Influence of age and health on immune functions and trace elements

Apparently healthy elderly donors were screened according to a simple protocol that included clinical examination and the determination of hematological and biochemical values. This screening was performed to detect subclinical alterations which might interfere with immune responses and trace element status. The elderly were divided into two groups. The first group consisted of 22 (age 76 +/- 1 years) positively selected elderly (PSE), i.e. healthy subjects with no hematological and laboratory alterations, the second one comprised 13 (age 75 +/- 1 years) negatively selected elderly (NSE). Data were then compared with those obtained from 40 (age 35 +/- 2 years) healthy young controls. In both groups of elderly donors, plasma zinc levels were normal, while plasma copper concentrations were increased. Intracellular values of zinc and copper in mono- and polymorphonuclear cells from both groups of elderly were within reference limits. After in vitro activation, granulocyte chemiluminescence activity was impaired only in NSE. A decrement in the number of circulating CD3 lymphocytes and an increase in CD8d, CD57 cells were found in PSE, while NSE showed an increased number of CD3,DR cells and CD8d, CD57, CD8b,CD57 and CD16,CD56 positive cells. Our results indicate that only plasma copper levels were affected by age, whereas subclinical alterations in hematological or biochemical values appear to impair immune responses in the elderly.     

Induction of Fos immunoreactivity in the brain by exposure to the elevated plus-maze

The log-rank test is commonly used to assess therapeutic effect in prospective, randomised clinical trials. This test is sensitive to differences in survival between treatment groups at a specific endpoint, but cannot determine whether such a difference is due to an enhanced cure rate or an enhanced survival time among uncured patients. To investigate the clinical impact of such limitations, an algorithm was constructed to simulate clinical, randomised, adjuvant therapy trials in patients with a cured fraction of 0.27 and a median survival time for uncured patients of 3.4 years. Hypothetical therapies were introduced to increase rate of cure, increase median survival time, or achieve a combination of these effects. For 500 simulated patients recruited over a 5 year period and then followed for three additional years, a 50% enhancement of median survival time (to 5.1 years) led to a survival increase detectable at the P = 0.05 level in 780 of 1000 trials, whereas a 50% enhancement of cured fraction (to 40.5%) led to a detectable increase at the same level in only 449 of 1000 trials. These findings suggest that, in clinical trials of adjuvant therapy for stage 2 breast cancer, the log rank test may be more sensitive to increases in tumour-related survival time than to increases in cured fraction.     

Regulation in the heart field of zebrafish

In many vertebrates, removal of early embryonic heart precursors can be repaired, leaving the heart and embryo without visible deficit. One possibility is that this 'regulation' involves a cell fate switch whereby cells, perhaps in regions surrounding normal progenitors, are redirected to the heart cell fate. However, the lineage and spatial relationships between cells that are normal heart progenitors and those that can assume that role after injury are not known, nor are their molecular distinctions. We have adapted a laser-activated technique to label single or small patches of cells in the lateral plate mesoderm of the zebrafish and to track their subsequent lineage. We find that the heart precursor cells are clustered in a region adjacent to the prechordal plate, just anterior to the notochord tip. Complete unilateral ablation of all heart precursors with a laser does not disrupt heart development, if performed before the 18-somite stage. By combining extirpation of the heart precursors with cell labeling, we find that cells anterior to the normal cardiogenic compartments constitute the source of regulatory cells that compensate for the loss of the progenitors. One of the earliest embryonic markers of the premyocardial cells is the divergent homeodomain gene, Nkx2.5. Interestingly, normal cardiogenic progenitors derive from only the anterior half of the Nkx2.5-expressing region in the lateral plate mesoderm. The posterior half, adjacent to the notochord, does not include cardiac progenitors and the posterior Nkx2.5-expressing cells do not contribute to the heart, even after ablation of the normal cardiogenic region. The cells that can acquire a cardiac cell fate after injury to the normal progenitors also reside near the prechordal plate, but anterior to the Nkx2.5-expressing domain. Normally they give rise to head mesenchyme. They share with cardiac progenitors early expression of GATA 4. The location of the different elements of the cardiac field, and their response to injury, suggests that the prechordal plate supports and/or the notochord suppresses the cardiac fate.     

