Biophysical cues enhance myogenesis of human adipose derived stem/stromal cells.

Adipose-derived stem/stromal cell (ASC)-based tissue engineered muscle grafts could provide an effective alternative therapy to autografts - which are limited by their availability - for the regeneration of damaged muscle. However, the current myogenic potential of ASCs is limited by their low differentiation efficiency into myoblasts. The aim of this study was to enhance the myogenic response of human ASCs to biochemical cues by providing biophysical stimuli (11% cyclic uniaxial strain, 0.5 Hz, 1h/day) to mimic the cues present in the native muscle microenvironment. ASCs elongated and fused upon induction with myogenic induction medium alone. Yet, their myogenic characteristics were significantly enhanced with the addition of biophysical stimulation; the nuclei per cell increased approximately 4.5-fold by day 21 in dynamic compared to static conditions (23.3 ± 7.3 vs. 5.2 ± 1.6, respectively), they aligned at almost 45° to the direction of strain, and exhibited significantly higher expression of myogenic proteins (desmin, myoD and myosin heavy chain). These results demonstrate that mimicking the biophysical cues inherent to the native muscle microenvironment in monolayer ASC cultures significantly improves their differentiation along the myogenic lineage.

In vitro studies on the mechanism of action of hepsulfam in chronic myelogenous leukemia patients.

In the present study we have characterized the cytotoxicity and DNA damage induced by hepsulfam and busulfan in cells isolated from both chronic myelogenous leukemia (CML) patients and normal donors. hepsulfam inhibited colony-forming units-granulocyte, macrophage to a greater extent than busulfan in peripheral blood cells (PBCs) isolated from CML patients. Normal PBCs were equally sensitive to both agents and were more sensitive than the cells isolated from CML patients. Hepsulfam induced DNA interstrand cross-links in PBCs and bone marrow from both CML and normal volunteers, whereas busulfan produced few or no DNA interstrand cross-links. In addition, hepsulfam induced higher levels of DNA interstrand cross-linking than busulfam in three samples isolated from CML patients in blast crisis. Busulfan did however cause a small number of DNA strand breaks to be formed in human cells. Both agents produced similar levels of DNA-protein cross-links in PBCs from CML patients. These results suggest that the mechanism of DNA reactivity of hepsulfam and busulfan differ and that hepsulfam may prove useful in the treatment of CML.

Functional impairment and co-occurring psychiatric disorders in medically hospitalized men.

BACKGROUND: Although previous research has described a high prevalence of psychiatric comorbidity among general medical and surgical patients, prevalence estimates based on diagnostic criteria and the assessment of health care outcomes including functional status has not been conducted for a broad range of psychiatric disorders. METHODS: A random sample of male medical and surgical admissions to 3 Department of Veterans Affairs Medical Centers was enrolled in the study. Subjects were administered a computerized structured psychiatric diagnostic interview and completed a multidimensional measure of health-related functioning, the Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Of 1007 medical and surgical inpatients, almost half (46.6%) met lifetime criteria for at least 1 Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition disorder, most commonly for alcohol abuse or dependence (32.5%), posttraumatic stress disorder (10.0%), and major depression or dysthymia (9.0%). Almost one fifth reported recent symptoms, most frequently for major depression or dysthymia (7.0%). Co-occurring psychiatric disorders were associated with substantial and significant (P<.001) impairment on all dimensions of functioning, with the greatest decrements observed in physical and emotional role functioning. Anxiety and mood disorders were associated with the most and somewhat similar reductions in functioning. CONCLUSIONS: The prevalence of co-occurring psychiatric disorders was substantial but consistent with other studies of populations receiving health services. Given the observed additional burden of psychiatric disorders on functioning in medically hospitalized patients, the study indicates the importance of identification and treatment of co-occurring psychiatric disorders in this high-risk and clinically challenging group of patients.

In vivo suppression of erythropoiesis by tumor necrosis factor-alpha (TNF-alpha): reversal with exogenous erythropoietin (EPO).

