Cell therapy for cardiac repair.

Cardiovascular diseases remain the leading cause of morbidity and mortality in Western society. Among these diseases, congestive heart failure continues to be a significant health care burden. Recent medical and surgical advances in therapy have improved the quality and quantity of life for patients with heart failure. However, none of these therapies address the fundamental problem of loss of functional cardiomyocytes. Cell regeneration therapies have become an exciting potential treatment for heart failure and other cardiovascular diseases. This emerging therapeutic field has been pursued experimentally with both embryonic-derived stem cells and adult-derived progenitor cells. The identification of resident cardiac progenitor cells has propelled the field of cardiac regenerative biology forward at astonishing rates. This review will examine current findings of various stem and progenitor cells that have been proposed as potential sources for cardiac regeneration, and the recent therapeutic findings from preliminary clinical trials using some of these cell types for cardiovascular repair.

Contribution to the knowledge of the folk plant medicine in Calabria region (Southern Italy).

A series of research on plants used in Calabria (Southern Italy) in the folk plant medicine was carried out in the last twenty years. The use of 104 taxa distributed into 42 families are described. Among the major findings: Ceterach officinarum as hypotensive; Heliotropium europaeum in the case of urinary inflammations; Silybum marianum for haemorrhoids; Arundo donax for pertussis and cystitis; Allium cepa for sties and flu; Laurus nobilis as galactagogue; Passiflora incarnata for burns, haemorrhoids and skin inflammations; Scrophularia canina for rhagas and wounds; Urtica membranacea for tussis and tonsillitis.

Unmasked residual neuromuscular block after administration of vecuronium for days.

IMPLICATIONS: Significant neuromuscular block may be present in patients who have received vecuronium for days.

Work of breathing during spontaneous ventilation in anesthetized children: a comparative study among the face mask, laryngeal mask airway and endotracheal tube.

Work of breathing (WOB) increases during general anesthesia in adults, but such information has been limited in pediatric patients. We studied WOB in 24 healthy children (mean age 2+/-1.9 yrs), during elective urogenital surgery under 1 minimum alveolar anesthetic concentration halothane-nitrous oxide anesthesia with a caudal block while breathing spontaneously. WOB was measured with an esophageal balloon, miniature flowmeter, and a computerized (Bicore) system. In each patient, WOB was computed under four conditions: a mask without oral airway (-AW), a mask with oral airway (+AW), a laryngeal mask airway (LMA), and an endotracheal tube (ETT). With each apparatus WOB was studied both with continuous positive airway pressure (CPAP) (5-6 cm H(2)O) and without CPAP (or zero end-expiratory pressure [ZEEP]). Under ZEEP, WOB (g x cm/kg) among the four apparatus were (mean +/- SEM): mask (-AW) (64 +/-19.2) > mask (+AW) (44+/-17.2), LMA (42+/-15.6) > ETT (25.4+/- 12.4) (P<0.05). WOB with CPAP significantly (P<0.05) decreased from WOB with ZEEP in three groups (mask [-AW], mask [+AW], and LMA), but not in the ETT group. Tidal volume (both ZEEP and CPAP) and end-tidal PCO(2) (with CPAP only) were significantly (P<0.05) decreased only in the ETT group, whereas no significant difference was found in respiratory rate or minute volume among the four airway apparatus groups, either with or without CPAP. The reduction in WOB, when breathing through ETT was primarily attributable to decreases in tidal volume and volume work. The finding that WOB decreases with CPAP in all groups except for the ETT group suggests that the decrease is a result of improved patency of the upper airway rather than of increases in functional residual capacity and lung compliance.

Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution.

OBJECTIVE: The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells. MATERIALS AND METHODS: The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design. RESULTS: Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment (absolute neutrophil count >0.5 x 10(9)/L day 10; platelet count >50 x 10(9)/L day 13). A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34+ selected or unselected autologous transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log reduction >3.12. CONCLUSIONS: CD34+Thy1+ HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable hematopoietic reconstitution at cell doses >0.8 x 10(6) CD34+Thy1+ HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.

