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BackgroundMalondialdehyde (MDA) is a candidate general marker of oxidative stress (OS). We sought to assess the relation of MDA to Gulf War illness (GWI) and to a variety of exposures.MethodsThis is an observational study involving subjects from Southern California recruited from October 2011 to May 2014. MDA was assessed in 81 participants (41 GWI-cases, 40 controls). General and Gulf-specific exposures were elicited. MDA case-control comparison was restricted to 40 matched pairs. The potential association between MDA and exposures was assessed using regression analyses. Gulf-specific exposures were incorporated into a case-specific model.ResultsPlasma MDA was significantly lower in GWI-cases than controls. Composite pesticide and fuel-solvent exposures negatively predicted MDA in the total sample, as well as in the analyses that included either GWI-cases or controls only. Self-reported exposure to organophosphate (OP) nerve gas was a strong predictor for lower MDA level in veterans with GWI.ConclusionPast pesticide exposures predicted lower MDA in both veterans with GWI and in healthy controls.

Physicians are among those prescribed statins and therefore, subject to potential statin adverse effects (AEs). There is little information on the impact of statin AEs on physicians affected by them. We sought to assess the character and impact of statin AEs occurring in physicians and retired physicians, and to ascertain whether/how personal experience of AEs moderated physicians' attitude toward statin use. Seven active or retired physicians from the United States communicated with the Statin Effects Study group regarding their personal experience of statin AEs. AE characteristics, experience with (their own) physicians, and impact of AE was ascertained. We inquired whether or how their experience altered their own attitude toward statins or statin AEs. Patient A: Atorvastatin 40 then 80 mg was followed by cognitive problems, neuropathy, and glucose intolerance in a Radiologist in his 50s (Naranjo criteria: probable causality). Patient B: Atorvastatin 10 mg was followed in 2 months by muscle weakness and myalgia in an Internist in his 40s (probable causality). Patient C: Atorvastatin, ezetimibe/simvastatin, rosuvastatin at varying doses was followed shortly after by irritability, myalgia, and fatigue in a Cardiac Surgeon in his 40s (probable causality). Patient D: Simvastatin 20 then 40 mg was followed in 4 years by mitochondriopathy, myopathy, neuropathy, and exercise intolerance in an Emergency Medicine physician in his 50s (definite causality). Patient E: Simvastatin 20 mg and niacin 1000 mg was followed in one month by muscle weakness and myalgia in a Physical Medicine and Rehabilitation physician in his 50s (probable causality). Patient F: Lovastatin 20 mg then simvastatin 20 mg, atorvastatin 20 mg, rosuvastatin 5 mg, niacin 20 mg and ezetimbe 10 mg was followed by muscle weakness and myalgia in an Obstetrician/Gynecologist in his 70s (definite causality). Patient G: Ezetimibe/simvastatin and atorvastatin (dose unavailable) was followed shortly after by cognitive problems in a Radiologist in her 80s (probable causality). Thus AEs affected multiple quality-of-life relevant domains, often in combination, encompassing muscle (N = 5), fatigue (N = 2), peripheral neuropathy (N = 2), cognitive (N = 2), dysglycemia (N = 1) and behavioral manifestations (N = 1). In five, the AEs affected the physician professionally. Five physicians experienced dismissive attitudes in some of their own healthcare encounters. One noted that his experience helped not only his own attention to statin AEs, but that of other physicians in his community. Several stated that their experience altered their understanding of and/or attitude toward statin AEs, and/or their view of settings in which statin use is warranted. Statin AEs can have profound impact in high functioning professionals with implications to the individual, their professional life, and those whom they serve professionally.

We present a case series of four previously healthy, employed adults without significant prior medical history in each of whom symptoms developed while on fluoroquinolones (FQs), with progression that continued following discontinuation evolving to a severe, disabling multisymptom profile variably involving tendinopathy, muscle weakness, peripheral neuropathy, autonomic dysfunction, sleep disorder, cognitive dysfunction and psychiatric disturbance. Physicians and patients should be alert to the potential for FQ-induced severe disabling multisymptom pathology that may persist and progress following FQ use. Known induction by FQs of delayed mitochondrial toxicity provides a compatible mechanism, with symptom profiles (and documented mechanisms of FQ toxicity) compatible with the hypothesis of an exposure-induced mitochondrial neurogastrointestinal encephalomyopathy.

PurposeWe sought to assess the relation of dietary trans fatty acid (dTFA) consumption to word-memory.MethodsWe analyzed cross-sectional data from the 1999-2005 UCSD Statin Study. Participants were 1018 adult men and non-procreative women age ≥20 without diagnosed diabetes, CVD, or extreme LDL-cholesterol. Primary analyses focused on men, as only men (N = 694) were effectively represented in younger adult ages. "Recurrent words" assessed word memory. dTFA (grams/day) estimates were calculated from the Fred Hutchinson Food Frequency Questionnaire. Regression, stratified at age 45, assessed the relation between memory and dTFA in various adjustment models. Major findings were replicated in the full sample (including women). Potential mediators were examined.ResultsAn age-by-dTFA interaction was significant. dTFA adversely predicted memory in younger adults (only), robust to adjustment model. Each gram/day dTFA was associated with an estimated 0.76 fewer words recalled (full model) (SE = 0.27, 95%CI = 0.22,1.3, P = 0.006). Adjustment for systolic blood pressure, waist circumference and BMI (but not lipid or glycemic variables) attenuated the relationship, consistent with mediation by factors involving, relating to, or concurrently influencing, these factors.ConclusionGreater dTFA was significantly associated with worse word recall in younger adults. Prooxidant and energetic detriments of dTFA and triangulation with other evidence offer prospects for causality.

Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case–control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored. [ABSTRACT FROM AUTHOR]

Irritability, aggression and other adverse behavioural effects have been associated with the use of statins (3-hydroxy-3-methyl-glutarylcoenzyme A reductase inhibitors) and other drug classes. A number of studies have also linked low cholesterol with aggression and violence. This paper presents the cases of two first-degree male relative patients (father and son) identified by self-referral to the University of California in San Diego Statin Effects Study. Both patients experienced behavioural adverse effects on statins including irritability and aggression, however neither patient recognised a significant change in their behaviour. This may be the first report of behavioural adverse effects manifested on statins by first-degree male relatives, which may suggest possible familial/biological predisposition. These cases also highlight the issue of externalisation by patients of the origin of interpersonal discord, which may serve as an obstacle to adverse effects reporting and lead to negative outcomes for patients, and for those around them. [ABSTRACT FROM AUTHOR]

Sleep problems have been reported as an adverse effect of statins. In a randomised trial, simvastatin at 20 mg produced significantly worse sleep quality than either placebo or pravastatin 40 mg. A possible relation to sleep apnoea was hypothesised. Here, the case of a 67-year-old man who experienced sleep apnoea on simvastatin 20 mg is presented. Objective nightly testing showed a prompt, marked, sustained and statistically significant improvement in the obstructive apnoea index when the patient switched to pravastatin 20 mg. [ABSTRACT FROM AUTHOR]