Repeat transcranial Doppler ultrasound imaging in Kuwaiti children with sickle cell disease after a 10-year interval: A prospective, cohort study.

Objectives: Transcranial Doppler imaging (TCDI) of the cerebral arteries is the method of choice to predict patients with sickle cell disease (SCD) at risk for stroke. This study reports TCDI follow-up of cerebral blood flow in a cohort of Kuwaiti children with SCD after a 10-year interval. Methods: Twenty-one pediatric patients with SCD, aged 16.0 ± 1.6 years were initially studied when they were aged 6.5 ± 1.2 years. TCDI scanning was carried out using a phased-array transducer of 1-3 MHz through the trans-temporal window. Peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged mean of the maximum velocity (TAMMV), resistive index (RI), and pulsatility index (PI) were obtained in the anterior and posterior Circle of Willis vessels. Results: The follow-up indices were mostly lower than in the initial study although they remained within the normal range in all the arteries. TAMMV was less than 170 cm/s, and PSV did not exceed 200 cm/s in all vessels. The initial and follow-up TAMMV (mean ± SD) were: 77.3 ± 20.9 and 71.6 ± 9.9 in the terminal internal carotid artery, 94.3 ± 25.8 and 82 ± 18.2 in the middle cerebral artery, 76.6 ± 25.6 and 70.6 ± 10.7 in the anterior cerebral artery, and 59.1 ± 15.8 and 63.9 ± 8.5 in the posterior cerebral artery, respectively. The mean differences between the old and follow-up data for RI, and PI were statistically significant (p < 0.05). Conclusions: Kuwaiti patients with SCD appear to be largely protected from cerebral artery vasculopathy in childhood.

The genetic landscape of autosomal dominant polycystic kidney disease in Kuwait.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal monogenic disease, characterized by bilateral accumulation of renal fluid-filled cysts leading to progressive renal volume enlargement and gradual impairment of kidney function, often resulting in end-stage renal disease. Kuwait could provide valuable genetic insights about ADPKD, including intrafamilial phenotypic variation, given its large household size. This study aims to provide a comprehensive description of the pathogenic variants linked to ADPKD in the Kuwaiti population using multiple genetic analysis modalities and to describe and analyse the ADPKD phenotypic spectrum in terms of kidney function, kidney volume and renal survival. Methods: A total of 126 ADPKD patients from 11 multiplex families and 25 singletons were recruited into the study. A combination of targeted next-generation sequencing (tNGS), long-range polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification were utilized for genetic diagnosis. Clinical evaluation was conducted through renal function testing and ultrasonographic kidney volume analysis. Results: We identified 29 ADPKD pathogenic mutations from 36 families achieving an overall molecular genetic diagnostic rate of 112/126 (88.9%), including 29/36 (80.6%) in families. A total of 28/36 (77.8%) families had pathogenic mutations in PKD1, of which 17/28 (60.7%) were truncating, and 1/36 (2.8%) had a pathogenic variant in the IFT140 gene. A total of 20/29 (69%) of the identified ADPKD mutations were novel and described for the first time, including a TSC2-PKD1 contiguous syndrome. Clinical analysis indicated that genetically unresolved ADPKD cases had no apparent association between kidney volume and age. Conclusion: We describe for the first time the genetic landscape of ADPKD in Kuwait. The observed genetic heterogeneity underlining ADPKD along with the wide phenotypic spectrum reveal the level of complexity in disease pathophysiology. ADPKD genetic testing could improve the care of patients through improved disease prognostication, guided treatment and genetic counselling. However, to fulfil the potential of genetic testing, it is important to overcome the hurdle of genetically unresolved ADPKD cases.

Comparison of radiation doses between diagnostic full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT): a clinical study.

