Relationship Between Physical Functioning and Physical Activity in the Lifestyle Interventions and Independence for Elders Pilot

OBJECTIVES: To determine whether participation in usual moderate‐intensity or more‐vigorous physical activity (MVPA) is associated with physical function performance and to identify sociodemographic, psychosocial, and disease‐related covariates that may also compromise physical function performance. DESIGN: Cross‐sectional analysis of baseline variables of a randomized controlled intervention trial. SETTING: Four academic research centers. PARTICIPANTS: Four hundred twenty‐four older adults aged 70 to 89 at risk for mobility disability (scoring <10 on the Short Physical Performance Battery (SPPB)) and able to complete the 400‐m walk test within 15 minutes. MEASUREMENTS: Minutes of MVPA (dichotomized according to above or below 150 min/wk of MVPA) assessed according to the Community Healthy Activities Model Program for Seniors questionnaire, SPPB score, 400‐m walk test, sex, body mass index (BMI), depressive symptoms, age, and number of medications. RESULTS: The SPPB summary score was associated with minutes of MVPA (ρ=0.16, P=.001). In multiple regression analyses, age, minutes of MVPA, number of medications, and depressive symptoms were associated with performance on the composite SPPB (P<.05). There was an association between 400‐m walk time and minutes of MVPA (ρ=?0.18; P<.001). In multiple regression analyses, age, sex, minutes of MVPA, BMI, and number of medications were associated with performance on the 400‐m walk test (P<.05). CONCLUSION: Minutes of MVPA, sex, BMI, depressive symptoms, age, and number of medications are associated with physical function performance and should all be taken into consideration in the prevention of mobility disability.     

The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit

Thrombopoietin (c-Mpl ligand) has recently been purified and is considered to be the humoral regulator of platelet production. To see whether this molecule possessed the physiologic characteristics necessary to mediate the feed-back loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass. We developed a model of nonimmune thrombocytopenia in rabbits by the subcutaneous administration of busulfan. Compared with pretreatment plasma, plasma taken from all thrombocytopenic rabbits at their platelet nadir contained increased amounts of thrombopoietin. All of this activity was neutralized by soluble c-Mpl receptor. We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan. As the platelet mass declined, levels of thrombopoietin increased inversely and proportionally and peaked during the platelet nadir. With return of the platelet mass toward normal, thrombopoietin levels decreased accordingly. When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased. In addition, platelets were observed to remove thrombopoietin from thrombocytopenic plasma in vitro. These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor.     

Genetic bases of estrogen-induced pituitary growth in an intercross between the ACI and Copenhagen rat strains: dominant mendelian inheritance of the ACI phenotype.

Estrogens stimulate cell proliferation in a variety of tissues and are widely believed to be contributing factors in the etiology of certain cancer types in humans. The molecular mechanisms through which estrogens regulate cell proliferation are currently unknown. Estrogens stimulate proliferation of the PRL-producing lactotroph of the rat anterior pituitary gland and induce development of PRL-producing pituitary tumors in several inbred rat strains. Therefore, the lactotroph provides a well defined model for identifying the mechanisms through which estrogens regulate cell proliferation and/or survival. Data from our laboratory and others indicate that the relative sensitivity to the pituitary growth-promoting actions of estrogens is highly strain specific. This allows genetics-based approaches to be used to address the molecular mechanisms through which estrogens stimulate lactotroph proliferation and induce pituitary tumor development. In the present study we have examined the ability of diethylstilbestrol (DES) to induce pituitary growth in the genetically related AxC-Irish (ACI) and Copenhagen (COP) strains and their derived F1, F2, and backcross progeny. The data presented herein indicate that the anterior pituitary gland of the ACI strain displays approximately a 2-fold greater growth response to administered DES than does the pituitary gland of the COP strain. The average pituitary weight in male ACI rats was increased from 9.2 +/- 0.2 mg (mean +/- SD in untreated rats to 63.7 +/- 12.6 mg in rats treated with DES for 12 weeks, whereas in male COP rats, DES increased pituitary weight from 12.7 +/- 0.9 to 38.1 +/- 8.2 mg. The ACI phenotype was inherited in the F1, F2, and backcross progeny of an ACI x COP intercross as a dominant genetic trait, and the approximately 30 mg of additional pituitary growth displayed by the DES-treated ACI rat, relative to that of the treated COP rat, appeared to result from the actions of a single locus. Moreover, in F1 progeny from an ACI x Brown Norway intercross, the ACI phenotype was inherited as a dominant or incompletely dominant genetic trait. These data, when compared with findings of previous studies using the Fischer 344 rat strain, provide the first indication that distinct genetic pathways contribute to regulation of estrogen-induced pituitary growth and induction of PRL-producing pituitary tumors in the ACI and F344 rat strains.     

