Biomechanics of tendons and tendon failure

Research into the biomechanical properties of tendons had led to a better understanding of the functional and pathophysiologic processes that occur in vivo, particularly in the setting of tendon injury and failure. Increasingly, biomechanical information is being utilized in the clinical setting, guiding patient management in certain circumstances. Differentiating minor and self-limiting abnormalities from those in which specific treatment may prevent further disability from altered biomechanics may become an important role for imaging. This article examines normal tendon anatomy and its relationship to tendon biomechanics under both physiological and pathologic conditions. Imaging characteristics of tendons in the physiologic and pathologic states are discussed. We have focused primarily on MRI, as this modality has been studied most intensively and has been shown to offer additional information regarding unsuspected pathology.     

Geographic variance in access to renal transplantation in Australia

BACKGROUND: Geographic disparities in access to transplantation in Australia during the past 15 years have been accentuated by the increasing size of the transplant waiting lists in each state and by low cadaveric donation rates. Access to dialysis treatment is similar in all states of Australia, although there are fewer elderly dialysis patients in South Australia. RESULTS: Access to the transplant waiting list varies significantly between the states, with one state having 39 per million population (pmp) on their list compared with the two most populous states at 113 pmp and 101 pmp. Patients between the ages of 25 and 54 years in one state had twice the chance of being on the waiting list compared with another.Transplantation rates reflect both the cadaveric donor rate (16.9 transplants pmp) and the large contribution from living donors (39% of all transplants in 2001). Transplantation with a kidney in Australia is dependent both upon age and the state of residence, with one state performing transplantations with 15% of their dialysis population each year but all other states achieving less than 10%, with an average of 8% for the country as a whole. CONCLUSIONS: Criteria for access to the transplantation waiting list in each state vary, depending perhaps upon whether a general community or individual patient perspective is the dominant policy. Access to transplantation on the other hand is reflective of each states' cadaveric donation rate modified by increasing use of living donors, especially in younger patients.     

Perioperative blood pressure control,delayed graft function,and acute rejection after renal transplantation

BACKGROUND: Blood pressure (BP) control immediately after renal transplantation is poorly understood, with patients experiencing both high and low BP levels. Donor kidneys lack the ability to autoregulate their blood flow, meaning high pressures are directly translated to the graft endothelium, whereas reduced perfusion may augment ischemic injury. We hypothesize that early BP control may therefore influence the early alloimmune response. METHODS: A total of 276 patients undergoing primary cadaveric renal transplantation who received cyclosporine-based therapy were followed; standard transplant variables were identified. BP was serially recorded before, during, and after reperfusion until 50 hr after surgery. Variables predicting acute rejection and delayed graft function were identified using Cox and logistic regression models. RESULTS: The mean (SD) BP after surgery was 161(19) mm Hg systolic and 73(12) mm Hg diastolic. Forty-two percent had perioperative hypertension defined by conventional parameters. Increasing postoperative systolic BP, measured as standardized area-under-the-curve, was associated with an increased risk for acute rejection (hazard ratio [per mm Hg]=1.008), independent of other covariables including the preoperative BP level. Diastolic BP was inversely associated with the risk of delayed graft function (odds ratio [per mm Hg]=0.956). CONCLUSIONS: Early hypertension is common after renal transplantation. Early BP control has the potential to influence the risk of allograft rejection and delayed graft function.     

Temporal factors and the prevalence of transient exposures at the time of an occupational traumatic hand injury

Temporal factors and the prevalence of exposure to transient risk factors for occupational traumatic hand injury were analyzed among 1166 subjects participating in a case-crossover study. Temporal factors included time of injury and elapsed time to injury since the start of the work shift. Transient exposures included work equipment, work practice, and worker-related factors. The highest frequency of injury was observed from 08:00 am to 12:00 pm (54.6%), with a peak from 10:00 to 11:00 am (14.9%). The median time into the work shift for injury was 3.5 hours. Subjects injured 2 to 3 hours into their work shift most often reported using a machine, tool, or work material that performed differently than usual (23.9%). These results suggest that acute hand injuries occur earlier in the workday and safety programs should place increased vigilance on these times.     

Synthesis and biological evaluation of 5-substituted derivatives of the potent antiherpes agent (north)-methanocarbathymine

The conformationally locked nucleoside, (north)-methanocarbathymine (1a), is a potent and selective anti-herpes agent effective against herpes simplex type 1 (HSV1) and type 2 (HSV2) viruses. Hereby, we report on the synthesis and biological evaluation of a small set of 5-substituted pyrimidine nucleosides belonging to the same class of bicyclo[3.1.0]hexane nucleosides. Both the 5-bromovinyl (4) and the 5-bromo analogue (3) appeared to be exclusive substrates of HSV1 thymidine kinase (TK), contrasting with the 5-iodo analogue (2), which was significantly phosphorylated by the human cytosolic TK. The binding affinity constant and catalytic turnover for HSV1 TK were measured to assess the influence of the substitution on these parameters. In the plaque reduction and cytotoxicity assays, the 5-bromo analogue (3) showed good activity against HSV1 and HSV2 with less general toxicity than 1a. Against varicella-zoster virus (VZV), the north-locked 5-bromovinyl analogue (4) proved to be as potent as its conformationally unlocked 2'-deoxyriboside equivalent BVDU. The three compounds were also tested in vitro as prodrugs used in a gene therapy context on three osteosarcoma cell lines, either deficient in TK (TK(-)), nontransduced, or stably transduced with HSV1 TK. The 5-iodo compound (2, CC(50) 25 +/- 7 microM) was more efficient than ganciclovir (GCV, CC(50) 75 +/- 35 microM) in inhibiting growth of HSV1-TK transfected cells and less inhibitory than GCV toward TK(-) cells, whereas compound 3 inhibited transfected and nontransfected cell lines in a relatively similar dose-dependent manner.     

