Muscle activation patterns in the Nordic hamstring exercise: Impact of prior strain injury.

This study aimed to determine: (a) the spatial patterns of hamstring activation during the Nordic hamstring exercise (NHE); (b) whether previously injured hamstrings display activation deficits during the NHE; and (c) whether previously injured hamstrings exhibit altered cross-sectional area (CSA). Ten healthy, recreationally active men with a history of unilateral hamstring strain injury underwent functional magnetic resonance imaging of their thighs before and after six sets of 10 repetitions of the NHE. Transverse (T2) relaxation times of all hamstring muscles [biceps femoris long head (BFlh); biceps femoris short head (BFsh); semitendinosus (ST); semimembranosus (SM)] were measured at rest and immediately after the NHE and CSA was measured at rest. For the uninjured limb, the ST's percentage increase in T2 with exercise was 16.8%, 15.8%, and 20.2% greater than the increases exhibited by the BFlh, BFsh, and SM, respectively (P < 0.002 for all). Previously injured hamstring muscles (n = 10) displayed significantly smaller increases in T2 post-exercise than the homonymous muscles in the uninjured contralateral limb (mean difference -7.2%, P = 0.001). No muscles displayed significant between-limb differences in CSA. During the NHE, the ST is preferentially activated and previously injured hamstring muscles display chronic activation deficits compared with uninjured contralateral muscles.

Effect of leaded glasses and thyroid shielding on cone beam CT radiation dose in an adult female phantom.

OBJECTIVES: This study aims to demonstrate the effectiveness of leaded glasses in reducing the lens of eye dose and of lead thyroid collars in reducing the dose to the thyroid gland of an adult female from dental cone beam CT (CBCT). The effect of collimation on the radiation dose in head organs is also examined. METHODS: Dose measurements were conducted by placing optically stimulated luminescent dosemeters in an anthropomorphic female phantom. Eye lens dose was measured by placing a dosemeter on the anterior surface of the phantom eye location. All exposures were performed on one commercially available dental CBCT machine, using selected collimation and exposure techniques. Each scan technique was performed without any lead shielding and then repeated with lead shielding in place. To calculate the percent reduction from lead shielding, the dose measured with lead shielding was divided by the dose measured without lead shielding. The percent reduction from collimation was calculated by comparing the dose measured with collimation to the dose measured without collimation. RESULTS: The dose to the internal eye for one of the scans without leaded glasses or thyroid shield was 0.450 cGy and with glasses and thyroid shield was 0.116 cGy (a 74% reduction). The reduction to the lens of the eye was from 0.396 cGy to 0.153 cGy (a 61% reduction). Without glasses or thyroid shield, the thyroid dose was 0.158 cGy; and when both glasses and shield were used, the thyroid dose was reduced to 0.091 cGy (a 42% reduction). CONCLUSIONS: Collimation alone reduced the dose to the brain by up to 91%, with a similar reduction in other organs. Based on these data, leaded glasses, thyroid collars and collimation minimize the dose to organs outside the field of view.

Significant reduction in dental cone beam computed tomography (CBCT) eye dose through the use of leaded glasses.

OBJECTIVE: In light of the increased recognition of the potential for lens opacification after low-dose radiation exposures, we investigated the effect of leaded eyeglasses worn during dental cone-beam computerized tomography (CBCT) procedures on the radiation absorbed dose to the eye and suggest simple methods to reduce risk of radiation cataract development. STUDY DESIGN: Dose measurements were conducted with the use of 3 anthropomorphic phantoms: male (Alderson radiation therapy phantom), female (CIRS), and juvenile male (CIRS). All exposures were performed on the same dental CBCT machine (Imtec, Ardmore, OK) using 2 different scanning techniques but with identical machine parameters (120 kVp, 3.8 mA, 7.8 s). Scans were performed with and without leaded glasses and repeated 3 times. All measurements were recorded using calibrated thermoluminescent dosimeters and optical luminescent dosimetry. RESULTS: Leaded glasses worn by adult and pediatric patients during CBCT scans may reduce radiation dose to the lens of the eye by as much as 67% (from 0.135 ± 0.004 mGy to 0.044 ± 0.002 mGy in pediatric patients). CONCLUSIONS: Leaded glasses do not appear to have a deleterious effect on the image quality in the area of clinical significance for dental imaging.

Acquisition of metastatic tissue from patients with bone metastases from breast cancer.

