Military women’s perspectives on health care during deployment

Approximately 367,000 women serve in the U.S. military and regularly deploy with their units to austere military environments. A survey was used to describe 841 military women’s perceptions about the health care provider that is available them during deployment and their perceptions of barriers to adequate diagnosis and treatment of gynecologic infections in these austere environments. The study findings have implications for military provider training, sick call policy, predeployment training, and development of self-care alternatives for military women during deployment.     

Improved perfusion and contractile reserve after transmyocardial laser revascularization in a model of hibernating myocardium

Background. Transmyocardial laser revascularization (TMR) has been demonstrated effective for relieving angina, although prior studies have yielded inconsistent results regarding postoperative myocardial perfusion and function. This study evaluated long-term changes in myocardial perfusion and contractile reserve after TMR in a model of hibernating myocardium.

Methods. Miniswine had subtotal left circumflex coronary artery occlusion to reduce resting blood flow to 10% of baseline. After 2 weeks in the low-flow state, positron emission tomography and dobutamine stress echocardiography were performed to document ischemic, viable (hibernating) myocardium in the left circumflex distribution. Animals then had sham redo thoracotomy (n = 4) or TMR (n = 6). Six months later the positron emission tomography and dobutamine stress echocardiography studies were repeated.

Results. Myocardial blood flow in the left circumflex distribution as measured by positron emission tomography was significantly reduced in all animals after 2 weeks in the low-flow state. In animals that had TMR, there was significant improvement in myocardial blood flow to the lased regions 6 months postoperatively. No significant change in myocardial blood flow was seen in sham animals at 6 months. Dobutamine stress echocardiography after 2 weeks of low-flow demonstrated severe hypocontractility at rest in the left circumflex region of all animals, with a biphasic response to dobutamine consistent with hibernating myocardium. In animals that had TMR, there was a trend toward improved resting function and significantly improved regional stress function in the lased segments 6 months postoperatively, consistent with a reduction in ischemia. Global left ventricular wall motion at peak stress improved significantly as well. There was no change in wall motion 6 months postoperatively in sham-operated animals.

Conclusions. This study found improvements in myocardial perfusion and regional and global contractile reserve 6 months after TMR in a porcine model of hibernating myocardium. This improved perfusion and function likely accounts for the clinical benefits of the procedure.     

Economic analysis of finasteride: a model-based approach using data from the Proscar Long-Term Efficacy and Safety Study.

Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in older men in the United States. BPH is often associated with a reduction in quality of life and may progress to acute urinary retention (AUR), the inability to pass any urine. Recently, a 4-year placebo-controlled clinical trial known as the Proscar Long-Term Efficacy and Safety Study (PLESS) demonstrated that finasteride use reduces the risk of developing AUR by 57% and the need for BPH-related surgery by 55%. The economic implications of these findings were investigated using a model-based decision-analytic approach to compare finasteride with both watchful waiting and alpha-blocker therapy. The modeling used the longest-term published controlled data concerning alpha-blockers, which were for the alpha-blocker terazosin. The base case considered a 64-year-old man (the mean age of a PLESS patient) with prostatic enlargement on digital rectal examination and moderate-to-severe symptoms of BPH. The model suggested savings in surgical and AUR costs with finasteride versus watchful waiting, with an estimated 25% of total finasteride costs recouped in savings on surgical events avoided in the first year. Over 2 years, the expected cost per patient starting finasteride therapy was $2304, whereas the expected cost per patient starting terazosin was $2334. Analyses also explored the variation in economic results by baseline levels of prostate-specific antigen (PSA), a proxy for prostate volume. For patients with PSA levels > or =1.4 ng/mL, expected 2-year costs with finasteride and terazosin were $2342 and $2479, respectively. For patients with PSA levels > or =3.3 ng/mL, expected 2-year costs with finasteride were $373 less than with terazosin ($2347 vs $2720). Results were robust over a range of model assumptions and cost estimates. The analyses illustrate that all medical interventions, including watchful waiting, have associated costs. Finasteride shows cost offsets compared with watchful waiting and cost savings compared with terazosin over 2 years. Finasteride appears to be more economical in men with higher PSA levels.     

Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine.

Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a lambda(max) of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions at m/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase.     

The Quality of Residential and Day Services for Adults with Intellectual Disabilities in Eight Local Authorities in England: Objective Data Gained in Support of a Social Services Inspectorate Inspection

Objective data on the quality of 15 residential homes and 17 day centres were collected as part of a Social Services Inspecorate inspection of services for adults with learning disabilities in eight local authorities in England. A sample of 56 residents was drawn from the former and information collected on their behavioural characteristics, social and community integration, autonomy, receipt of attention and assistance from staff, and participation in activity. The activity timetables of the latter were analysed to determine their emphases. Representative group activities taking place within the centres were observed and user:staff ratios, user receipt of attention from staff and user engagement in activity recorded. Findings from the residential settings demonstrated that the frequency of community integration, the extent of autonomy and the level of activity were associated with resident ability. However, there was a lack of association between staff:resident interaction and resident needs for support. Given the ranges on the quality of life indicators investigated, people with more severe disabilities were found to lead segregated and under occupied existences. These findings add weight to the need to be more precise about the determinants of quality and, in particular, the role and performance of staff. A cluster analysis of day centres based on their activity distributions produced two clusters in common with an earlier Welsh survey; centres with an emphasis on ‘recreation and personal development’ or ‘recreation’. The English sample, however, had a lesser emphasis on both contract work and open employment and contained centres which had a greater representation of personal development and education. Developing consensus on the functions and goals of day services is required if day service reform is to lead to the most effective organisational and operational arrangements.     