INTRODUCTION: There are increasing concerns about radiation exposure among women who undergo full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT). The main aim of this study was to compare the entrance surface dose (ESD) and average glandular dose (AGD) from FFDM and DBT for different breast thicknesses. METHODS: The ESD and AGD for FFDM in craniocaudal, mediolateral oblique and DBT in craniocaudal projection were recorded from a GE Senographe Essential FFDM unit. The accuracy of the ESD and AGD from the FFDM unit was verified during regular quality assurance programme. Patients were categorised according to their compressed breast thicknesses. X-ray tube potential and target filter combinations were varied with ESD and AGD recorded directly from the FFDM unit. The non-parametric Kruskal-Wallis, Mann-Whitney and Wilcoxon signed-rank tests were performed. RESULTS: The median and interquartile range (IQR) age of the patients were 48 and 11 years, respectively. The highest median for ESD and median total AGD for different breast thicknesses were ranged from 3.3 to 9.1 mGy and 3.3 to 6.0 mGy, respectively, for two-view FFDM. However, it ranged from 3.1 to 8.9 mGy and 1.8 to 4.0 mGy, respectively, for single-view DBT. Both ESD and AGD were significantly lower for DBT (P < 0.001) compared with FFDM. There was a significant difference (P = 0.001) in the ESD and AGD values for different breast thicknesses in FFDM and DBT techniques. CONCLUSIONS: The AGD for a single-view DBT was lower than the two-view FFDM technique.

Pattern of Renal Blood Flow and Renovascular Parameters in Adult Patients With Sickle Cell Disease.

OBJECTIVES: To evaluate renal blood flow patterns and renovascular parameters in adult patients with sickle cell disease (SCD) without laboratory evidence of renal impairment. METHODS: Sixty-five steady-state adult patients with SCD (50 hemoglobin SS [HbSS], 12 HbSß0 , and 3 HbSD) and 30 age- and sex-matched healthy controls were studied. The kidney length, echo pattern, peak systolic velocity (PSV), end-diastolic velocity, renal-to-aortic ratio, resistive index (RI), acceleration time (AT), and renal vein velocity were acquired, recorded, and analyzed with a 1-5-MHz curvilinear transducer through the abdomen. RESULTS: The mean age ± SD of the patients with SCD was 32.89 ± 13.89 years. The highest means for the ultrasound-measured renal length and cortical thickness in the SCD and control groups were 11.78 ± 1.30 and 11.27 ± 0.77 cm and 1.86 ± 0.41 and 1.78 ± 0.28 cm, respectively. The figures were significantly higher in the SCD group than the control group (P < .05). Fifty-nine (90.8%) patients had a mild diffuse increase in cortical echogenicity with preserved renal cortical thickness. The highest mean extrarenal PSVs in the SCD and control groups were 138.46 ± 56.32 and 101.75 ± 31.48 cm/s (P < .05). However, the highest intrarenal RI and AT in SCD and control groups were 0.69 ± 0.07 and 0.06 ± 0.02 seconds and 0.63 ± 0.05 and 0.04 ± 0.01 seconds (P < .05). There was no significant correlation between the RI, AT, and PSV among the patients with SCD (P > .05). CONCLUSIONS: Increased renal length and cortical echogenicity with elevated PSV, RI, and AT values can serve as early ultrasound changes in adult patients with SCD without renal impairment.

Changes in Vertebral Artery Hemodynamics Associated With McKenzie Therapeutic Cervical Movements: An Exploration Using Duplex Ultrasound Imaging.

OBJECTIVE: The purpose of this study was to explore vertebral artery hemodynamic changes associated with McKenzie therapeutic cervical movements in healthy individuals. METHODS: A single-group repeated-measure design was used to examine 20 healthy participants aged 22.05 (1.69) years, mean (standard deviation). Vertebral artery volume flow, diameter, resistive index, time-averaged maximum velocity, and pulsatility index were measured using Duplex ultrasound. Vertebral artery hemodynamics were measured at cervical neutral positions then compared against vertebral artery hemodynamics measured during end-range loading and after repeated McKenzie therapeutic movements. Wilcoxon signed rank tests were used for comparisons, and standardized mean differences (SMDs) were calculated to quantify the changes in size. RESULTS: Repeated retraction with extension in a sitting position and end-range retraction with extension in supine position were significantly associated with an increase in vertebral artery volume flow, P ≤ .01, and the SMD suggests small-medium changes in size. Statistical significant vertebral artery dilation was observed in the sitting position with protraction, combined retraction with extension, and flexion, P ≤ .01, yet the SMD suggested small changes in size. End-range flexion was significantly associated with a reduction in vertebral artery pulsatility index, and the SMD suggested large changes in size. Repeated retraction with extension in supine position was significantly associated with an increase in vertebral artery time-averaged maximum velocity, yet the SMD revealed no clinically important difference. CONCLUSION: For the healthy participants in this study, McKenzie cervical movements were mostly associated with an increase in vertebral artery hemodynamics.

