Genetic information but not termination: pregnant women's attitudes and willingness to pay for carrier screening for deafness genes.
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Biomedical subjects
Publications and source records attributed to M Hall.
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BACKGROUND: Most cases of Creutzfeldt-Jakob disease (CJD) in recipients of human cadaveric growth hormone present with a cerebellar syndrome. Dementia is thought to occur late and as a minor feature of the illness. However, neuropsychology data published on these cases are largely qualitative and anecdotal. The first published case does include a neuropsychological assessment seven months after the onset of a cerebellar syndrome, showing evidence of intellectual decline. Subsequent reports hint that cognitive problems may be present in the initial stages of the illness. OBJECTIVE: To assess early cognition in Creutzfeldt-Jakob disease in recipients of pituitary derived human growth hormone. METHODS: Detailed neuropsychology assessment is reported at referral (mean 4.5 months from the onset of symptoms; range 4 to 6 months) in five patients with histologically proven human growth hormone derived CJD. RESULTS: All cases presented with a cerebellar syndrome and only one had noticed mild memory problems. On formal testing, however, four had demonstrable mild intellectual decline, as measured on the WAIS-R. One case showed selective visual memory impairment and frontal executive dysfunction. CONCLUSIONS: These findings suggest that, although not the presenting feature, mild cognitive decline may be evident in the early stages of CJD associated with human cadaveric growth hormone treatment.
The most common sonographic abnormality found in the fetal urinary tract is collecting system dilatation, accounting for 4.5% of examinations. Numerous renal pelvis measurements and various gestational age cut-off points have been recommended in the assessment of obstructive fetal uropathy. As a result, renal pelvic measurements are not well standardized. The first measurements of the renal pelvis diameter in the 80's suggested that a threshold value of 10 mm was significant in order to distinguish between physiologic and pathologic dilatations. The routine use of prenatal ultrasound and the improving resolution of ultrasound equipment allow the detection of smaller dilatations. The third-trimester threshold value for the antero-posterior renal pelvis diameter of 7 mm is the best ultrasound criterion to predict postnatal renal abnormalities with a positive predictive value of 69%. A renal pelvis dilatation during the second trimester of pregnancy can be used as a warning sign for urinary tract malformation, and should not be ignored even if there is no further progression in the third trimester, because this finding may reveal a significant urologic abnormality in 12% of cases. Isolated pyelectasis can signal the presence of vesico-ureteral reflux. Normal appearing urinary tract on 2 successive neonatal ultrasound rarely coexist with significant abnormal findings on voiding cysto-urethrography. Therefore, in such cases, invasive investigations are not justified.
Provision of care to an older adult with dementia is an important societal resource. This resource may also come at a high cost to informal caregivers, most of whom are family members. In this paper we provide an overview of recent research on dementia caregiving and caregiver interventions. First, we provide background information on the prevalence and costs of Alzheimer's disease and related disorders. Second, we describe the specific stressors and broader mental and physical health outcomes of dementia caregiving. Third, recent evidence of the efficacy of caregiver interventions for both caregiver and patient outcomes is reviewed. Throughout the paper, we describe promising new directions for future research in this area, including assessment and intervention with family caregivers of older patients with comorbid dementia and depression, and the focus on sleep disturbance as a critical health consequence of dementia caregiving.
A retrospective analysis was performed, in a single institution, of patients with locally advanced pancreatic carcinoma without evidence of distant metastases, who were treated with chemoradiation. Between 1994 and 2000, 24 patients were treated with radiation and 5-fluorouracil (5-FU). The standard dose of radiation prescribed was 45 Gy to the 95% isodose in 25 fractions over 5 weeks. 5-FU was given as a 60 min infusion on days 1-5 and 29-33 at 350 mg/m2, following low dose folinic acid. Actuarial survival, local control and toxicity rates were assessed for the group. The median survival was 12 months, with a 48% 1-year survival and a 29% 2-year survival. The median time to progression was 8 months. The treatment was well tolerated and all patients achieved 100% compliance. In terms of radiological tumour response, five patients (22%) had a complete response, 10 patients (45%) demonstrated partial tumour shrinkage and a further three additional patients had radiological stable disease. The majority of patients experienced a symptomatic improvement. Chemoradiation can produce effective local control with symptomatic improvement in patients with localised carcinoma of the pancreas. Further studies are needed to determine the most effective combination of chemotherapy agents, combined with radiotherapy in the management of this disease.
