Neuromuscular fatigue and recovery after strenuous exercise depends on skeletal muscle size and stem cell characteristics.

Hamstring muscle injury is highly prevalent in sports involving repeated maximal sprinting. Although neuromuscular fatigue is thought to be a risk factor, the mechanisms underlying the fatigue response to repeated maximal sprints are unclear. Here, we show that repeated maximal sprints induce neuromuscular fatigue accompanied with a prolonged strength loss in hamstring muscles. The immediate hamstring strength loss was linked to both central and peripheral fatigue, while prolonged strength loss was associated with indicators of muscle damage. The kinematic changes immediately after sprinting likely protected fatigued hamstrings from excess elongation stress, while larger hamstring muscle physiological cross-sectional area and lower myoblast:fibroblast ratio appeared to protect against fatigue/damage and improve muscle recovery within the first 48 h after sprinting. We have therefore identified novel mechanisms that likely regulate the fatigue/damage response and initial recovery following repeated maximal sprinting in humans.

HB-EGF is produced in the peritoneal cavity and enhances mesothelial cell adhesion and migration.

BACKGROUND: The mesothelial cell monolayer lining the peritoneal membrane needs constant repair in response to peritonitis and to the toxicity of peritoneal dialysate. In many continuous ambulatory peritoneal dialysis (CAPD) patients, the repair process progressively fails, and membrane dysfunction and fibrosis occur. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has an important role in wound repair and is also fibrogenic, and thus may be involved in these processes in the peritoneal cavity. METHODS: The presence of HB-EGF, its receptors, and its associated proteins was determined in peritoneal membrane biopsies, cultured human peritoneal mesothelial cells (HPMCs), and peritoneal macrophages from CAPD patients by reverse transcription-polymerase chain reaction, flow cytometry, and immunofluorescence immunocytochemistry with confocal microscopy. HB-EGF effects on HPMC adhesion were measured by a static adhesion assay, on integrin expression by flow cytometry, and on migration by wound healing and chemotaxis assays. RESULTS: HB-EGF, its receptors HER-1 and HER-4, and the associated proteins CD9, CD44, and integrin alpha(3)beta(1) were expressed by HPMCs and peritoneal macrophages. HB-EGF colocalized with HER-1 and HER-4 in HPMCs and induced their adhesion to collagen type I, expression of beta 1 integrins, and migration. CONCLUSIONS: HB-EGF is produced by cells in the peritoneal cavity of CAPD patients and has functional effects on HPMCs that would facilitate repair of the mesothelial layer.

Expression of defensin antimicrobial peptides in the peritoneal cavity of patients on peritoneal dialysis.

OBJECTIVE: To investigate the expression and regulation of defensins in the peritoneal cavity of peritoneal dialysis (PD) patients. DESIGN: The presence of defensins in the peritoneal cavity was assessed using reverse transcription polymerase chain reaction (RT-PCR). In vivo defensin expression was analyzed in human peritoneal membrane biopsies and in peritoneal cavity leukocytes isolated from spent dialysate. Defensin expression in vitro was assessed in cultured human peritoneal mesothelial cells (HPMC) and confirmed with PCR Southern blot and DNA sequencing. The effect of tumor necrosis factor alpha (TNFalpha) and epidermal growth factor (EGF) on beta2 defensin expression in HPMC was analyzed by Northern blot analysis and RT-PCR respectively. RESULTS: Both alpha and beta classes of defensins are expressed in the peritoneal cavity of PD patients. Messenger RNA for the alpha-defensin human neutrophil peptide 3 and for beta-defensin-1 (hbetaD-1) were found in preparations containing predominantly peritoneal leukocytes, whereas beta-defensin-2 (hbetaD-2) is expressed by HPMC. HPMC isolated from different individuals displayed variability in both basal hbetaD-2 expression and in response to stimulation by TNFalpha. Conversely, EGF consistently downregulated the level of hbetaD-2 message in HPMC. CONCLUSION: Alpha- and beta-defensins are expressed in the peritoneal cavity, and hbetaD-2 is the main defensin present in the peritoneal membrane. Variable levels of expression of hbetaD-2 by mesothelial cells were seen, with evidence of regulation by cytokines and growth factors. This provides evidence for a previously unknown mechanism of innate immunity at that site.

Evidence-based guidelines for teaching patient-centered interviewing.

In a rare study of effectiveness of an interviewing method, we previously reported a randomized controlled trial demonstrating that training in a step-by-step patient-centered interviewing method improved residents' knowledge, attitudes, and skills and had a consistently positive effect on trained residents' patients. For those who wish to use this evidence-based patient-centered method as a template for their own teaching, we describe here for the first time our training program--and propose that the training can be adapted for students, physicians, nurse practitioners, physician assistants, and other new learners as well. Training was skills-oriented and experiential, fostered positive attitudes towards patient-centered interviewing, and used a learner-centered approach which paid special attention to the teacher-resident relationship and to the resident's self-awareness. Skills training was guided by a newly identified patient-centered interviewing method that described the step-by-step use of specific behaviors.

