The value of bronchoalveolar lavage for discrimination between healthy and diseased individuals.

BACKGROUND: Bronchoalveolar lavage (BAL) is standard diagnostic procedure. Procedural recommendations have been made by pneumological societies including normal values for interpretation of BAL cytology. These normal values derive from small studies in healthy volunteers and have never been analysed for their sensitivity and specificity. OBJECTIVES: This study aims to analyse sensitivity and specificity of these normal values by assessing lavage cell composition in healthy and diseased individuals. METHODS: More than 6000 BAL were retrospectively analysed for their cellular distribution including BALs of 250 healthy individuals. All BALs were obtained under similar conditions. RESULTS: Bronchoalveolar lavage cytology of healthy individuals mirrors data from previous studies with smoking being the most important manipulator of BAL cytology. Analyses of proposed normal values demonstrate specificity between 80% and 95%, whereas sensitivity ranges between 35% and 65%. Using different mathematical models, a value summing up the differences to ATS-proposed normal values of the cytological pattern was found to best discriminate between healthy and diseased individuals with a sensitivity of nearly 60% with a predefined specificity of 95%. CONCLUSION: In summary, our analysis confirmed prior results for healthy volunteers and enlarged these findings by analysing sensitivity and specificity of lavage results in an independent validation cohort of diseased individuals. Thereby, the study may influence the acceptance of BAL in the diagnostic workup of individuals with pulmonary diseases. Additionally, the study proposes a novel value that facilitates lavage interpretation and may therefore be useful in further studies.

Dose-response relationship between ambulatory load magnitude and load-induced changes in COMP in young healthy adults.

OBJECTIVE: To determine the dose-response relationship between ambulatory load magnitude during a walking stress test and load-induced changes in serum concentration of cartilage oligomeric matrix protein (sCOMP) in healthy subjects. DESIGN: sCOMP was assessed before and after a 30-min walking stress test performed on three test days by 24 healthy volunteers. In each walking stress test, one of three ambulatory loads was applied in a block randomized crossover design: normal body weight (BW) (100%BW = normal load); reduced BW (80%BW = reduced load); increased BW (120%BW = increased load). Knee kinematics and ground reaction force (GRF) were measured using an inertial sensor gait analysis system and a pressure plate embedded in the treadmill. RESULTS: Load-induced increases in sCOMP rose with increasing ambulatory load magnitude. Mean sCOMP levels increased immediately after the walking stress test by 26.8 ± 12.8%, 28.0 ± 13.3% and 37.3 ± 18.3% for the reduced, normal or increased load condition, respectively. Lower extremity kinematics did not differ between conditions. CONCLUSIONS: The results of this study provide important evidence of a dose-response relationship between ambulatory load magnitude and load-induced changes in sCOMP. Our data suggests that in normal weight persons sCOMP levels are more sensitive to increased than to reduced load. The experimental framework presented here may form the basis for studying the relevance of the dose-response relationship between ambulatory load magnitude and load-induced changes in biomarkers involved in metabolism of healthy articular cartilage and after injury.

Development and validation of a novel prognostic score to predict survival in patients with metastatic colorectal cancer: the metastatic colorectal cancer score (mCCS).

AIM: Published prognostic scores for metastatic colorectal cancer (mCRC) are based on data from highly selected patient subgroups with specified first-line treatments and may not be applicable to routine practice. We have therefore developed and validated the metastatic colorectal cancer score (mCCS) to predict overall survival (OS) for patients with mCRC. METHOD: A total of 1704 patients from the prospective, multicentre cohort study Tumour Registry Colorectal Cancer were separated into learning (n = 796) and validation (n = 908) samples. Using a multivariate Cox regression model, the six-factor mCCS was established. RESULTS: The six independent prognostic factors for survival are as follows: two or more metastatic sites at the start of first-line treatment, tumour grading ≥ G3 at primary diagnosis, residual tumour classification ≥ R1/unknown, lymph node ratio (of primary tumour) ≥ 0.4, tumour stage ≥ III/unknown at primary diagnosis and KRAS status mutated/unknown. The mCCS clearly separated the learning sample into three risk groups: zero to two factors (low risk), three factors (intermediate risk) and four to six factors (high risk). The prognostic performance of the mCCS was confirmed in the validation sample and additionally stratified a large sample of patients with known (K)RAS mutation status. CONCLUSION: The novel prognostic score, mCCS, clearly defines three prognostic groups for OS at start of first-line therapy. For oncologists, the mCCS represents a simple and easy-to-apply tool for routine clinical use, as it is based on objective tumour characteristics and can assist with treatment decision-making and communication of the prognosis to patients.