Biopsies of metastatic tissue are increasingly being performed. Bone is the most frequent site of metastasis in breast cancer patients, but bone remains technically challenging to biopsy. Difficulties with both tissue acquisition and techniques for analysis of hormone receptor status are well described. Bone biopsies can be carried out by either by standard posterior iliac crest bone marrow trephine/aspiration or CT-guided biopsy of a radiologically evident bone metastasis. The differential yield of these techniques is unknown. Results from three prospective studies of similar methodology were pooled. Patients underwent both an outpatient posterior iliac crest bone marrow trephine/aspiration and a CT-guided biopsy of a radiologically evident bone metastasis. Samples were assessed for the presence of malignant cells and where possible also for estrogen (ER) and progesterone receptor (PgR) expression. 40 patients were enrolled. Bone marrow aspiration/trephine biopsy was completed in 39/40 (97.5%) and CT-guided biopsy was completed in 34/40 (85%) of patients. Sufficient tumor cells for hormone receptor analysis were available in 19/39 (48.8%) and 16/34 (47%) of and bone marrow aspiration/trephine and CT-guided biopsies, respectively. Significant discordance in ER and PgR between the primary and the bone metastasis was also seen. Nine patients had tissue available from both bone marrow and CT-guided bone biopsies. ER and PgR concordance between these sites was 100 and 78%, respectively. Performing studies on human bone metastases is technically challenging, with relatively low yields regardless of technique. Given resource issues and similar success rates when comparing both techniques, bone marrow examination may be utilized first and if inadequate tissue is obtained, CT-guided biopsies can then be used.

Prognostic value of absent end-diastolic flow within the first week following renal transplantation.

BACKGROUND: Doppler sonogram of the graft is used as a routine assessment in renal transplantation. When the resistance index (RI) equals 1, absent end-diastolic flow (AEDF) is observed; the prognostic value of AEDF is presently unknown. PATIENTS AND METHODS: Between 1988 and 1996, 342 patients received a first cadaveric kidney transplant in our ward. AEDF was observed in 30 patients who were compared with 60 controls who showed an RI < 0.75 within the first 7 days after transplantation. They were matched for year of transplantation (+/-1 year); recipient age (+/-2 years); recipient sex; and HLA antibodies (3 classes: 0%, 1-75%, >75%). The follow-up was 4 years. RESULTS: AEDF was observed at day 1 in 64%, at day 3 in 96%, and at day 7 in 28%. Recipient age, donor age, recipient sex, cold and warm ischemia durations, HLA A, B, and DR mismatches, and cytomegalovirus (CMV) status were not different between the 2 groups. Immediate graft function and 3- to 24-month creatinine levels were better in the control than the AEDF group. However, there was no difference in serum creatinine at 3 and 4 years or in patient and graft survivals during follow-up. CONCLUSIONS: AEDF observed within the first week following transplantation is associated with impaired renal functional recovery. However, whether AEDF is a prognostic marker of poor long-term graft function or survival remains to be proven.

Impact of a polymorphism in the IL-12p40 gene on the outcome of kidney transplantation.

A number of factors interfere with the outcome of renal transplantation. Revealing genetic factors that impact on graft outcome may have consequences for clinical practice. Interleukin-12 (IL-12), by stimulating interferon gamma (IFNgamma) production, plays a crucial role in immune responses against both graft and viral agents. An A-to-C single nucleotide polymorphism (SNP) within the 3'-untranslated region (3'UTR) of the IL-12p40 gene has been reported to be both functionally and clinically relevant. Since the impact of this SNP on kidney graft outcome has never been reported, we investigated the impact of the 3'UTR polymorphism on clinical events after transplantation among 253 kidney recipients transplanted between 1995 and 2003. The polymorphism was genotyped using the restriction fragment length polymorphism method. Our results showed that the 3'UTR polymorphism affected neither graft survival (P = .768) nor the occurrence of delayed graft function (DGF; P = .498). C allele carriers in our study displayed more acute rejections in the first year than patients with the A/A genotype, but it did not reach statistical significance (P = .108). In contrast, the C allele appeared to be a significant risk factor for cytomegalovirus infection (odds ratio = 1.77; P = .027). In conclusion, IL12B 3'UTR polymorphism did not affect graft survival, DGF, or acute rejection episodes, but had an impact on the occurrence of cytomegalovirus infection.

Early pulse pressure and low-grade proteinuria as independent long-term risk factors for new-onset diabetes mellitus after kidney transplantation.

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts. We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Caucasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years). The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (<1 g/day) (HR: 2.04 [1.25-3.33], p = 0.0042) and very low-grade (<0.3 g/day) (HR: 2.21 [1.32-3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07-3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03-1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12-1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure >60 mmHg. Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.

Disappearance of tophi in familial juvenile hyperuricemic nephropathy after kidney transplantation.

