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Biomedical subjects

J Morris

Publications and source records attributed to J Morris.

At least 91 records · Page 5Linked to original sources

Development. PARallels in axis formation.

There is an intricate network of molecules called cell fate determinants that instruct the cells of the embryo to take on either an anterior or posterior fate. In a lively Perspective, Lehmann and her colleagues discuss new findings in the fruit fly that identify a key protein, PAR-1, which ensures that the cell fate determinants are themselves located in the correct region of the oocyte. In this way, the anterior-posterior axis is set up in the fruit fly egg before fertilization.

Actin Cytoskeleton↗

Cognitive resource limitations during sentence comprehension in Parkinson's disease.

Patients with idiopathic Parkinson's disease (PD) were asked to identify the agent of the action in orally presented sentences with subject-relative or object-relative center-embedded clauses while simultaneously performing a secondary task that was less resource-demanding (finger tapping) or more resource-demanding (recognition span). We found that a subgroup of PD patients with impaired sentence comprehension at baseline (no secondary task) did not differ from random in their accuracy understanding all types of sentences during the more demanding (recognition span) condition and also had difficulty understanding the most complex sentences during the less demanding (finger tapping) condition. Control subjects and PD patients without baseline sentence comprehension difficulty were random only in their comprehension of the most complex sentences under the more demanding (recognition span) secondary task condition. Examination of response latencies for accurately understood sentences revealed only an effect for the type of sentence, and this was equally evident across all groups of subjects and regardless of the condition under which the sentences were administered. The sensitivity of PD patients' sentence comprehension accuracy to secondary task resource demands is most consistent with the hypothesis that limited cognitive resources contribute to sentence comprehension difficulty in PD.

Aged↗

Willingness to pay for new chemotherapy for advanced ovarian cancer.

AIMS: To investigate whether health care professionals had differing attitudes about cost and survival issues in regard to the treatment of advanced ovarian cancer. METHODS: A questionnaire designed for the study was mailed to hospital doctors, hospital nurses, Crown Health Enterprise (CHE) managers and health authority managers who were working in the same geographical area. A total of 391 questionnaires were mailed and 186 were completed reflecting an overall response rate of 47%. Replies were received from 46% of the health authority managers, 61% of the CHE managers, 59% of the doctors and 27% of nurses. RESULTS: Results indicated a threshold for how much individuals were willing to pay. Group differences were evident with the nurses and CHE managers willing to spend less than the other two groups. In addition, those with experience of cancer treatment were willing to spend less than those with no such experience. CONCLUSIONS: There are differences in attitudes to costs and benefits of treatment between individuals working in different areas of health care. Health sector workers value treatments which extend life expectancy without necessarily being curative.

Adult↗

Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis.

A series of new nitrogen-carbon-linked (azolylphenyl)oxazolidinone antibacterial agents has been prepared in an effort to expand the spectrum of activity of this class of antibiotics to include Gram-negative organisms. Pyrrole, pyrazole, imidazole, triazole, and tetrazole moieties have been used to replace the morpholine ring of linezolid (2). These changes resulted in the preparation of compounds with good activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. The unsubstituted pyrrolyl analogue 3 and the 1H-1,2,3-triazolyl analogue 6 have MICs against H. influenzae = 4 microgram/mL and M. catarrhalis = 2 microgram/mL. Various substituents were also placed on the azole moieties in order to study their effects on antibacterial activity in vitro and in vivo. Interesting differences in activity were observed for many analogues that cannot be rationalized solely on the basis of sterics and position/number of nitrogen atoms in the azole ring. Differences in activity rely strongly on subtle changes in the electronic character of the overall azole systems. Aldehyde, aldoxime, and cyano azoles generally led to dramatic improvements in activity against both Gram-positive and Gram-negative bacteria relative to unsubstituted counterparts. However, amide, ester, amino, hydroxy, alkoxy, and alkyl substituents resulted in no improvement or a loss in antibacterial activity. The placement of a cyano moiety on the azole often generates analogues with interesting antibacterial activity in vitro and in vivo. In particular, the 3-cyanopyrrole, 4-cyanopyrazole, and 4-cyano-1H-1,2,3-triazole congeners 28, 50, and 90 had S. aureus MICs </= 0.5-1 microgram/mL and H. influenzae and M. catarrhalis MICs = 2-4 microgram/mL. These analogues are also very effective versus S. aureus and S. pneumoniae in mouse models of human infection with ED(50)s in the range of 1. 2-1.9 mg/kg versus 2.8-4.0 mg/kg for the eperezolid (1) control.

Administration, Oral↗

Review of the treatment literature for encopresis, functional constipation, and stool-toileting refusal.