Epidermal growth factor modifies the expression and function of extracellular matrix adhesion receptors expressed by peritoneal mesothelial cells from patients on CAPD.

BACKGROUND: Efficient peritoneal dialysis depends on an intact layer of mesothelial cells that line the peritoneal membrane. This layer is disrupted in patents on continuous ambulatory peritoneal dialysis during episodes of peritonitis (acute injury) and replaced by fibrous tissue during extended dialysis (chronic injury). Little is understood of human peritoneal mesothelial cell (HPMC) responses to wounding and episodes of peritonitis. METHODS: HPMC were harvested from spent peritoneal dialysis effluent and maintained under defined in vitro conditions. Adhesive interactions with extracellular matrix (ECM) molecules and chemotactic and wound-healing responses were measured in vitro using purified ECM molecules. RESULTS: HPMC express multiple functional cell receptors recognizing and binding to ECM molecules, including several members of the integrin family. HPMC exhibit directed migration in wound healing and chemotaxis assays with ECM molecules. Epidermal growth factor (EGF) stimulates a reversible change to a fibroblastic phenotype, accompanied by increased expression of beta1 integrins, particularly alpha2beta1, increased adhesion to type I collagen, and significantly greater HPMC migration on type I collagen in wound healing and chemotaxis assays. CONCLUSIONS: HPMC possess the migratory capacity to contribute to the efficient repair of damaged peritoneal membrane after acute injury, and growth factors, such as EGF, facilitate peritoneal membrane healing by augmenting cell adhesion and migration.

The effectiveness of intensive training for residents in interviewing. A randomized, controlled study.

BACKGROUND: Interviewing and the physician-patient relationship are crucial elements of medical care, but residencies provide little formal instruction in these areas. OBJECTIVE: To determine the effects of a training program in interviewing on 1) residents' attitudes toward and skills in interviewing and 2) patients' physical and psychosocial well-being and satisfaction with care. DESIGN: Randomized, controlled study. SETTING: Two university-based primary care residencies. PARTICIPANTS: 63 primary care residents in postgraduate year 1. INTERVENTION: A 1-month, full-time rotation in interviewing and related psychosocial topics. MEASUREMENTS: Residents and their patients were assessed before and after the 1-month rotation. Questionnaires were used to assess residents' commitment to interviewing and psychosocial medicine, estimate of the importance of such care, and confidence in their ability to provide such care. Knowledge of interviewing and psychosocial medicine was assessed with a multiple-choice test. Audiotaped interviews with real patients and videotaped interviews with simulated patients were rated for specific interviewing behaviors. Patients' anxiety, depression, and social dysfunction; role limitations; somatic symptom status; and levels of satisfaction with medical visits were assessed by questionnaires and telephone interviews. RESULTS: Trained residents were superior to untrained residents in knowledge (difference in adjusted post-test mean scores, 15.7% [95% CI, 11% to 20%]); attitudes, such as confidence in psychological sensitivity (difference, 0.61 points on a 7-point scale [CI, 0.32 to 0.91 points]); somatization management (difference, 0.99 points [CI, 0.64 to 1.35 points]); interviewing of real patients (difference, 1.39 points on an 11-point scale [CI, 0.32 to 2.45 points]); and interviewing (data gathering) of simulated patients (difference, 2.67 points [CI, 1.77 to 3.56 points]). Mean differences between the study groups were consistently in the appropriate direction for patient satisfaction and patient well-being, but effect sizes were too small to be considered meaningful. CONCLUSION: An intensive 1-month training rotation in interviewing improved residents' knowledge about, attitudes toward, and skills in interviewing.

Medical ethics--when to stop treatment.

Several misunderstandings regarding the question of when to stop treatment are examined by considering two frameworks for sorting out the different dimensions of the question. One framework addresses what is meant, and what is not meant, by 'stopping treatment'. The other plots various strategies of stopping treatment on a continuum of increasing degrees of invasiveness. While significant disagreements remain at important points, there is evidence of an emerging consensus in Western medicine: (1) that palliative care and counselling through the dying process should be increased whenever curative or life-sustaining treatment is curtailed; (ii) that any treatment that is not curative, but merely life-sustaining, should be stopped whenever a patient makes an authentic request to have it stopped; (iii) that genuinely futile treatment should not be offered even if requested; (iv) that much more thought and discussion is required to achieve a workable agreement about the definitions of 'futile' and 'inappropriate' treatment; and (v) that assistance in dying, although profoundly problematic, is no longer unthinkable.

Painful thyroid gland: an atypical presentation of Graves' disease.

An adolescent with Graves' disease presented with acute painful swelling of the thyroid gland and overlying erythema simulating acute suppurative or subacute thyroiditis. She had an elevated radioactive iodine uptake, thyroid stimulating antibodies, thyrotrophin binding inhibiting immunoglobulins, and a normal sedimentation rate and leucocyte count. The course of the thyrotoxicosis and painful thyroid was protracted, and the pain and tenderness of the thyroid recurred on two subsequent relapses.