A 40-year-old man who had been on hemodialysis for 25 months due to familial juvenile hyperuricemic nephropathy (FJHN) received a kidney transplant. Biopsy of his native kidney had shown tubulo-interstitial nephropathy. Genetic analysis confirmed abnormal uromodulin expression due to a mutation in the exon 4 of the UMOD gene. He had multiple tophi on the day of transplantation, including some on his fingers. He received immunosuppressive treatment including polyclonal antilymphocyte antibodies, mycophenolate mofetil, steroids and cyclosporine and achieved excellent renal function, with serum creatinine at 13 mg/L on day 10 posttransplantation and 9.4 mg/L at 6 months. His uric acid excretion rate increased from 4.4% at day 2 posttransplantation to 7.7% 6 months after transplantation. The number and sizes of the tophi were reduced 3 months posttransplantation, and nearly disappeared at month 6. Serum uric acid level decreased slowly from 650 mumol/L before transplantation to 300 mumol/L. Reduction of tophi was probably due to the absence of the mutated UMOD gene in the transplanted kidney.

Urinary albumin excretion and the risk of graft loss and death in proteinuric and non-proteinuric renal transplant recipients.

BACKGROUND: Microalbuminuria and macroalbuminuria constitute risk factors for ESRD and death in non-transplanted populations. Whether microalbuminuria (especially in non-proteinuric patients) and macroalbuminuria constitute risk factors for graft loss and death is presently unknown in renal transplantation. METHODS: We retrospectively assessed the association between urinary albumin excretion (UAE) and ESRD and death in renal transplantation. RESULTS: UAE was measured in 616 (397 proteinuric; 219 non-proteinuric patients) renal transplant recipients. They were grafted for 62 months (range: 6-192). During the 40 months (3.7-99) thereafter, 31 patients underwent dialysis and 32 died. Microalbuminuria (vs. normoalbuminuria) and macroalbuminuria (vs. microalbuminuria) were powerful risk factors for graft loss [OR: 14.25 (2.88-52.3) and 16.41 (7.46-36.0), respectively, both p < 0.0001], even after adjustments on renal function and diabetes. Among the 219 non-proteinuric patients, microalbuminuria (vs. normoalbuminuria) was a significant risk factor for graft loss [OR: 23.09 (1.93-276.4), p = 0.0132]. Both microalbuminuria (vs. normoalbuminuria) [OR: 5.55 (2.43-12.66), p < 0.0001] and macroalbuminuria (vs. microalbuminuria) [OR: 4.12 (1.65-10.29), p = 0.0024] were predictive of death. CONCLUSIONS: Microalbuminuria and macroalbuminuria are powerful independent predictors of ESRD and death. Microalbuminuria is a risk factor for graft loss even in non-proteinuric patients. UAE provides additional information on renal and patient prognosis as compared to proteinuria and renal function.

Estimation of the glomerular filtration rate through different methods in kidney transplant recipients: correlation with the creatinine clearance measurement.

The measurement of the glomerular filtration rate (GFR) is an important tool for physicians to follow kidney transplant recipients. Indeed, renal function has been shown to be predictive of graft outcome in retrospective studies. Several methods have been proposed to measure GFR. In the present study we evaluated the correlation of GFR between a reference method (calculation through the urine to plasma ratio of creatinine [UV/P] formula) and three estimation equations (Cockcroft and Gault; Nankivell; modification of diet in renal disease) in 81 kidney transplant recipients at 3 and 12 months posttransplantation. We showed a significant correlation between the three predictive formulas and UV/P, but none of the predictive equations showed an excellent correlation. The best correlation between an estimation equation and the UV/P formula was the CG formula. Further studies are required to compare the estimated GFR with better reference methods, such as the use of isotopic markers in kidney graft recipients.

Long-term results of monoclonal anti-Il2-receptor antibody versus polyclonal antilymphocyte antibodies as induction therapy in renal transplantation.

We compared the influence of induction therapy on 5-year patient and graft survival as well as on renal function in 100 kidney graft recipients at low immunological risk treated with antilymphocyte globulin (n = 50) versus anti-IL-2R monoclonal antibody (n = 50) in a prospective multicenter study. Long-term immunosuppressive treatment included cyclosporine, mycophenolate mofetil, and a short course of steroids in all patients. Five year graft (86% vs 86%) and patient (94% vs 94%) survivals were identical in both study arms. Moreover, neither serum creatinine or proteinuria were significantly different between the two groups. Our results showed that the choice of the induction therapy seemed to not have a major impact on long-term outcomes among renal recipients at low immunological risk.

Early proteinuria is a strong indicator of donor renal lesions, ischemia-reperfusion injury and immunological aggression.

