Peroneus Longus Rupture at Its Origin Managed With Platelet Rich Plasma.

Tears of the peroneus longus muscle are unusual, and typically involve the distal insertion at the musculotendon junction. Although tears of the mid-portion of the peroneus longus muscle/tendon complex have been reported, no reports of a tear at the origin of the peroneus muscle have been published, to the authors' knowledge. Herein a case of proximal peroneus longus muscle tear and its subsequent management with platelet rich plasma is reported.

Suicide: an existentialist reconceptualization.

The phenomenon of suicide is one of the primary concerns for mental health professions. The health-care literature is dominated by discussions that focus variously on local and national suicide prevention policies, on the assessment of those individuals judged to be at risk of committing suicide as well as the appropriateness and efficacy of interventions for those who express suicidal ideation and display suicidal behaviours. What appear less frequently in the literature, however, are critical analyses of the concept of suicide and, in particular, critical reflections on the manner in which the concept of suicide has been, and continues to be, understood or 'framed'. In an attempt to respond to this apparent omission, this paper will suggest that the work of Albert Camus, and his philosophical work The Myth of Sisyphus in particular, can be understood as providing a significant reconceptualization and reframing of suicide. In doing so, it will be suggested that Camus's work not only challenges how the concept of suicide has traditionally been situated within the context of mental illness, but can also be understood as challenging the efficacy of the interventions that have been associated with an understanding of suicide within that context.

Ghrelin receptor-knockout mice display alterations in circadian rhythms of activity and feeding under constant lighting conditions.

Ghrelin is an orexigenic hormone produced by the stomach. Ghrelin, however, may also be a modulator of the circadian system given that ghrelin receptors are expressed in the master clock, the suprachiasmatic nucleus (SCN) and several outputs of this region. To investigate this, we performed analyses of running wheel activity and neuronal activation in wild type (WT) and growth hormone secretagogue receptor-knockout (GHSR-KO) mice under various lighting conditions. GHSR-KO and WT mice were maintained under constant dark (DD) or constant light (LL) with ad libitum access to food before being placed on a schedule of temporally restricted access to food (4 h/day) for 2 weeks. There were no differences between KO and WT mice in free-running period under DD, but GHSR-KO mice required more days to develop a high level of food anticipatory activity, and this was lower than that observed in WT mice. Under LL, GHSR-KO mice showed greater activity overall, lengthening of their circadian period, and more resistance to the disorganisational effects of LL. Furthermore, GHSR-KO mice showed greater activity overall, and greater activity in anticipation of a scheduled meal under LL. These behavioral effects were not correlated with changes in the circadian expression of the Fos, Per1 or Per2 proteins under any lighting conditions. These results suggest that the ghrelin receptor plays a role in modulating the activity of the circadian system under normal conditions and under restricted feeding schedules, but does so through mechanisms that remain to be determined.

Telerheumatology: an idea whose time has come.

Australia is a vast country with one-third of the population living outside capital cities. Providing specialist rheumatologist services to regional, rural and remote Australians has generally required expensive and time-consuming travel for the patient and/or specialist. As a result, access to specialist care for remote Australians is poor. Rheumatoid arthritis is a common disease, but like many rheumatic diseases, it is complex to treat. Time-dependent joint damage and disability occur unless best evidence care is implemented. The relatively poor access to rheumatologist care allotted to nonmetropolitan Australians therefore represents a significant cause of potentially preventable disability in Australia. Telehealth has the potential to improve access to specialist rheumatologists for patients with rheumatoid arthritis and other rheumatic diseases, thereby decreasing the burden of disability caused by these diseases. Advances in videoconferencing technology, the national broadband rollout and recent Federal government financial incentives have led to a heightened interest in exploring the use of this technology in Australian rheumatology practice. This review summarises the current evidence base, outlines telehealth's strengths and weaknesses in managing rheumatic disease, and discusses the technological, medicolegal and financial aspects of this model of care. A mixed model offering both face-to-face and virtual consultations appears to be the best option, as it can overcome the barriers to accessing care posed by distance while also mitigating the risks of virtual consultation.

Ghrelin-deficient mice have fewer orexin cells and reduced cFOS expression in the mesolimbic dopamine pathway under a restricted feeding paradigm.