Tumor necrosis factor-alpha (TNF-alpha) selectively kills tumor cells in vitro and in vivo and is being tested as a cancer therapeutic agent. We have shown that TNF-alpha significantly suppresses late-stage erythropoiesis, leading to anemia in chronically treated mice. These erythropoietic effects could limit the clinical use of TNF-alpha. Therefore, we have examined whether erythropoietin (EPO) could be used to prevent TNF-alpha-induced erythroid suppression. Normal mice were treated with a single dose of recombinant murine TNF-alpha (10(5) U/mouse, i.p.) with and without various concentrations of recombinant human EPO. After 3 days, effects on late-stage erythropoiesis were measured by determining the number of mature erythroid colony-forming cells (CFU-E) in the spleen and bone marrow. Simultaneous treatment with EPO abrogated the suppressive effect of TNF-alpha in a dose-dependent manner. EPO treatment also prevented the decrease in peripheral blood-hematocrit that was observed with chronic (5 x 10(4) U/mouse/day for 5 days) administration of TNF-alpha. TNF-alpha-induced hemorrhagic necrosis of tumors and stimulation of macrophage (CFU-M) progenitors were unaffected by EPO treatment. These results demonstrate that simultaneous injection of EPO can abrogate the TNF-alpha-induced suppressive effects on erythropoiesis.

Potentiation by adrenaline of thrombin-induced elevation of pHi is not essential for synergistic activation of human platelets.

Gel-filtrated human platelets were stimulated with thrombin in the absence and presence of adrenaline. Adrenaline markedly enhanced the thrombin-induced increase in cytoplasmic pH (pHi) in BCECF-loaded platelets. This rise in pHi was strongly inhibited by the Na+/H+ exchange blocker EIPA. The potentiation by adrenaline of thrombin-induced PLC activation measured as [32P]PA formation and final platelet responses was, however, not blocked by EIPA, even at low concentrations of thrombin. These results indicate that the enhancement by adrenaline of thrombin-induced cytoplasmic alkalinization may be a secondary effect which is not essential for the potentiation by adrenaline of platelet activation by thrombin.

Increasing patients' knowledge of radiation therapy.

Scripts for a set of patient education programs were developed by a multidisciplinary team of health care professionals to provide information to cancer patients receiving a 4-7 week course of external beam radiation therapy. The programs were designed to be presented sequentially at three critical points during a course of treatment: Pretreatment, Treatment Week 2, and Final Treatment Week. A total of 72 patients, 24 per program, with cancers of the lung, breast, or prostate, were assessed for their level of knowledge after hearing the audiotape appropriate to their treatment phase (posttest). Half of the patients, on a random basis, were also assessed prior to hearing their tape (pretest). This split design allowed the differentiation of true learning effects from effects of multiple assessments. Knowledge test items were developed from learning objectives for each program. Posttest results indicate a very high level of patient learning for all three programs, significantly exceeding the target of 75% correct. For patients tested twice, posttest scores were significantly higher than pretest scores. No testing effects were found for the Pretreatment and Treatment Week 2 programs. Final Treatment Week subjects who were pretested scored slightly higher on the posttest than their controls who were not pretested; however, additional analysis demonstrated true learning effects for this group as well. The results indicate that the programs are effective for increasing patients' knowledge regarding their treatment program, its side effects, and strategies to manage those side effects. Further research and intervention programs are discussed.

Accommodation and presbyopia in the human eye. Changes in the anterior segment and crystalline lens with focus.