PKD1 Duplicated regions limit clinical Utility of Whole Exome Sequencing for Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited monogenic renal disease characterised by the accumulation of clusters of fluid-filled cysts in the kidneys and is caused by mutations in PKD1 or PKD2 genes. ADPKD genetic diagnosis is complicated by PKD1 pseudogenes located proximal to the original gene with a high degree of homology. The next generation sequencing (NGS) technology including whole exome sequencing (WES) and whole genome sequencing (WGS), is becoming more affordable and its use in the detection of ADPKD mutations for diagnostic and research purposes more widespread. However, how well does NGS technology compare with the Gold standard (Sanger sequencing) in the detection of ADPKD mutations? Is a question that remains to be answered. We have evaluated the efficacy of WES, WGS and targeted enrichment methodologies in detecting ADPKD mutations in the PKD1 and PKD2 genes in patients who were clinically evaluated by ultrasonography and renal function tests. Our results showed that WES detected PKD1 mutations in ADPKD patients with 50% sensitivity, as the reading depth and sequencing quality were low in the duplicated regions of PKD1 (exons 1-32) compared with those of WGS and target enrichment arrays. Our investigation highlights major limitations of WES in ADPKD genetic diagnosis. Enhancing reading depth, quality and sensitivity of WES in the PKD1 duplicated regions (exons 1-32) is crucial for its potential diagnostic or research applications.

Comparison of Digital Breast Tomosynthesis and Digital Mammography for Detection of Breast Cancer in Kuwaiti Women.

OBJECTIVE: To investigate the sensitivity and specificity of digital mammography (DM) and digital breast tomosynthesis (DBT) for the detection of breast cancer in comparison to histopathology findings. SUBJECTS AND METHODS: We included 65 breast lesions in 58 women, each detected by two diagnostic mammography techniques - DM and DBT using Senographe Essential (GE Healthcare, Buc, France) - and subsequently confirmed by histopathology. The Breast Imaging Reporting and Data System was used for characterizing the lesions. RESULTS: The average age of women was 48.3 years (range 26-81 years). There were 34 malignant and 31 benign breast lesions. The sensitivity of DM and DBT was 73.5 and 100%, respectively, while the specificity was 67.7 and 94%, respectively. Receiver operating characteristic curve analysis showed an overall diagnostic advantage of DBT over DM, with a significant difference between DBT and DM (p < 0.001). By performing Cohen's kappa test, we found that there was a strong level of agreement according to Altman guidelines between DBT and histopathology findings (0.97), but a weak agreement between DM and histopathology findings (0.47). CONCLUSION: DBT improves the clinical accuracy of mammography by increasing both sensitivity and specificity. We believe that this improvement is due to improved image visibility and quality. These results could be of interest to health care institutions as they may impact their decision on whether to upgrade to DBT not only for diagnosis, but also for screening.

Pattern of cerebral blood flow and the interrelationship of vascular parameters of transcranial Doppler imaging in children with sickle cell disease.

PURPOSE: We assessed the pattern of cerebral blood flow and the relationship between the different transcranial Doppler imaging (TCDI) vascular parameters in children with sickle cell disease (SCD). METHODS: Forty-three SCD pediatric patients with a stable condition (21 HbSS, 19 HbSß0 Thal, and 3 HbSD), aged 10.1 ± 3.9 years were studied. A control group of 26 with age and sex-matched, were included for comparison. TCDI scanning was carried out using a phased array transducer of 1-3 MHz through the trans-temporal window. Peak systolic velocity (PSV), end diastolic velocity (EDV), time-averaged mean of the maximum velocity (TAMxV), pulsatility index (PI), and resistive index (RI) were in the anterior circle of Willis vessels and posterior cerebral artery. RESULTS: The highest mean ± SD values for the middle cerebral artery PSV, EDV, TAMxV, PI, and RI were 130.30 + 26.5, 145.0 ± 21.9; 58.60 + 13.70, 67.90 ± 13.3; 84.90 + 14.50, 94.80 ± 17.9; 0.95 + 0.20, 0.80 ± 0.20; 0.58 + 0.09, 0.50 ± 0.10 in the control and SCD groups, respectively. Independent t-test showed significant difference (P < .05) for all vascular parameters in all vessels in each side between both groups. There was a positive significant correlation between TAMxV, PSV, and EDV (P = .001, r = .96), and a negative significant correlation between TAMxV and PI in the SCD group (P = .001, r = -.46) but not in the control group (P > .05, r = -.62). CONCLUSIONS: There was a direct relationship between TAMxV and PSV and EDV, and an inverse relationship between TAMxV and PI in a group of SCD patients with normal TCDI values.