Ghrelin is an orexigenic stomach peptide previously found to be important for the full display of anticipatory locomotor activity and hypothalamic neuronal activation that precedes a daily scheduled meal in mice. Ghrelin is also important for food-related motivation and seems to have direct effects in the mesocorticolimbic dopamine reward system. Here we hypothesized that neuronal activation in reward-related areas in anticipation of a scheduled meal could be mediated by elevated ghrelin induced by scheduled feeding, and therefore this would be attenuated in ghrelin receptor knock-out (GHSR KO) animals. We found that this was indeed the case for the ventral tegmental area and the shell, but not the core, of the nucleus accumbens. In addition, our results show a reduction in the proportion of activated orexin-immunoreactive (IR) neurons in GHSR KO animals in anticipation of the scheduled meal in comparison to the proportion of activated orexin neurons in wild type (WT) mice. Interestingly we observed that both GHSR and ghrelin KO mice had fewer orexin-IR cells than their WT littermates suggesting that lack of ghrelin or sensitivity to ghrelin may play a role in the development of the orexin system. Our data also suggest that ghrelin may mediate food anticipation, in part, by stimulating both the orexin system and the mesolimbic reward system.

Competing clocks: metabolic status moderates signals from the master circadian pacemaker.

Food anticipation and its behavioural manifestation, food anticipatory activity (FAA), require entrainment of a suprachiasmatic nucleus (SCN) independent circadian mechanism, a food entrainable oscillator (FEO), with an unknown neural substrate. While the FEO entrains to fasting/feeding related cues and drives FAA independently of the pacemaker in the SCN, it must disengage the suppressing signals of the SCN for the behavioural and physiological manifestations of meal anticipation to occur outside of the typical period of arousal. This review provides a brief overview of mammalian circadian biology before summarizing experimental data demonstrating several mechanisms by which this may occur, including: reducing activation of SCN cells receiving retinal input, transient disorganization of SCN outputs, and reduced sensitivity to SCN signals in hypothalamic sites responsible for integrating homeostatic and circadian information. Further investigation of these mechanisms will be key to elucidating pharmacological or behavioural interventions that suppress the negative psychological and health effects of light-driven circadian rhythms in humans, specifically those with work schedules that do not conform to the solar day.

Canadian hepatitis C look-back investigation to detect transmission from an infected general surgeon.

BACKGROUND: In February 2007, a general surgeon in Charlottetown, Prince Edward Island, tested positive for hepatitis C virus (HCV). The surgeon's infection onset date could not be determined; however, episodic hepatic enzyme elevations were first detected in November 2004 and again in February 2007. HCV transmission during surgery, alhough rare, has been documented. A phased look-back HCV screening program was conducted to detect HCV transmission from this surgeon to patients who underwent the highest-risk procedures in the three years before his positive test. METHODS: Highest-risk procedures were defined as exposure-prone procedures (EPP) in which exposure to the surgeon's blood was most likely. EPP patients from January 2004 to February 2007 were identified using hospital and administrative records. Linkages with the provincial notifiable disease for HCV was performed, and death records for deceased EPP patients were reviewed. Eligible patients were invited for screening. RESULTS: Of 6248 patients seen in phase 1, 272 (4.4%) were identified to be EPP. Of the 272 patients, 248 (91.1%) were invited for HCV testing and 24 (8.8%) were deceased. To date, 231 of 248 (93.1%) patients have presented for screening. Two patients (one alive, one deceased) were HCV positive before their EPP. Viral sequence of the surgeon's isolate is unrelated to the first patient; the second individual has a resolved infection (polymerase chain reaction negative). No new transmission events were identified in the screened patients. The 95% CI of the transmission probability was estimated to be 0 to 0.016. INTERPRETATION: HCV transmission from the surgeon during a 38-month look back was unlikely. In the absence of protocols for investigating HCV transmission from infected health care workers, screening was initially prioritized to the highest-risk patients. The investigation has been satisfactorily terminated based on these results.

Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice.