[Gaps of Evidence in ENT-Surgery - a Qualitative Survey]. / Qualitative Umfrage zur Identifizierung von Evidenzlücken in der HNO-Heilkunde.

INTRODUCTION: As in other disciplines, the burgeoning knowledge in ENT medicine long ago surpassed our ability to adequately absorb it and maintain a proper overview. This can give rise to actual or assumed knowledge gaps that can impede the progress of the discipline and evidence-based treatment of patients. Clinics and medical practices also hold to traditional doctrines that shape day-to-day medicine, without these schools being challenged based on evidence. METHODS: Between February and June 2015, 160 ENT clinics, including 34 university hospitals, and 2,670 ENT practices took part in a two-arm online survey on existing or perceived evidentiary gaps in ENT medicine using a previously development questionnaire. The survey used for half the participants was open in form; the other half were given a closed survey with systematics of the field for orientation. The survey was augmented with additional data such as the number of publications and focus areas in the clinics and the age and type of practice of the established physicians. RESULTS: The return rate from the clinics was 39.7%; the return rate of the closed surveys was 29.3%. Of the physicians in medical practice, 14.6% responded to the closed and 18.6% to the open survey. There were no major differences between the two forms of survey. Otological and oncological issues comprised approximately 30% of the list of answers from clinics. Corresponding questions were formulated regarding the current diagnostic and therapeutic problems, such as with stage-related tumor treatment or implantable hearing aids. Diagnostic procedures, e.g., special new procedures in audiology and vestibulogy, dominated the surveys from the practices. However clinics and practices alike cited marginal areas of the discipline that are of daily relevance. DISCUSSION: The cited knowledge gaps then needed to be verified or refuted and clarified based on research of the literature as to whether the existing evidence actually reached healthcare providers in the form of guidelines, publications, conferences or continuing training for application in daily practice. Other steps would include prioritizing future research, evidence mapping, deciding on further systematic reviews, and targeted studies in conjunction with procuring third-party funding and in cooperation with patient associations. The knowledge thus gained should ultimately be transferred in improved form for application in daily clinical practice. Ten questions of key importance each needed to be formulated for the hospitals and practices.

Patient education with or without manual therapy compared to a control group in patients with osteoarthritis of the hip. A proof-of-principle three-arm parallel group randomized clinical trial.

OBJECTIVE: To investigate the effectiveness of a patient education (PE) program with or without the added effect of manual therapy (MT) compared to a minimal control intervention (MCI). METHODS: In a single-center university hospital setting, a total of 118 patients with clinical and radiographic unilateral hip osteoarthritis (OA) from primary care were randomized into one of three groups: PE, PE plus MT or MCI. The PE was taught by a physiotherapist involving five sessions. The MT was delivered by a chiropractor involving 12 sessions and the MCI included a home stretching program. Primary outcome was self-reported pain severity on an 11-box numeric rating scale (NRS) immediately following a 6-week intervention period. Patients were followed for 1 year. RESULTS: Primary analysis included 111 patients (94%). In the combined group (PE + MT), a clinically relevant reduction in pain severity compared to the MCI of 1.90 points (95% confidence interval (CI) 0.9-2.9) was achieved. Effect size (Cohen's d) for the PE + MT minus the MCI was 0.92 (95% CI 0.41-1.42). Number needed to treat for PE + MT was 3 (95% CI 2-7). No difference was found between the PE and MCI groups, with mean difference 0.0 (95% CI -1.0 to 1.0). At 12 months, not including patients receiving hip surgery the statistically significant difference favoring PE + MT was maintained. CONCLUSIONS: For primary care patients with OA of the hip, a combined intervention of MT and PE was more effective than a MCI. PE alone was not superior to the MCI. TRIAL REGISTRATION: clinicaltrials.govNCT01039337.

X-linked agammaglobulinemia in community-acquired pneumonia cases revealed by immunoglobulin level screening at hospital admission.