Diastolic versus systolic ankle-brachial pressure index using ultrasound imaging & automated oscillometric measurement in diabetic patients with calcified and non-calcified lower limb arteries.

BACKGROUND: Ankle-brachial pressure index-systolic (ABI-s) can be falsely elevated in the presence of calcified lower limb arteries in some diabetic patients and therefore loses its value in this cohort of patients. We aim at investigating the feasibility of using the diastolic (ABI-d) instead of ABI-s to calculate the ABI in diabetic patients with calcified limb arteries. METHODS: A total of 51 patients were chosen from the diabetic foot clinic. Twenty six of these patients had calcified leg arteries by Duplex scan (Group A) and 25 patients did not have calcifications in their leg arteries (Group B). Twenty five healthy volunteers were enrolled in the study for group C and they were matched with other participants from group B and A in age and sex. ABI measurement was performed using "boso ABI-system 100 machine". Systolic ABI (ABI-s) and diastolic ABI (ABI-d) were calculated based on bilateral brachial and ankle oscillometric pressures. ABI is considered normal when it is ≥0.9. Repeated measures ANOVA test was used to test for comparing mean scores for ABI-s and ABI-d across the three groups. Statistical significance is considered when P < .05. RESULTS: The mean age of all participants (±SD) was 64.30 ± 7.1 years (range, 50-82 years). ABI-s mean ± SD was 1.3 ± 0.10 (range, 1.18-1.58) in group A patients, 1.07 ± 0.05 (range, 1-1.16) in group B patients, and 1.06 ± 0.05 (range, 1-1.16) in group C volunteers. While ABI-d mean ± SD was 1.07 ± 0.05 (range, 1.1-1.17) in group A patients, 1.06 ± 0.05 (1-1.14) in group B patients, and 1.05 ± 0.04 (range, 1.01-1.14) in group C volunteers. In group A, repeated measures ANOVA test showed statistical significant difference between ABI-s and ABI-d (P < 0.001) whereas in group B & C was not (P > 0.05). CONCLUSIONS: ABI-d may be helpful and can be used as a complementary measure instead of ABI-s in falsely elevated ABI caused by partial incompressible vessel.

Changes in the diameter and valve closure time of leg veins in primigravida women during pregnancy.

OBJECTIVE: The aim of this study was to monitor the changes that develop in leg veins of primigravida women during pregnancy. METHODS: Sixty primigravida women volunteered to undergo clinical evaluation and duplex ultrasound examination of both lower limb veins to monitor changes in vein diameter and valve closure time (VCT) during pregnancy and 3 months postpartum by duplex ultrasound. A total of four readings were taken for each subject, one reading for each trimester and the last reading at 3 months postpartum. RESULTS: The mean (± standard deviation) age of participants was 26.82 ± 2.47 years; 39 limbs (32.5%) and 65 limbs (54.2%) developed C1-C3 venous changes during the second and third trimesters, respectively. Three months post partum, 36 limbs (30%) continued to have C1-C2 changes. Only four limbs in four subjects developed varicose veins along the great saphenous vein, and their VCT was more than 1 second. These subjects were found to have a family history of varicose veins. Duplex examinations showed that there was a gradual increase in the diameter and VCT from the second trimester through the third trimester of pregnancy in all examined venous segments. These changes were statistically significant by Friedman and related-samples Wilcoxon signed rank tests within the same legs (P = .001) but not between legs in the same subject (P > .05), even with adjustment for body mass index (P = .001-.049). CONCLUSIONS: In primigravida women, lower limb veins showed gradual increase in vein diameter and in VCT starting from the second trimester. These changes reverted to baseline in most cases 3 months after delivery.