OBJECTIVE: The purpose of this study was to evaluate the effects of birth weight on cord serum lipid and apolipoprotein levels in preterm infants with and without respiratory distress syndrome (RDS). METHODS: Cord serum lipid and apolipoprotein levels were evaluated in preterm infants (39 with RDS and 68 controls without RDS). Based on morbidity and mortality risk, RDS and non-RDS infants were separated into four birth weight groups (2,000-2,499 g, 1,500-1,999 g, 1,000-1,499 g, < 1,000 g) and evaluated for effects of birth weight on cord serum levels. RESULTS: RDS infants with birth weight of 2,000-2,499 g had significantly higher levels of cholesterol, triglyceride, total fatty acids and apolipoprotein A-I, but not arachidonic acid, than controls. RDS infants weighing 1,000-1,999 g had lower total fatty acids and apolipoprotein B levels, including arachidonic acid, than non-RDS infants. Cord serum lipid and apolipoprotein levels were significantly elevated in large (2,000-2,499 g) RDS infants, but lower levels were found in smaller (1,000-1,999 g) RDS infants. CONCLUSIONS: Cord serum arachidonic acid and apolipoprotein levels found in RDS infants suggest that lipid transport across the placenta may be abnormal. Inadequate total fatty acid supplies in utero could interfere with normal fetal growth and maturation, leading to development of neonatal RDS as one manifestation of risk for postnatal morbidity and mortality.
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A new venous bag has been developed, prototyped, and tested. The new bag has its inlet, outlet purge, and infusion tubes extending upward from the top of the bag, and are threaded through, bonded to, and sealed within a flat rigid top plate. This design allows the bag to be hung from its top plate by its tubes. It also allows the bag to be: 1) dropped into or removed from its holder, as is done with existing hard-shell reservoirs so that its weight pulls it into the holder without the need for eyelets and hooks and 2) placed closer to the floor so that gravity drainage is facilitated. The V-Bag (VB) is easily sealed within an accompanying rigid housing. Once sealed, vacuum applied to the housing is transmitted across the flexible walls of the bag to the venous blood. Thus, vacuum-assisted venous drainage (VAVD) is obtained as it is with a hard-shell reservoir, but without any contact of air with the blood. Bench tests, using a circuit that simulated the venous side of the cardiopulmonary bypass (CPB) circuit, showed that applying suction to the housing increased venous flow, and the fractional increase in flow was not a function of the venous cannula, but of the level of vacuum applied. In the gravity drainage mode, the bubble counts at the outlet of the V-Bag compared to two other bags were lower at any pumping condition. When used in the VAVD mode, bubble counts were two orders of magnitude lower than when using kinetically assisted venous drainage (KAVD) with a centrifugal pump. Results obtained with the VB suggest its clinical usefulness.
We compared the implementation of secondary prevention some 18 months following acute myocardial infarction or coronary artery bypass surgery in Ireland in 1994 to that in 15 European countries, including Ireland, in 2000. While there were substantial improvements in the use of statins, b-blockers and the availability of rehabilitation programmes since the early 1990s, more patients now smoke, take no exercise and are overweight. The prevalence of non-insulin dependent diabetes has increased by 70%. In comparison with other European countries, we have the highest use of aspirin and the highest prevalence of smoking in women. Despite a considerable improvement in the use of drug therapy we will not achieve the full potential of secondary prevention unless lifestyle factors, including smoking, overweight and exercise receive greater attention by patients with coronary heart disease.
BACKGROUND: The excitatory amino acid domoic acid, a glutamate and kainic acid analog, is the causative agent of amnesic shellfish poisoning in humans. No studies to our knowledge have investigated the potential contribution to short-term neurotoxicity of the brain microglia, a cell type that constitutes circa 10% of the total glial population in the brain. We tested the hypothesis that a short-term in vitro exposure to domoic acid, might lead to the activation of rat neonatal microglia and the concomitant release of the putative neurotoxic mediators tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinases-2 and-9 (MMP-2 and -9) and superoxide anion (O2-). RESULTS: In vitro, domoic acid [10 microM-1 mM] was significantly neurotoxic to primary cerebellar granule neurons. Although neonatal rat microglia expressed ionotropic glutamate GluR4 receptors, exposure during 6 hours to domoic acid [10 microM-1 mM] had no significant effect on viability. By four hours, LPS (10 ng/mL) stimulated an increase in TNF-alpha mRNA and a 2,233 % increase in TNF-alpha protein In contrast, domoic acid (1 mM) induced a slight rise in TNF-alpha expression and a 53 % increase (p < 0.01) of immunoreactive TNF-alpha protein. Furthermore, though less potent than LPS, a 4-hour treatment with domoic acid (1 mM) yielded a 757% (p < 0.01) increase in MMP-9 release, but had no effect on MMP-2. Finally, while PMA (phorbol 12-myristate 13-acetate) stimulated O2- generation was elevated in 6 hour LPS-primed microglia, a similar pretreatment with domoic acid (1 mM) did not prime O2- release. CONCLUSIONS: To our knowledge this is the first experimental evidence that domoic acid, at in vitro concentrations that are toxic to neuronal cells, can trigger a release of statistically significant amounts of TNF-alpha and MMP-9 by brain microglia. These observations are of considerable pathophysiological significance because domoic acid activates rat microglia several days after in vivo administration.