In children with primary immunodeficiencies, the onset of symptoms precedes the diagnosis and the initiation of appropriate treatment by months or years. This delay in diagnosis is due to the fact that while these disorders are rare, some of the infections seen in immunodeficient patients are common. Defective antibody production represents the largest group among these disorders, with otitis, sinusitis and pneumonia as the most frequent initial manifestation. We performed a prospective study of humoral immunity in children hospitalized due to community-acquired pneumonia in tertiary care hospital. Out of 254 patients (131 boys, 123 girls, median age 4.5 years) recruited over 3 years, we found 2 boys (age 11 and 21 months) lacking serum immunoglobulins and circulating B cells. Subsequent genetic analysis confirmed diagnosis of X-linked agammaglobulinemia. Despite their immunodeficiency, the pneumonia was uncomplicated in both patients and did not call for immunological evaluation. However, the immunoglobulin screening at admission allowed for an early diagnosis of the immunodeficiency and timely initiation of immunoglobulin substitution, the key prerequisite for a favorable course of the disease.Simple and inexpensive immuno-globulin measurement during the manage-ment of hospitalized children with community-acquired pneumonia may help in early identification of patients with compromised humoral immunity and prevent serious complications.

Eating disorder risks and awareness among female elite cyclists: an anonymous survey.

BACKGROUND: Eating disorders (EDs) are an increasingly recognized concern in professional sports. Previous studies suggests that both female gender and endurance sports put athletes at risk. Female elite cyclists are hence of specific interest. The present study aimed at evaluating the distribution of the individual risk of ED in this group. Further the association between individual risk and both the awareness for the topic ED and the deviation from "normal" weight was depicted. METHODS: Female cyclists registered with the Union Cycliste Internationale were contacted via email or facebook and asked to complete a survey comprising age, weight, the Eating-Attitude-Test (EAT-26), and questions regarding ED awareness. The observed distribution of the EAT-26 score was compared to results from previous studies in normal subjects and athletes. The distribution of the ED awareness was described and ED awareness was correlated with the EAT-26 score. Both the deviation from ideal weight and the body mass index (BMI) were correlated with the EAT-26 score. RESULTS: Of the 409 registered athletes 386 could be contacted, 122 completed the questionnaire. Age ranged from 20-44yrs, BMI from 17.0 to 24.6 kg/m2. In the EAT-26, 39 cyclists (32.0%) scored above 20 points indicating a potential benefit from clinical evaluation, 34 cyclists (27.9%) scored 10-19 points suggesting disordered eating. Sixteen athletes (13.2%) had been treated for an ED. About 70% of athletes had been pressured to lose weight. The mean EAT-26 score was above the average observed in normal female populations. It was also above the average observed in many female athlete populations, but lower than in other leanness focussed sports. More than 80%of athletes perceived elite cyclists at risk for developing ED. Increased ED awareness and deviation from the ideal weight were associated with higher EAT-26 scores, but not the body mass index. CONCLUSION: Female cyclists are at risk of developing ED and they are aware of this risk. To improve their health and well-being, increased efforts to support elite cyclists and their teams in preventive activities and early detection are crucial.

Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer.

The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h⁻¹ (range 176-726 l h⁻¹). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P=0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P=0.04) and ABCC1 g.7356253C>G (P=0.04).

Identification of asymptomatic type 2 diabetes mellitus patients with a low, intermediate and high risk of ischaemic heart disease: is there an algorithm?

AIMS/HYPOTHESIS: The leading cause of death in type 2 diabetes is cardiovascular disease (CVD). We examined the prevalence of myocardial ischaemia in type 2 diabetes patients and tried to establish an algorithm to identify patients with a high risk of ischaemic heart disease. METHODS: Type 2 diabetes patients who had no known or suspected CVD, and had been referred consecutively to a diabetes clinic for the first time (n=305; age 58.6+/-11.3 years; diabetes duration 4.5+/-5.3 years) were screened for myocardial ischaemia using myocardial perfusion scintigraphy (MPS). RESULTS: The univariate predictors of myocardial ischaemia were: atypical or typical angina pectoris, two or more traditional risk factors for CVD, BMI >32 kg/m2, systolic blood pressure >140 mmHg, HbA1c >8.5%, high-sensitivity C-reactive protein >4.0 mg/l, N-terminal pro-brain natriuretic peptide >300 pg/ml, left atrial volume index >32 ml/m2, left ventricular ejection fraction <50%, and carotid and peripheral arterial disease. The algorithm identified low (n=96), intermediate (n=65) and high risk groups (n=115), in which the prevalence of myocardial ischaemia was 15%,23% and 43%, respectively. Overall the algorithm reduced the number of patients referred to MPS from 305 to 144.However, the sensitivity and specificity of the algorithm was just 68% and 62%, respectively. CONCLUSIONS/INTERPRETATION: Our algorithm was able to stratify which patients had a low, intermediate or high risk of myocardial ischaemia based on MPS. However, the algorithm had low sensitivity and specificity, combined with high cost and time requirements. TRIAL REGISTRATION: clinicaltrials.gov NCT00298844 FUNDING: The study was funded by the Danish Cardio vascular Research Academy (DaCRA), The Danish Diabetes Association and The Danish Heart Foundation.