The effect of high- and low-frequency H-wave therapy upon skin blood perfusion: evidence of frequency-specific effects

The current study was designed to assess the putative physiological effects of H-wave therapy (HWT, a mode of therapeutic electro-stimulation) on skin blood flow in humans and to determine the relevance of frequency to any such effects. Laser Doppler flowmetry was used to record changes in blood perfusion on the dominant forearm of healthy human volunteers (n=36), who were each assigned, under randomized double blind conditions, to one of three experimental groups: placebo or HWT at 2 or 60 Hz. HWT stimulation was applied for 20 min, during which time concomitant skin temperature was recorded using three surface skin thermistors. Statistical analysis of perfusion measurement and skin temperature changes pre-, during and for up to 18 min post-HWT stimulation showed a highly significant increase in skin blood flow in the 2 Hz group when compared to placebo and 60 Hz (P ≤ 0·01). This was associated with a significant increase in skin temperature during the period of stimulation (P ≤ 0·05). No such differences were observed in the 60 Hz group. These results provide evidence that low-frequency HWT may produce direct localized effects on cutaneous blood flow, a finding relevant for clinicians working in the field of tissue repair.     

The neural basis of naming impairments in Alzheimer's disease revealed through positron emission tomography.

The naming impairments in Alzheimer's disease (AD) have been attributed to a variety of cognitive processing deficits, including impairments in semantic memory, visual perception, and lexical access. To further understand the underlying biological basis of the naming failures in AD, the present investigation examined the relationship of various classes of naming errors to regional brain measures of cerebral glucose metabolism as measured with 18 F-Fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). Errors committed on a visual naming test were categorized according to a cognitive processing schema and then examined in relationship to metabolism within specific brain regions. The results revealed an association of semantic errors with glucose metabolism in the frontal and temporal regions. Language access errors, such as circumlocutions, and word blocking nonresponses were associated with decreased metabolism in areas within the left hemisphere. Visuoperceptive errors were related to right inferior parietal metabolic function. The findings suggest that specific brain areas mediate the perceptual, semantic, and lexical processing demands of visual naming and that visual naming problems in dementia are related to dysfunction in specific neural circuits.     

INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53

The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products. To compare the impact of these loci on tumor development and treatment response, the Emu-myc transgenic lymphoma model was used to generate genetically defined tumors with mutations in the INK4a/ARF, Rb, or p53 genes. Like p53 null lymphomas, INK4a/ARF null lymphomas formed rapidly, were highly invasive, displayed apoptotic defects, and were markedly resistant to chemotherapy in vitro and in vivo. Furthermore, INK4a/ARF(-/-) lymphomas displayed reduced p53 activity despite the presence of wild-type p53 genes. Consequently, INK4a/ARF and p53 mutations lead to aggressive tumors by disrupting overlapping tumor suppressor functions. These data have important implications for understanding the clinical behavior of human tumors.     

Triple-technique (MR imaging, single-photon emission CT, and CT) coregistration for image-guided surgical evaluation of patients with intractable epilepsy.

Ictal and interictal single-photon emission CT (SPECT) play an increasingly important role in the surgical evaluation of patients with epilepsy. We present a method of coregistration of MR, SPECT, and CT images to correlate structural data (MR imaging), blood flow changes (SPECT), and location of subdural electrodes (CT) for patients undergoing image-guided surgical treatment of epilepsy. MR-SPECT root mean square (rms) mismatch distances were 2.1 to 2.5 mm, and MR-CT rms mismatch distances were 1.0 to 4.5 mm. Coregistration assisted in image-guided placement of subdural electrodes and in surgical resection of the suspected epileptogenic focus.     

Treatment of baseline drifts in fMRI time series analysis.

PURPOSE: Gradual drifting of baseline signal intensity is common in functional MRI (fMRI) time course data. Methods for dealing with this effect are studied. METHOD: Simulations and fMRI data are used to study three statistical models that account for baseline drift. A method is proposed in which the time course data are linear least-squares fit to a reference function that includes the slope of the baseline drift as a free parameter. RESULTS: It is shown that the least-squares method is equivalent to cross-correlation with Gram-Schmidt orthogonalization. Additionally, it is shown that certain paradigm designs improve the sensitivity of statistical tests when using any of the drift correction methods commonly employed. The least-squares method results in a variety of useful parameters such as activation amplitude, with a well characterized error. CONCLUSION: Very simple techniques can effectively account for observed drifts. It is important to design paradigms that are symmetric about the midpoint of the time series. In calculating confidence levels, a proper statistical model that accounts for baseline drifts is necessary to ensure accurate confidence level assessment.