Patient preference for self-collected cultures for group B streptococcus in pregnancy

The purpose of this study was to examine the factors which affect the level of fatigue among patients participating in clinical trials in which this symptom had been assessed with the EORTC QLQ-C30. Data were assembled from 2390 patients in ten clinical trials in which the QLQ-C30 had been used to assess baseline and on-study quality of life. The relationship between the level of fatigue reported by the patients on the fatigue scale of this questionnaire and patient and disease characteristics was assessed in univariate and multivariate cross-sectional analyses. In addition, changes in fatigue scores were compared in a longitudinal analysis among patients on two arms of an anti-emetic trial whose emesis control was markedly different. Baseline fatigue levels differed substantially among patients taking part in the different trials. Factors associated with greater fatigue severity on univariate analysis included: female gender, presence of metastatic disease, and poorer performance status. In addition, on multivariate analyses the oldest patients were found to have less fatigue, as were patients with breast cancer, while patients with ovarian and lung cancer experienced greater fatigue. Patients on the arm of the anti-emetic trial in which emesis was better controlled showed significantly less increase in fatigue after receiving chemotherapy. The fatigue scale of the QLQ-C30 appears to provide a useful approach to assessing this important symptom. The relationships found between fatigue and patient and disease characteristics need further exploration as does the degree to which the QLQ-C30 fully captures this dimension of quality of life.     

Reengineering a surgical service line: focusing on core process improvement

Integrating principles from a variety of theory has led to the development of a conceptual framework for reengineering in a clinical care delivery setting to improve the value of services provided to the customer. A conceptual framework involving the identification of three high level core processes to reengineer can provide clarity and focus for clinicians to begin directing reengineering efforts. Those core processes are: clinical management of the patient's medical needs, patient operational processes to support the clinical processes, and administrative decision-making processes to support the implementation of the clinical and operational processes. Improvement in any one of these areas has the potential to increase value, but the concurrent targeting of these core processes for reengineering has provided a synergy that has accelerated the achievement of the desired outcomes in the area of surgical services.     

The effects of limbic lesions on locomotion and stereotypy elicited by dopamine agonists in the rat

The purpose of this experiment was to investigate the functional contributions of various limbic structures to locomotion and stereotypy induced by dopaminergic drugs. Female rats were randomly assigned to one of 5 groups (n = 10-14 rats/group) that received either a lesion of the hippocampus (colchicine + kainic acid), basolateral amygdala (quinolinic acid), frontal cortex (aspiration), nucleus accumbens (ibotenic acid), or served as unoperated controls. Beginning at least 2 weeks following surgery locomotion (measured as photocell beam breaks) elicited by D-amphetamine (0.0, 0.32, 1.0 and 3.2 mg/kg), SKF 82958 (0.0, 0.04, 0.08 and 0.16 mg/kg) or quinpirole (0.0, 0.25, 0.1 and 0.5 mg/kg) was determined. In agreement with previous results rats with hippocampal lesions were hyperactive in response to amphetamine. In comparison to these changes in drug-induced locomotion, lesions of the basolateral amygdala, and frontal cortex had only minor effects on drug-induced locomotion. Lesions of the nucleus accumbens produced consistent hyperactivity that was suppressed by doses of amphetamine or quinpirole that elicited behavioral stereotypy. These results provide evidence suggesting that, in comparison to other limbic structures that have substantial inputs to the nucleus accumbens, the hippocampus play a relatively prominent role in the modulation of drug-induced locomotion.     

Teaching secondary students with learning disabilities to self-manage classroom survival skills

This multiple baseline study investigated the effectiveness of a cognitive-behavioral self-management training package on the consistent use of specific classroom survival skills. Participants were three adolescent males with learning disabilities in Grades 7 and 8. The training package involved a multicomponent strategy focused on the improvement, maintenance, and cross-classroom generalization of targeted classroom preparedness skills. Following intervention, the training procedures were systematically faded. Results demonstrated more consistent use of targeted classroom survival skills by all three students in both learning support and mainstream generalization settings. Long-term maintenance of the intervention effects was observed for two students in both settings. Three social validity measures revealed positive results. Implications for self-management in secondary education settings are discussed.     

An in vitro model of traumatic neuronal injury: loading rate-dependent changes in acute cytosolic calcium and lactate dehydrogenase release

We developed a new in vitro model of neuronal injury using NT2-N cells to examine the effects of hydrodynamic loading rate on intraneuronal calcium dynamics and lactate dehydrogenase (LDH) release. Our apparatus consisted of a parallel disk viscometer which induced fluid shear stress with well-defined magnitudes and loading rates to cultured cells. We found that the deformation response of the cells was dependent on the severity of the insult, with increased cellular strains generated for higher shear stresses at a constant loading rate. Peak intracellular free calcium concentration correlated with strain, suggesting that mechanical deformation may regulate calcium response. Slowly applied fluid shear stress elicited no response, whereas high loading rates resulted in peak calcium increases 2.9 to 3.6 times baseline values as injury severity was increased. LDH release measured within 5 min after the insult correlated with loading rate. In addition, LDH release continued to increase out to 24 h following high loading rate conditions, demonstrating that the application of fluid shear stress led to prolonged cell damage. The acute response in NT2-N cells subjected to an insult with the CSID is dependent on the loading rate, and these results suggest that initial membrane deformation may trigger subsequent events.