1.01-1.29), that related to exposure to any furry pet was 1.39 (95% CI 1.00-1.95). Among cohort studies, exposure to cats yielded a relative risk of 0.72 (95% CI 0.55-0.93). For rhinitis, the pooled relative risk of exposure to any furry pet was 0.79 (95% CI 0.68-0.93). CONCLUSIONS: Exposure to cats exerts a slight preventive effect on asthma, an effect that is more pronounced in cohort studies. On the contrary, exposure to dogs increases slightly the risk of asthma. Exposure to furry pets of undermined type is not conclusive. More studies with exact measurement of exposure are needed to elucidate the role of pet exposures in atopic diseases.

Long-term persistence with orlistat and sibutramine in a population-based cohort.

OBJECTIVE: Orlistat and sibutramine are widely prescribed antiobesity agents that are approved for 2 years of continuous use. Previous 1-4-year randomized, placebo-controlled trials of these drugs have reported average weight losses of <5 kg, significant adverse effects and attrition rates of up to 60%. The objective of this study was to determine the long-term persistence with orlistat and sibutramine therapy outside a clinical trial setting. DESIGN, SETTING AND PATIENTS: Population-based administrative data from British Columbia, Canada, were used to create an inception cohort of orlistat and sibutramine users and determine the 2-year persistence with therapy. MAIN OUTCOME MEASURE: Persistence with therapy at 2 years. Drug discontinuation was defined as the failure to refill a prescription within 120 days. Patients discontinuing therapy were censored at the 60-day mark. RESULTS: Nearly 17 000 users of orlistat and 3500 users of sibutramine were identified. For both orlistat and sibutramine, 1-year persistence rates were <10% and 2-year persistence rates were 2%. CONCLUSION: This population-based, retrospective cohort analysis demonstrated very poor long-term persistence rates with orlistat and sibutramine and discontinuation rates that were much higher than those reported in clinical trials.

Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies.

OBJECTIVE: To quantitatively pool findings from observational studies on the risk of fracture outcomes associated with exposure to five antihypertensive drug classes: angiotensin-converting enzyme (ACE) inhibitors, diuretics (in particular thiazide diuretics), beta-blockers, calcium-channel blockers and alpha-blockers. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Publications listed in the MEDLINE, EMBASE and LILACS databases, the ISI proceedings, and bibliographies of retrieved articles. Sources were searched from the earliest possible dates through December 2005. REVIEW METHODS: We included case-control and cohort studies presenting relative risks and confidence intervals (CIs) for the association between exposure to antihypertensive agents and fracture outcomes. Data were extracted onto a standardized computer worksheet. Study quality was assessed using a 10-point questionnaire specific to case-control or cohort study design. RESULTS: Fifty-four studies were identified. Pooled estimates were computed using the software HEpiMA. The pooled relative risk (RR) of any fracture with use of thiazide diuretics was 0.86 (95% CI 0.81-0.92) and 1.14 (95% CI 0.84-1.54) with use of nonthiazide diuretics. There was a statistically significant reduction of any fracture with use of beta-blockers, (RR 0.86, 95% CI 0.70-0.98). The one study with ACE inhibitor data showed protection (RR 0.81, 95% CI 0.73-0.89). No significant associations were found between fractures and exposure to alpha-blockers or calcium-channel blockers. CONCLUSIONS: Thiazide diuretics and beta-blockers appear to lower the risk of fractures in older adults. However, these agents cannot be recommended as preventive therapies for fractures until data from randomized controlled trials have established their efficacy. Patients who use these inexpensive drugs as treatments for hypertension may also benefit from a reduction in fracture risk.

Furosemide use and hospitalization for benign prostatic hyperplasia.

OBJECTIVE: Recent studies have shown that furosemide may have anti-inflammatory properties. We explored whether exposure to furosemide would reduce the risk of being hospitalized with prostatism, a marker of benign prostatic hyperplasia. METHODS: Using record linkage and the computerized health insurance databases of the province of Québec, Canada, we identified a cohort of men 65 years of age and older within which we conducted a case-control study. Cases were individuals hospitalized with prostatism (ICD-9 code 600) between January 1991 and June 1993, with the index date taken as the date of hospitalisation. Controls were those not having experienced the event during the study period, with an index date selected randomly during their follow-up. Cases and controls were required to have at least 2 (1/2) years of health coverage prior to index date in order to identify risk factors for benign prostatic hyperplasia and establish baseline medical history. We assessed the subjects' exposure to furosemide and various other diuretics in the period 180 to 900 days preceding the index date. Logistic regression was used to evaluate the association between the use of furosemide and hospitalization for prostatism, adjusting for potential confounders. RESULTS: The cohort included 8,814 subjects, of which 231 were cases and 8,583 controls. The rate of hospitalization for prostatism was lower for users of furosemide compared to non-users (adjusted rate ratio 0.49; 95% CI: 0.25-0.95). There was no association with the use of thiazide or potassium sparing diuretics (adjusted rate ratio 0.95; 95% CI: 0.65-1.37). Results suggestive of a protective effect associated with corticosteroid use were observed (adjusted rate ratio 0.64; 95% CI: 0.44-0.93). CONCLUSIONS: This study supports the hypothesis that furosemide can reduce the risk of hospitalization for prostatism, a marker of benign prostatic hyperplasia.

Quantifying the interaction between angiotensin-converting enzyme inhibitors and aspirin: are we using the right method?

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with heart failure and coronary artery disease. Recently, there has been growing concern about the possible interaction between ACE inhibitors and aspirin. Numerous investigators have addressed this issue; however, results are equivocal. Most researchers used a statistical test of interaction, but the use of this method has been criticized. To assess the interaction between ACE inhibitors and aspirin properly, an additive model-more specifically, the Rothman Synergy Index-should be used. Further investigation with this model, however, is needed.

Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease: a meta-analysis of randomised controlled trials.

BACKGROUND: Recent case reports and letters have alerted practitioners to the risk of sleep attacks, usually preceded by somnolence, in patients with Parkinson's disease treated with pramipexole and ropinirole. OBJECTIVE: To quantify the risk of somnolence with the new dopamine agonists pramipexole and ropinirole in patients with Parkinson's disease. METHODS: We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts and Cochrane Library, contacted experts and pharmaceutical manufacturers, and manually reviewed all references retrieved to identify possible articles to include. Information on randomisation, blinding, type of treatment and reporting of somnolence were abstracted by 2 independent reviewers. Disagreements were resolved by a third author. ANALYSIS: We made 2 separate analyses. The first analysis compared the risk of somnolence in patients taking either pramipexole or ropinirole to that in patients taking placebo. The second analysis compared the risk of somnolence with these drugs (plus levodopa) versus that with levodopa alone. We calculated pooled relative risk estimates using the random effects model and when no heterogeneity was detected we used the fixed effects model. RESULTS: Four trials were included in the analysis of patients taking pramipexole or ropinirole compared with those taking placebo. The pooled relative risk of somnolence in this analysis was 4.98 [95% confidence interval (CI) 1.79 to 13.89]. Seven trials were included in the analysis of patients taking levodopa and pramipexole or ropinirole compared with those taking levodopa alone. The pooled relative risk was 2.06 (95% CI 1.47 to 2.88). CONCLUSION: Patients with Parkinson's disease using pramipexole or ropinirole are at higher risk of experiencing somnolence relative to patients taking placebo. Patients taking levodopa plus either one of these dopamine agonists are at higher risk than those taking levodopa alone. Clinicians should carefully weigh this risk against the benefit of these agents when prescribing these drugs.

Interpreting meta-analyses of pharmacologic interventions: the pitfalls and how to identify them.

Meta-analyses are key components of evidence-based decision making. The numbers of meta-analyses published in different areas of health care increased dramatically during the past 10 years. Many of them covered different pharmacologic interventions, making them useful resources to clinical pharmacists. Although a well-conducted meta-analysis may be valuable, a poorly conducted one may have false conclusions and thus incorrectly alter a clinician's recommendations. Several key concepts must be considered when appraising meta-analyses of pharmacologic interventions.

Evidence-based pharmacotherapy: review of basic concepts and applications in clinical practice.

OBJECTIVE: To introduce concepts that may assist pharmacists in the use and application of scientific evidence in clinical practice. These concepts are followed by examples of clinical trials as well as case scenarios that guide the reader through solving clinical problems using the tools discussed in the article. BACKGROUND: The introduction of evidence-based practice in the 1990s has had a positive impact on the practices of medicine and pharmacy. Part of this impact has been in the area of drug therapy. Although much literature has been published on the principles of evidence-based practice in the past few years, most of this material was intended for practicing physicians. We are not aware of any articles on the use of the evidence-based principles intended for clinical pharmacists. We are also aware that discussing all of these principles is an enormous task and thus beyond the scope of this article. Therefore, we focused this discussion on a brief summary of different study designs, factors affecting the strength of scientific evidence, and interpretation of the data. An approach in the use of these concepts is discussed through the use of case scenarios. RECOMMENDATIONS: Clinical pharmacists must use concepts in evidence-based practice when making pharmacotherapeutic decisions.

Shoulder symptoms in healthy athletes: a comparison of outcome scoring systems.

We used the Rowe, ASES, UCLA, Constant-Murley, and the Simple Shoulder Test scoring systems to determine the presence and severity of shoulder symptoms in "healthy" collegiate athletes at mid-season. Intercollegiate athletes were surveyed with a single, specific, comprehensive questionnaire regarding both of their shoulders at the mid-season of their respective sport. The questionnaire compiled the previously mentioned scoring systems and additional inquiries. Shoulders were divided into three groups for analysis: dominant-never injured, nondominant-never injured, and history of injury. Significant shoulder symptoms exist in athletes during full participation in their respective sport. Pain was the most frequent symptom, with 47% of all shoulder having some degree of pain. The frequency and degree of symptoms was significantly greater in shoulders with a history of injury. The UCLA scoring system is the most sensitive for evaluating "healthy" athletes at mid-season. However, the ideal shoulder scoring system for athletes has yet to be developed. To expect a "normal" or "symptom-free" shoulder after injury or surgery may be inappropriate. This information can serve as a reference for clinicians when evaluating the results of surgery and other treatment programs.

Identification and characterization of two isozymic forms of arylamine N-acetyltransferase in Syrian hamster skin.

Arylamine N-acetyltransferase (EC 2.3.1.5) activity was examined using skin from Syrian hamster. Two isozymes of arylamine N-acetyltransferase, designated NAT-1 and NAT-2, were detected on anion-exchange high-performance liquid chromatography analysis. Both enzyme activities had indistinguishable molecular masses (30 kDa), but differed significantly in their specificity toward the aromatic amines including serotonin, dopamine, methoxytryptamine, tryptamine, para-phenetidine, para-aminobenzoic acid, and sulphamethazine. Specifically, NAT-2 but not NAT-1 catalyzed acetylation of dopamine to N-acetyldopamine and acetylation of serotonin to form N-acetylserotonin, a direct precursor of melatonin. The two isozymes were also distinguishable based upon their sensitivity toward methotrexate inhibition (50% inhibiting dose for NAT-1 = 380 microM; NAT-2 > 2 mM). The presence of these two activities in the skin raises new questions about the physiologic role of this enzyme in general and in the skin-specific functions in particular.