The Appleton Consensus: suggested international guidelines for decisions to forego medical treatment.

Thirty-three physicians, bioethicists, and medical economists from ten different countries met at Lawrence University, Appleton, Wisconsin, to create The Appleton Consensus: International Guidelines for Decisions to Forego Medical Treatment. The guidelines deal with four specific decision-making circumstances: 1. Five guidelines were created for decisions involving competent patients or patients who have executed an advance directive before becoming incompetent, and those guidelines fell into three categories. 2. Thirteen guidelines were created for decisions involving patients who were once competent, but are not now competent, who have not executed an advance directive. 3. Seven guidelines were created for decisions involving patients who are not now and never have been competent, for whom 'no substituted judgement' can be rendered. 4. Eleven guidelines were created for decisions involving the scarcity of medical resources, which exists in all communities. Five concepts were identified as being critical in the establishment of priorities, given the reality of scarce health resources (1). The term 'physician' is used in the American sense, synonymous with 'medical practitioner'.

Deterioration of semen quality during summer in New Orleans.

A retrospective investigation of semen quality was undertaken at a fertility clinic in New Orleans. Semen specimens obtained during the summer had significantly lower sperm concentration, total sperm per ejaculate, percent motile sperm, and motile sperm concentration than samples provided at other times of year. Substantial summer deterioration in semen quality was likely to occur only among men whose work places were probably not air-conditioned. These findings suggest that the deleterious effects of summer heat on spermatogenic cells or on epididymal spermatozoa may reduce male fertility and account, at least partially, for the deficit of spring births in warm climates throughout the world.

More fiddling with the definition of death?

KIE: Stanley contends that G.R. Gillett, in the last paragraph of an otherwise excellent article, "Why let people die?" (Journal of Medical Ethics 1986 Jun; 12(2): 83-86), is "fiddling about" with the definition of death when he argues that the patient in a persistent vegetative state is, in an ethical sense, no longer alive as a person; that what remains is a body in which the former patient has no futher interest. Stanley maintains that the determination of the nonreversibility of decortication is uncertain while brain stem death is not reversible. Furthermore, decorticate patients are still biologically alive and decisions concerning their treatment and who makes the decisions are important questions for the medical profession and for society to address. The author concludes that these problems should not be solved by extending the definition of death to include neocortical death.^ieng

Heart disease in workers exposed to dinitrotoluene.

To determine whether the carcinogenicity of dinitrotoluene (DNT) in rodent bioassays was predictive for humans, we examined the mortality experience of exposed workers at two ammunition plants. Cohorts of 156 and 301 men who had worked a month or more during the 1940s and 1950s at jobs with opportunity for substantial DNT exposure were followed through the end of 1980. Numbers of expected deaths and standardized mortality ratios (SMRs) were computed, using mortality rates of US white males as the standard. No evidence of a carcinogenic effect was found, but unsuspected excesses of mortality from ischemic heart disease were noted at both plants (SMRs) 131 and 143; 95% confidence limits 65 to 234 and 107 to 187, respectively). Deaths from ischemic heart disease remained high even when compared with expected numbers derived using mortality rates of the counties in which the plants were located. Additional analyses revealed evidence of a 15-year latent period and suggested a relationship with duration and intensity of exposure. Epidemiologic investigations of other heavily exposed populations are needed to confirm the etiologic significance of the association between DNT and heart disease described here.

The effects of short term flotation REST on relaxation: a controlled study.

The purpose of this study was to compare the effects of restricted environmental stimulation using a flotation tank (Flotation REST) to the effects of a normal sensory environment on relaxation. All of the subjects were first introduced to a simple relaxation program to be used during the experimental sessions. The program consisted of guided point-to-point relaxation, breathing techniques, and visual imagery techniques. Subjects were then pre-tested on measurements of electromyogram (EMG), galvanic skin response (GSR), peripheral skin temperature, and systolic and diastolic blood pressure. The experimental group experienced ten 45-minute sessions practicing the relaxation program in a Flotation REST environment. The control subjects practiced the same relaxation program in a similar body position for 45 minutes in a normal sensory environment. All subjects answered a five-question Subjective Relaxation Questionnaire on trials five through ten and were then post-tested on EMG, GSR, skin temperature, and blood pressure. The results indicated significant differences between groups from pre-test to post-test on systolic and diastolic blood pressure; the experimental group showed greater reductions. Significant differences also were observed on three of five questions on the Subjective Relaxation Questionnaire; the experimental group reported greater subjective relaxation and trends in a similar direction on the remaining two questions. The results of this study indicate that flotation REST enhances point-to-point relaxation, breathing techniques, and visual imagery techniques and, when combined with these techniques, can be an effective means of teaching normal subjects to lower systolic and diastolic pressure and heighten their subjective perception of relaxation.