A study of the adjustment made by twenty-four adult male patients who have rheumatic heart disease

Thesis (M.S.)--Boston University, 1947. This item was digitized by the Internet Archive

Characterization of lower urinary tract symptoms in patients with idiopathic normal pressure hydrocephalus

AIMS: The purpose of this study was to evaluate lower urinary tract symptoms (LUTS) in idiopathic normal pressure hydrocephalus (iNPH). METHODS: Patients with new-onset iNPH were prospectively evaluated for LUTS via detailed history and physical, and administration of questionnaires from the International Consultation on Incontinence to assess incontinence (ICIq-UI), overactive bladder (ICIq-OAB), and quality of life (ICIq-LUTqol), as well as the American Urological Association Symptom Score bother scale. All patients with moderate-to-severe LUTS were offered urodynamic testing. Sub-analysis was performed based on gender, medical comorbidities, and age. RESULTS: Fifty-five consecutive patients with iNPH completed the initial evaluation and surveys. Total urinary incontinence score was mild to moderate (8.710.64: 0-21 scale) with 90.9% experiencing leakage and 74.5% reporting urge incontinence. The most common OAB symptom was nocturia (2.2 +/- 0.14: 0-4 scale) with urge incontinence the most bothersome (3.71 +/- 0.44: 0-10 scale). Quality-of-life impact was moderate (4.47 +/- 0.4: 0-10 scale) and American Urological Association Symptom Score bother scale was 2.89 +/- 0.22 (0-6 scale). Urodynamics testing revealed 100% detrusor overactivity and mean bladder capacity of 200mL. Several differences were identified based on gender, medical comorbidities, and age. CONCLUSIONS: Patients with iNPH present with mild-moderate incontinence of which nocturia is the most common symptom, urge incontinence the most bothersome, with 100% of patients having detrusor overactivity. Younger patients experienced greater bother related to LUTS. To our knowledge, this is the only prospective evaluation of urinary symptoms in patients with new-onset iNPH

Context, ethics and pharmacogenetics

Most of the literature on pharmacogenetics assumes that the main problems in implementing the technology will be institutional ones (due to funding or regulation) and that although it involves genetic testing, the ethical issues involved in pharmacogenetics are different from, even less than, 'traditional' genetic testing. Very little attention has been paid to how clinicians will accept this technology, their attitudes towards it and how it will affect clinical practice. This paper presents results from interviews with clinicians who are beginning to use pharmacogenetics and explores how they view the ethics of pharmacogenetic testing, its use to exclude some patients from treatment, and how this kind of testing fits into broader debates around genetics. In particular this paper examines the attitudes of breast cancer and Alzheimer's disease specialists. The results of these interviews will be compared with the picture of pharmacogenetics painted in the published literature, as a way of rooting this somewhat speculative writing in clinical practice

Prospective assessment of white matter integrity in adult stem cell transplant recipients

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05). There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT

Forward Masking Estimated by Signal Detection Theory Analysis of Neuronal Responses in Primary Auditory Cortex

Psychophysical forward masking is an increase in threshold of detection of a sound (probe) when it is preceded by another sound (masker). This is reminiscent of the reduction in neuronal responses to a sound following prior stimulation. Studies in the auditory nerve and cochlear nucleus using signal detection theory techniques to derive neuronal thresholds showed that in centrally projecting neurons, increases in masked thresholds were significantly smaller than the changes measured psychophysically. Larger threshold shifts have been reported in the inferior colliculus of awake marmoset. The present study investigated the magnitude of forward masking in primary auditory cortical neurons of anaesthetised guinea-pigs. Responses of cortical neurons to unmasked and forward masked tones were measured and probe detection thresholds estimated using signal detection theory methods. Threshold shifts were larger than in the auditory nerve, cochlear nucleus and inferior colliculus. The larger threshold shifts suggest that central, and probably cortical, processes contribute to forward masking. However, although methodological differences make comparisons difficult, the threshold shifts in cortical neurons were, in contrast to subcortical nuclei, actually larger than those observed psychophysically. Masking was largely attributable to a reduction in the responses to the probe, rather than either a persistence of the masker responses or an increase in the variability of probe responses

Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86823/1/j.1399-0004.2011.01739.x.pd

MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic Normal Pressure Hydrocephalus

BACKGROUND: The objective was to identify changes in quantitative MRI measures in patients with idiopathic normal pressure hydrocephalus (iNPH) occurring in common after oral acetazolamide (ACZ) and external lumbar drainage (ELD) interventions. METHODS: A total of 25 iNPH patients from two clinical sites underwent serial MRIs and clinical assessments. Eight received ACZ (125-375 mg/day) over 3 months and 12 underwent ELD for up to 72 hours. Five clinically-stable iNPH patients who were scanned serially without interventions served as controls for the MRI component of the study. Subjects were divided into responders and non-responders to the intervention based on gait and cognition assessments made by clinicians blinded to MRI results. The MRI modalities analyzed included T1-weighted images, diffusion tensor Imaging (DTI) and arterial spin labelling (ASL) perfusion studies. Automated threshold techniques were used to define regions of T1 hypo-intensities. RESULTS: Decreased volume of T1-hypointensities and decreased mean diffusivity (MD) within remaining hypointensities was observed after ACZ and ELD but not in controls. Patients responding positively to these interventions had more extensive decreases in T1-hypointensites than non-responders: ACZ-responders (4,651 ± 2,909 mm(3)), ELD responders (2,338 ± 1,140 mm(3)), ELD non-responders (44 ± 1,188 mm(3)). Changes in DTI MD within T1-hypointensities were greater in ACZ-responders (7.9% ± 2%) and ELD-responders (8.2% ± 3.1%) compared to ELD non-responders (2.1% ± 3%). All the acetazolamide-responders showed increases in whole-brain-average cerebral blood flow (wbCBF) estimated by ASL (18.8% ± 8.7%). The only observed decrease in wbCBF (9.6%) occurred in an acetazolamide-non-responder. A possible association between cerebral atrophy and response was observed, with subjects having the least cortical atrophy (as indicated by a positive z-score on cortical thickness measurements) showing greater clinical improvement after ACZ and ELD. CONCLUSIONS: T1-hypointensity volume and DTI MD measures decreased in the brains of iNPH patients following oral ACZ and ELD. The magnitude of the decrease was greater in treatment responders than non-responders. Despite having different mechanisms of action, both ELD and ACZ may decrease interstitial brain water and increase cerebral blood flow in patients with iNPH. Quantitative MRI measurements appear useful for objectively monitoring response to acetazolamide, ELD and potentially other therapeutic interventions in patients with iNPH