PURPOSE: To characterize changes in the sagittal dimensions of the human crystalline lens and anterior segment as a function of accommodation, to determine the potential age dependence of these changes, and to evaluate these changes in relation to the development of presbyopia. METHODS: Scheimpflug slit-lamp photography, as well as a variety of standard ophthalmologic methods, was used to collect information about lens and anterior segment sagital dimensions in a population of 82 adults with refractive error < or = magnitude of 2.0 diopters and at least 0.25 diopter of accommodation for subjects 18 to 70 years of age. Data were analyzed statistically for dependence on accommodation, age, and age dependence of accommodative rate. RESULTS: The rate of change per diopter of accommodation for each measured variable within the lens is independent of age for the entire adult age range. With increasing accommodation, the lens becomes thicker and the anterior chamber shallower along the polar axis. This increase in sagittal lens thickness is entirely because of an increase in the thickness of the lens nucleus. Because the anterior and posterior halves of the nucleus increase in thickness at approximately the same rate with accommodation, the increase in lens thickness results from equal changes in the lengths of the anterior and posterior portions. CONCLUSIONS: Because changes along the sagittal axis of the anterior segment with accommodation are independent of age, any explanation of presbyopia that relies on simple changes in the rates of lens thickening and anterior chamber shallowing with age does not hold. In light of other age-related changes in the anterior segment and lens (e.g., increased sharpness of lens curvature, increased lens sagittal thickness, decreased anterior chamber depth), it appears that compensatory mechanisms to preserve far vision with age also preserve the rate of change per diopter of sagittal spacings.

Toward establishing procedural, criterion, and discriminant validity for PTSD in early childhood.

OBJECTIVE: To explore several key aspects of the diagnosis and assessment for posttraumatic stress disorder (PTSD) in infants and young children. METHOD: Fifteen traumatized, clinic-referred children, and a comparison sample of 12 at-risk children, all younger than 48 months of age, were assessed with a standardized procedure and a semistructured diagnostic interview. The assessments were videotaped and reviewed by two blind raters for scoring DSM-IV PTSD criteria and an alternative set of PTSD criteria for young children. Raters were debriefed and consensus ratings were used to make best-estimate diagnoses. RESULTS: The investigation of procedural validity showed that 12% of the diagnostic criteria present in these children could be detected by a clinician through direct observation or interaction with the children. The remainder of criteria were apparent only through caregiver report. Problematic aspects of parental reporting were most evident for the avoidance/numbing of responsiveness criteria. The traumatized subjects showed significantly more alternative criteria of PTSD than DSM-IV criteria of PTSD. The main sources of rater disagreement are described. CONCLUSIONS: Additional sources of information would complement the multidimensional assessment of PTSD in young children. The set of alternative criteria appears to show greater criterion validity than the DSM-IV criteria.

Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy.

OBJECTIVE: To ascertain if hydrosalpinges are associated with reduced pregnancy rates and increased pregnancy loss after IVF-ET. Increased volume and leakage of hydrosalpinx fluid may exert negative effects on follicular development and embryo quality and/or render the uterine environment hostile to embryogenesis. We undertook this study to examine the effect of hydrosalpinx fluid on murine embryogenesis in vitro. DESIGN: Descriptive study. SETTING: Tertiary care facility. PATIENT(S): Premenopausal females undergoing salpingectomy or salpingostomy for hydrosalpinges. INTERVENTION(S): Collection of discarded hydrosalpinx fluid and development of a dose response curve for the effect of hydrosalpinx fluid on murine embryogenesis. MAIN OUTCOME MEASURE(S): Development of single cell mouse embryos in vitro. RESULT(S): All samples of tubal fluid obtained from hydrosalpinges demonstrated a significant embryo toxic effect at either the 100% or 10% concentration. Hydrosalpinx fluid demonstrated pH values (8.45 to 8.65) significantly higher than the physiologic range. Correction of pH to that of media did not affect cavitation rate. CONCLUSION(S): There is a well-defined and significant toxic effect of hydrosalpinx fluid. Procedures such as salpingectomy or proximal tubal occlusion to circumvent the passage of hydrosalpinx fluid into the uterine cavity may have beneficial effects on the developmental environment for embryos in vivo.

Comparison of the efficacy and metabolic effects of nicardipine and hydrochlorothiazide in hypertensive black men and women.