PET/CT in cancer: Methodological considerations for comparative diagnostic phase II studies with paired binary data.

OBJECTIVES: When the combined diagnostic imaging technique PET/CT is considered promising with respect to diagnosis/staging of a certain cancer type, a systematic investigation by means of clinical diagnostic studies in the target population is necessary to evaluate the usefulness of PET/CT compared to the current standard. It is often difficult to decide in advance whether it is appropriate to plan a superiority or non-inferiority study. We propose a statistical analysis strategy which is flexible enough to cope with both aims alike. METHODS: In opposition to clinical studies on drugs, each patient can be subjected to both PET/CT and the current standard, leading to paired observations of binary data (e.g., cancer = yes/no, stage = 0/1+). The analysis strategy focuses on point estimates and confidence intervals for the difference (or relative increase) in accuracy measures. RESULTS: Formulas for approximate 95% confidence intervals for the differences in sensitivity, specificity, positive and negative predictive values between PET/CT and the standard procedures are given, respectively. The strategy can also be applied if results obtained with a golden standard are not available in patients in whom both PET/CT and the standard procedure gave negative results. Sample sizes can and should be determined in an adaptive manner. CONCLUSIONS: Diagnostic studies to assess the merit of PET/CT in the diagnostic work-up of cancer patients can and should start with phase II studies focusing on 95% confidence intervals for differences in diagnostic measures. Even if the gold standard procedure is incomplete, the statistical analysis strategy given here may still be applicable.

Size diversity in Swiss Bronze Age cattle.

To date, osteometric data for Swiss Bronze Age cattle, particularly from Alpine sites, are scarce. In the present study, using a large dataset generated by combining preexisting data with recent data obtained from a large Alpine site, cattle size from the Late Neolithic to the Late Bronze Age (LBA) in populations from different sites and regions was evaluated using the logarithmic size index and other statistical analysis. Additionally, the finite mixture model and a meta-analytic technique were used to observe possible effects of sex ratios on cattle size. Results indicated that sex ratios did not affect size distribution. Cattle populations did not differ over time, but the Alpine cattle were smaller than the Central Plateau cattle. There were two distinct sizes in the Alpine cattle populations. It is suggested that the different economic interrelationships between Alpine and other geographically related communities might have led to the emergence of size diversity in Swiss Bronze Age cattle. Further interdisciplinary studies with larger sample sizes are required to confirm these possibilities.

Evidence gaps in ENT surgery - a qualitative survey.

Introduction: As in other disciplines, the burgeoning knowledge in ENT medicine long ago surpassed our ability to adequately absorb it and maintain a proper overview. This can give rise to actual or assumed evidence gaps that can impede the progress of the discipline and evidence-based treatment of patients. Clinics and medical practices also hold to traditional doctrines that shape day-to-day medicine, without these schools being challenged based on evidence. Methods: Between February and June 2015, 160 ENT clinics, including 34 university hospitals, and 2,670 ENT practices took part in a two-arm online survey on existing or perceived evidentiary gaps in ENT medicine using a previously developed questionnaire. The survey used for half of the participants was open in form; the other half were given a closed survey with systematics of the field for orientation. The survey was augmented with additional data such as the number of publications and focus areas in the clinics and the age and type of practice of the established physicians. Results: The return rate from the clinics was 39.7%; the return rate of the closed surveys was 29.3%. Of the physicians in medical practice, 14.6% responded to the closed and 18.6% to the open survey. There were no major differences between the two forms of survey. Otological and oncological issues comprised approximately 30% of the list of answers from clinics. Corresponding questions were formulated regarding the current diagnostic and therapeutic problems, such as with stage-related tumor treatment or implantable hearing aids. Diagnostic procedures, e.g., special new procedures in audiology and vestibulogy, dominated the surveys from the practices. However clinics and practices alike cited marginal areas of the discipline that are of daily relevance. Discussion: The cited evidence gaps then needed to be verified or refuted and clarified based on research of the literature as to whether the existing evidence actually reached healthcare providers in the form of guidelines, publications, conferences, or continuing training for application in daily practice. Other steps would include prioritizing future research, evidence mapping, deciding on further systematic reviews, and targeted studies in conjunction with procuring third-party funding and in cooperation with patient associations. The knowledge thus gained should ultimately be transferred in improved form for application in daily clinical practice. Ten questions of key importance each needed to be formulated for the hospitals and practices.