Employee competence and performance-based assessment: A college of American pathologists Q-probes study of larboratory personnel in 522 institutions.

OBJECTIVE: To survey employee competence assessment practices in departments of pathology and laboratory medicine and provide suggestions for improvement. DESIGN: A 3-part study consisting of a questionnaire about current competence assessment practices, an evaluation of compliance with stated competence assessment practices using personnel records of 30 employees, and a written appraisal of competence of 5 specimen-processing staff members per institution. SETTING: A total of 522 institutions participating in the College of American Pathologists 1996 Q-Probes program. MAIN OUTCOME MEASURES: Institutional competence assessment practices, compliance of each institution with their own practices, and determination of competence of specimen-processing personnel. RESULTS: Of the participating institutions, 89.8% had a written competence plan and 98.1% reported reviewing employee competence at least yearly. General competence was reviewed by direct observations (87.5%), review of test or quality control results (77.4%), review of instrument preventive maintenance (60.0%), written testing (52.2%), and/or other methods (20.8%). In 8.6% of institutions, employees who failed competence assessment were not allowed to continue their usual work. On review of records of 14 029 employees for adherence to the laboratory's general competence plan, adherence was 89.7% for direct observations, 85.8% for review of quality control and test results, 78.0% for review of instrument records, and 74.0% for written testing. Employee failure rate ranged from 0.9% to 6.4%, depending on the competence evaluated. Adherence to an institution's plan was 90.4% for new employees, 93.1% for computer skills, 95.8% for laboratory safety, and 92.1% for continuing education. When a written competence assessment was given to 2853 specimen-processing staff members, 90.0% responded satisfactorily. CONCLUSIONS: Opportunities for improvement in employee competence assessment are numerous, and we provide several specific suggestions.

Socially shared cognition, affect, and behavior: a review and integration.

In this article, we review 4 classes of models of socially shared cognition and behavior: supraindividual models, information-processing models, communication models, and social interaction models. Our review draws on research and theory in social psychology, sociology, and organization behavior. We conclude that these innovative perspectives on socially shared behavior represent a new approach to the study of groups and are distinct from traditional models of the group mind and crowd behavior. The key processes implicated in these models focus on the potency of immediate interaction, reciprocal influence processes between individuals and groups, goal-directed behavior, negotiated processing of information and ideas, and the maintenance and enhancement of social identity. This approach to socially shared understanding is not antagonistic toward the analysis of individual-level processes but rather maintains that individual-level processes are necessary but not sufficient to build a social psychology of shared understanding.

Identification of IL-16 as the lymphocyte chemotactic activity in the bronchoalveolar lavage fluid of histamine-challenged asthmatic patients.

OBJECTIVE: We have previously demonstrated that the earliest lymphocyte chemotactic factors present in bronchoalveolar lavage fluid (BALF) of subjects with atopic asthma after subsegmental antigen challenge are IL-16 and MIP-1alpha, of which IL-16 appears to contribute a majority of the chemotactic activity. Because IL-16 is released in vitro after histamine stimulation of CD8+ T cells and epithelial cells, we evaluated the potential role of histamine in the release of IL-16 into the airways of allergic asthmatics in vivo. METHODS: Eight allergic asthmatic subjects, six normal subjects, and six atopic nonasthmatic subjects were challenged with saline in the lingula and with serial concentrations of histamine (1 x 10(-7) to 5 x 10(-5) mol/L) in the right middle lobe followed by bronchoalveolar lavage (BAL) 15 minutes and 6 hours later. RESULTS: The BALF from saline- and histamine-challenged lobes of normal subjects and atopic nonasthmatic subjects contained no significant lymphocyte chemoattractant activity. In six of the eight atopic asthmatic subjects, the histamine-challenged but not saline-challenged segment contained IL-16 chemotactic activity but no other identifiable lymphocyte chemoattractant activities at 6 hours. CONCLUSIONS: IL-16 appears in the airways after histamine challenge and therefore could contribute to the earliest infiltration of CD4+ T cells and eosinophils observed after antigen challenge due to histamine release from mast cells.