A double-blind, randomised, parallel study compared the BP and metabolic responses in black hypertensive patients following monotherapy with nicardipine or hydrochlorothiazide (HCTZ). Following a single-blind placebo wash-out period of 1-4 weeks, the study drug, nicardipine 20-40 mg three times daily or HCTZ 25-100 mg four times daily, was administered in a double-blind fashion for 12 weeks. Doses were titrated to control sitting DBP (< or = 90 mmHg). Both drugs were effective in reducing sitting SBP and DBP as compared with baseline values (nicardipine: 152.5 +/- 1.6/102.0 +/- 0.6, HCTZ: 152.5 +/- 1.5/101.4 +/- 0.5 mmHg). DBP responses (reduction from baseline; nicardipine: -10.9, HCTZ: -12.7 mmHg), and the percentage of patients achieving a response < or = 90 mmHg (nicardipine: 54%, HCTZ: 63%) to the two drugs were similar. Although SBPs at baseline and endpoint (137.3 +/- 1.6 on nicardipine and 132.1 +/- 1.4 mmHg on HCTZ), and the percentage of patients achieving a response < or = 140 mmHg (nicardipine: 70%, HCTZ: 79%), were comparable between the two treatments, the SBP reduction with HCTZ was statistically greater (P = 0.026). A comparison of the metabolic responses in the two treatment groups showed significant differences. Nicardipine caused no significant changes in blood chemistry, whereas HCTZ caused statistically significant decreases (P < 0.001) in sodium and potassium and increases (P < or = 0.01) in glucose, BUN, creatinine, uric acid, cholesterol and LDL compared with baseline. In 12.7% of the patients in the HCTZ group, serum potassium dropped to levels < 3.5 meq/l, which occurred in only 1.4% of the patients who used nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

The zones of discontinuity in the human lens: development and distribution with age.

Statistical analysis of Scheimpflug images from the crystalline lenses of 100 emmetropic human subjects ranging in age from 18 to 70 yr confirms that specific zones of discontinuity are a function of lens development and growth. At and beyond the age of 40 yr, as many as four sharply demarcated and complementary zones are seen within the anterior and posterior lens cortex. The locations of the inner edges of the anterior cortical zones of discontinuity were characterized relative to the central sulcus of the lens. Consecutively from the central sulcus, the distances were 1.094, 1.415, 1.695, and 1.994 (+/- 0.11 mm). Since nuclear thickness in the adult lens is age-independent and the rate of cortical growth has been characterized, the location of the inner margins of the zones are indicative of the age at which they originated; these ages were 4 (+/- 1 yr), 9 (+/- 2 yr), 19 (+/- 4yr), and 46 (+/- 10 yr). All of the zones become broader along the outer margin and more dense upon aging, with specific zones appearing to merge in older presbyopic lenses. While lens fetal nuclear transparency decreases with age, it does not feature zones of discontinuity; instead, symmetrically amorphous regions appear centrally in the anterior and posterior nucleus. This demonstration of the onset of specific zones of discontinuity in emmetropic individuals, at defined periods of lens growth that are synchronous the production of successively more complex lens sutures, strongly suggests a causal relationship between lens sutures and the zones of discontinuity.

Aging of the human crystalline lens and anterior segment.

Changes in the unaccommodated human crystalline lens were characterized as a function of subject age for 100 normal emmetropes over the age range 18-70 yr by Scheimpflug slit-lamp photography. With increasing age, the lens becomes thicker sagittally, but since the distance from the cornea to the posterior lens surface remains unchanged, this indicates that the center of lens mass moves anteriorly and the anterior chamber becomes shallower. Sagittal nuclear thickness is independent of age, but both anterior and posterior cortical thicknesses increase with age, shifting the location of the nucleus and the central sulcus in the anterior direction. The amount of light scattered by the lens at high angles, as represented by normalized and integrated lens densities from the digitized images, increases with increasing age in an exponential fashion. Similar relationships to age are observed for the major anterior zone of discontinuity (maximum density) and the central sulcus (minimum density). The relationships of these results to accommodation and presbyopia are discussed.

