Cervical arthroplasty: the beginning, the middle, the end?

Cervical arthroplasty has developed as an alternative to spinal fusion for the treatment of cervical radiculopathy and myelopathy. The popularity of artificial discs has grown as the evidence of complications following arthrodesis has increased, making the theoretical advantages (motion preservation, altering the natural history of disease, prevention of adjacent segment disease) of disc replacement more attractive. However, as more discs are implanted and the length of follow-up increases, reported complications such as heterotopic ossification, device migration and spontaneous fusion of arthroplasty devices are growing. As a result, surgeons and patients face a challenge when deciding between motion-preserving or fusion surgery. Currently, there is inadequate evidence to promote extensive use of artificial discs for cervical spondylosis, despite promising short-term and intermediate clinical outcomes. However, there is also insufficient evidence to cease using them completely. The use of arthroplasty over fusion in the long term can only be justified if the incidence of adjacent segment disease decreases as a result. Despite the level of investment and research into arthroplasty outcomes, long-term follow-up has yet to be completed and has not convincingly demonstrated the effect of artificial discs on adjacent segment disease. Further long-term randomised trials are necessary to determine whether cervical arthroplasty is able to reduce the incidence of adjacent segment disease and, in doing so, replace arthrodesis as the gold standard treatment for cervical spondylosis.     

Interleukin-6 and diabetes: the good, the bad, or the indifferent?

Inflammatory mechanisms play a key role in the pathogenesis of type 1 diabetes. Individuals who progress to type 2 diabetes display features of low-grade inflammation years in advance of disease onset. This low-grade inflammation has been proposed to be involved in the pathogenetic processes causing type 2 diabetes. Mediators of inflammation such as tumor necrosis factor-alpha, interleukin (IL)-1beta, the IL-6 family of cytokines, IL-18, and certain chemokines have been proposed to be involved in the events causing both forms of diabetes. IL-6 has in addition to its immunoregulatory actions been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells, adipocytes, hepatocytes, pancreatic beta-cells, and neuroendocrine cells. Here we argue that IL-6 action-in part regulated by variance in the IL-6 and IL-6alpha receptor genes-contributes to, but is probably neither necessary nor sufficient for, the development of both type 1 and type 2 diabetes. Thus, the two types of diabetes are also in this respect less apart than apparent. However, the mechanisms are not clear, and we therefore propose future directions for studies in this field.     

Introduction—Targeting the lesion,not the organ

The current diagnostic and therapeutic strategy for localized prostate cancer is not working. In fact, it is severely flawed and, as such, fraught with controversy. Our current strategy has arisen from the imprecision of our diagnostic pathway. We do not know where the cancer is, so we subject the prostate to randomly placed needles in the hope of hitting the tumor. This leads to overdiagnosis, underdiagnosis, missclassification of risk and overtreatment and undertreatment. If we do find cancer, we usually subject the entire prostate to radiotherapy or surgery, which damages the surrounding structures—neurovascular bundles, external urinary sphincter, rectum, and bladder neck. Multiparametric magnetic resonance imaging, coupled with an intensive sampling strategy (targeted biopsies), might be able to rule out clinically significant lesions with a negative predictive value in the order of 90% to 95%. Focal therapy certainly leads to less genitourinary and rectal side effects. Current data from more than 3,000 men treated internationally show that incontinence after focal therapy is 0% to 5% (radical therapy can lead to incontinence in 15%–20%) whereas erectile dysfunction occurs in 5% to 10% of men with good baseline function (radical therapy rates vary between 30% and 60%). Early to medium cancer control using biopsies after treatment shows between 80% and 90% of patients have a successful treatment, with 10% to 15% of men requiring redo-treatment with minimal additional morbidity.     

Iron and a Man’s Reproductive Health: the Good,the Bad,and the Ugly

Purpose of Review

To discuss the physiologic and pathologic effects of iron on men’s reproductive health.

Recent Findings

Iron overload diseases are associated with hypogonadotropic hypogonadism, infertility, and sexual dysfunction in men. Recent findings have elucidated the roles by which iron may affect the male reproductive axis.

Summary

Iron is requisite for life. Iron can also catalyze the production of reactive oxygen species. To maintain balance, the human body tightly regulates dietary iron absorption. Severe iron overload disorders—e.g., hereditary hemochromatosis and β-thalassemia—occur when these regulatory mechanisms are deficient. While iron is necessary, the male reproductive system is particularly sensitive to iron overload. Hypogonadotropic hypogonadism, infertility, and sexual dysfunction commonly occur if excess iron from iron overload disorders is not removed. The average male in the USA consumes significantly more iron than needed to replace daily losses. How this degree of iron loading may affect one’s reproductive health remains less clear, but there is evidence it may have adverse effects.

     

Tolerance and addiction; the patient,the parent or the clinician?