IL-16 inhibition of CD3-dependent lymphocyte activation and proliferation.

We have recently described the cDNA and predicted protein structure of a natural soluble CD4 ligand, IL-16. IL-16 is chemotactic for CD4+ T cells and induces functional IL-2 receptors in CD4+ T cells. The binding of IL-16 to CD4 results in activation of p56(lck), whose adaptor function is essential for the chemotactic response. Subsequently, increases in intracellular Ca2+ and phosphatidylinositol 1,4,5-trisphosphate occur, as does translocation of protein kinase C from cytosol to membrane. Because of the similarities between these signals and functions and those noted for the CD4 ligand HIV-1 gp120, we investigated the potential regulatory effects of IL-16 on CD3/TCR-mediated lymphocyte activation. Preincubation of human T cells with IL-16 up to 24 h before activation with plate-bound anti-CD3 Abs reduced T cell activation by 80%, as monitored by IL-2R expression and [3H]thymidine uptake. If IL-16 was added following anti-CD3 activation, no suppression was noted. The suppressive effects of preincubation with IL-16 were not rescued by the addition of rIL-2 and were not the result of priming for anti-CD3-induced apoptosis. In addition, IL-16 had no effect on surface expression of CD3 or CD4. However, IL-16 did reduce the magnitude of the anti-CD3-induced intracellular Ca2+ increase. These studies indicate that while the interaction of CD4 with its natural ligand, IL-16, results in Ag-independent chemotaxis and IL-2R expression, this pro-inflammatory state is associated with subsequent transient inhibition of responsiveness via the CD3/TCR complex.

CD4 ligand IL-16 inhibits the mixed lymphocyte reaction.

CD4 participation in TCR/CD3-associated activation through interaction with the MHC class II Ags results in formation of a CD4-TCR/CD3 complex capable of maximal signal transduction. When CD4 binds to alternative ligands such as HIV-1 gp120 or anti-CD4 Abs, Ag stimulation of TCR/CD3 is markedly inhibited, and an unresponsive state develops. To determine if the natural CD4 ligand interleukin-16 also induces unresponsiveness, we tested the effects of rIL-16 on T cell proliferation in mixed lymphocyte reactions. rIL-16 suppressed T cell proliferation in a dose-dependent manner at concentrations of 10(-11) to 10(-7) M. Inhibition of proliferation was present on days 5 to 9 of the mixed lymphocyte reaction. rIL-16 did not modulate membrane CD4, significantly change basal [3H]thymidine incorporation in resting T lymphocytes, or alter viability. The suppressive effect was specifically blocked by preincubation with neutralizing anti-rIL-16 mAb or with recombinant soluble CD4. While the expression of IL-2R on responder cells was unaffected by rIL-16, the addition of exogenous rIL-2 did not restore T cell responsiveness. The unresponsiveness induced by rIL-16 is distinct from that of other CD4 ligands in that CD4 and IL-2R expression are unaffected. The failure of rIL-2 to restore proliferation suggests that the decrease in T cell responsiveness induced by rIL-16 may result from an interruption in the IL-2R-signaling mechanism. These results may help explain how CD4 delivers both activating and inhibitory signals and provides a rationale for the role of IL-16 in the regulation of immune responses.

Nutrition education of young women.

