Comparison of three stationary phases in the separation of polyphenyls by liquid chromatography.

We present herein new analytical protocols for the separation and structural elucidation of polyphenyls. Three commercially available chromatographic stationary phases are compared in the separation of these non-polar, unfunctionalized, positional isomers. Baseline separation of nine terphenyl and quaterphenyl isomers is achieved in under ten minutes using a rapid gradient elution HPLC method. Complete separation of these, and a further five polyphenyls, is demonstrated. We finally present a linear correlation between solvent accessible surface area and the retention times of these closely related compounds.

Hypermobility Assessment in 1,004 Adult Patients Presenting with Hip Pain: Correlation with Diagnoses and Demographics.

BACKGROUND: The strength of the association between hypermobility and developmental dysplasia of the hip (DDH) in adults is unknown. We sought to analyze this relationship in a prospective, blinded, institutional review board-approved, observational study. The hypothesis was that the prevalence of generalized joint hypermobility (GJH) would be significantly higher in patients with hip dysplasia than in those with other hip diagnoses on the basis of clinical observations of joint laxity. METHODS: One thousand and four consecutive new patients (390 males and 614 females) seen over a 4-year period were evaluated for hypermobility of the hip using 2 criteria: the Beighton 9-point physical examination criteria and the Hakim-Grahame 5-item history questionnaire. Diagnosis, age, sex, and race were tested as predictors of hypermobility. Patient-reported outcome scores from the International Hip Outcome Tool (iHOT-12) and the modified Harris hip score (mHHS) were also assessed. RESULTS: DDH was the primary diagnosis in 33.2% of the patient population. Patients who had dysplasia without osteoarthritis (OA) had a significantly elevated prevalence of GJH (77.9%) compared with those with nondysplastic hips (32.8%; p < 0.0001) or with patients who had dysplasia and OA (35.7%; p < 0.0001) according to either method. The odds ratio (OR) for patients with DDH versus those with other diagnoses was 7.1 (95% confidence interval [CI]: 5.1 to 10.0). The prevalence of hypermobility was significantly greater in females than in males (OR = 4.2 [95% CI: 3.2 to 5.5]; p < 0.0001). The prevalence of GJH was inversely proportional to age. There was a significantly reduced prevalence of GJH observed in Hispanic patients (p < 0.05) compared with other races. GJH was not a predictor of patient-reported outcome scores (p = 0.51 for iHOT-12 and p = 0.44 for mHHS). CONCLUSIONS: To our knowledge, this study is the first to establish a strong association between hypermobility and DDH in adults, confirming the hypothesis. We recommend utilizing both the Beighton and Hakim-Grahame scoring systems together as routine components of the history and physical examination for patients with hip dysplasia. Further research is warranted to explore the genetic basis and potential causal relationships between soft-tissue laxity and skeletal dysplasia, as well as improvements in assessment tools. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Preterm birth with placental evidence of malperfusion is associated with cardiovascular risk factors after pregnancy: a prospective cohort study.

OBJECTIVE: Preterm birth (PTB) is associated with excess maternal cardiovascular disease risk. We considered that women with PTB and placental evidence of maternal malperfusion would be particularly affected. DESIGN: Pregnancy cohort study. SETTING: Pittsburgh, PA, USA. POPULATION: Women with PTB (n = 115) and term births (n = 210) evaluated 4-12 years after pregnancy. METHODS: Cardiometabolic risk markers were compared in women with prior PTB versus term births; pre-eclampsia and growth restriction cases were excluded. Placental evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, intervillous fibrin deposition), acute infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of unknown aetiology (chronic inflammation) was used to classify PTBs. MAIN OUTCOME MEASURES: Carotid artery intima-media thickness (IMT), fasting lipids, blood pressure (BP) and inflammatory markers measured after delivery. RESULTS: Women with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and systolic BP (+4.0 mmHg) at follow up compared with women with term births, accounting for age, race, pre-pregnancy BMI, and smoking (P < 0.05). Women with PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P < 0.05), adjusted for pre-pregnancy features. Carotid IMT was higher in this group (+0.037 cm, P = 0.031) accounting for pre-pregnancy factors; differences were attenuated after adjusting for BP and atherogenic lipids at follow up (+0.027, P = 0.095). CONCLUSION: PTBs with placental malperfusion were associated with an excess maternal cardiometabolic risk burden in the decade after pregnancy. The placenta may offer insight into subtypes of PTB related to maternal cardiovascular disease. TWEETABLE ABSTRACT: Preterm births with placental malperfusion may mark women at higher cardiovascular disease risk.