The prognostic value of angiogenesis by Chalkley counting in a confirmatory study design on 836 breast cancer patients.

This study addresses the prognostic value of estimating angiogenesis by Chalkley counting in breast cancer. A population-based group consisting of 836 patients with operated primary, unilateral invasive breast carcinomas was included from a predefined region and period of time. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. The Chalkley count was obtained by a 25-point grid within three, subjectively selected, vascular tumor areas of highest microvessel density. The Chalkley count was analyzed in three categories using predefined Chalkley cutoff points at five and seven. There were significant correlations between high Chalkley counts and axillary lymph node metastasis, large tumor size, high histological malignancy grade, and histological type. A high Chalkley count showed lower probabilities of recurrence-free survival (P < 0.0001) and overall survival (P < 0.0001). In the Cox multivariate analysis, the hazard ratio (and 95% confidence interval) showed that the increased risk to die were: 1.55 (1.19-2.03) with Chalkley counts between 5 and 7; 2.26 (1.72-2.98) with counts > or =7 compared with counts < or =5; and 1.46 (1.14-1.87) with counts > or =7 compared with counts between 5-7. The study confirmed that estimation of angiogenesis by Chalkley counting had independent prognostic value in breast cancer patients. The Chalkley count could be useful to stratify node-negative patients for adjuvant treatment.

The impact of bariatric surgery on quality of life: a systematic review and meta-analysis.

This study aims to review the obesity literature in order to assess the impact of bariatric surgery on quality of life and the between-study variation by examining the standardized mean magnitude of effect in change in the levels of quality of life. The following databases EMBASE, PubMed, PsycINFO, CINAHL, the Cochrane Library and Web of Science were systematically searched for studies examining change in quality of life in adults receiving bariatric surgery for obesity. Seventy-two studies were included with a total of 9,433 participants treated for obesity with bariatric surgery. The average impact of bariatric surgery on quality of life corresponded to an effect size of 0.88 (95% CI: 0.80-0.96), indicating that bariatric surgery has a significant positive influence on quality of life in general. The impact varied considerably across studies with bariatric surgery showing a significantly greater positive influence on physical quality of life compared to mental quality of life. Bariatric surgery is effective in improving quality of life, especially when looking at physical well-being. Greater focus on the psychological well-being of the person undergoing surgery for obesity may lead to a better post-surgery prognosis for more people.

Course, patterns, and risk-factors for chemotherapy-induced emesis in cisplatin-pretreated patients: a study with ondansetron.

Vomiting and nausea are the most distressing side-effects of cancer chemotherapy. With standard antiemetic regimens (e.g. metoclopramide based combinations) sufficient antiemetic control is achieved in 50-70% of cisplatin treated patients. Ondansetron, a selective 5-HT3-receptor antagonist has shown efficacy in cisplatin-induced emesis. In the present study, we evaluated the safety and efficacy of ondansetron in cisplatin pretreated patients who had suffered from severe emesis in spite of antiemetic prophylaxis. Complete antiemetic control was reached in 43.5% on the day of treatment and in 27.2% of the patients regarding a worst day analysis. 25% of the patients suffered from severe cisplatin-induced emesis (greater than 5 emetic episodes per 24 h). We try to characterise risk-factors for cisplatin-induced emesis by performing a multivariate analysis. Sex, cisplatin dose, and combination therapy with cisplatin plus anthracyclines seem to be independent risk-factors for vomiting on day 1 and on worst day. Delayed emesis occurred less often when sufficient antiemetic protection from acute vomiting had been obtained. Female sex, cisplatin dose and recurrent disease seem to influence the probability for occurrence of delayed vomiting.

