Enhanced understanding of the relationship between erection and satisfaction in ED treatment: application of a longitudinal mediation model.

To apportion the direct effect and the indirect effect (through erections) that sildenafil (vs placebo) has on individual satisfaction and couple satisfaction over time, longitudinal mediation modeling was applied to outcomes on the Sexual Experience Questionnaire. The model included data from weeks 4 and 10 (double-blind phase) and week 16 (open-label phase) of a controlled study. Data from 167 patients with erectile dysfunction (ED) were available for analysis. Estimation of statistical significance was based on bootstrap simulations, which allowed inferences at and between time points. Percentages (and corresponding 95% confidence intervals) for direct and indirect effects of treatment were calculated using the model. For the individual satisfaction and couple satisfaction domains, direct treatment effects were negligible (not statistically significant) whereas indirect treatment effects via the erection domain represented >90% of the treatment effects (statistically significant). Week 4 vs week 10 percentages of direct and indirect effects were not statistically different, indicating that the mediation effects are longitudinally invariant. As there was no placebo arm in the open-label phase, mediation effects at week 16 were not estimable. In conclusion, erection has a crucial role as a mediator in restoring individual satisfaction and couple satisfaction in men with ED treated with sildenafil.

Erectile function, erection hardness and tolerability in men treated with sildenafil 100 mg vs. 50 mg for erectile dysfunction.

AIM: To compare efficacy and tolerability between 100-mg and 50-mg sildenafil doses in five double-blind, placebo-controlled (DBPC) fixed-dose studies. METHODS: Doses were compared for the change (baseline to end of 8-12 weeks of DBPC treatment) in score on the Erectile Function (EF) domain of the International Index of Erectile Function (IIEF; from five fixed-dose studies, > 1500 men); the per-patient estimated percentage of occasions that a specified Erection Hardness Score (EHS; from two of the five fixed-dose studies, > 500 men) was achieved, computed from logistic regression; the odds ratio (OR) of achieving EHS3 (hard enough for penetration, but not completely hard) and EHS4 (fully hard and completely rigid); and the adverse event incidence by treatment (from all five fixed-dose studies). RESULTS: For the 100-mg vs. 50-mg dose, IIEF-EF score improvement was consistently greater across the five studies and was statistically significant when data from two studies with similar design were pooled (10.7 ± 0.64 vs. 8.9 ± 0.83, p = 0.0287); and during the first 2 weeks of treatment, the odds of achieving EHS4 erections were almost doubled in one study (OR = 1.77, p = 0.0398). Sildenafil was generally well tolerated at either dose. CONCLUSION: Men with erectile dysfunction treated with 100-mg compared with 50-mg sildenafil may be more likely to achieve a greater improvement in erectile function and, within the first 2 weeks, completely hard and fully rigid erections, with little or no greater risk to tolerability.

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate.

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.

Counterfeit phosphodiesterase type 5 inhibitors pose significant safety risks.

Counterfeit drugs are inherently dangerous and a growing problem; counterfeiters are becoming increasingly sophisticated. Growth of the counterfeit medication market is attributable in part to phosphodiesterase type 5 inhibitor (PDE5i) medications for erectile dysfunction (ED). Millions of counterfeit PDE5is are seized yearly and account for the bulk of all counterfeit pharmaceutical product seizures. It has been estimated that up to 2.5 million men in Europe are exposed to illicit sildenafil, suggesting that there may be as many illegal as legal users of sildenafil. Analysis of the contents of counterfeit PDE5is shows inconsistent doses of active pharmaceutical ingredients (from 0% to > 200% of labelled dose), contaminants (including talcum powder, commercial paint and printer ink) and alternative ingredients that are potentially hazardous. In one analysis, only 10.1% of samples were within 10% of the labelled tablet strength. Estimates place the proportion of counterfeit medications sold over the Internet from 44% to 90%. Of men who purchase prescription-only medication for ED without a prescription, 67% do so using the Internet. Counterfeit PDE5is pose direct and indirect risks to health, including circumvention of the healthcare system. More than 30% of men reported no healthcare interaction when purchasing ED medications. Because > 65% actually had ED, these men missed an opportunity for evaluation of comorbidities (e.g. diabetes and hypertension). Globally, increased obstacles for counterfeiters are necessary to combat pharmaceutical counterfeiting, including fines and penalties. The worldwide nature of the counterfeit problem requires proper coordination between countries to ensure adequate enforcement. Locally, physicians who treat ED need to inform patients of the dangers of ordering PDE5is via the Internet.