Using chiral ionic liquid additives to enhance asymmetric induction in a Diels-Alder reaction.

A bis-oxazoline ligand has been complexed using Cu(ii) and Zn(ii) trifluoromethanesulfonate and a range of chiral ionic liquid (CIL) additives based on natural products were used as a co-catalyst for a Diels-Alder reaction. The catalytic performance of these systems was compared for the asymmetric Diels-Alder reaction between N-acryloyloxazolidinone and cyclopentadiene with and without the presence of a CIL additive. In the absence of the CIL, both catalysts resulted in low enantioselectivities in conventional solvents and ionic liquids. However, whilst only a minor effect of the CIL was observed for the Cu based catalyst, in the case of the Zn based catalyst, significant enhancements in endo enantioselectivity of up to 50% were found on the addition of a CIL.

Fish oil supplementation does not lower C-reactive protein or interleukin-6 levels in healthy adults.

BACKGROUND: The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may prevent a range of chronic conditions through anti-inflammatory actions. However, as clinical trials using these fatty acids for primary prevention are yet unavailable, their putative role in disease prevention rests, in part, on evidence of anti-inflammatory actions in healthy individuals. OBJECTIVE: To investigate in a double-blind, placebo-controlled clinical trial whether supplementation with a moderate dose of EPA+DHA reduces common biomarkers of chronic, systemic inflammation in healthy individuals. METHODS: A total of 261 healthy individuals aged 30-54 years who were free of inflammatory conditions and consumed ≤ 300 mg per day EPA+DHA were included in the study. Participants were randomly assigned to 18 weeks of either fish oil supplementation providing 1400 mg per day EPA+DHA or matching placebo. Outcome measures were serum levels of C-reactive protein (CRP) and interleukin (IL)-6. In a substudy, ex vivo cytokine production was measured. Missing data for CRP and IL-6 were estimated using regression imputation. Data analyses conformed to intention-to-treat principles. RESULTS: Participant blinding was verified. Red blood cell EPA+DHA increased by 64% in the active treatment group, but serum CRP and IL-6 were not affected by supplementation (P ≥ 0.20). Findings were consistent with and without imputed values and across subgroups. Similarly, EPA+DHA supplementation did not alter ex vivo production of four pro-inflammatory cytokines (P ≥ 0.20). CONCLUSIONS: Supplementation with 1400 mg EPA+DHA did not reduce common markers of systemic inflammation in healthy adults. Whether this or a higher dose affects other measures of inflammation, oxidative stress or immune function warrants examination.

Matrilysin/matrix metalloproteinase-7(MMP7) cleavage of perlecan/HSPG2 creates a molecular switch to alter prostate cancer cell behavior.

Perlecan/HSPG2, a large heparan sulfate (HS) proteoglycan, normally is expressed in the basement membrane (BM) underlying epithelial and endothelial cells. During prostate cancer (PCa) cell invasion, a variety of proteolytic enzymes are expressed that digest BM components including perlecan. An enzyme upregulated in invasive PCa cells, matrilysin/matrix metalloproteinase-7 (MMP-7), was examined as a candidate for perlecan proteolysis both in silico and in vitro. Purified perlecan showed high sensitivity to MMP-7 digestion even when fully decorated with HS or when presented in native context connected with other BM proteins. In both conditions, MMP-7 produced discrete perlecan fragments corresponding to an origin in immunoglobulin (Ig) repeat region domain IV. While not predicted by in silico analysis, MMP-7 cleaved every subpart of recombinantly generated perlecan domain IV. Other enzymes relevant to PCa that were tested had limited ability to cleave perlecan including prostate specific antigen, hepsin, or fibroblast activation protein α. A long C-terminal portion of perlecan domain IV, Dm IV-3, induced a strong clustering phenotype in the metastatic PCa cell lines, PC-3 and C4-2. MMP-7 digestion of Dm IV-3 reverses the clustering effect into one favoring cell dispersion. In a C4-2 Transwell® invasion assay, perlecan-rich human BM extract that was pre-digested with MMP-7 showed loss of barrier function and permitted a greater level of cell penetration than untreated BM extract. We conclude that enzymatic processing of perlecan in the BM or territorial matrix by MMP-7 as occurs in the invasive tumor microenvironment acts as a molecular switch to alter PCa cell behavior and favor cell dispersion and invasiveness.

