Is Internet-based support for dyspnea self-management in patients with chronic obstructive pulmonary disease possible? Results of a pilot study

BACKGROUND: As of 2003, approximately 67% of US adults have Internet access. The purpose of this study was to determine the feasibility and preliminary efficacy of an Internet-based dyspnea self-management program (iDSMP) for people with chronic obstructive pulmonary disease. A related aim was to compare the differential effects of the iDSMP on 2 different groups: (1) to test a "booster" effect and (2) to evaluate the program as a primary intervention. METHODS: Two groups (n = 16) were evaluated at baseline and at 3 months after completing the iDSMP, which included education, exercise, self-monitoring, and support. Dyspnea, self-efficacy, perception of available support, and exercise behavior were measured. Paired, independent t tests and Mann-Whitney U tests were used. RESULTS: Most subjects (87%) reported that the program increased their access to information and resources for managing dyspnea. Dyspnea with activities of daily living and self-efficacy for managing the symptom showed significant improvements (both P < .01), whereas more modest changes were noted in perceived support and exercise behavior in the overall sample. There were no differences between the 2 groups on these outcomes. CONCLUSIONS: The findings suggest that additional investigations of Internet-based interventions to promote self-management in patients with chronic obstructive pulmonary disease are warranted.     

CLINICAL,PHYSIOLOGICAL AND PATHOLOGICAL OBSERVATIONS IN A CASE OF PROGRESSIVE AUTONOMIC NERVOUS SYSTEM DEGENERATION ASSOCIATED WITH HOLMES-ADIE SYNDROME AND PERIPHERAL NEUROPATHY

The case history is reported of a woman aged 40 years who presented with weight loss, postural hypotension and paræsthesia in the hands and feet. The diagnosis of widespread autonomic nervous system degeneration with associated peripheral neuropathy and Holmes-Adie syndrome was made from the results of a series of clinical and physiological tests. Laboratory investigation failed to disclose a cause for the degenerative changes, and symptomatic treatment with 9-alpha fluorohydrocortisone and digitalis was commenced in an effort to combat the patient's postural hypotension. On this régime there was transient improvement in her clinical state, but over a period of six months her general condition gradually deteriorated and she eventually died. At autopsy, widespread amyloid infiltration of the sympathetic ganglia, peripheral nerves, heart and alimentary canal was found, and this appears to have been the pathological basis for the clinical and physiological findings.     

Identification of three F5 gene mutations associated with inherited coagulation factor V deficiency in two Chinese pedigrees

To investigate the molecular defects in two Chinese pedigrees with inherited factor V (FV) deficiency. A 37-year-old male (proband 1) and an 18-month-old boy (proband 2) were diagnosed as inherited coagulation FV deficiency by severely reduced plasma levels of FV activity and antigen. All 25 exons and their flanking sequence of F5 gene were amplified by polymerase chain reaction (PCR) for both probands and the PCR products were directly sequenced. Total RNA was extracted from the peripheral lymphocytes of proband 1 for detecting the changes at mRNA level. The homozygous deletion IVS8 -2A>G was identified in the F5 gene of proband 1 and complementary DNA (cDNA) analysis revealed the abolishment of the canonical splicing site by the mutation and the activation of the cryptic acceptor site 24 bp upstream instead. The insertion introduced eight additional amino acids (AA) into the FV protein. Two heterozygous mutations of F5 gene were discovered in proband 2. The 2238-9del AG in exon 13 introduced a premature termination code at 689 AA and the substitution of G6410 by T in exon 23 lead to the missense mutation Gly2079Val. Three F5 gene mutations, IVS8 -2A>G, 2238-9del AG and G6410T, have been identified in two Chinese pedigree with congenital FV deficiency, respectively.     

In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos

Mice deficient in the Flk-1 receptor tyrosine kinase are known to die in utero because of defective vascular and hematopoietic development. Here, we show that flk-1(-/-) embryonic stem cells are nevertheless able to differentiate into hematopoietic and endothelial cells in vitro, although they give rise to a greatly reduced number of blast colonies, a measure of hemangioblast potential. Furthermore, normal numbers of hematopoietic progenitors are found in 7.5-day postcoitum flk-1(-/-) embryos, even though 8. 5-day postcoitum flk-1(-/-) embryos are known to be deficient in such cells. Our results suggest that hematopoietic/endothelial progenitors arise independently of Flk-1, but that their subsequent migration and expansion require a Flk-1-mediated signal.     

Four categories of gamma-globin gene triplications: DNA sequence comparison of low G gamma and high G gamma triplications

The human fetal gamma chains are produced by closely linked G gamma and A gamma genes, and unequal crossing over between them leads to gamma gene deletions and triplications. Nine gamma gene triplications from seven ethnic groups were analyzed for G gamma and hemoglobin F (Hb F) values of heterozygotes and for the presence of polymorphic XmnI restriction sites 5' to the gamma genes. Four categories of triplication were found: I had low G gamma and low Hb F values and lacked XmnI sites 5' to the three gamma genes [---]. II had high G gamma and slightly elevated Hb F values but was also [---]. III was similar to II, except that XmnI was [+--]. IV had very high G gamma and slightly elevated Hb F values, and XmnI was [++-]. One case each of triplications I and IV were cloned into Charon 35. For both, the two 5' gamma gene code for G gamma chain, while the 3' gamma gene codes for A gamma chain. DNA sequencing showed that the unequal crossover occurred between 472 and 398 base pairs (bp) 5' to the gamma gene Cap sites (- 472 and -398) for the type IV triplication and between -271 and codon 136 for the type I triplication. In addition, type I had a 4-bp deletion of AGCA from -225 to -222. The high G gamma values of the type IV triplication are explained by its -G gamma-G gamma-A gamma-gene arrangement and the XmnI sites 5' to the G gamma genes. We hypothesize that the low G gamma value of the type I triplication, which is also -G gamma-G gamma-A gamma-, is due to inactivation of the middle G gamma gene by the AGCA deletion at -225 to -222.     

Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population

CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.     

Gift wrapping ourselves: the final gift exchange

OBJECTIVE: This qualitative study examines the "final gift exchange" process by which older adults give cherished possessions in return for lasting appreciation. METHODS: We interviewed 54 middle- and upper-middle-class people (39 women) aged 50-90 who had to dispose of personal objects when moving to smaller residences. RESULT: We used Goffman's spiraling strategy in our analysis of people's reports of disposing of personal possessions. We identified three salient dimensions (family, economy, and self) of this process and created a heuristic describing eight ideal-type gift exchange scenarios by categorizing objects as valued or not valued by family and the economy as well as being an important aspect of the gift giver's material self. DISCUSSION: By applying the heuristic, we observed that a lack of shared definitions of the meaning and value of objects created dilemmas in disposing of personal objects, particularly those connected to a person's material self. We also offer suggestions for making the process go more smoothly, such as inquiring about the preferences of others and telling stories associated with objects to create shared definitions of the objects' significance to the giver and/or to family history.     

Effects of age on responses to isometric exercise. Isometric handgrip in noninvasive screening for cardiovascular disease.

Isometric handgrip (IHG) imposes an acutely increased afterload on the left ventricle. Utilizing systolic time intervals, we studied various responses to IHG, measured as changes from resting values with near-maximum IHG, in old normal (ON) subjects, young normal (YN) subjects, and old patients with hypertensive heart disease (HHD) and patients with coronary artery disease (CAD). There were no differences in responses to IHG between ON and patients with HHD or patients with CAD. However, there were clear differences between the responses of ON and YN subjects. Increase in heart rate (HR) was much more prominent in YN (ON vs. YN = +11.6 +/- 2.6 vs. +15.6 +/- 5.7 beats per minute p less than 0.001). Pre-ejection period (PEP) end isovolumic contraction time (IVCT) increased in ON but decreased in YN (PEP + 6.2 +/- 1.7 vs. -11.0 +/- 3.7 msec., p less than 0.001; IVCT +8.1 +/- 2.2 vs. -13.8 +/- 3.4 msec., p less than 0.001. Shortening of LVET was much more marked in YN (-6.5 +/- 4.1 VS. -63.3 +/- 9.9 msec. p less than 0.001), but this was entirely due to the HR differences since there was no difference in ejection time index (+ 5.1 +/- 3.4 vs. -0.4 +/- 7.3 msec. p greater than 0.5). IHG produced no significant differences between ON and YN in the timing of the "mitral" component of the first heart sound (q-Im), in the ratio PEP/LVET, or in pulse transmission time (PTT). By contrast, resting control PTT was markedly short in ON, especially those with CAD. Resting PTT in ON was 27.1 +/- 2.6 msec.; in YN 43.7 +/- 1.4 msec.; in CAD patients 20.7 +/- 1.3 msec. We conclude that even near-maximal IHG does not seem to be an adequate noninvasive screening test for cardiovascular disease in that age alone seems to have the most significant influence on the responses.     

Physiological responses to prompt and sustained squatting. Measurement by systolic time intervals.

Ten healthy men, ages 22 to 35, were studied non-invasively standing (control), at the onset of squatting ('prompt squat'), and at two minutes of squatting. Squatting produced decreases in heart rate, isovolumic contraction time, pre-ejection period, and pulse transmission time from onset of depolarisation to the first heart sound, left ventricular ejection time, and the ejection time index. These results of systolic time intervals are consistent with the bradycardia and increased ventricular filling induced by squatting. Major changes from control measurements were found at the onset of squatting, showing the impact of prompt squat of left ventricular performance.     

Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. Echo-Persantine International Cooperative (EPIC) and Echo-Dobutamine International Cooperative (EDIC) Study Groups

OBJECTIVES: The study compared the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease. BACKGROUND: Extensive information is available on the relative diagnostic accuracy of the two tests assessed in a head-to-head fashion, whereas comparative data on their prognostic yield are largely preliminary to date. METHODS: Dipyridamole (up to 0.84 mg/kg over 10 min) atropine (up to 1 mg over 4 min) (DIP) and dobutamine (up to 40 microg/kg/min)-atropine (1 mg over 4 min) (DOB) stress tests were performed in 460 patients with known or suspected coronary artery disease. Patients were followed up for 38+/-21 months. RESULTS: The DIP was negative in 253 and positive in 207 patients. The DOB was negative in 242 and positive in 218 patients. During the follow-up, there were 80 cardiac events. For all cardiac events, the negative and positive predictive value were 83% and 17% for DOB, 84% and 19% for DIP, respectively (p = NS). Considering only cardiac death, by univariate analysis Wall-Motion Score Index (WMSI) at DIP peak dose (chi-square 13.80, p<0.0002) was the strongest predictor, followed by WMSI DOB (chi2 = 8.02, p<0.004) and WMSI at rest (chi2 = 6.85, p<0.008). By stepwise analysis, WMSI at DIP peak dose was the most important predictor (RR [relative risk] 7.4, p<0.0001). CONCLUSIONS: In patients at low-to-moderate risk of cardiac events, pharmacological stress echocardiography with either dobutamine or dipyridamole allows effective and grossly comparable, risk stratification on the basis of the presence, severity and extension of the induced ischemia.