This study examined quantitative measures of sleep electroencephalogram (EEG) and phasic rapid eye movements (REM) as correlates of remission and recovery in depressed patients. To address correlates of remission, pre-treatment EEG sleep studies were examined in 130 women outpatients with major depressive disorder treated with interpersonal psychotherapy (IPT). To address correlates of recovery, baseline and post-treatment EEG sleep studies were examined in 23 women who recovered with IPT alone and 23 women who recovered with IPT+fluoxetine. Outcomes included EEG power spectra during non-rapid eye movement (NREM) sleep and REM sleep and quantitative REMs. IPT non-remitters had increased phasic REM compared with remitters, but no significant differences in EEG power spectra. IPT+fluoxetine recoverers, but not IPT recoverers, showed increases in phasic REM and REM percentage from baseline to recovery. In NREM sleep, the IPT+fluoxetine group showed a decrease in alpha power from baseline to recovery, while the IPT group showed a slight increase. The number of REMs was a more robust correlate of remission and recovery than modeled quantitative EEG spectra during NREM or REM sleep. Quantitative REMs may provide a more direct measure of brainstem function and dysfunction during REM sleep than quantitative sleep EEG measures.
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Immunochromatographic assays have become popular diagnostic tools in a variety of settings because they are sensitive, fast, and easy to use. Here, we describe the use of a novel reporter, upconverting phosphors (UCP), in this assay format. UCP are submicron-sized, inorganic crystals that are excited with infrared light and that emit photons in the visible range depending on the ion composition of the crystal. Using human chorionic gonadotropin (hCG) as a model analyte to describe the properties of phosphors in immunochromatographic assays, a detection limit of 10 pg hCG in a 100-microl sample has been achieved on a regular basis, with occasional detection of 1 pg hCG. This represents at least a 10-fold improvement over conventional reporter systems such as colloidal gold or colored latex beads. Quantitation of analytes is possible over at least 3 orders of magnitude. Furthermore, an example is given of how UCP can be used for analyte multiplexing using a two-plexed wick for the detection of mouse IgG and ovalbumin. Thus, UCP lateral flow assays can be used for applications that are currently limited by assay sensitivity, and they can increase the probability of a diagnosis by verifying the presence of several analytes in the same sample.
Glucocorticoids are agents endowed with powerful immunosuppressive and anti-inflammatory properties partially related to the inhibition of adhesion-related processes. We have previously demonstrated that glucocorticoids inhibit LFA-1 and CD2 expression in human peripheral blood mononuclear cells (PBMC) by down-regulating mRNA steady-state levels. In this study, we investigated whether glucocorticoids could also act indirectly by modulating the effect/function of cytokines whose expression are known to inhibit. To test this hypothesis, we replenished the following cytokines IL-2, IL-7, IL-15, TNF-alpha, IL-1beta, IL-4 and IL-10, in an in vitro PBMC culture system. Our results indicate that only the IL-2Rgamma-chain-dependent cytokines IL-2, IL-7 and IL-15, among the cytokines of this panel, could reverse the inhibition of glucocorticoids on PBMC adhesion molecule expression and the related functions of intercellular aggregation and proliferation. Furthermore, we also demonstrated that IL-2, IL-7 and IL-15 could induce de novo the synthesis of LFA-1 and CD2. Taken together, these data suggest that glucocorticoids inhibit PBMC LFA-1 and CD2 expression not only directly by modulating transcriptional events, but also indirectly through the inhibition of IL-2Rgamma-dependent cytokines.