PPARα gene polymorphisms modulate the association between physical activity and cardiometabolic risk.

BACKGROUND AND AIMS: Habitual physical activity is understood to help prevent type 2 diabetes and atherosclerotic cardiovascular disease via beneficial effects on both metabolism and the vascular system. However, individuals do not have uniform cardiometabolic responses to physical activity. Here we explore the extent to which variation in the proliferator-activated receptor-alpha (PPARα) gene, which modulates carbohydrate and lipid metabolism, vascular function, and inflammation, predicts the overall cardiometabolic risk (CMR) profile of individuals engaging in various levels of physical activity. METHODS AND RESULTS: 917 unrelated, community volunteers (52% female, of Non-Hispanic European ancestry) aged 30-54 years, participated in the cross-sectional study. Subjects were genotyped for 5 single nucleotide polymorphisms in the PPARα gene, from which common haplotypes were defined. A continuous measure of CMR was calculated as an aggregate of 5 traditional risk factors: waist circumference, resting blood pressure, fasting serum triglycerides, HDL-cholesterol and glucose. Regression models were used to examine the main and interactive effects of physical activity and genetic variation on CMR. One common PPARα haplotype (H-23) was associated with a higher CMR. This association was moderated by daily physical activity (B = -0.11, SE = 0.053, t = -2.05, P = 0.04). Increased physical activity was associated with a steeper reduction of CMR in persons carrying the otherwise detrimental H-23 haplotype. CONCLUSIONS: Variations in the PPARα gene appear to magnify the cardiometabolic benefits of habitual physical activity.

Regional grey matter shrinks in hypertensive individuals despite successful lowering of blood pressure.

The aim of the study was to determine whether the reduction in brain grey matter volume associated with hypertension persisted or was remediated among hypertensive patients newly treated over the course of a year. A total of 41 hypertensive patients were assessed over the course of a 1-year successful anti-hypertensive treatment. Brain areas identified previously in cross-sectional studies differing in volume between hypertensive and normotensive individuals were examined with a semi-automated measurement technique (automated labelling pathway). Volumes of grey matter regions were computed at baseline after a year of treatment and compared with archival data from normotensive individuals. Reductions in regional grey matter volume over the follow-up period were observed despite successful treatment of blood pressure (BP). The comparison group of older, but normotensive, individuals showed no significant changes over a year in the regions tested in the treated hypertensive group. These novel results suggest that essential hypertension is associated with regional grey matter shrinkage, and successful reduction of BP may not completely counter that trend.

A novel Ocular Anaesthetic Scoring System, OASS, tool to measure both motor and sensory function following local anaesthesia.

BACKGROUND/AIMS: To devise and evaluate a novel Ocular Anaesthetic Scoring System (OASS) for non-topical local anaesthesia. METHODS: In OASS, a score of between 0 (poor) and 14 (excellent) was devised measuring motor (ocular motility, levator and orbicularis function) and sensory functions (digital spear pressure at limbus and topical anaesthetic sting). 40 patients were studied prospectively to analyse interobserver consistency in OASS. A further 100 patients were collected into four groups receiving either sub-Tenon or peribulbar block with 150 or 300 units of hyaluronidase. Patient satisfaction was determined using the Visual Analogue Pain Scale and Iowa Satisfaction with Anaesthesia Scale. RESULTS: There was no significant difference in OASS scores between two independent observers (p = 0.8910). The sub-Tenon approach achieved significantly better OASS scores than the peribulbar approach (p<0.0004). 300 units of hyaluronidase gave significantly higher OASS scores in both sub-Tenon (p<0.0001) and peribulbar groups (p<0.0001). Spearman rank correlation showed that OASS correlates significantly with VAPS (-0.82, p<0.0001) and ISAS (0.70, p<0.0001). The median satisfaction score was significant in order of magnitude: sub-Tenon with 300 units of hyaluronidase>sub-Tenon with 150 units of hyaluronidase>peribulbar with 300 units of hyaluronidase>peribulbar with 150 units of hyaluronidase. CONCLUSION: OASS is a simple and robust system for assessing and comparing non-topical local anaesthetic techniques. Of the techniques evaluated, a sub-Tenon block with 300 units of hyaluronidase gives the best anaesthesia, analgesia and patient satisfaction results.