White women aged 25-34 years (n 264) from the lower socio-economic classes (C2, D and E) were classified according to their motivation in respect of health and their educational attainment and arithmetical ability. They were randomly allocated to three groups. One group (test) was given a course in basic nutrition consisting of a video and booklet, each embellished with motivational material. Those classed as of low ability also received the training material in simplified format. A second group (control) received a video and booklet with no motivational or simplified materials. The third group (baseline) received no tuition and represented a control of publicly available information during the period of the experiment. The participants answered a series of questions by administered questionnaire to measure their nutritional knowledge before and one week after they viewed the video programme. All participants achieved significantly higher scores at the second questionnaire. The test and control groups achieved significantly higher scores than the baseline group but there was no significant difference between the test and control groups. The presentation of motivational or simplified materials had no significant effect on learning ability though those classified as more highly motivated and of higher ability achieved higher scores at each questionnaire. The results indicate that young adult females can be taught basic nutrition irrespective of their motivation or ability.

Adenoma of type 2 pneumocytes with oncocytic features.

An adenoma of type 2 pneumocytes in the periphery of the left lung was an incidental finding at the autopsy of a 28-year-old woman. Light microscopy revealed a predominantly papillary growth with oncocytic features. Ultrastructurally, multilaminated bodies and many mitochondria were found in the tumor cells and tubular myelin in the extracellular spaces. Immunohistochemistry revealed surfactant apoprotein in tumor cells and extracellularly.

Effect of exercise level on ventilatory adaptation to respirator use.

The effect of exercise on the adaptation to an air-purifying respirator type load (dead space + inspiratory resistance) was studied in a group of 13 volunteers with a rapidly incremental exercise protocol. The difference between loaded and unloaded breathing at each exercise level was determined for each subject for a series of parameters describing the ventilatory work to overcome the respirator load pattern of breathing and metabolic work. Linear regression and t tests determined the average effect of the respirator load and the extent to which this effect was affected by the level of exercise. The inspiratory time and duty cycle were increased by the load, and exercise did not significantly affect the magnitude of this adaptation. High exercise did, however, increase the magnitude of the effect of the respiratory load on ventilatory work. These findings suggest that constraints to respiratory pattern adjustment, which may decrease respirator tolerance, occur at high exercise levels.

Predictors of falls among elderly people. Results of two population-based studies.

A study was performed to identify and rank risk factors for falling among populations of institutionalized (fallers, N = 79, nonfallers, N = 70) and noninstitutionalized (fallers, N = 34, nonfallers, N = 34) elderly persons. Fallers were matched by age, sex, and living location to nonfaller control subjects. A nurse practitioner performed a comprehensive physical assessment in all subjects using a standardized protocol and physician consultation. Fallers in both populations were significantly more physically and functionally impaired than control subjects. Logistic regression identified hip weakness, poor balance, and number of prescribed medications as factors most strongly associated with falling among institutionalized subjects. A fall prediction model was developed from these findings yielding 76% overall predictive accuracy (89% sensitivity, 60% specificity). Using the model, the predicted 1-year risk of falling ranged from 12% for persons with none of the three risk factors to 100% for persons with all three risk factors. Findings among noninstitutionalized subjects were similar. These data support the concept of performing focused fall risk assessments to identify elderly patients at high risk for falling.

Primary papillary serous neoplasia of the peritoneum: a clinicopathologic and ultrastructural study of eight cases.

