Compliance: the patient, the doctor, and the medication?

Noncompliance can be defined as covert nonadherence to prescribed medication used for the prophylaxis of allograft rejection and threatening impaired kidney histology or function. It is an increasingly significant long-term problem in transplantation as the failure rates from other causes have diminished. Formal approaches to diagnosis, prophylaxis, and treatment, together with a greater understanding of what should be regarded as a syndrome, are thus increasingly important components of reducing the chronic attrition of graft function and survival. It is possible to classify noncompliant behavior using four facets of the syndrome: timing, frequency, origin, and diagnostic certainty. There are a number of different ways of approaching diagnosis, such as observation of behavior through pill counting or electronic measurements of pill container opening; blood level measurement of relevant drugs; physical examination; and observation of the consequences. However, the only certainty of diagnosis comes from direct patient admission of nonadherence to the prescribed immunosuppression. It is possible to define the highest risk patients through assessment of a number of patient-, drug-, and physician-associated variables, and then to influence the outcome through education, compliance monitoring, and simplified regimens targeted to the highest risk patients. It is important for all transplant units to address the issues raised by noncompliance if the chronic loss of allografts is to be reduced.     

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.

     

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.     

Which Outcome Measure is the Best? Evaluating Responsiveness of the Disabilities of the Arm,Shoulder, and Hand Questionnaire,the Michigan Hand Questionnaire and the Patient-Specific Functional Scale Following Hand and Wrist Surgery

The purpose of this study was to determine and compare the responsiveness of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, the Michigan Hand Questionnaire (MHQ), and the Patient-Specific Functional Scale (PSFS) in patients with carpal tunnel syndrome, wrist pain, finger contracture, or tumor. Eighty-one subjects prospectively completed each questionnaire shortly before and 3 and 6 months after surgery. Data were analyzed using one-way analysis of variance and Newman–Keuls multiple comparison tests. Responsiveness to clinical change was calculated using standardized response means. The DASH was responsive for those with carpal tunnel syndrome (0.77), wrist pain (0.61), and tumor (0.55); the MHQ was responsive for those with carpal tunnel syndrome (1.04), wrist pain (0.87), and finger contracture (0.62); and the PSFS was responsive for those with carpal tunnel syndrome (0.65) and finger contracture (0.64). The interval during which the highest responsiveness occurred for the carpal tunnel, wrist pain, and finger contracture groups was the preoperative to 6-month period. The tumor group experienced the highest responsiveness during the preoperative to 3-month period. Our results indicate that one or more of the instruments evaluated are suitable for outcomes research related to surgery to treat carpal tunnel syndrome, wrist pain, finger contracture, and tumor.     

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.     

Which questionnaire is best? The reliability, validity and ease of use of the Patient Evaluation Measure, the Disabilities of the Arm, Shoulder and Hand and the Michigan Hand Outcome Measure

The Patient Evaluation Measure (PEM), The Michigan Hand Outcome Questionnaire (MHQ) and the Disabilities of the Arm, Shoulder and Hand (DASH) score were assessed independent of their originators for reliability, construct and criterion validity and acceptability, using an ease of use questionnaire. These were administered in random order to 100 patients with different hand and wrist disorders and with different impairments of movement, pain, sensation and strength. The internal consistency of all three questionnaires was very high suggesting redundancy in the questions. All questionnaires were reproducible and valid for finger and wrist disorders, but less for nerve disorders. All had poor construct validity. The PEM was the easiest to understand and complete, taking the least time. Correlation between the scales is high and conversion equations were calculated. All three are reliable and reproducible patient completed questionnaires, but the PEM is the easiest to use. The validity of all is suspected for nerve disorders.     

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.     

Morphodynamics and Surgical Correction of the Body’s Creases,Folds, and Wrinkles

The aesthetics of the human body are a balance of furrows and orifices, and artists of every period have studied the distance between ear and eye, eye and nostrils, nostrils and mouth, nipple and submammary crease, subgluteus folds and iliac crest and so on, to create a code for all body proportions. Currently, the ideal of female beauty prefers more elongated shapes than in the past, and surgical body modeling, performed in accordance with anthropometric rules, uses a combination of techniques to alter the orientation and depth of aesthetic reference points, such as body folds and curves. These must be integrated into the bodys biodynamics to both prevent and correct defects and irregularities of the body, which has an inherent disposition to change shape, both because of the physical forces acting on it and because of constant tissue replacement.     

What Is the Association Among Epiphyseal Rotation,Translation, and the Morphology of the Epiphysis and Metaphysis in Slipped Capital Femoral Epiphysis?