Grading infantile cataracts.

PURPOSE: To introduce and describe two methods of grading the severity of infantile cataracts, and thereby propose a useful clinical guide for early surgical intervention. METHODS: Thirty-three subjects, aged 1 week to 8 years, participated in the study. Twenty-two were evaluated soon after birth (1 week), and 11 in childhood (3-8 years). All had isolated infantile cataracts, of which 16 were bilateral and 17 unilateral. Nine cataract types were examined; nuclear (n = 9), lamellar (n = 9), posterior lenticonus (n = 4), persistent hyperplastic primary vitreous (n = 4), posterior polar (n = 3) and single cases of total, cortical, sutural and anterior polar. Grading the infantile cataracts was performed subjectively based on the cataract morphology, density and position using an 11-point (0-10) ordinal scale. Objective measures of the cataracts were performed by scanning and then digitising photo-slit lamp images to provide cataract intensity profiles. Subjects without cataracts acted as controls. RESULTS: Subjective gradings of 0 and 10 were assigned to the clear, cataract-free lens and the total cataract, respectively. Fixed grades of 1 (anterior polar, sutural) and 6 (posterior polar) were assigned to the three remaining cataracts with static morphologies. The five cataracts which were all progressive were given grading ranges, reflecting the initial and likely final morphological states. Objective measures were found to be valuable in indicating the exact position and relative density of the cataract, as well as accurately defining boundaries. CONCLUSIONS: The magnitude and severity of infantile cataracts can be usefully characterised by an 11-point ordinal subjective grading scale. Although subjective grading alone is satisfactory, it can be greatly assisted by objective measures, particularly in the documentation of cataract progression. Cataracts assigned grades 1-4 were considered minor obstructions to vision and therefore not candidates for early surgery. Cataracts graded 5 and above were considered major visual defects, and ideally should be removed early in life.

Hypertension labelling was associated with poorer self-rated health in the Third US National Health and Nutrition Examination Survey.

Individuals labelled as having hypertension tend to report poor self-rated health (SRH), but it is unclear whether this association is independent of actual hypertension, socioeconomic status and adiposity, and extends across racial and ethnic groups. In a cross-sectional study we compared hypertensive and normotensive individuals (N = 19,057) who varied in whether they had ever been labelled hypertensive. Blood pressure was measured in participants' homes and mobile examination centres in the United States as part of the Third National Health and Nutrition Examination Survey, 1988-1994. The main outcome measure was global SRH. Hypertensive labelling was associated with poorer SRH and was independent of established SRH predictors, antihypertensive medication use, body mass index, and hypertension status (adjusted odds ratio (OR) = 1.79, 95% confidence interval (CI), 1.61-1.99). Hypertension was also associated with poorer SRH (OR = 1.26; 95% CI 1.09-1.46) but this association was eliminated by adjustment for hypertensive labelling (OR 1.06; 95% CI 0.92-1.22). These effects were consistent across non-Hispanic white, non-Hispanic black, and Hispanic subgroups. Individuals labelled hypertensive are more likely to have lower SRH and this labelling effect predominates over that of actual hypertension. Public health efforts to increase the number of individuals screened for high blood pressure may successfully detect the presence of hypertension but may also reduce health-related quality of life as measured by global SRH.

Reduced cerebral blood flow response and compensation among patients with untreated hypertension.