Ghrelin, an orexigenic hormone produced by the stomach, is secreted in anticipation of scheduled meals and in correlation with anticipatory locomotor activity. We hypothesized that ghrelin is directly implicated in stimulating locomotor activity in anticipation of scheduled meals. To test this hypothesis, we observed 24 h patterns of locomotor activity in mice with targeted mutations of the ghrelin receptor gene (GHSR KO) and wild-type littermates, all given access to food for 4 h daily for 14 days. While wild type (WT) and GHSR KO mice produced increases in anticipatory locomotor activity, anticipatory locomotor activity in GHSR KO mice was attenuated (P<0.05). These behavioral measures correlated with attenuated levels of Fos immunoreactivity in a number of hypothalamic nuclei from GHSR KO placed on the same restricted feeding schedule for 7 days and sacrificed at ZT4. Interestingly, seven daily i.p. ghrelin injections mimicked hypothalamic Fos expression patterns to those seen in mice under restricted feeding schedules. These data suggest that ghrelin acts in the hypothalamus to augment locomotor activity in anticipation of scheduled meals.

Selection of natural health products for clinical trials: a preclinical template.

In preparation for a clinical trial on the efficacy of Echinacea products with a pediatric population, a rational method for selection of test products was developed, based on phytochemical and bioassay evaluation. Ten currently available commercial products of Echinacea angustifolia (EA) or Echinacea purpurea (EP) were selected, and 3 bottles of each of 2 different lots were purchased for each product. Investigators were blinded to product identity before phytochemical analysis. Lot-to-lot variation was small, but product variation due to species and formulation was large. Products derived from ethanol extracts had low polysaccharide content and high levels of alkamides (EA), echinacoside (EA), cynarin (EA), cichoric acid (EP), and caftaric acid (EP). These products possessed high antiviral activities that differed between EA and EP products, but limited immune activation properties. In contrast, products derived without ethanol extraction had higher polysaccharide levels, but low levels of other components. These aqueous compounds showed immunostimulant activity as measured in a mouse macrophage model and a somewhat different antiviral profile. The choice of Echinacea product for clinical trial must therefore consider the impact of immune enhancement, the specific viral infection targeted, and the potential to reduce symptoms via antiinflammatory activity. Product selection may also depend on whether the intent of the trial is prophylaxis or treatment.

Drug-induced lupus associated with synthetic conjugated estrogens.

OBJECTIVE: To report a case of drug-induced lupus (DIL) in a patient taking Cenestin, a combination product of synthetic conjugated estrogens. CASE SUMMARY: A 54-year-old white female presented with a 4 month history of bilateral arm pain that developed and progressively worsened after initiating Cenestin 0.625 mg daily. The patient's symptoms, findings on physical examination (eg, degenerative changes of the acromioclavicular joint), and laboratory test results (eg, antinuclear antibody titer 1-640 [normal <1-40]) were suggestive of DIL. Her symptoms rapidly resolved with discontinuation of Cenestin and promptly resumed with reinitiation of the drug. Laboratory test values also improved significantly with discontinuation of Cenestin. Based on these findings and the Naranjo probability scale score, this reaction was probably associated with Cenestin. DISCUSSION: DIL differs from systemic lupus erythematosus in that it is caused by prolonged exposure at adequate doses to a drug rather than being an autoimmune reaction. The most commonly reported and studied medications are hydralazine, quinidine, and procainamide. Other medications have been associated with DIL; however, data are limited in these reports, especially with estrogen. There have been no previous reports in the literature of synthetic estrogen products associated with DIL. CONCLUSIONS: A diagnosis of DIL can be very challenging to make, especially since there are no clear criteria on which to base it. While estrogen has rarely been reported to be associated with DIL, it may be considered as a possible cause.

Restricted access to food, but not sucrose, saccharine, or salt, synchronizes the expression of Period2 protein in the limbic forebrain.

Restricted feeding schedules (RF) in which daily access to food is limited to a few hours each day can entrain the rhythms of expression of circadian clock genes in the brain and periphery in rodents. The critical factors mediating the effect of RF on rhythms of clock gene expression are unknown. Previously, we demonstrated that daytime RF shifts the phase of expression of the clock protein, Period2 (PER2) in the oval nucleus of the bed nucleus of the stria terminalis in rats kept on a 12-h light/dark cycle, and restored the rhythm of PER2 expression in rats housed in constant light. We now report that RF also modifies the rhythms of PER2 expression in the central and basolateral nuclei of the amygdala and in the dentate gyrus, such that all three areas become synchronized, peaking 12 h after the time of food presentation. Daily limited access to sucrose or saccharine in freely fed rats or scheduled access to saline in sodium-deprived rats had no effect on these PER2 rhythms. Thus, it would appear that the rhythms of PER2 in limbic forebrain structures are sensitive to signals that arise from the alleviation of a negative metabolic state associated with scheduled feeding and that access to rewarding substances in the absence of food deprivation or metabolic challenges, per se, is not sufficient to alter the rhythms of PER2 expression in these regions.