Risk factors for AMA discharge from VA inpatient alcoholism treatment programs.

This study was designed to identify those risk factors associated with discharge from inpatient alcoholism treatment against medical advice (AMA) and the underlying reasons for these discharges. Data on the characteristics of patients and their index hospitalization were obtained from the systematic review of medical records for 186 alcoholics who were discharged AMA and 201 alcoholics who completed treatment. Comorbid medical diagnosis reduced the risk of AMA discharge by one quarter, whereas court referral to treatment reduced the risk by one half. A college education, vocational or other training, being employed, and having a history of previous AMA discharges significantly increased the risk. The most common reasons for AMA discharge, as perceived by treatment providers, were psychosocial problems, difficulties in the treatment program, and lack of interest in treatment. The clinical implications of these findings for the inpatient treatment of alcoholics are discussed.

Relationship between inpatient alcoholism treatment and longitudinal changes in health care utilization.

OBJECTIVE: The purpose of the study was to evaluate changes in health care utilization associated with inpatient alcoholism treatment in alcoholics of low socioeconomic status with different histories of treatment relapse. METHOD: The sample consisted of more than 85,000 male alcoholics using inpatient care in Department of Veterans Affairs medical centers in fiscal year 1987. Five treatment groups were identified to represent a continuum of length and intensity of alcoholism treatment, including formal inpatient alcoholism treatment, short detoxification and hospitalizations for primary diagnoses other than alcoholism. All inpatient and outpatient health services for 3 years before and 3 years after the index hospitalization were examined for differential changes in utilization associated with the five treatment groups after controlling for patient predisposing, enabling and need characteristics. RESULTS: Both total inpatient days and outpatient visits increased significantly for all treatment groups, with the greatest increases occurring in the group completing inpatient alcoholism treatment (both p < .0001). However, use of inpatient medical care decreased and substance abuse inpatient care increased significantly for most groups, with the largest increases in substance abuse care found for the completed treatment group. CONCLUSIONS: In a hospital system that does not deny care on the basis of ability to pay, certain groups of chronic alcoholics who cannot sustain prolonged remission will continue to be heavy utilizers of services. Alcoholism treatment may be associated with higher short-term costs but it remains to be seen whether provision of more focused treatment services is able to achieve longer term better outcomes and, ultimately, lower costs.

Postpartum teaching priorities: the viewpoints of nurses and mothers.

OBJECTIVE: To compare mothers' and nurses' perceptions of postpartum learning needs and effective teaching modalities. DESIGN: Cross-sectional research design. Mothers were given a questionnaire during their postpartum stay to rate how important it was for them to learn about 44 maternal-infant topics before discharge. Nurses rated similar items on the basis of their perception of what is most important for mothers to learn during their postpartum stay. SETTING: Postpartum units in six hospitals that are part of a large midwestern health care system. PARTICIPANTS: English-speaking women who delivered either vaginally or by cesarean section without complications and the nurses on their postpartum units. MAIN OUTCOME MEASURES: Identification of preferred topics and methods for postpartum teaching. RESULTS: Mothers and nurses agreed that topics related to immediate physical health needs were most important. Unmarried mothers considered topics related to personal care and mobility as particularly important. First-time mothers rated more topics as important than did experienced mothers. Individual teaching was rated most effective by both groups. Classroom teaching and the use of audiovisual media were considered less effective. CONCLUSIONS: This study supports postpartum education that focuses on the physical needs of mothers and infants, as well as individual teaching models. The special learning needs of new mothers, including those who are not married, must be considered.

Attributions about spouse abuse in cases of bidirectional battering.