Clinically meaningful improvement on the quality of erection questionnaire in men with erectile dysfunction.

Defining the minimal clinically meaningful improvement (MCMI) is crucial to understanding the treatment effects on health-status measures. We estimated the MCMI on the quality of erection questionnaire (QEQ), a validated measure specific to assess erectile quality during sexual intercourse. Data were from two controlled trials of an investigational phosphodiesterase type 5 inhibitor. Improvement on the Erectile Function domain of the International Index of Erectile Function was used as the anchor. For men who improved by exactly 1 erectile dysfunction severity category (anchor group (n=95)), clinically meaningful improvement (CMI, estimated with mean QEQ total change score from baseline to end of treatment) and MCMI (estimated with the lower limit of the 95% confidence interval of the mean) were 22.4 (s.d., 2.2) and 18.0 points, respectively. For the difference between the anchor group and men with no change in severity category (n=116), CMI and MCMI were 17.7 (s.d., 2.9) and 12 points, respectively. Distribution-based analyses (baseline s.e. of measurement (s.e.m.)=7.99, end-of-treatment s.e.m.=8.22 and s.e. of difference=11.46) supported a proposed MCMI of 12 points. Convergence of anchor-based and distribution-based criteria supports at least a 12-point difference in QEQ scores between treatments as clinically important.

Self-esteem, confidence and relationship satisfaction in men with erectile dysfunction: a randomized, parallel-group, double-blind, placebo-controlled study of sildenafil in Mexico.

Erectile dysfunction (ED) negatively impacts self-esteem and relationship satisfaction. The Self-Esteem and Relationship (SEAR) questionnaire is a validated, ED-specific, patient-reported instrument that specifically addresses self-esteem and relationship issues within the context of ED. Effective ED treatment with sildenafil in a double-blind, placebo-controlled clinical trial conducted in Brazil, Mexico, Australia and Japan showed pooled cross-cultural improvements in self-esteem, confidence and relationship satisfaction. This report focuses on the results from the subgroup of men from nine Mexican centers who participated in the multinational study. A total of 95 men aged >or=18 years with clinically diagnosed ED and currently in a stable relationship were randomized to placebo (n=47) or sildenafil (n=48). The SEAR results for Mexican men showed that sildenafil treatment led to significant improvements in self-esteem, confidence and relationship satisfaction. These data support an earlier study showing that Latin American men taking sildenafil have similar safety and efficacy profiles compared to non-Latin counterparts.

An assessment of patient-reported outcomes for men with erectile dysfunction: Pfizer's perspective.

Patient-reported outcomes (PROs) for men with erectile dysfunction (ED) have blossomed in the published literature and at professional conferences. These outcomes have been central to study the science of ED itself and to evaluate efficacy of treatment for men with ED. In this review article we highlight and distinguish among seven key PROs: the International Index of Erectile Function, for sexual function including erectile function; the Sexual Health Inventory for Men (SHIM), for diagnosis of ED; the Quality of Erection Questionnaire, for satisfaction with quality of erections; the Erectile Dysfunction Inventory of Treatment Satisfaction, for personal evaluation of treatment received; the Self-Esteem And Relationship questionnaire, for emotional well-being; the Erection Hardness Score (EHS), for targeting erection hardness and the Sexual Experience Questionnaire, for erection (both function and quality), individual satisfaction and couples satisfaction. Depending on the purpose of the investigation, all seven PROs have merit for use in clinical trials and at least deserve consideration in clinical practice. The SHIM and the EHS, given their aims and brevity, deserve special consideration in clinical practice. As a unit these seven PROs complement and supplement each other. Which ones to choose in a particular undertaking depends on the objective or purpose of a given study. These PROs acknowledge that sexual dysfunction and its treatment have multiple dimensions. Each of these instruments represents a significant contribution to sexual medicine research and, when used judiciously and appropriately, can help to provide optimal patient care and management.