This review summarizes the literature on randomized, controlled, published studies involving medical, behavioral, psychological, and biofeedback treatments for encopresis/functional constipation and stool-toileting refusal in preschool-age and school-age children. Nine such studies were located in the literature involving school-age children. No randomized, controlled treatment studies involving preschool-age children have been published. This review revealed no evidence to support the routine use of psychotherapy or anal sphincter biofeedback in the treatment of pediatric fecal elimination dysfunctions, beyond those benefits derived from a comprehensive medical-behavioral intervention. Further, this review indicated that paradoxical constriction of the External Anal Sphincter does not influence the treatment outcome of either biofeedback or medical-behavioral interventions. There are remarkably few controlled treatment outcome studies in this most important clinical area. More research is needed that employs standard treatment outcome variables.

Adolescent↗

Differential engraftment of genetically modified CD34(+) and CD34(-) hematopoietic cell subsets in lethally irradiated baboons.

OBJECTIVE: To test gibbon ape leukemia virus (GALV) pseudotype vector transduction of marrow subpopulations that contribute to hematopoietic reconstitution in vivo. MATERIALS AND METHODS: Autologous CD34(+) Lin(-), CD34(+) Lin(+), and CD34(-) Lin(-) marrow cells, transduced by coculture with PG13/LN, PG13/LNX, and PG13/LNY vector-producing cells, respectively, were transplanted in three female baboons. Two female baboons also were transplanted with fresh allogeneic CD34(-)Lin(-) marrow cells from MHC-matched male siblings and, to ensure survival, with autologous CD34(+)Lin(-) and CD34(+)Lin(+) marrow cells transduced with PG13/LN and PG13/LNX, respectively. The LN, LNX, and LNY vectors are identical except for different length sequences at the 3' end of the bacterial neomycin phosphotransferase (neo) gene. RESULTS: LN(+) and LNX(+) cells from CD34(+)Lin(-) and CD34(+)Lin(+) cells, respectively, but no LNY(+) from CD34(-)Lin(-) cells were detectable in blood and marrow of all animals after transplant. LN(+), CD34(+)Lin(-) cells contributed to reconstitution of the T, B, and myeloid lineages. LNX(+), CD34(+)Lin(+) cells contributed only to B and myeloid lineages. Male cells, CD34(-)Lin(-), were detected by polymerase chain reaction in blood and marrow of the two allogeneic transplanted animals at estimated frequencies of </=0.001% 1 month after transplant in both animals. Male cells became undetectable in one animal and have remained detectable, with declining frequency, in the other for more than 15 months. In this animal, no male CD34(+) or colony-forming cells have been detected. CONCLUSIONS: CD34(+)Lin(-) and CD34(+)Lin(+) marrow cells can serve as targets for GALV pseudotype retrovirus-mediated gene transfer. CD34(+)Lin(-) cells contribute to reconstitution of all hematopoietic lineages. Autologous CD34(-)Lin(-) cells were either not transduced by GALV pseudotype retrovirus vectors using current approaches or did not contribute significantly to reconstitution, as suggested by allogeneic transplants.

Animals↗

Palliative care consultations: how do they impact the care of hospitalized patients?

To provide a detailed description of the recommendations of a Palliative Care Service (PCS) and to describe the impact of these recommendations on the care of terminally ill patients in an academic medical center, we describe data from all consecutive patients referred by their attending physicians to the PCS of an academic teaching hospital over a 15-month period. All patients were seen within 24 hours of consultation request. Data were collected prospectively on the day of discharge or death. Attention was focused on six recommendations and their implementation: 1) discussion about prognosis and goals of care; 2) pursuing documentation of advance directives; 3) discussion about foregoing specific treatments and/or diagnostic interventions; 4) family and patient support; 5) discharge planning; and 6) symptom management. Over a 15-month period, we collected data on 325 patients. The most frequent diagnoses were cancer, dementia, and HIV disease. The patients were followed for a mean of 7.6 days. The average number of recommendations was 4.2 per patient and 91% of the recommendations were implemented (3.8 per patient). Recommendations increased to 5.3 per patient and the implementation rate increased to 97% (5.1 per patient) for the 44 patients transferred to the Palliative Care Unit (PCU). PCS consultations result in multiple recommendations with a very high implementation rate. The number of recommendations and the high implementation rate suggest a strong need for palliative care services within acute care hospitals.

Adult↗

The EEG consistency index as a measure of ADHD and responsiveness to medication.