Daily restricted feeding rescues a rhythm of period2 expression in the arrhythmic suprachiasmatic nucleus.

Second only to light, daily restricted feeding schedules can entrain circadian rhythms in mammals [Neurosci Biobehav Rev 4 (1980) 119; J Biol Rhythms 17 (2002) 284]. Contrary to light, however, such feeding schedules have been found not to affect the master circadian clock in the suprachiasmatic nucleus (SCN) [Genes Dev 14 (2000) 2950; Eur J Neurosci 13 (2001) 1190]. Here, we show that in rats that are arrhythmic as a consequence of prolonged housing in constant light, a daily restricted feeding schedule not only restores behavioral rhythmicity, as previously shown [Physiol Behav 53 (1993) 509], but in addition, induces a rhythm of the clock protein, Period2 in the SCN. These findings challenge the idea that the SCN is invulnerable to feeding schedules and call for a reevaluation of the role of the SCN clock in the circadian effects of such schedules.

Prognostic disclosure to patients with cancer near the end of life.

BACKGROUND: Patients' understanding of their prognosis informs numerous medical and nonmedical decisions, but patients with cancer and their physicians often have disparate prognostic expectations. OBJECTIVE: To determine whether physician behavior might contribute to the disparity between patients' and physicians' prognostic expectations. DESIGN: Prospective cohort study. SETTING: Five hospices in Chicago, Illinois. PATIENTS: 326 patients with cancer. INTERVENTION: Physicians formulated survival estimates and also indicated the survival estimates that they would communicate to their patients if the patients insisted. MEASUREMENTS: Comparison of the formulated and communicated prognoses. RESULTS: For 300 of 311 evaluable patients (96.5%), physicians were able to formulate prognoses. Physicians reported that they would not communicate any survival estimate 22.7% (95% CI, 17.9% to 27.4%) of the time, would communicate the same survival estimate they formulated 37% (CI, 31.5% to 42.5%) of the time, and would communicate a survival estimate different from the one they formulated 40.3% (CI, 34.8% to 45.9%) of the time. Of the discrepant survival estimates, most (70.2%) were optimistically discrepant. Multivariate analysis revealed that older patients were more likely to receive frank survival estimates, that the most experienced physicians and the physicians who were least confident about their prognoses were more likely to favor no disclosure over frank disclosure, and that female physicians were less likely to favor frank disclosure over pessimistically discrepant disclosure. CONCLUSIONS: Physicians reported that even if patients with cancer requested survival estimates, they would provide a frank estimate only 37% of the time and would provide no estimate, a conscious overestimate, or a conscious underestimate most of the time (63%). This pattern may contribute to the observed disparities between physicians' and patients' estimates of survival.

Chemotherapy in the management of squamous-cell carcinoma of the head and neck.

Previously reserved for palliation, chemotherapy is now also a central component of several curative approaches to the management of patients with advanced-stage head and neck cancer. Here we review the results of both induction chemotherapy and chemoradiotherapy trials in patients with curable disease, and chemotherapy trials in patients with recurrent and metastatic disease, and we highlight current areas of investigation. Compared with traditional treatment modalities, chemotherapy given on induction schedules to patients with advanced laryngeal cancer allows greater organ preservation without compromise to survival; when given concomitantly with radiotherapy to patients with resectable or unresectable advanced disease, chemotherapy again improves survival.

Extent and determinants of error in doctors' prognoses in terminally ill patients: prospective cohort study.