Tolerance has been recognized for some time where chronic exposure to certain drugs, particularly benzodiazepines and opioids, is associated with apparent tachyphylaxis. When these drugs are stopped or progressively reduced as in 'tapering', withdrawal symptoms may result. Tolerance and the flip side of the coin, withdrawal, are the determinants of addiction. It is increasingly apparent that tolerance can occur acutely, even within the time span of a single anesthetic for a surgical procedure. Addiction is caused by agents, foreign to the body, that provoke adaptation by homeostatic biological processes. When these agents are withdrawn, the adaptive mechanisms, devoid of substrate, take time to diminish and produce symptoms recognizable under the term of 'withdrawal'. Children may be exposed to these agents in different ways; in utero, as a result of substances that the mother ingests by enteral, parenteral or inhalational means that are transmitted to the infant via the placenta; as a result of an anesthetic for surgery; or as a result of sedation and analgesia administered to offset the stresses and trauma inherent from intensive care treatment in the neonatal intensive care unit or pediatric intensive care unit. Additionally, anesthetic and intensive care staff are exposed to powerful and addictive drugs as part of everyday practice, not simply by overt access, but also by subliminal environmental exposure.     

Carotid endarterectomy in the elderly: are the patient characteristics, the early outcome, and the predictors the same as those in younger patients?

BACKGROUND: The study was conducted to detect possible differences in patient characteristics, in early outcome, and in predictors for 30-day combined stroke and death rate between younger and older patients undergoing CEA. METHODS: Between March 1988 and November 2005, we recorded prospectively the data from every patient who underwent carotid artery surgery. Cardiovascular risk factors, comorbidities, anesthetic and surgical techniques, outcome, and survival were reviewed and compared between <75 age and >or=75 age group. RESULTS: We performed 1028 procedures in 742 patient. A total of 286 carotid endarterectomies were done in 213 patients 75 years or older. The number of cardiovascular risk factors per patient decreased with age. The risk factors tobacco use, hyperlipidemia, and the combination tobacco, hypertension, and hyperlipidemia were predominant in the younger group. Hypertension as only risk factor and the combination hypertension and hyperlipidemia were more present in the older group. The perioperative combined minor and major stroke and death rate was 2.8% in both groups. Attendant predictors for adverse outcome in the >or=75 age group were female sex and the combination of the risk factors diabetes, tobacco use, and hypertension. CONCLUSIONS: The type, the number, and the combinations of cardiovascular risk factors and the predictors for adverse outcome are different in the 2 age groups. Our observations indicate that people 75 years or older with small number of cardiovascular risk factors can undergo CEA with the same risk of perioperative stroke and death as the younger patients.     

Measuring the whole or the parts? Validity, reliability, and responsiveness of the Disabilities of the Arm, Shoulder and Hand outcome measure in different regions of the upper extremity.

The Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure was developed to evaluate disability and symptoms in single or multiple disorders of the upper limb at one point or at many points in time. PURPOSE: The purpose of this study was to evaluate the reliability, validity, and responsiveness of the DASH in a group of diverse patients and to compare the results with those obtained with joint-specific measures. METHODS: Two hundred patients with either wrist/hand or shoulder problems were evaluated by use of questionnaires before treatment, and 172 (86%) were re-evaluated 12 weeks after treatment. Eighty-six patients also completed a test-retest questionnaire three to five days after the initial (baseline) evaluation. The questionnaire package included the DASH, the Brigham (carpal tunnel) questionnaire, the SPADI (Shoulder Pain and Disability Index), and other markers of pain and function. Correlations or t-tests between the DASH and the other measures were used to assess construct validity. Test-retest reliability was assessed using the intraclass correlation coefficient and other summary statistics. Responsiveness was described using standardized response means, receiver operating characteristics curves, and correlations between change in DASH score and change in scores of other measures. Standard response means were used to compare DASH responsiveness with that of the Brigham questionnaire and the SPADI in each region. RESULTS: The DASH was found to correlate with other measures (r > 0.69) and to discriminate well, for example, between patients who were working and those who were not (p<0.0001). Test-retest reliability (ICC = 0.96) exceeded guidelines. The responsiveness of the DASH (to self-rated or expected change) was comparable with or better than that of the joint-specific measures in the whole group and in each region. CONCLUSIONS: Evidence was provided of the validity, test-retest reliability, and responsiveness of the DASH. This study also demonstrated that the DASH had validity and responsiveness in both proximal and distal disorders, confirming its usefulness across the whole extremity.     

Xenotransplantation: the good,the bad,and the ugly or how far are we to clinical application?

On the way to successful clinical XTP many obstacles have to be overcome, and new difficulties might still arise. For clinical XTP all "players of the concert" have to harmonize. It is not enough if one molecule is recognized by its receptor. A chain is only as strong as its weakest link; this is also true for xenogeneic immunology, physiology, and pharmacology. The phylogeneic distance between man and pig comprises 180 million years. This tremendous distance has to be bridged by new and still unknown methods to outwit evolution.