OBJECTIVE: To determine whether MR imaging, including MR urography, is able to assess complicated duplex kidneys and to determine the possible role of MRI compared to other imaging techniques in such uropathies. MATERIAL AND METHODS: Twenty consecutive patients (age 1 month-11 years) presenting with a suspicion of a complicated duplex kidney were prospectively studied with MRI and MR urography. The examinations were performed on a 0.5-T machine using routinely available sequences that were optimised to the patient's age and size. MR images were reviewed separately by two observers blinded to the patient history. They were asked to assess the presence of a duplex kidney, the presence of an abnormality that may require surgery and to indicate the type of the inferior ureteric insertion. A qualitative gradation of these results was performed on the basis of the final diagnosis provided at endoscopy (n = 6) or surgery (n = 14). MR results were compared to those provided by US examinations and excretory urography, when available, and a non-parametric statistical analysis was performed. RESULTS: MRI differentiated well between the upper and the lower poles of the kidneys and correctly answered the three questions in all 20 patients. The two observers agreed completely in all the 20 patients. MR was statistically superior to both US and excretory urography in the evaluation of the distal ureter (P < 0.05). CONCLUSIONS: MRI provides a precise assessment of the complications associated with duplex kidneys. Its optimal role seems to be the assessment of ectopic extra-vesical ureteric insertions and whenever an occult upper pole is suspected.
Renal dysplasia (RD) is a common cause of chronic renal failure (CRF) in children. The evolution towards end-stage renal failure is unpredictable due to the paucity of early prognostic factors. In order to identify early prognostic clinical criteria, we have retrospectively analyzed renal function and growth in 11 infants with RD and CRF from birth up to 4 years of age. Children with obstructive RD were not included. Glomerular filtration rate (GFR) was estimated from Schwartz formula. In infants with a GFR below 15 ml/min per 1.73 m2 at 6 months of age (group A, n=5), kidney function did not further improve; 4 reached end-stage renal failure between 8 months and 6 years of age. In contrast, infants with a GFR above 15 ml/min per 1.73 m2 at 6 months of age (group B, n=6) experienced a significant improvement in renal function during follow-up, and none required renal replacement therapy. During the first 3 months of life all infants with RD and CRF developed severe growth retardation. Between 6 months and 4 years of age, children from group B grew significantly better than those from group A. In conclusion, our experience suggests that GFR, estimated from Schwartz formula at 6 months of age, is a useful prognostic factor in infants with RD and CRF. Infants with a GFR below 15 ml/min per 1.73 m2 are at risk of severe growth delay and the need for early renal replacement therapy, whereas those with a GFR above 15 ml/min per 1.73 m2 have a relatively favorable long-term prognosis.
Five geese flocks were surveyed to gather data on the prevalence and clinical manifestation of traumatic myiasis and the fly species involved. Myiasis was recorded in all the flocks and the total number of infested geese was 26 (ca. 0.1% of the total numbers). The first cases were observed at the end of May, the last ones in August. Most birds (16/26) were infested in August. Each affected goose had only one lesion, which was located more frequently on the wings (14/26) than on any other body. In seven geese, Wohlfahrtia magnifica (Diptera: Sarcophagidae) was the only myiasis-causing species. In these cases the detransformed mean number of larvae per wound was 18.1 (range 5-40). Lucilia sericata (Diptera: Calliphoridae) was found to be solely responsible for the lesions of 12 birds, with detransformed mean of 94.0 (range 2-893) larvae per goose. The larvae of this species appeared to be generally less invasive than those of W. magnifica, but in three cases they were also deeply embedded in the wounds. In seven geese larvae of both fly species developed together in and around the wounds. With the exception of one lesion, there were more larvae of W. magnifica (detransformed mean of 21.8 with a range of 1-55) than that of L. sericata (detransformed mean of 11.2 with a range of 2-61) in these mixed infections. Predisposing conditions for development of traumatic myiasis in geese included plucking of feathers, other injuries and bacterial infections (e.g. inflammation of the phallus).
The objectives of the paper were to identify barriers to community participation in road safety activities and to recommend strategies to reduce those barriers. Information was obtained from: a review of relevant literature, from the authors' extensive community-based experiences, from undertaking community-based research, and from interviews with key stakeholders in road safety in Western Australia. Ten significant barriers to community participation were identified. These are classified into two groups: personnel and planning issues. The former includes: reasons why people are often reluctant to become involved in projects in their communities, a lack of leadership, and a lack of skills. The latter includes: inappropriate program foci, inappropriate program evaluation, lack of resources, and a lack of sustainability. It was concluded that the barriers to community involvement in road safety initiatives are similar in many parts of Australia and overseas and apply to a wide range of health promotion interventions besides road safety. Awareness of the barriers and knowledge of their solutions can ensure that appropriate steps are taken to maximise the likelihood of community participation.