GLUT4 expression at the plasma membrane is related to fibre volume in human skeletal muscle fibres.

In this study we examined the relationship between GLUT4 expression at the plasma membrane and muscle fibre size in fibre-typed human muscle fibres by immunocytochemistry and morphometry in order to gain further insight into the regulation of GLUT4 expression. At the site of the plasma membrane, GLUT4 was more abundantly expressed in slow as compared to fast fibres at the same fibre diameter (p < 0.01) and the GLUT4 expression increased with increasing fibre radius independently of fibre type (p < 0.01). The GLUT4 density at the surface of slow fibres of both diabetic and obese was reduced compared to control subjects at the same diameter (p < 0.001). Fast fibres in obese and type 2 diabetic subjects expressed a fibre-volume-dependent GLUT4 expression (p < 0.001), while this did not reach significance in slow fibres (obese p = 0.18 and diabetic p = 0.06). Our results show that increasing fibre volume is associated with increasing GLUT4 expression in both slow and fast fibres. Based on the possible dependency of GLUT4 expression on volume, we hypothesize that the reduced GLUT4 expression in obesity and type 2 diabetes may partly be compensated for by physical activity.

GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance?

We have recently reported a progressive decline in the expression of glucose transporter isoform 4 (GLUT4) from control subjects through obese non-diabetics to obese type 2 diabetic subjects, indicating that the reduced GLUT4 in slow twitch fibres could be secondary to obesity. In this study we investigate the association of GLUT4 expression with the intracellular triglyceride (TG) content in the same muscle fibres and with plasma lipid parameters. We used histochemistry and stereology to study the relationship between TG content and GLUT4 expression in muscle fibres from obese, obese type 2 diabetic subjects, and young lean controls. TG density was significantly higher in slow compared to fast fibres in all studied subjects (p<0.05). We found an increased TG density in slow twitch fibres of obese diabetic subjects compared to obese (p<0.05) and lean controls (p<0.008). Intracellular TG densities in slow and fast fibres did not correlate with the corresponding GLUT4 density in the same fibres in our study groups (p>0.05). Plasma TG and FFA did not correlate with GLUT4 expression in slow or fast fibres (p>0.05). In conclusion, TG content was increased in diabetic slow fibres with a reduced GLUT4 expression. The GLUT4 expression was not associated with an increased intracellular triglyceride content or with increased plasma FFA levels. Thus, intracellular TG content and circulating FFA may not influence glucose transport directly through GLUT4 expression.

Cerebrospinal fluid shunting in idiopathic normal-pressure hydrocephalus of the elderly: effect of periventricular and deep white matter lesions.

OBJECTIVE: We investigated the effect of periventricular and deep white matter lesions (DWMLs) on outcome after cerebrospinal fluid shunting in a prospective series of elderly patients with idiopathic normal-pressure hydrocephalus. METHODS: White matter lesions were assessed with T2-weighted magnetic resonance scans according to a standard protocol in 41 patients with idiopathic normal-pressure hydrocephalus of the elderly who underwent subsequent shunting. In all patients, the diagnosis of idiopathic normal-pressure hydrocephalus had been established preoperatively by clinical and diagnostic investigations. RESULTS: At a mean follow-up of 16 months, clinical improvement was observed in 37 of 41 patients (90%). There was no persistent morbidity related to surgery. The degree of overall clinical improvement was negatively correlated with the extension of periventricular lesions (correlation coefficient r = -0.324 [P = 0.04]) and DWMLs (correlation coefficient r = -0.373 [P = 0.02]). This negative correlation was also noted when the analysis was conducted separately for each of the cardinal symptoms (gait disturbance, cognitive impairment, and urinary incontinence). There was no consistent pattern of periventricular and DWMLs in the four patients who failed to respond to shunting. CONCLUSION: Periventricular and DWMLs of varying degrees are common findings on magnetic resonance scans of patients with idiopathic normal-pressure hydrocephalus of the elderly. After careful preoperative selection of patients with idiopathic normal-pressure hydrocephalus, individuals with DWMLs suggestive of concomitant vascular encephalopathy may also benefit from cerebrospinal fluid diversion. Although, in general, the degree of improvement depends on the severity of periventricular and DWMLs, patients with more extensive WMLs still may derive clinical benefit from the operation.