OBJECTIVE: To determine whether memory performance in hypertensive subjects induces diminished parietal and prefrontal blood flow activation relative to normotensive subjects but compensatory amygdala/hippocampal activation. METHODS: Thirty-seven untreated hypertensive subjects and 59 normotensive control subjects performed in two memory and one sensorimotor task while global and regional cerebral blood flow (rCBF) was assessed with [15O]water and PET. Neuropsychological, carotid artery ultrasound, and MRI assessments were obtained. RESULTS: When they were engaged in memory tasks, increases of CBF in hypertensive subjects were less than in normotensive subjects in the posterior parietal area, as expected; blunted responses were also shown within the middle posterior arterial watershed and thalamus. Relative to all other participants, hypertensive subjects that performed relatively well on verbal memory showed an enhanced rCBF response in the right amygdala/hippocampus. Furthermore, hypertensive, but not normotensive, subjects showed task-induced rCBF in the amygdala/hippocampal area that was significantly correlated with task-induced prefrontal rCBF. No confounding influences were identified from carotid artery or MRI measures. CONCLUSIONS: Memory performance in hypertensive individuals is related to a blunted regional cerebral blood flow (rCBF) response, particularly in parietal cortex. Potentially compensatory rCBF responses appear to occur in midbrain and correlate with prefrontal rCBF.

Pain on injection of prilocaine plain vs. lidocaine with epinephrine. A prospective double-blind study.

BACKGROUND: Prilocaine has been described as causing less pain on injection than lidocaine with epinephrine, possibly because of the higher pH of the prilocaine anesthetic solution. METHODS: Three hundred ten consecutively seen patients in a general practice received a total of 334 maxillary buccal infiltration or inferior alveolar block injections, administered under clinical conditions by one of two dentists. Immediately afterward, patients rated the pain from each injection on a six-point scale. Twenty of these patients (in 21 separate appointments) received, and were asked to rate the pain associated with, a second injection of a contralateral tooth. The authors analyzed the pain response by operator, location of injection, patient's age, patient's sex and anesthetic. RESULTS: The difference in perceived pain between lidocaine and prilocaine was not statistically significant. Regardless of the anesthetic used, the perceived pain was usually no more than mild. Of 334 injections, 292 (87 percent) were rated as causing either no pain or mild pain. CONCLUSIONS: Under clinical conditions, there is no statistically significant difference between injection pain associated with prilocaine plain vs. that associated with lidocaine with 1:100,000 epinephrine. CLINICAL IMPLICATIONS: Since there is no significant difference in associated pain on injection between prilocaine plain and lidocaine with 1:100,000 epinephrine, dentists may prefer lidocaine with epinephrine. Since there is less anesthetic in each cartridge of lidocaine, it may require the use of less anesthetic per patient, and the vasoconstrictor can prolong its duration.

The nature of the association between diet and serum lipids in the community: a twin study.

Diet is commonly thought to be an environmental influence on serum lipid concentrations. This study evaluated whether total caloric and fat intake predict total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TRIG) concentrations for environmental, as compared with genetic, reasons among 137 monozygotic and 67 dizygotic young adult twins. When genetic influences were controlled by correlating differences between monozygotic co-twins, a significant association remained between diet and TC, LDL, and HDL, suggesting that these dietary and serum lipid measures correlate for environmental reasons. Twin structural equation modeling confirmed these results. Overall, these results provide additional support for the hypothesis that diet is an environmental influence on TC, LDL, and HDL.

Instability after total knee arthroplasty with the Miller-Gallante II total knee: 5- to 7-year follow-up.

A consecutive series of 64 posterior cruciate-retaining hybrid total knee arthroplasties in 50 patients were reviewed with an average 57-month follow-up. Seven patients died or were lost to follow-up. One patient was revised for infection in the early postoperative period, and there were no cases of aseptic loosening. Four revisions were performed for recurrent effusions and progressive instability at a mean of 55 months postoperatively. There were statistically significant correlations between manual stability testing (anteroposterior, mediolateral, and pivot shift) and Hospital for Special Surgery and Knee Society scores. At intermediate follow-up, the Miller-Gallante II total knee arthroplasty is functioning well except in a subgroup of patients with progressive instability resulting from a combination of patient and implant factors.

Using human immunodeficiency virus type 1 sequences to infer historical features of the acquired immune deficiency syndrome epidemic and human immunodeficiency virus evolution.