Correlations between increased erection hardness and improvements in emotional well-being and satisfaction outcomes in men treated with sildenafil citrate for erectile dysfunction.

To explore relationships between erection hardness and other outcomes in men with erectile dysfunction (ED). Pooled analyses were conducted on 27 randomized, double-blind, placebo-controlled trials and six open-label trials from the worldwide sildenafil database. Outcomes included erection hardness graded subjectively, hardness and sexual satisfaction questions from the International Index of Erectile Function, general and sexually-specific emotional well-being from the self-esteem and relationship questionnaire, and the erectile dysfunction inventory of treatment satisfaction. Hardness outcomes improved (with a possible dose-response relationship for the achievement of fully hard and rigid erections) and correlated positively with the other outcomes. Sildenafil 100 mg produced optimal erection hardness (fully hard and rigid erections) in a substantial proportion of men with ED. Because optimal erection hardness correlated positively with some emotional well-being and satisfaction outcomes, sildenafil 100 mg may be the most appropriate dosage for treatment of ED for most men.

A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis.

OBJECTIVE: Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS). METHODS: This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed. RESULTS: After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE. CONCLUSION: Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables.

Minimal time to successful intercourse after sildenafil citrate: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the minimal time to successful intercourse after taking sildenafil citrate for erectile dysfunction (ED). METHODS: Male patients with ED (mean age 60 years; mean ED duration 7.0 years) who were successfully treated with sildenafil (100 mg) for 2 months or longer were randomized to sildenafil (n = 115) or placebo (n = 113) for 4 weeks of double-blind treatment. Using a stopwatch, patients recorded the time needed to obtain an erection hard enough for sexual intercourse after taking the study drug at least 2 hours after eating. RESULTS: Within 14 and 20 minutes of sildenafil dosing, 35% and 51% of sildenafil-treated patients, respectively, versus 22% and 30% of placebo-treated patients, respectively, had an erection that led to successful intercourse (P <0.05 for both). The median time to erection leading to successful intercourse after sildenafil dosing was 36 minutes compared with 141 minutes for placebo. CONCLUSIONS: In this study, slightly more than one half of a population of prior sildenafil responders achieved an erection that led to successful sexual intercourse within 20 minutes of sildenafil administration, suggesting that the onset of action of sildenafil can be less than 30 minutes in men with ED.

Patient and partner satisfaction with Viagra (sildenafil citrate) treatment as determined by the Erectile Dysfunction Inventory of Treatment Satisfaction Questionnaire.

OBJECTIVES: To assess the efficacy and safety of Viagra (sildenafil citrate) in male outpatients with erectile dysfunction and patient and partner satisfaction with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). METHODS: A total of 247 patients with erectile dysfunction of broad-spectrum etiology were treated in a randomized, double-blind, parallel-group, multicenter study conducted at outpatient clinics. Patients receiving oral sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo during a 12-week period. The principal efficacy measures were responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) on the International Index of Erectile Function and three global efficacy questions. Patient and partner satisfaction with treatment were assessed, for the first time, using the EDITS questionnaire. RESULTS: Efficacy scores for the International Index of Erectile Function questions and the global efficacy questions were significantly higher for patients receiving sildenafil than for those receiving placebo (P <0.001). Both patients and partners receiving sildenafil also had significantly higher EDITS scores than those receiving placebo (P <0.001). Adverse events were chiefly mild or moderate. Two patients receiving sildenafil and none receiving placebo discontinued treatment because of adverse events. CONCLUSIONS: Sildenafil was an effective, well-tolerated treatment for erectile dysfunction in an outpatient setting. Partner evaluations corroborated patient assessments. The results from the EDITS questionnaire indicated that after 12 weeks of receiving sildenafil both patients and partners reported higher levels of treatment satisfaction relative to placebo.