The well-documented but rare primary papillary serous peritoneal tumors are difficult problems for the pathologist and the clinician. Because of their unusual location, these tumors are often classified as mesothelioma or advanced ovarian carcinoma. In this study, we report the clinicopathologic features of eight primary peritoneal serous papillary tumors and compare their histologic and ultrastructural features to 12 serous ovarian tumors and 16 epithelial mesotheliomas (two peritoneal and 14 pleural). The eight peritoneal serous papillary tumors occurred in women aged 19 to 75 years; two were serous tumors of low malignant potential (borderline) and six were serous carcinomas. The tumors were located in the mesosalpinx, left pelvis, omentum, and/or surface of the ovary. The two patients with borderline neoplasms had long disease-free survival (11 years and 20 years), while three of the four patients with carcinoma with more than 1 year of follow-up died of disease. The peritoneal serous papillary tumors were morphologically identical to serous ovarian tumors of equivalent grade. Well-differentiated papillary structures with distinct fibrovascular cores and one or several layers of columnar, crowded cells, dense overlapping nuclei with a long axis perpendicular to the surface of the papillary cores, and numerous psammoma bodies were features of the peritoneal and ovarian serous tumors. In contrast, the tubulo-alveolar, solid, or poorly defined papillary structures lined by well-spaced polygonal to cuboidal cells with abundant cytoplasm, absence of nuclear polarity, and infrequent psammoma bodies characterized the mesotheliomas. Epithelial mucin and carcinoembryonic antigen (CEA) immunoreactivity, when present, supported a diagnosis of serous tumor in these generally mucin-poor and CEA-negative neoplasms. Ultrastructurally, the cells of serous tumors had slender, straight microvilli of variable length interspersed with or without cilia, while the nonciliated cells of mesothelioma had long, exuberant, wavy microvilli. The morphologic and clinical features of the peritoneal papillary serous tumors are distinctive enough to warrant their separation from mesotheliomas.

Effects of respirator dead space, inspiratory resistance, and expiratory resistance ventilatory loads.

The effects of respiratorlike inspiratory resistance (IR), expiratory resistance (ER), and dead space (DS) were assessed in a group of 11 normal volunteers during moderate steady-state (SS) and rapidly incremented (RI) exercise. The physiologic effects of IR were predominant, increasing inspiratory time, duty cycle, and several measures of ventilatory work. Effects of DS appear related to increased minute ventilation and include increasing flow rates and duty cycle and requiring greater ventilatory work; during RI exercise, the DS effect became relatively smaller at higher exercise levels. ER compressed expiratory time. These results characterize the response to IR, ER, and DS loads and suggest that DS may be relatively less physiologically significant than IR.

Determinants of pattern of breathing during respirator use.

The relationship between the pattern of breathing in response to respirator-type loads and an individual's psychophysiologic sensitivity to loads (load scaling sensitivity, LSS) was investigated in the study of 11 normal volunteers. LSS was measured by having the subjects numerically rate a series of resistors; Steven's Psychophysical Law was used to evaluate sensitivity as the slope relating log (sensation) to log (stimulus). Peak pressure and actual added resistance were the stimuli. Inspiratory time, peak pressure, duty cycle, and tidal volume were inversely related to independently measured LSS during exercise and with a respiratory-type dead space and inspiratory resistance load. Because the need for changes in respiratory timing is a major adaptation in respirator use, it suggests that workers who are very sensitive to loads may have limited ability to adapt to respirator use.

Predictors of recurrence and survival of patients with breast cancer.

In this study, the characteristics of 646 patient's primary breast carcinomas, including histologic grade (HG), nuclear grade (NG), mitotic grade (MG), final grade (FG), estrogen receptor (E2R) status, and patient's lymph node status (LN) at the time of surgery were correlated with recurrence-free interval and patient survival in order to determine whether any one parameter or group of parameters serve as adequate predictors of tumor behavior and, therefore, patient's prognosis. The authors' results showed that LN, tumor size, and tumor grade were themselves significant predictors of early recurrence and breast cancer death. Each unit increase in LN or MG increased the risk of death by a factor of 1.5 and 2.0, respectively. However, prediction of time to recurrence or death was considerably more accurate when those parameters were used in conjunction, rather than individually. E2R was also significant in predicting death. MG separated patients within a single LN group or E2R group into two subsets having clinically and statistically different prognoses. It was found that patients who had negative lymph nodes and whose tumors were MG1 had a better prognosis than those with MG2,3 tumors; in these latter patients recurrence and death patterns were similar to those of patients with MG1 tumors having one to three positive lymph nodes. Similarly, whereas patients with four or more positive lymph nodes had bad prognoses, those bearing MG1 tumors tended to behave more like those with MG2,3 tumors and having only one to three positive lymph nodes.