Oral and written language in late adulthood: findings from the Nun Study

As a part of the Nun Study, a longitudinal investigation of aging and Alzheimer's disease, oral and written autobiographies from 118 older women were analyzed to examine the relationship between spoken and written language. The written language samples were more complex than the oral samples, both conceptually and grammatically. The relationship between the linguistic measures and participant characteristics was also examined. The results suggest that the grammatical and conceptual characteristics of oral and written language are affected by participant differences in education, cognitive status, and physical function and that written language samples have greater power than oral language samples to differentiate between high- and low-ability older adults.     

Differences in alveolar size in inbred mouse strains

In this paper we examined structural differences in alveolar size among inbred mouse strains which are known to have significant differences in lung pressure-volume relations. Accordingly, we assessed whether the relative size or number of alveoli in the C3H/HeJ, C57BL/6J, and A/J strains are related to these lung volume differences. Lungs from each of these strains were fixed in situ and then excised for quantitative morphometric analysis of airspace chord lengths. Mean chord lengths (in microm) were significantly different (P < 0.0001) among the three strains, with the largest alveoli found in the C3H/HeJ mice (45 +/- 5), the smallest in the C57BL/6J mice (35 +/- 3), and intermediate in the A/J strain (38 +/- 2). These findings provide clear evidence that there are significant genetic differences in the lung structure among different mouse strains. However, since the A/J and C57BL/6J mice had similar lung volumes, there does not yet seem to be a clear link between the macroscopic manifestations of the microscopic structure. We speculate that these structural differences might have significant influence on several mouse models of lung disease, especially those involving the development of emphysema.     

PEEP-induced changes in epithelial permeability in inbred mouse strains

Inbred mouse strains have demonstrated a range of susceptibilities to inhaled environmental irritants. C57Bl/6J mice are highly susceptible while C3H/HeJ mice are resistant to ozone exposures, as assessed by lavaged protein. However, lavaged protein reflects a loss of both the endothelial and epithelial barrier. To determine whether basal differences exist in the epithelial barrier, we measured soluble tracer ((99m)technetium-diethylenetriamine pentaacetic acid, (99m)Tc-DTPA) clearance from the lung in spontaneously breathing, anesthetized mice and mice ventilated with increased lung volume with applied positive end-expiratory pressure (PEEP; 1, 6, or 10cmH(2)O). Both strains showed more rapid clearance during ventilation with 10cmH(2)O PEEP compared with other ventilation pressures (p<0.001). There was a substantial difference in clearance between the two strains during ventilation with 10cmH(2)O PEEP (mean half time for C57Bl/6J mice=19+/-4min versus 34+/-3min for C3H/HeJ mice; p<0.001). Thus, when lung volume is increased, the susceptible C57Bl/6J strain shows a greater change in epithelial barrier than the resistant C3H/HeJ strain. These results may reflect fundamental differences in lung architecture.     

Targeted chemotherapy by intratumour injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450.

The prognosis of pancreatic adenocarcinoma is poor and current treatment ineffective. A novel treatment strategy is described here using a mouse model system for pancreatic cancer. Cells that have been genetically modified to express the cytochrome P450 2B1 enzyme are encapsulated in cellulose sulphate and implanted into pre-established tumours derived from human pancreatic cells. Cytochrome P450 2B1 converts the chemotherapeutic agent ifosfamide to toxic metabolites. Administration of ifosfamide to tumour-bearing mice that were recipients of implanted encapsulated cells results in partial or even complete tumour ablation. These results suggest that in situ chemotherapy with genetically modified cells in an immunoprotected environment may prove useful for application in man.     

Pain reduction and improvement in range of motion after daily consumption of an açai (Euterpe oleracea Mart.) pulp-fortified polyphenolic-rich fruit and berry juice blend

Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active? fruit juice, predominantly containing a?ai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.     

Dyspnea as a prognostic factor in anaplastic thyroid carcinoma

Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer. In this study, we review a single institution’s experience with ATC over past 34 years. Through retrospective review, we attempted to identify the prognostic factors affecting the survival at our institution. We reviewed the records of 33 patients diagnosed with ATC by pathology over the last three decades. At our institution, median age at diagnosis was 68 years, the male to female ratio was 1.1:1, mean survival was 10 months and median survival was 4.7 months. Thirty-nine percentage of patients were treated with chemotherapy and 52% received radiation treatment. Thirty-six percentage received both chemotherapy and radiation and 58% of patients were treated with surgical intervention. Four of the patients received surgical intervention with curative intent. Tracheotomy was performed in 40% of patients. Eight patients survived more than 10 months. Univariate analysis showed that age greater than 60 and dyspnea at presentation were associated with decreased survival and that surgical intervention was associated with increased survival. Multivariate analysis identified only dyspnea at the time of presentation to be a significant independent prognostic factor affecting the mortality. While long-term survival is possible in some patients, ATC has a poor prognosis despite the attempts at aggressive treatment. In this study, we report that dyspnea was the only independent factor found to negatively affect the survival. This finding is unique in our study and supports the role of using signs at the time of presentation as potential prognostic factors for those patients with this aggressive disease.     

Short-term growth hormone treatment and microcirculation: Effects in patients with chronic kidney disease

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and contributes significantly to the high long-term cardiovascular morbidity and mortality. The short-term cardiovascular effects of recombinant human growth hormone (rhGH) in CKD patients (stages III–V) and healthy controls (n = 15 each) were explored in a single-center, non-randomized pilot study. Subjects were investigated before, after a 7 day treatment with rhGH, and after a 7 day wash-out period. Microcirculation was assessed by nailfold capillaroscopy and leg strain gauge plethysmography. Echocardiography was performed and serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) were determined. Before the start of rhGH therapy, mean post-ischemic maximum flow velocity of erythrocytes (V_RBC) and leg blood flow (LBF) in CKD patients were significantly reduced to 68% and 75% of that seen in controls, whereas V_RBC and LBF under resting conditions were comparable. Treatment with rhGH significantly increased V_RBC and LBF under resting conditions. Whereas maximum post-ischemic V_RBC was improved by rhGH in patients and controls, maximum post-ischemic LBF increased in controls only. This was paralleled by a non-significant reduction of total vascular resistance, and increased heart rate and cardiac index. In conclusion, CKD patients respond to short-term rhGH treatment with significantly improved capillary blood flow, whereas only minor effects on total peripheral resistance and cardiac output were noted.