Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis

OBJECTIVE: Electrical vagus nerve stimulation inhibits proinflammatory cytokine production and prevents shock during lethal systemic inflammation through an alpha7 nicotinic acetylcholine receptor (alpha7nAChR)-dependent pathway to the spleen, termed the cholinergic anti-inflammatory pathway. Pharmacologic alpha7nAChR agonists inhibit production of the critical proinflammatory mediator high mobility group box 1 (HMGB1) and rescue mice from lethal polymicrobial sepsis. Here we developed a method of transcutaneous mechanical vagus nerve stimulation and then investigated whether this therapy can protect mice against sepsis lethality. DESIGN: Prospective, randomized study. SETTING: Institute-based research laboratory. SUBJECTS: Male BALB/c mice. INTERVENTIONS: Mice received lipopolysaccharide to induce lethal endotoxemia or underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive electrical, transcutaneous, or sham vagus nerve stimulation and were followed for survival or euthanized at predetermined time points for cytokine analysis. MEASUREMENTS AND MAIN RESULTS: Transcutaneous vagus nerve stimulation dose-dependently reduced systemic tumor necrosis factor levels during lethal endotoxemia. Treatment with transcutaneous vagus nerve stimulation inhibited HMGB1 levels and improved survival in mice with polymicrobial sepsis, even when administered 24 hrs after the onset of disease. CONCLUSIONS: Transcutaneous vagus nerve stimulation is an efficacious treatment for mice with lethal endotoxemia or polymicrobial sepsis.     

Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava

Kava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125 to 2 g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1 g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment- related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions.     

Return to youth with Sox17

Maturation of hematopoietic stem cells (HSCs) from fetal to adult state and differentiation to progenitors are thought to follow a one-way street. In this issue of Genes & Development, He and colleagues (pp. 1613-1627) show that overexpression of Sox17 can convert adult multipotential progenitors to self-renewing HSCs that possess fetal properties. These findings challenge the irreversibility of hematopoietic development, and open up new perspectives to understand the different forms of HSC self-renewal at distinct stages of ontogeny and during transformation.     

A health economic analysis of the use of rhBMP-2 in Gustilo–Anderson grade III open tibial fractures for the UK, Germany, and France

The purpose of this study was to determine the cost savings from a societal perspective for recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III A and B open tibial fractures treated with a locked intramedullary nail and soft-tissue management in the UK, Germany, and France. Health care system costs (direct health care costs) and costs for productivity losses (indirect health care costs) were calculated using the raw data from the Bone Morphogenetic Protein Evaluation Group in Surgery for Tibial Trauma “BESTT study”. Return-to-work time for estimation of productivity losses was assumed to correspond with the time of fracture healing. For calculation of secondary interventions costs and productivity losses the respective 2007/2008 national tariffs for surgical procedures and average national wages for the UK, Germany, and France were used. For a 1 year perspective, overall treatment costs per patient after the initial surgery of the control vs. the rhBMP-2 group were €44,757 vs. €36,847 for the UK, €50,197 vs. €40,927 for Germany and €48,766 vs. €39,474 for France in favour of rhBMP-2 with overall savings overall savings per case of rhBMP-2 treatment of €7911 for the UK, €9270 for Germany, and €9291 for France which was mainly due to reduced productivity losses by significant faster fracture healing in the rhBMP-2 group (p = 0.01). These savings largely offset the upfront price of rhBMP-2 of €2266 (£1790) in the UK, €2970 in Germany, and €2950 in France. Total net savings can be estimated to be €9.6 million for the UK, €14.5 million for Germany, and €11.4 million for France. The results depend on the methodology used particularly for calculation of productivity losses and return-to-work time which was assumed to correspond with fracture healing time. In summary, despite the apparent high direct cost of rhBMP-2 in grade III A and B open tibial fractures, at a national level there are net cost savings from a societal perspective for all three countries.     

Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls

CONTEXT: Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear. OBJECTIVE: The objective of the study was to assess the degree of hyperandrogenemia across puberty in obese girls and assess overnight sex steroid changes in Tanner stage 1-3 girls. DESIGN: This was a cross-sectional analysis. SETTING: The study was conducted at general clinical research centers. SUBJECTS: Thirty normal-weight (body mass index for age < 85%) and 74 obese (body mass index for age >or= 95%) peripubertal girls. INTERVENTION: Blood samples (circa 0500-0700 h) were taken while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1-3 girls. MAIN OUTCOME MEASURES: Hormone concentrations stratified by Tanner stage were measured. RESULTS: Compared with normal-weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, whereas fasting insulin was 3-fold elevated in obese Tanner 1-3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05) but not in more mature girls. In a subgroup of normal-weight Tanner 1-3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P 相似文献   

Tumor-induced osteomalacia

Tumor-induced osteomalacia, also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome in which vitamin D resistant osteomalacia occurs due to the presence of a tumor. The following case report describes a young woman who seeks a second opinion from a rheumatologist and is found to have oncogenic osteomalacia. Not often discussed in the rheumatology literature, oncogenic osteomalacia is a rare and interesting disease entity in which diagnosis is often more challenging than treatment.     

