Effects of cholinergic stimulation on pituitary hormone release

Physostigmine was infused into human volunteers to assess the effect of central cholinergic stimulation on memory and on neuroendocrine function. Methscopolamine bromide, a peripheral anticholinergic agent, was given simultaneously. The lower dose of physostigmine (1.0 mg) produced no change in AVP, cortisol, melatonin, GH or LH in those subjects without unpleasant cholinergic side effects. Larger doses of physostigmine usually produced nausea, and were associated with marked elevations of AVP, cortisol and prolactin, but no change in GH, LH or melatonin. Thus, cholinergic agents easily induce a stress response, but the GH component of this response can be suppressed by peripheral cholinergic blockade.     

Acute Metabolic Effects of Nitrogen Mustard and Thiotepa on Rabbit Articular Cartilage and Synovium

Metabolic alterations in immature rabbit joint tissues were examined following in vitro and in vivo exposure to the alkylating agents Thiotepa and nitrogen mustard. Brief exposure in vitro to either agent resulted in marked suppression of incorporation of radiolabeled precursors of protein, RNA, and glycosaminoglycan synthesis in articular cartilage, which was partially reversible after Thiotepa exposure. In vivo, nitrogen mustard had little effect on synovium and transient inhibitory effects on cartilage vital processes, whereas Thiotepa caused a prolonged inhibition of synovial metabolism with little effect on cartilage. Autoradiographic localization of labeled agents indicated that synovial tissue and cartilage were readily penetrated by nitrogen mustard, but only a few synovial lining cells and superficial chondrocytes were labeled with ³⁵S-Thiotepa. Furthermore, trypsin significantly reduced labeling of cartilage with ¹⁴C-nitrogen mustard. These data suggest that alkylating agents differentially affect metabolic processes in joint tissues in vivo and that with Thiotepa, this interference occurs primarily in the synovium. The degree of interference is apparently dependent upon time of exposure to the agents and the relative DNA-RNA synthetic activity of the joint tissue.     

Great Names in American Medical History

This is one of a series of biographic sketches of outstanding physicians of the past from each of the 50 states. The subjects have been selected by the medical society of each state or its designated committee.     

What are the experiences of adults returning to work following recovery from Guillain-Barré syndrome? An interpretative phenomenological analysis

Purpose.?Guillain-Barré syndrome (GBS) is a transient inflammatory disorder affecting peripheral nerves, characterised by weakness and numbness in limbs, upper body and face. Residual problems affect a large minority, and complicate return to work. This qualitative study explored the experiences of people who returned to work following their diagnosis of GBS and recovery, to gain insight into factors that facilitated or inhibited this process.

Method.?Five people participated in in-depth interviews. Individual and common experiences were explored through interpretative phenomenological analysis.

Findings.?Three recurring themes are presented: the perceived value of work; losing and recovering a familiar identity at work; and dilemmas around using support and adaptations at work. Certain individual issues also emerged but are beyond the scope of this article. Participants tended to measure their recovery in terms of returning to work yet continued to experience certain physical and psychosocial difficulties at work related to GBS, which required active coping strategies. Limited public awareness of GBS was perceived as a hindrance when returning to work.

Conclusion.?This study provides a rich account of the experiences that people encounter returning to work following GBS. Rehabilitation specialists may offer more effective preparation for this process, drawing upon the issues identified.     

Biophysical Regulation of Stem Cell Differentiation

Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells—the most broadly studied source of osteoblastic progenitors—undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.     

New options for the treatment of obesity and type 2 diabetes mellitus (narrative review)

Moderate weight loss (> 5%), which has been associated with improvements in glycemic parameters in patients with dysglycemia, also reduces the presence of other comorbidities, including dyslipidemia and hypertension, culminating in a reduced risk of cardiovascular disease. Lifestyle changes are the recommended preliminary approach to weight loss, with an initial weight-loss goal of 10% of body weight achieved over 6 months at a rate of 1–2 pounds per week selected as an appropriate target to decrease the severity of obesity-related risk factors. Implementing and maintaining the lifestyle changes associated with weight loss can, however, be challenging for many patients. Therefore, additional interventions sometimes may be necessary. Bariatric surgery can also be a highly effective option for weight loss and comorbidity reduction, but surgery carries considerable risks and is still applicable only to selected patients with type 2 diabetes. Thus, attention is turning to the use of weight-loss medications, including 2 recently approved compounds: twice-daily lorcaserin and a once-daily combination of phentermine and topiramate extended-release, both shown to be safe and effective therapies in the management of obesity in patients with type 2 diabetes.     

Development of the patient approach and views toward healthcare communication (PAV-COM) measure among older adults

ABSTRACT: BACKGROUND: This study examines the psychometric properties of 9 items on the Patient Activation component of the Medicare Current Beneficiary Survey (MCBS) that assess how patients approach and communicate with their physicians. The MCBS is a nationally representative, cross-sectional survey of Medicare beneficiaries. METHODS: We analyzed MCBS data collected in 2002 and 2005 from 15,165 adults aged 65 and older. Exploratory factor analysis was conducted using maximum likelihood to estimate a polychoric correlation matrix on the 2002 data, and confirmatory factor analysis was performed using the 2005 data. RESULTS: Exploratory factor analysis of the 2002 data showed a 2-factor solution: approach to interactions (5 items) and views about physician's healthcare communication (6 items). Findings were confirmed using the 2005 data. Items were combined to form the Patient Approach and Views toward Healthcare Communication (PAV-COM) scale (range 1 to 100; Cronbach's alpha of 0.75, and item-rest correlations between 0.33 and 0.54). Higher PAV-COM scores were associated with greater fulfillment of preventive health behaviors such as vaccinations and cancer screenings. CONCLUSIONS: The PAV-COM measure is a valid tool for assessing patient approaches and views toward communication with physicians. This measure can be used to evaluate interventions to improve patient participation during healthcare encounters.     

Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era

Staphylococcus aureus is the leading cause of bacterial infections in developed countries and produces a wide spectrum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Although S. aureus infections were historically treatable with common antibiotics, emergence of drug-resistant organisms is now a major concern. Methicillin-resistant S. aureus (MRSA) was endemic in hospitals by the late 1960s, but it appeared rapidly and unexpectedly in communities in the 1990s and is now prevalent worldwide. This Review focuses on progress made toward understanding the success of community-associated MRSA as a human pathogen, with an emphasis on genome-wide approaches and virulence determinants.