OBJECTIVE: To describe doctors' prognostic accuracy in terminally ill patients and to evaluate the determinants of that accuracy. DESIGN: Prospective cohort study. SETTING: Five outpatient hospice programmes in Chicago. PARTICIPANTS: 343 doctors provided survival estimates for 468 terminally ill patients at the time of hospice referral. MAIN OUTCOME MEASURES: Patients' estimated and actual survival. RESULTS: Median survival was 24 days. Only 20% (92/468) of predictions were accurate (within 33% of actual survival); 63% (295/468) were overoptimistic and 17% (81/468) were overpessimistic. Overall, doctors overestimated survival by a factor of 5.3. Few patient or doctor characteristics were associated with prognostic accuracy. Male patients were 58% less likely to have overpessimistic predictions. Non-oncology medical specialists were 326% more likely than general internists to make overpessimistic predictions. Doctors in the upper quartile of practice experience were the most accurate. As duration of doctor-patient relationship increased and time since last contact decreased, prognostic accuracy decreased. CONCLUSION: Doctors are inaccurate in their prognoses for terminally ill patients and the error is systematically optimistic. The inaccuracy is, in general, not restricted to certain kinds of doctors or patients. These phenomena may be adversely affecting the quality of care given to patients near the end of life.

Extent and determinants of error in physicians' prognoses in terminally ill patients: prospective cohort study.

Objectives To describe physicians' prognostic accuracy in terminally ill patients and to evaluate the determinants of that accuracy. Design Prospective cohort study. Setting Five outpatient hospice programs in Chicago. Participants A total of 343 physicians provided survival estimates for 468 terminally ill patients at the time of hospice referral. Main outcome measures Patients' estimated and actual survival. Results Median survival was 24 days. Of 468 predictions, only 92 (20%) were accurate (within 33% of actual survival); 295 (63%) were overoptimistic, and 81 (17%) were overpessimistic. Overall, physicians overestimated survival by a factor of 5.3. Few patient or physician characteristics were associated with prognostic accuracy. Male patients were 58% less likely to have overpessimistic predictions. Medical specialists excluding oncologists were 326% more likely than general internists to make overpessimistic predictions. Physicians in the upper quartile of practice experience were the most accurate. As the duration of the doctor-patient relationship increased and time since last contact decreased, prognostic accuracy decreased. Conclusions Physicians are inaccurate in their prognoses for terminally ill patients, and the error is systematically optimistic. The inaccuracy is, in general, not restricted to certain kinds of physicians or patients. These phenomena may be adversely affecting the quality of care given to patients near the end of life.

Paradoxes in cancer patients' advance care planning.

PURPOSE: To determine the frequency of advance care planning (ACP) in hospitalized cancer patients and to assess their reactions to a proposed policy in which medical housestaff would offer to discuss ACP at the time of hospital admission. METHODS: Structured interviews with 111 consecutively admitted cancer patients on the oncology inpatient service of a tertiary care medical center. RESULTS: We found that 69% (77/111) of patients had discussed their advance care preferences with someone, usually a family member, and 33% (37/111) had completed at least one formal advance directive (e.g., a living will or durable power of attorney for health care); 32% (36/111) had done both; and 30% (33/111) had done neither. However, only 9% (10/111) of patients reported having discussed their advance care preferences with their clinic oncologists and only 23% (23/101) of the remaining patients stated that they wished to do so. By contrast, 58% (64/110) of patients supported a policy in which medical housestaff would offer to discuss these advance care preferences as a part of the admission history. CONCLUSIONS: Our data suggest that while oncology inpatients frequently have ACPs that they discuss with family and/or document in formal advance directives, they rarely discuss or wish to discuss these ACPs with clinic oncologists. We also show that most of the reticent patients would nevertheless consider discussing the same ACPs with admitting housestaff on the day of hospital admission.

Some elements of prognosis in terminal cancer.

Predicting the survival of terminal cancer patients is a difficult task. To better understand this difficulty, we divide prognostication into two distinct elements: foreseeing and foretelling. Foreseeing is a physician's silent cognitive estimate about a patient's illness. Foretelling is the physician's communication of that prediction to the patient or significant others. In this article, we review the impact of each element of prognosis on physicians' overall prognostic accuracy. We show that physicians often make unwitting, large, and generally optimistic errors in foreseeing patients' prognoses. They also may make more conscious, but equally large, optimistic errors in foretelling prognoses to patients. The net effect is that patients may become twice removed from the truth about their illness, both times toward a falsely optimistic prognosis. We also describe the possible consequences of these optimistic prognostic errors. Finally, we review techniques that may improve physicians' prognostic accuracy. We conclude that part of the challenge of providing humane, compassionate end-of-life care to cancer patients may involve accurately foreseeing and foretelling their prognoses.