Use of cidofovir in polyomavirus BK viral nephropathy in two renal allograft recipients

Polyomavirus BK viral allograft nephropathy is a potentially reversible cause of deteriorating function of kidney allografts. Initial treatment involves reducing immunosuppressive medications, with low-dose cidofovir an effective alternative in refractory cases. We describe two cases of BK viral allograft nephropathy responding to low-dose cidofovir after a reduction in immunosuppressive medications failed to clear the virus or stabilize the deterioration in renal function. There were no significant side-effects from this treatment in either patient.     

Repeated rating improves value of diagnostic dopaminergic challenge tests in Parkinson's disease

Summary. Clinicians use acute challenges with levodopa (LD) and/or apomorphine (A) for diagnostic dopaminergic response tests in Parkinson's disease (PD) patients. We consecutively compared the value of both drugs with performance of repeated ratings and adverse effect recording. Oral administration of 200 mg LD was superior to subcutaneous injection of 4 mg A in terms of tolerability and onset of temporary UPDRS motor score decline ([previously untreated PD patients] LD: 4.02 [mean] ± 2.45 [SD] {significant decrease: p = 1.42E-07} vs. A: 1.58 ± 3.38 {not significant decrease: p = 0.14}, p = 0.0009; [treated PD patients] LD: 7.71 ± 4.35 {significant decrease: p = 2.48E-06} vs. A: 5.19 ± 4.32 {significant decrease: p = 7.83E-05}, p = 0.07). We suggest diagnostic acute challenge test performance with LD as first- and A as second choice due to better tolerability and valuation in combination with repeated scoring procedures to improve sensitivity and specifity. Received December 12, 2002; accepted January 20, 2003 Published online April 7, 2003 Authors' address: Prof. Dr. Th. Müller, Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany, e-mail: thomas.mueller@ruhr-uni-bochum.de     

Epidemiology of congenital hearing loss in Victoria, Australia

The aim of this study was to report the incidence, prevalence and clinical characteristics of congenital hearing loss sufficient to require hearing aid fitting in the first 6 years of life for the 1993 birth cohort of the state of Victoria (population 4.4 million), Australia. In 1993, 64,116 infants born in the state of Victoria survived the neonatal period. Subjects included all children with congenital hearing loss for which hearing aids were fitted, at any time up to and including 31 December 1999, when the youngest member of the cohort reached 6 years of age. Data on the degree, type and etiology of hearing loss were available from the Australian Hearing database for all subjects. Sociodemographic and health data were available from the Victorian Infant Hearing Screening Program (VIHSP) and parent questionnaires. The known prevalence of identified congenital hearing loss increased as the cohort aged. By the time the youngest member had reached the age of 6 years, 134 children (78 boys, 56 girls) had been fitted with hearing aids for permanent congenital hearing loss of any degree (2.09/1000). Fifty-four (40%) of these had known mild losses (20-40 dB HL). The prevalence of known moderate or greater loss (> 40 dB HL) was 1.12/1000; the data suggest that over 90% could have been detectable by neonatal hearing screening. A further seven children from the birth cohort were fitted with hearing aids due to acquired forms of hearing loss (0.11/1000). The etiology was known in only 57 (43%) congenital cases, with known non-syndromal genetic causes accounting for 21 (37%) of these. This study reports on the prevalence of congenital hearing loss requiring hearing aid fitting for an entire birth cohort. These data indicate the possible yield from neonatal screening, and hence the likely benefit of such screening. For a large proportion of cases, the etiology remains unknown. These data have implications for health service delivery and illustrate the usefulness of a population database in monitoring the prevalence of congenital hearing loss.     

Apolipoprotein E genotype, vascular risk and early cognitive impairment in an African Caribbean population

A reduced risk of Alzheimer's disease (AD) associated with the apolipoprotein E (APOE) epsilon4 allele is reported in populations of African origin. In order to clarify possible reasons for this, we examined the association between APOE genotype and early cognitive impairment in a community-based African Caribbean UK population aged 55-75 years. APOE genotype was available for 202 participants, 57 (28%) of whom were classified as having relative cognitive impairment on a battery of neuropsychological tests. Cognitive impairment was negatively associated with epsilon2 and positively but more weakly associated with epsilon4. Effects of both alleles increased markedly after age 70. The effect of epsilon4 was increased in combination with hypertension, diabetes or lower educational attainment, but these factors did not influence epsilon2 effects. Cholesterol and triglyceride levels partially explained effects of epsilon2, but did not account for those of epsilon4. A reduced association between epsilon4 and later AD in populations of African origin is unlikely to be explained by reduced cognitive effects or by differential mortality. However, it may be accounted for by vascular comorbidity. The different patterns of association between epsilon2 and epsilon4 alleles suggest different pathways of effect.