BACKGROUND: Early proteinuria is associated with reduced long-term graft survival. However, the determinants and mechanisms of proteinuria early after transplantation have not been identified. METHODS: Parameters associated with proteinuria within the first 3 months following transplantation were retrospectively assessed among 484 renal transplant recipients. RESULTS: Proteinuria was more abundant in patients with a history of two or more rejection episodes (0.42 +/- 0.68 vs 0.18 +/- 0.39 g/d; P = .02). Proteinuria was greater when donor age was 60 or more (OR: 4.43; P = .003), when recipient death was due to cardiovascular causes (OR: 1.98; P = .002), or when cold (OR: 1.77; P = .006) or warm (1.21; P = .09) ischemia times were prolonged. CONCLUSIONS: Proteinuria early after transplantation was related to pretransplant renal lesions, ischemia-reperfusion, and immunologic injuries.

The effect of hemodialysis and dialyzer biocompatibility on erythrocyte glutathione-defense system in chronic hemodialysis patients.

BACKGROUND: Uremic patients, especially those receiving regular hemodialysis (HD) treatment, are at high risk of oxidative damage by noxious free radicals and reactive oxygen species (ROS). The erythrocyte glutathione-defense system (GSH-DS) is one of the major enzymatic means of scavenging and detoxifying ROS. This study aimed to elucidate the effect of HD and dialyzer biocompatibility on erythrocyte GSH-DS in uremic patients on maintenance HD treatment. METHODS: Twenty-five healthy volunteers and 42 HD patients were enrolled in this study. Blood samples were drawn immediately before and after HD session, and erythrocyte glutathione (GSH) level as well as the activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-Rd), and glutathione S-transferase (GST) were measured. To evaluate the effect of dialyzer type on the studied parameters the patients were were subdivided into two groups: those who had dialysis with cuprophane (CU) membranes (n=23) and those who received dialysis with the aid of polysulfone (PS) membranes (n=19). RESULTS: The activities of G6PD and GSH-Px as well as GSH level were significantly decreased in HD patients as compared with controls. On the other hand, the activities of GSSG-Rd and GST were significantly elevated among HD patients in comparison with control values. A single HD session, regardless of the type of dialyzer, did not induce any significant effect on any of the measured parameters, although G6PD activity increased significantly after dialysis. CU membrane did not result in any change in GSH or its metabolizing enzymes, while PS dialyzers exerted a minor but significant restoration in GSH-DS. CONCLUSION: The antioxidant pool, as represented by GSH-DS, is significantly affected by dialyzer type in HD patients being significantly corrected with polysulfone dialyzer.

[Cyclosporin-induced toxic neuromyopathy]. / Neuromyopathie toxique induite par la ciclosporine.

INTRODUCTION: Cyclosporine is an immunosuppressive treatment whose side effects limit its usefulness. Among neurological side effects, neuropathies or myopathies have been reported, specially inpatients given combinations of cyclosporine with co-enzyme A reductase inhibitors. CASE REPORT: We report here the case of a 67-year-old woman who developed few months after a kidney graft sensorimotor disorders which progressed rapidly. Since all etiologies of such a disorder were ruled out, the hypothesis of toxicity exclusively induced by cyclosporine was suggested and confirmed by the improvement observed after its withdrawal. CONCLUSION: This observation highlights the fact that cyclosporine may induce neuromyopathies even when given alone at the therapeutic dosage.

Cost-minimization study comparing Simulect vs. Thymoglobulin in renal transplant induction.

PURPOSE: Based on the data of clinical trial CHI-F-02 comparing the efficacy and safety of basiliximab (Simulect) vs. anti-thymocyte globulin (Thymoglobulin) in renal transplant induction, we carried out an economic evaluation. METHOD: This pharmacoeconomic study was a cost-minimization study, i.e. given the equivalent efficacy of the products, the strategy that minimized the cost of care was considered better. The cost of care was analyzed from the hospital perspective. MATERIAL: This 'piggyback' study of 100 patients estimated the direct medical costs incurred over 6 months of use of two strategies for renal transplant induction therapy. Direct medical costs are those of utilized medical resources: medications, hospital stays, dialysis, and physician visits and investigations not scheduled in the protocol. RESULTS: In the Simulect arm, significant reductions were found in the initial hospital stay duration and number of infectious episodes. Therefore, although the average cost of treatment was slightly higher with Simulect) than with Thymoglobulin (2964 vs. 2298 Euros), the cost of the initial hospitalization was significantly lower in the Simulect arm (10 907 vs. 11 967 Euros; p = 0.02). Furthermore the mean cost of infectious episodes was significantly lower in the Simulect arm (1056 vs. 1790 Euros, p = 0.03). Cytomegalovirus infection accounted for a significantly smaller proportion of this cost in the Simulect arm than in the Thymoglobulin arm (30% vs. 53%, p = 0.001). CONCLUSION: This study showed direct medical cost savings of 1159 Euros per patient in the Simulect arm, which more than compensated for the higher price of this immunosuppressive drug.

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.