Care of post-traumatic spinal cord injury patients in India: An analysis

Background:

The spinal cord injured patients if congregated early in spinal units where better facilities and dedicated expert care exist the outcome of treatment and rehabilitation, can be improved. The objective of this study is to find out the various factors responsible for a delay in the presentation of spinal injury patients to the specialized spinal trauma units and to suggest steps to improve the quality of care of the spinal trauma patients in the Indian setup.

Materials and Methods:

Sixty patients of traumatic spinal cord injury admitted for rehabilitation between August 2005 and May 2006 were enrolled into the study and their data was analyzed.

Results:

Eighty-five per cent of the spinal cord injured patients were males and the mean age was 34 years (range 13-56 years). Twenty-nine (48.33%) of the spinal injuries occurred due to fall from height. There was an average of 45 days (range 0-188 days) of delay in presentation to a specialized spinal unit and most of the time the cause for the delay was unawareness on the part of patients and/or doctors regarding specialized spinal units. In 38 (62.5%) cases the mode of transportation of the spinal cord injured patient to the first visited hospital was by their own conveyance and the attendants of the patients did not have any idea about precautions essential to prevent neurological deterioration. Seventeen (28.33%) patients were given injection solumedrol with conservative treatment, 35 (60%) patients were given only conservative treatment and seven patients were operated (11.66%) upon at initially visited hospital. Of the seven patients operated five were fixed with posterior Harrington instrumentation (71.42%) and two (28.57%) were operated by short segment posterior pedicle screw fixation. None of the patients were subjected to physiotherapy-assisted transfers or wheel chair skills or even basic postural training, proper bladder/ bowel training program and sitting balance.

Conclusion:

Awareness on the part of the general population, attendants of the patients, clinical and paraclinical team regarding spinal cord injury needs to be addressed. Safe mode of transportation of spinal cord injured patient and early presentation at tertiary spinal care center with comprehensive spinal trauma care team should be stressed upon.     

Clinical prediction of survival by surgeons for patients with incurable abdominal malignancy

Background and aim

Accurate prognosis facilitates decision-making and counselling in incurable cancer. However, predictions of survival are frequently inaccurate and survival is consistently overestimated. The prognostic skills of surgeons are sparsely documented, and the present study was undertaken to assess their prognostic accuracy for patients with advanced abdominal malignancy.

Patients and methods

Clinical predictions of survival were made by three consultant surgeons independently in consecutive patients with incurable abdominal cancer. Survival was predicted in intervals ranging from <1 week to 18-24 months. Prognoses were considered accurate when actual survival fell within the expected range. Performance status was classified according to the Eastern Cooperative Oncology Group (ECOG).

Results

243 assessments were made in 178 patients. Prognoses were accurate in 27%, over-optimistic in 42% and over-pessimistic in 31%. Accuracy was inversely related to length of actual survival and did not differ between surgeons (P = 0.466). The proportion of over-optimistic prognoses differed significantly between surgeons (P < 0.001). Prognostic accuracy was 44% in gastric cancer patients, 29% in pancreatic cancer patients and 22% in colorectal cancer patients (P = 0.052). ECOG performance status correlated well with survival.

Conclusions

Surgeons’ accuracy in determining prognosis is poor. There are considerable individual differences between surgeons, and accuracy is reduced in cases with prolonged life expectancy.     

Microteaching in dental education

Health professionals acknowledge that their education does not prepare them for teaching. However, society's increasingly high expectations of them demand that they be taught teaching techniques/skills and trained effectively. Microteaching is a teaching-simulation exercise that will provide immediate supportive feedback. It can be useful in honing soft emotional intelligence skills, presentation skills, and interpersonal skills. This focused approach encourages growth through practice and critique. The "teach, critique, reteach" model gives the faculty member immediate feedback and increases retention by providing an opportunity to learn good teaching values.     

Pelvic tuberculosis continues to be a disease of dilemma--case series

Tuberculosis (TB) has become a global epidemic again with emergence of HIV/AIDS and multi-drug resistant strains of TB. Female genital tuberculosis (GT) is typically a disease of young women and its occurrence in post menopausal women is rare. Amongst the genital disorders, GT is the most baffling especially because of its various presentations. So GT is notorious for evading diagnosis. A series of cases of females GT between the age 25 yrs to 40 yrs is being reported with women having spectrum of clinical features, creating diagnostic dilemma and so final diagnosis by histopathology after laparotomy. So a high degree of suspicion aided by intensive investigations may be required for the diagnosis of GT. Medical therapy is the main treatment, however some do need surgery. Research needs to be continued for early establishment of timely diagnosis of GT and modalities of effective therapies.