Changes in the diameter and valve closure time of leg veins across the menstrual cycle.

OBJECTIVES: The purpose of this study was to determine the changes (if any) in the diameter and valve closure time of the lower limb veins in healthy young nulliparous women at different phases of the menstrual cycle. METHODS: Fifty-three young nulliparous women were asked to undergo clinical evaluations and duplex ultrasound examinations of both lower limb veins to monitor changes in the vein diameter and valve closure time at different phases of their menstrual cycles. The vein diameter on B-mode imaging and valve closure time on pulsed Doppler tracing were calculated at days 1 to 4, 14 to 16, and 25 to 28 of the menstrual cycle. Freidman and related samples Wilcoxon signed rank tests were used to determine time-related changes in venous function. RESULTS: The volunteers' mean age ± SD was 20.60 ± 1.90 years, and their mean body mass index was 23.90 ± 4.90 kg/m(2). There was a gradual increase in the vein diameter and valve closure time at the specified phases of the menstrual cycle. Friedman and related samples Wilcoxon signed rank tests for venous segment diameter and valve closure time changes between the different phases of the menstrual cycle were performed and showed statistical significance for each venous segment within each limb (P = .003-.025). Also, when adjusted for body mass index, statistical significance existed for the same venous segments in the same limbs (P =.001-.049). There was no statistical significance for the same venous segments at the same phase of the menstrual cycle between limbs (related samples Wilcoxon signed rank test: P =.079-.97). CONCLUSIONS: During the menstrual cycle, the lower limb veins show an increase in their diameter and valve closure time. These changes are probably mediated by the female sex hormones.

Subject body mass index affects Doppler waveform in celiac artery by duplex ultrasound.

OBJECTIVE: The aim of this study is to evaluate the effect of body mass index (BMI) on peak systolic velocity (PSV) recording in the celiac artery (CA). SUBJECTS & METHODS: Forty male participants were entered prospectively into the study. The subjects were divided into two groups according to their body mass index. Group A included subjects with BMI ≤25 Kg/m(2) and those in group B with BMI >25 Kg/m(2). The diameter and PSV at the origin of CA of subjects in both groups were recorded while the subject positioned in supine and during expiration phase and fasted for 4 hours using duplex ultrasound. Both groups were matched for age and sex. Independent Student's t-test was used to test if there is any statistical significance between diameter and PSV in both groups. RESULTS: Group A's, average age (year, ±SD) was 29.35±1.35 and average BMI (Kg/m(2), ±SD) was 23.1±1.60. Group B's, average age was 30±2.1 and their average BMI was 31±5.1. The average diameter (cm, ±SD) of CA in group A was 0.66±0.076 and in group B was 0.80±0.066. However, the average PSV (cm/s, ±SD) was 117±28.1 in group A and 102±12.4 in group B. Independent student t-test showed statistical significance between both groups for the diameter (p=0.005) and just reached statistical significance for PSV (p=0.049). CONCLUSION: Subjects with higher BMI showed reduced PSV due to a larger CA diameter and probably due to more fatty tissue accumulation around the CA origin.

Transrectal ultrasound guided biopsy for detecting prostate cancer: can random biopsies be reduced using the 4-dimensional technique?

We present our experience with a new technique of real time 3-dimensional sonography -- "4-dimensional Transrectal ultrasound (TRUS)" guided prostate biopsy. A total of 64 patients suspected of having prostate cancer based on an elevated prostate-specific antigen (greater than 4 ng/ml) formed the study group. A voluson (General Electric Vivid 3) ultrasound machine equipped with a transrectal 5-8 MHz curvilinear transducer was used. Sonography-guided prostate biopsy was performed following prostate imaging and volume calculation using 3D and 4D imaging. Biopsies of tumor suspicious areas, if present, as well as random biopsies were done. Histopathology showed prostate cancer in 15 (23.4%) and benign prostatic conditions in 49 (76.6%). TRUS examination in the 15 detected prostatic cancers showed that 6(40%) were hypoechoic, 4 (26.7%) were of mixed hypo and hyper echogenicity, 1 (6.7%) was hyperechoic, and 4 (26.7%) were isoechoic. TRUS finding of a hypoechoic lesion was significantly associated with malignancy. Other TRUS findings such as texture, calcification, and cysts did not show any association with malignancy. Mortality was zero after ultrasound-guided prostate biopsy. TRUS is the diagnostic test of choice in detection of prostate cancer. With advances in the technique of TRUS, effort is being made to identify more subtle lesions in order to reduce random biopsies. 4-Dimensional TRUS does improve the diagnostic accuracy but there is still a group of patients with "invisible" cancers. Therefore, the policy of random biopsies has to be continued till this incidence can be eliminated.