In earlier work, human immunodeficiency virus type 1 (HIV-1) sequences were analysed to estimate the timing of the ancestral sequence of the main group of HIV-1, the virus that is responsible for the acquired immune deficiency syndrome pandemic, yielding a best estimate of 1931 (95% confidence interval of 1915-1941). That work will be briefly reviewed, outlining how phylogenetic tools were extended to incorporate improved evolutionary models, how the molecular clock model was adapted to incorporate variable periods of latency, and how the approach was validated by correctly estimating the timing of two historically documented dates. The advantages, limitations, and assumptions of the approach will be summarized, with particular consideration of the implications of branch length uncertainty and recombination. We have recently undertaken new phylogenetic analysis of an extremely diverse set of human immunodeficiency virus envelope sequences from the Democratic Republic of the Congo (the DRC, formerly Zaire). This analysis both corroborates and extends the conclusions of our original study. Coalescent methods were used to infer the demographic history of the HIV-1 epidemic in the DRC, and the results suggest an increase in the exponential growth rate of the infected population through time.

Protrusio acetabuli: diagnosis and treatment.

Idiopathic protrusio acetabuli is an uncommon disease process with both primary idiopathic and secondary forms. It is important to consider all etiologic possibilities before evaluating treatment options. Diagnosis is made on the basis of an anteroposterior radiograph of the pelvis that demonstrates a center-edge angle greater than 40 degrees and medialization of the medial wall of the acetabulum past the ilioischial line. For the skeletally immature patient, triradiate fusion (occasionally combined with intertrochanteric osteotomy) provides good results. For the young adult, valgus intertrochanteric proximal femoral osteotomy is recommended. In the older adult, this procedure may provide an acceptable result if there is minimal arthritis. For patients with more advanced arthritis, total hip arthroplasty with lateralization of the cup to a normal position provides a predictable long-term solution.

Femoral neck stress fractures and metabolic bone disease.

OBJECTIVE: To determine whether metabolic bone disease plays a role in the cause of femoral neck stress fractures. STUDY DESIGN: Twenty-three patients with femoral neck stress fractures were enrolled prospectively in the study. Examination included computed tomography bone densitometry, trace mineral analysis, and histomorphometric analysis of the iliac crest in thirteen patients who underwent surgical treatment of their stress fractures. A control group of fifteen patients undergoing iliac crest bone grafting for scaphoid nonunions underwent similar examinations. SETTING: Tertiary military medical center. RESULTS: Patients with femoral neck stress fractures had lower bone mineral density than did control patients (p = 0.010), but no trace mineral deficiencies or consistent histomorphometric differences were noted. CONCLUSIONS: Bone mineral density is decreased in patients with femoral neck stress fractures. Despite observations of decreased bone mineral density in the stress fracture group, osteoporosis, as determined by histomorphometry, is not a consistent finding.

Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials.

OBJECTIVE: To investigate the association between cholesterol lowering interventions and risk of death from suicide, accident, or trauma (non-illness mortality). DESIGN: Meta-analysis of the non-illness mortality outcomes of large, randomised clinical trials of cholesterol lowering treatments. STUDIES REVIEWED: 19 out of 21 eligible trials that had data available on non-illness mortality. INTERVENTIONS REVIEWED: Dietary modification, drug treatment, or partial ileal bypass surgery for 1-10 years. MAIN OUTCOME MEASURE: Deaths from suicides, accidents, and violence in treatment groups compared with control groups. RESULTS: Across all trials, the odds ratio of non-illness mortality in the treated groups, relative to control groups, was 1.18 (95% confidence interval 0.91 to 1.52; P=0.20). The odds ratios were 1.28 (0.94 to 1.74; P=0.12) for primary prevention trials and 1.00 (0.65 to 1.55; P=0.98) for secondary prevention trials. Randomised clinical trials using statins did not show a treatment related rise in non-illness mortality (0.84, 0.50 to 1.41; P=0.50), whereas a trend toward increased deaths from suicide and violence was observed in trials of dietary interventions and non-statin drugs (1.32, 0.98 to 1.77; P=0.06). No relation was found between the magnitude of cholesterol reduction and non-illness mortality (P=0.23). CONCLUSION: Currently available evidence does not indicate that non-illness mortality is increased significantly by cholesterol lowering treatments. A modest increase may occur with dietary interventions and non-statin drugs.