A particularly misunderstood type of domestic violence is the type of incident where both partners are violent, for example, where one partner is violent and the other is violent in self-defense. The present study examined third-party attributions about such battering. Subjects read a fictitious newspaper report of a domestic battering incident and then filled out rating scales about the participants and the event. The scenario described either an "asymmetric battering" incident where one party instigated the violence and was much more violent than the other, or an incident which was more of a mutual fight (symmetric battering). Both scenarios ended with one person seriously injuring the other. Each scenario had two versions, in which either the husband or the wife instigated the violence. Results showed that the person who had instigated the violence was judged more harshly and was given more responsibility for their actions in both the symmetric and asymmetric battering conditions. The less violent partner in the asymmetric conditions was judged to have more right to use force. In the symmetric battering, both parties were assigned blame.

Ethical dilemmas in driver reeducation.

This article illustrates ethical dilemmas faced by therapists who provide driver reeducation. The dilemmas discussed are (a) accepting a wide range of referral sources and client disabilities versus the inability to know enough to anticipate all driver performance errors, (b) the client's safety versus the client's right to independence, (c) financial constraints versus advantages of technology, and (d) the reporting of poor driving risk versus client confidentiality. A method for determining one's pattern of resolving ethical dilemmas is discussed.

Hemoproteids (Apicomplexa: Haemoproteidae) from South African tortoises (Cryptodira: Testudinidae).

Terrestrial tortoises, Chersina angulata (Schweigger, 1812), Kinixys belliana belliana Gray, 1831, K. lobatsiana Power, 1927, K. natalensis Hewitt, 1935, and Stigmochelys pardalis (Bell, 1828), both wild (n  =  84) and captive (n  =  70), were examined for hematozoans from the provinces of Gauteng, Kwazulu-Natal, North West, and Western Cape, South Africa. In Giemsa-stained blood films, 2 species of hemoproteids were identified, 1 previously described, that is, Haemoproteus testudinalis ( Laveran, 1905 ) Wenyon, 1915, the other unknown. Haemoproteus testudinalis occurred in 2/27 wild K. lobatsiana and 1/41 S. pardalis and 2/2 captive K. lobatsiana from the North West and Gauteng, respectively, whereas Haemoproteus sp. A was recorded in 1 of 3 captive K. natalensis from Kwazulu-Natal. Haemoproteus testudinalis had pale blue-stained, often vacuolated, halteridial macrogametocytes, pale pink-stained microhalterdial to halteridial microgametocytes, and dark, scattered, often bacillus-like hemozoin granules. Haemoproteus natalensis n. sp. had ameboid growth stages, blue-stained halteridial to circumnuclear macrogametocytes, purple-stained circumnuclear microgametocytes, and brownish, often clustered, pigment granules. It is recommended that Haemoproteus balazuci Dias, 1953, become a junior synonym of H. testudinalis.

Long-term Adjustment After Surviving Open Heart Surgery: The Effect of Using Prayer for Coping Replicated in a Prospective Design.

PURPOSE: despite the growing evidence for effects of religious factors on cardiac health in general populations, findings are not always consistent in sicker and older populations. We previously demonstrated that short-term negative outcomes (depression and anxiety) among older adults following open heart surgery are partially alleviated when patients employ prayer as part of their coping strategy. The present study examines multifaceted effects of religious factors on long-term postoperative adjustment, extending our previous findings concerning prayer and coping with cardiac disease. DESIGN AND METHODS: analyses capitalized on a preoperative survey and medical variables from the Society of Thoracic Surgeons' National Database of patients undergoing open heart surgery. The current participants completed a mailed survey 30 months after surgery. Two hierarchical regressions were performed to evaluate the extent to which religious factors predicted depression and anxiety, after controlling for key demographics, medical indices, and mental health. RESULTS: predicting lower levels of depression at the follow-up were preoperative use of prayer for coping, optimism, and hope. Predicting lower levels of anxiety at the follow-up were subjective religiousness, marital status, and hope. Predicting poorer adjustment were reverence in religious contexts, preoperative mental health symptoms, and medical comorbidity. Including optimism and hope in the model did not eliminate effects of religious factors. Several other religious factors had no long-term influences. MPLICATIONS: the influence of religious factors on the long-term postoperative adjustment is independent and complex, with mediating factors yet to be determined. Future research should investigate mechanisms underlying religion-health relations.