In vivo and in vitro assessment of human saphenous vein wall changes.

PURPOSE: To investigate if noradrenaline (NA) and 5-hydroxyptamine (5-HT) drugs induce responses of isolated control and varicose veins are altered by removal of the endothelium. SUBJECTS #ENTITYSTARTX00026; METHODS: Specimens of the great saphenous vein (GSV) were obtained from 12 subjects with primary varicose veins and 12 subjects from donor vessels at cardiac surgery. A total of 10 normal healthy volunteers were selected for comparison. The diameter changes of GSV during the resting phase, at the end of 5 minutes occlusion, and then every 30 seconds post deflation for five minutes were measured using B-mode ultrasound. Post-surgery the vein sample was collected in a tube of Krebs-Henseleit solution. RESULTS: The repeated measure ANOVA test for the diameter, percent, and difference changes of GSV diameter from maximum diameter at different time intervals showed significance difference within and between all groups. NA and 5-HT produced concentration-dependent contractions of control and varicose saphenous vein segments. There was no significant difference in the potency of NA and for 5-HT, but the maximum response, normalized for tissue weight, was less in varicose vein segments. Removal of the endothelium had no effect on the potency of NA or 5-HT but significantly (p<0.05) reduced the maximum response to NA and 5-HT in varicose vein segments but not to 5-HT in control veins. CONCLUSION: The venous endothelial damage may cause vascular smooth muscle contractions dysfunction that favours dilatation and secondary valvular insufficiency.

Five-year outcome study of deep vein thrombosis in the lower limbs.

OBJECTIVE: Venous disease was evaluated in relation to post-thrombotic syndrome 5 years after deep venous thrombosis (DVT) in patients treated with a regimen of low-molecular-weight heparin (LMWH) and warfarin in a Hospital-in-the-Home program. METHODS: The presence of flow, reflux and compressibility in 51 patients (102 limbs, 54 with DVT and 48 without DVT) was assessed by duplex ultrasound scanning. Blood tests were carried out for prothrombotic screening. Venous disease was related to pathologic severity of post-thrombotic syndrome, characterized by the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification on a scale of 0 to 6. RESULTS: In the 102 limbs studied, 30 patients (59%) had an underlying thrombophilic disorder. The most common cause of DVT was postoperation and prolonged immobilization not related to postoperation. The most common thrombophilic abnormalities were anticardiolipin antibody and a deficiency of protein C or S, or both. Twenty-six limbs (48%) had proximal involvement (proximal and proximal plus distal DVT); resolution (recanalization or normal vein) in these limbs was seen in 85% at 6 months and 96% at 5 years. After 5 years, 25 of these proximal DVT limbs (96%) developed reflux and there were 4 limbs in CEAP class 0, 8 in classes 1 to 3, and 14 in classes 4 to 6. All of the 28 limbs (52%) with distal DVT showed DVT resolution by 6 months. After 5 years, 10 limbs (36%) developed reflux, and 13 limbs were in class 0, 12 in classes 1 to 3, and 3 limbs in classes 4 to 6. No DVT was detected in the 48 contralateral limbs, but reflux was detected in 25 limbs (52%), predominately in the superficial veins (16 limbs, 64%). CONCLUSIONS: The resolution of thrombus was more rapid and complete in patients with distal DVT than in those with proximal DVT. Patients with proximal DVT developed a more severe form of post-thrombotic syndrome that was likely related to the development of deep venous reflux. An important finding of this study was an unexpectedly high incidence of venous reflux in the apparently unaffected limb. Although these non-DVT limbs were not investigated at presentation, our data is consistent with the hypothesis that DVT may result in a more systemic disorder of venous function.