A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells

BACKGROUND & AIMS: Constitutive expression of cyclooxygenase 2 (COX-2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. METHODS: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. RESULTS: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC-58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. CONCLUSIONS: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis. (Gastroenterology 1997 Dec;113(6):1883-91)     

Carrier testing and prenatal diagnosis of haemophilia — utilisation and psychological consequences

Summary. Attitudes towards prenatal diagnosis, and abortion vary widely between different countries, religions, cultures and over time. Carrier testing and prenatal diagnosis (PD) of haemophilia have become an integrated part of the comprehensive care for haemophilia in Sweden as well as in many other countries. Almost all carriers are interested in carrier testing if they are aware of the possibility. With the development of PD by chorionic villus sampling in the first trimester, the method became acceptable for many carriers, and it has in Sweden actually had an effect on the incidence of haemophilia in the 1990s. The use of PD is more common among women who perceive haemophilia as a very serious disease and who have a positive attitude towards legal abortion. The main reason for carriers not to use PD was that they do not find haemophilia to be a sufficiently serious disorder to justify an abortion. Women and their spouses are under a great deal of psychological pressure in association with the PD procedure, and the psychological consequences of having to terminate a pregnancy are long-lasting. At follow-up, about 6 years after PD and abortion, these women, however, do not have more signs of psychological distress than women without PD experience. Nevertheless, they must be offered qualified assistance both before and after PD as well as adequate follow-up after an abortion to help them cope with the emotional strain they are under.     

Relationship Between Literacy, Knowledge, Self-Care Behaviors, and Heart Failure-Related Quality of Life Among Patients With Heart Failure

BACKGROUND

We sought to examine the relationship between literacy and heart failure-related quality of life (HFQOL), and to explore whether literacy-related differences in knowledge, self-efficacy and/or self-care behavior explained the relationship.

METHODS

We recruited patients with symptomatic heart failure (HF) from four academic medical centers. Patients completed the short version of the Test of Functional Health Literacy in Adults (TOFHLA) and questions on HF-related knowledge, HF-related self-efficacy, and self-care behaviors. We assessed HFQOL with the Heart Failure Symptom Scale (HFSS) (range 0?C100), with higher scores denoting better quality of life. We used bivariate (t-tests and chi-square) and multivariate linear regression analyses to estimate the associations between literacy and HF knowledge, self-efficacy, self-care behaviors, and HFQOL, controlling for demographic characteristics. Structural equation modeling was conducted to assess whether general HF knowledge, salt knowledge, self-care behaviors, and self-efficacy mediated the relationship between literacy and HFQOL.

RESULTS

We enrolled 605 patients with mean age of 60.7 years; 52% were male; 38% were African-American and 16% Latino; 26% had less than a high school education; and 67% had annual incomes under $25,000. Overall, 37% had low literacy (marginal or inadequate on TOFHLA). Patients with adequate literacy had higher general HF knowledge than those with low literacy (mean 6.6 vs. 5.5, adjusted difference 0.63, p?p?p?p?CONCLUSION Low literacy was associated with worse HFQOL and lower HF-related knowledge, self-efficacy, and self-care behaviors, but differences in knowledge, self-efficacy and self-care did not explain the relationship between low literacy and worse HFQOL.     

Mediastinal staging of nonsmall cell lung carcinoma by endoscopic and endobronchial ultrasound-guided fine needle aspiration

Mediastinal staging is of vital importance in the treatment planning of patients with nonsmall cell lung cancer who do not have distant metastases. Nodal assessment is often a challenge, however, and the limitations of staging methods are well recognized. Noninvasive studies can yield a presumptive clinical stage, but invasive tests are often necessary to determine the status of nodes in the absence of extensive mediastinal infiltration. Endoscopic ultrasound-guided fine needle aspiration and endobronchial ultrasound-guided fine needle aspiration are minimally invasive additions to the staging armamentarium that facilitate nodal biopsy under direct visualization without full anesthesia. In some cases, these procedures offer the opportunity for a patient to receive both a tissue diagnosis and staging in one sitting. While their roles are debated and evolving, their availability is increasing and they are reducing the need for surgical staging. Radiologists contribute to the evaluation of patients who may benefit from these up-and-coming procedures and should become familiar with endoscopic ultrasound-guided fine needle aspiration and endobronchial ultrasound-guided fine needle aspiration.     

The use of permanent pacemakers in the detection of cardiac arrhythmias.

AIMS: To compare pacemaker telemetry with simultaneous Holter recordings in the diagnosis of atrial fibrillation and to evaluate the STOP-AF study telemetry criteria for the presence of atrial fibrillation. METHODS AND RESULTS: 18 consecutive patients enrolled in the STOP-AF study had simultaneous 24 h Holter recordings and down-loaded pacemaker telemetry. There was good agreement on heart rate, but the STOP-AF pacemaker criteria achieved only 57% sensitivity with 64% specificity for the presence of atrial fibrillation on Holter recording over 24 h. False-positives appeared to result from far-field sensing while false-negatives occurred with very short episodes of atrial fibrillation. The pacemaker's antitachycardia responses were not specific for the presence of atrial fibrillation. CONCLUSION: Pacemaker telemetry is a potentially important source of data on cardiac arrhythmias. Further studies are required to define the limitations of these data in specific devices before they can be interpreted with confidence.     

Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice

Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes.     

Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics

The acute leukemia associated with the t(4;11) chromosome rearrangement is characterized by relatively consistent clinical features: occurrence primarily in young individuals, hyperleukocytosis, and poor response to therapy. This study describes the morphological, ultrastructural, and immunologic characteristics of the leukemic cells from ten patients with this type of leukemia. The morphological features of the leukemic blasts vary from lymphoid-appearing to monocytic. Ultrastructurally and cytochemically, some of the lymphoid-appearing blasts possess features of myeloid origin. The immunologic phenotype is characteristically E- SIg- CALLA- BA-1- BA-2+ HLA-DR+ and TdT+. These findings suggest that the t(4;11)-associated acute leukemia represents a proliferation of an early myeloid progenitor cell.