BackgroundContemporary studies have described the rotational mechanism in patients with slipped capital femoral epiphysis (SCFE). However, there have been limited patient imaging data and information to quantify the rotation. Determining whether the epiphysis is rotated or translated and measuring the epiphyseal displacement in all planes may facilitate planning for surgical reorientation of the epiphysis.Questions/purposes(1) How does epiphyseal rotation and translation differ among mild, moderate, and severe SCFE? (2) Is there a correlation between epiphyseal rotation and posterior or inferior translation in hips with SCFE? (3) Does epiphyseal rotation correlate with the size of the epiphyseal tubercle or the metaphyseal fossa or with epiphyseal cupping?MethodsWe identified 51 patients (55% boys [28 of 51]; mean age 13 ± 2 years) with stable SCFE who underwent preoperative CT of the pelvis before definitive treatment. Stable SCFE was selected because unstable SCFE would not allow for accurate assessment of rotation given the complete displacement of the femoral head in relation to the neck. The epiphysis and metaphysis were segmented and reconstructed in three-dimensions (3-D) for analysis in this retrospective study. One observer (a second-year orthopaedic resident) performed the image segmentation and measurements of epiphyseal rotation and translation relative to the metaphysis, epiphyseal tubercle, metaphyseal fossa, and the epiphysis extension onto the metaphysis defined as epiphyseal cupping. To assess the reliability of the measurements, a randomly selected subset of 15 hips was remeasured by the primary examiner and by the two experienced examiners independently. We used ANOVA to calculate the intraclass and interclass correlation coefficients (ICCs) for intraobserver and interobserver reliability of rotational and translational measurements. The ICC values for rotation were 0.91 (intraobserver) and 0.87 (interobserver) and the ICC values for translation were 0.92 (intraobserver) and 0.87 (intraobserver). After adjusting for age and sex, we compared the degree of rotation and translation among mild, moderate, and severe SCFE. Pearson correlation analysis was used to assess the associations between rotation and translation and between rotation and tubercle, fossa, and cupping measurements.ResultsHips with severe SCFE had greater epiphyseal rotation than hips with mild SCFE (adjusted mean difference 21° [95% CI 11° to 31°]; p < 0.001) and hips with moderate SCFE (adjusted mean difference 13° [95% CI 3° to 23°]; p = 0.007). Epiphyseal rotation was positively correlated with posterior translation (r = 0.33 [95% CI 0.06 to 0.55]; p = 0.02) but not with inferior translation (r = 0.16 [95% CI -0.12 to 0.41]; p = 0.27). There was a positive correlation between rotation and metaphyseal fossa depth (r = 0.35 [95% CI 0.08 to 0.57]; p = 0.01), width (r = 0.41 [95% CI 0.15 to 0.61]; p = 0.003), and length (r = 0.56 [95% CI 0.38 to 0.75]; p < 0.001).ConclusionThis study supports a rotational mechanism for the pathogenesis of SCFE. Increased rotation is associated with more severe slips, posterior epiphyseal translation, and enlargement of the metaphyseal fossa. The rotational nature of the deformity, with the center of rotation at the epiphyseal tubercle, should be considered when planning in situ fixation and realignment surgery. Avoiding placing a screw through the epiphyseal tubercle—the pivot point of rotation— may increase the stability of the epiphysis. The realignment of the epiphysis through rotation rather than simple translation is recommended during the open subcapital realignment procedure. Enlargement of the metaphyseal fossa disrupts the interlocking mechanism with the tubercle and increases epiphyseal instability. Even in the setting of a stable SCFE, an increased fossa enlargement may indicate using two screws instead of one screw, given the severity of epiphyseal rotation and the risk of instability. Further biomechanical studies should investigate the number and position of in situ fixation screws in relation to the epiphyseal tubercle and metaphyseal fossa.Level of EvidenceLevel III, prognostic study.     

TRP channels in prostate cancer： the good,the bad and the ugly？

During the last decade, transient receptor potential (TRP) channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that expression profile of some TRP channels, notably TRP melastatin 8 (TRPM8), TRP vanilloid 6 (TRPV6),TRP canonical (TRPC6) and TRPV2, is changing during the development and the progression of prostate cancer towards the hormone-refractory stages. The link between the change in expression levels and the functional role of these channels in prostate cancer is step by step being elucidated. These recent advances are here described and discussed.     

β-defensins and the epididymis: contrasting influences of prenatal,postnatal, and adult scenarios

β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant expression of a variety of β-defensins in the postnatal epididymis of different species. A gradient of region- and cell-specific expression of these proteins is observed in the epithelium of the postnatal epididymis. Their secretion into the luminal fluid and binding to spermatozoa as they travel along the epididymis has suggested their involvement in reproduction-specific tasks. Therefore, continuous attention has been given to various β-defensins for their role in sperm function and fertility. Although β-defensins are largely dependent on androgens, the underlying mechanisms regulating their expression and function in the epididymis are not well understood. Recent investigation has pointed out to a new and interesting scenario where β-defensins emerge with a different expression pattern in the Wolffian duct, the embryonic precursor of the epididymis, as opposed to the adult epididymis, thereby redefining the concept concerning the multifunctional roles of β-defensins in the developing epididymis. In this review, we summarize some current views of β-defensins in the epididymis highlighting our most recent data and speculations on their role in the developing epididymis during the prenatal-to-postnatal transition, bringing attention to the many unanswered questions in this research area that may contribute to a better understanding of epididymal biology and male fertility.