EDITS: development of questionnaires for evaluating satisfaction with treatments for erectile dysfunction.

OBJECTIVES: To develop Patient and Partner versions of a psychometrically sound questionnaire, the EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction), to assess satisfaction with medical treatments for erectile dysfunction. METHODS: Treatment satisfaction differs from treatment efficacy as it focuses on a person's subjective evaluation of treatment received. Twenty-nine items representing the domain of treatment satisfaction for men and 20 representing partner satisfaction were generated. Two independent samples of 28 and 29 couples completed all items at two points in time. Spearman rank-order correlations were derived to assess test-retest reliability and couple coefficients of validity. Internal consistency coefficients were calculated for both Patient and Partner versions and a content validity panel was used to analyze content validity. RESULTS: Only items that met all the following criteria were selected to comprise the final questionnaires: (a) range of response four or more out of five; (b) test-retest reliability greater than 0.70; (c) ratings by at least 70% of the content validity panel as belonging in and being important for the domain; and (d) significant correlation between the subjects' and partners' responses. Eleven patient items met criteria and formed the Patient EDITS; five partner items met criteria and formed the Partner EDITS. Scores on the two inventories were normally distributed with internal consistencies of 0.90 and 0.76, respectively. Test-retest reliability for the Patient EDITS was 0.98; for the Partner EDITS, it was 0.83. CONCLUSIONS: Reliability and validity were well established, enabling the EDITSs to be used to assess satisfaction with treatment modalities for erectile dysfunction and to explore the impact of patient and partner satisfaction on treatment continuation.

Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine.

We have previously described the inhibition of human immunodeficiency virus serotype 1 (HIV-1) using the antimalarial hydroxychloroquine (HCQ), a weak base that inhibits the posttranslational modification of glycoprotein 120 (gp 120) in T cells and monocytes. The mechanism of inhibition of gp 120 production was presumed to be the ability of HCQ to increase endosomal pH and therefore alter enzymes required for gp120 production. To further clarify this action, we have determined the effect of HCQ and its enantiomers on endosomal pH. Pretreatment of cells with HCQ and the levo- and dextro-enantiomers at concentrations demonstrated to suppress anti-HIV-1 activity increased endosomal pH to levels similar to increases seen with chloroquine and ammonium chloride, two other weak bases, and decreased gp 120 production. The dextro- and levo-enantiomers suppressed HIV-1 replication to a similar extent and were no more toxic than racemic HCQ. We next compared the anti-HIV-1 effect of HCQ with zidovudine (ZDV) in both newly and chronically HIV-1-infected T-cell and monocytic cell lines (63 and 63HIV). HCQ suppressed HIV-1 replication in a dose-dependent manner in both recently and chronically infected T-cell and monocytic cell lines. In contrast, ZDV pretreatment had potent anti-HIV-1 activity in the newly infected T and monocytic cells but not in chronically infected cells. An additive effect of HCQ with ZDV was observed in the newly infected T and monocytic cells but not in the chronically infected cells. Although the anti-HIV-1 effect of HCQ was less than that of ZDV, HCQ may still be potentially useful either as an alternative HIV-1 treatment or in combination with other anti-HIV-1 agents, especially in patients who have rheumatic manifestations of HIV-1 infection.

Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1.

Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in vitro in T cells and monocytes by inhibiting posttranscriptional modification of the virus. These in vitro observations have been expanded into an in vivo study of HCQ as a potential anti-HIV-1 agent in HIV-1-infected patients. A randomized, double-blind, placebo-controlled clinical trial was conducted in 40 asymptomatic HIV-1-infected patients who had CD4+ counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive either HCQ 800 mg/d or placebo for 8 weeks. Virologic and immunologic parameters, including HIV-1 ribonucleic acid (RNA) via use of polymerase chain reaction, viral culture, antigen and mitogen responses, and proinflammatory cytokine levels were measured at the beginning and end of the study. The amount of recoverable HIV-1 RNA in plasma declined significantly in the HCQ group over the 8-week period (P = 0.022), while it increased in the placebo group. The percentage of CD4+ T cells remained stable in the HCQ-treated group (18.1 +/- 9.2% before treatment vs 18.6 +/- 10.5% after treatment) and fell significantly in the placebo group (21 +/- 7% before treatment vs 19.3 +/- 6.3% after treatment; P = 0.032). However, this was not reflected as a change in absolute CD4+ counts for either group (HCQ, 262.8 +/- 166 cells/mm3 vs 251 +/- 163 cells/mm3; placebo, 312 +/- 121 cells/mm3 vs 321 +/- 124 cells/mm3). Mitogen- and antigen-specific responses remained constant in the HCQ group while T cell proliferative responses to Candida decreased in the placebo group (4.8 +/- 3.6 x 10(3) SI [stimulation index] vs 3.0 +/- 3.0 x 10(3) SI; P = 0.032). Lastly, serum interleukin 6 levels declined in the HCQ group (14.3 +/- 13.5 U/mL vs 12.0 +/- 16.7 U/mL; P = 0.023) but not in the placebo group (11.3 +/- 8.8 U/mL vs 7.0 +/- 11.7 U/mL); this was coincident with a decrease in serum immunoglobulin (Ig)G (2563 +/- 1352 mg/mL vs 2307 +/- 1372 mg/dL; P = 0.032), compared with the placebo group (2733 +/- 1473 mg/dL vs 2709 +/- 1501 mg/dL). No other parameters, including serum p24 and beta-2 microglobulin levels, were altered by HCQ therapy. HCQ thus may be useful in the treatment of patients with HIV-1 infection.

Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells.

To study the effect of hydroxychloroquine on cytokine production by monocytes and T cells, cells were pretreated with varying concentrations of hydroxychloroquine and stimulated with lipopolysaccharide (monocytes), phytohemagglutinin or anti-CD-3 monoclonal antibodies (T cells). Interleukin 1 alpha (IL-1-alpha), IL-6 and tumor necrosis factor alpha (TNF-alpha) production were measured from the stimulated monocytes and IL-2, IL-4 and gamma interferon (IFN-gamma) were measured from the stimulated T cells. Hydroxychloroquine inhibited production of IL-1-alpha (monocytes) and IL-6 (T cells and monocytes). In contrast IL-2, IL-4, TNF-alpha and IFN-gamma production were not affected. Preferential inhibition of IL-1-alpha production by monocytes and IL-6 production by T cells and monocytes may contribute to its antiinflammatory effect in autoimmune diseases.

The relevance of antimalarial therapy with regard to thrombosis, hypercholesterolemia and cytokines in SLE.

Hydroxychloroquine has several less well-known actions that may have clinical relevance in treating systemic lupus erythematosus (SLE). (1) Hydroxychloroquine has a possible anti-thrombotic action. It is a platelet inhibitor and appears to decrease the risk of thromboembolism in patients with anticardiolipin antibodies. (2) Hydroxychloroquine is associated with lower serum cholesterol and low-density lipoprotein levels compared to those present in patients who are taking corticosteroids but not antimalarials for SLE. (3) It may also decrease abnormal levels of cytokines. Interleukin-6 (IL-6), soluble CD8 and soluble IL-2 receptors (sIL-2R) are lower in patients taking antimalarials compared to those on corticosteroids alone or on neither medication. Serum levels of CD8 and sIL-2R decrease after 6 weeks of hydroxychloroquine treatment. These findings may help explain the favorable response of SLE patients treated with antimalarials.

Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes.

Chloroquine and its analogue hydroxychloroquine (HCQ) have been shown to inhibit a variety of viral infections including influenza and adenovirus through blockade of viral entry via inhibition of endosomal acidification. We have extended these observations to human immunodeficiency virus type 1 (HIV-1) infection utilizing primary T cells and monocytes, a T cell line (CEM), and a monocytic cell line (U-937). HCQ inhibited HIV-1 replication (> 75%), as measured by reverse transcriptase activity, in the primary T cells and monocytes as well as the T cell and monocytic cell lines. HCQ itself had no anti-reverse transcriptase activity and was not toxic to the cells at concentrations inhibitory to viral replication. Intracytoplasmic staining with an anti-p24 antibody, 24 h after infection, revealed the presence of intracytoplasmic virus, suggesting that the drug does not block viral entry. The production of steady-state HIV-1 mRNA was not affected by HCQ in that comparable levels of HIV-1 mRNA could be detected by Northern blot analysis and by in situ hybridization in both the HCQ-treated and untreated cells. However, HCQ does appear to affect production of infectious HIV-1 virions because viral isolates from HCQ-treated cells could not infect target CEM cells. These data suggest that HCQ may be useful adjunctive therapy in the treatment of HIV-1 infection.

Cholesterol-lowering effect of hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of steroids on lipids.

PURPOSE: The effects of hydroxychloroquine (HCQ) on serum levels of cholesterol, triglycerides, and high- (HDL) and low-density lipoprotein (LDL) were studied in patients with rheumatoid arthritis or systemic lupus erythematosus. PATIENTS AND METHODS: A total of 155 women were divided into the following treatment groups: Group A: patients taking HCQ and no steroids (n = 58); Group B: patients taking steroids and no HCQ (n = 35); Group C: patients receiving both HCQ and steroids (n = 18); and Group D: patients receiving neither HCQ nor steroids (n = 44). RESULTS: HCQ therapy had a high statistical association with low serum levels of cholesterol (181 mg/dL; p = 0.0006), triglycerides (106 mg/dL; p = 0.0459), and LDL (101 mg/dL; p = 0.0004), irrespective of concomitant steroid administration. The HCQ-treated group (A) had lower cholesterol (181 mg/dL; p = 0.0039) and LDL (101 mg/dL; p = 0.007) levels than those receiving neither HCQ nor steroids (205 mg/dL) and 128 mg/dL) (Group D). No HDL differences were observed. CONCLUSION: The effects of HCQ do not appear to be due to changes in diet or weight, and the drug was well tolerated. Although the mechanism of cholesterol lowering by HCQ is not known, this drug deserves further investigation for its lipid-lowering properties.

Differential effects of anti-arthritic agents on subnormal plasma iron levels in adjuvant arthritic rats.

Nonsteroidal anti-inflammatory drugs (NSAID's) and other antirheumatic compounds such as disease modifying antirheumatic drugs (DMARD's), immunosuppressives and glucocorticoids were tested to determine if daily medication for two weeks could elevate subnormal levels of plasma iron in adjuvant-arthritic (AA) rats. Aspirin, indomethacin, ibuprofen and phenylbutazone were chosen as representative carboxylic acids and pyrazole NSAID's. Although NSAID's at all doses significantly reduced noninjected paw swelling, no NSAID significantly enhanced subnormal plasma iron levels in AA rats. In contrast, the standard DMARD's auranofin and gold sodium thiomalate, as well as the glucocorticoid, dexamethasone and the immunosuppressives, methotrexate and cyclosporin-A all significantly restored plasma iron levels 28 to 100 percent. Plasma iron depression, a parameter of the acute phase response probably under regulation by pro-inflammatory cytokines, is not reversed by NSAID treatment. This appears to be a useful method for distinguishing NSAID's from other anti-arthritic compounds.