The primary diagnostic procedure for Attention-Deficit/Hyperactivity Disorder (ADHD) is the clinical interview, because psychological, neuropsychological, and neurological tests to date have not had sufficient specificity. Currently, there is no objective means to measure severity of ADHD, or the extent to which it is benefited by various dosages of medication. We recently reported that a certain EEG profile, the Consistency Index, occurring during the transition between two easy cognitive tasks clearly differentiated ADHD from non-ADHD boys between the ages of 8 and 12. The current study replicated this with older males (19-25) using different tasks, and a double blind, placebo versus Ritalin controlled crossover design. Seven ADHD subjects were found to have a significantly lower Consistency Index than 6 non-ADHD males while transitioning from 2 Simple tasks during placebo condition, while only the ADHD subjects demonstrated a significant improvement in their Consistency Index while on Ritalin. Similar but nonsignificant trends were observed while transitioning across Hard tasks.

Adolescent↗

Evaluation of an integrated curriculum using problem-based learning in a clinical environment: the Manchester experience.

DESCRIPTION OF COURSE: In 1994, a new problem-based leaning (PBL) curriculum for year 1 medical students was introduced at the University of Manchester. The use of PBL has continued into the clinical clerkships. Year 3 of the curriculum is based entirely in a clinical environment with PBL groups meeting in three teaching hospitals. During this year, all students undertake two integrated 14-week modules with overarching themes. Each week, groups of eight students discuss a trigger problem connected to the relevant theme. The steps the groups use in the PBL process have been amended to encourage students to link their discussion with clinical experience. EVALUATION: At the end of each module, all 309 students were requested to complete an evaluation questionnaire. The response rates were 80% (n=247) and 89% (n=275) for the two core modules. RESULTS: The students have remained 'happy with the way the course is going' (83% at the end of module 2). They were also asked to rate a number of statements on a 5-point Likert scale (5=strongly agree). Concerning PBL, the students remained confident about working in a group (median 4), producing a set of learning objectives (median 4) and linking clinical experience with other knowledge (median 4). However, there were changes over the year. Fewer students agreed at the end of module 2 that 'the working problems were stimulating' (P=0.002) or 'motivated them to learn' (P < 0.001), but the clinical firms were seen as providing more appropriate experience (P=0.01) and being aware of the new curriculum and responding to it (P=0.018). We also surveyed the PBL tutors and had 65 returns from 78 people involved in the 38 PBL groups in year 3. The great majority of these are doctors employed by the National Health service. Virtually all the responders were happy to continue being a tutor (97%) and would recommend it to a colleague (93%). CONCLUSIONS: The evaluation has been positive with PBL having been successfully implemented in a clinical environment. We have identified significant changes over the year, which we need to address as we consolidate the curriculum.

Clinical Clerkship↗

Promoting secure attachment, maternal mood and child health in a vulnerable population: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of an early home-based intervention on the quality of maternal-infant attachment, maternal mood and child health parameters in a cohort of vulnerable families. METHODOLOGY: A total of 181 families were recruited to the study in the immediate postnatal period on the basis of a self report questionnaire relating to known family vulnerability factors. Families were assigned randomly to intervention (90), or control (91) groups. The intervention group received a series of home visits from a child health nurse (weekly to 6 weeks, fortnightly to 3 months), with a subgroup receiving home based short-term dynamic therapy from a social worker. Parent/family function was assessed at inception and at 4 months by the Parenting Stress Index and the Edinburgh Post Natal Depression Scale. At 4 months the quality of the home environment was assessed, utilizing the Home Observation for Measurement of the Environment Inventory, as were child and family health parameters and satisfaction with the community child health service. RESULTS: At 4 month follow-up, 160 families (80 intervention, 80 control) were available for assessment. The intervention improved family functioning at 4 months. All aspects of the home environment, including the quality of maternal-infant attachment and mothers' relationship with their child, were significantly enhanced. In particular, significant and positive differences were found in parenting with the intervention group feeling less restrictions imposed by the parenting role, greater sense of competence in parenting, greater acceptability of the child, and the child being more likely to provide positive reinforcement to the parent. Early differences in maternal mood were not maintained at 4 months. Various child health parameters were enhanced including immunization status, fewer parent-reported injuries and bruising, and researcher confirmed lack of smoking in the house or around the infant. The families were consistently more satisfied with their community health service. CONCLUSIONS: This form of early home based intervention targeted to vulnerable families promotes an environment conducive for infant mental and general health and hence long-term psychological and physical well-being, and is highly valued by the families who receive it.

Adult↗

Acute isolated cerebral mucormycosis in a patient with high grade non-Hodgkins lymphoma.

A 57-year-old female in complete remission of grade IV non-Hodgkin lymphoma whilst on intensive chemotherapy, suddenly developed unilateral hemispheric stroke with a fatal outcome in 3 days. She was apyrexial and had received antifungal prophylaxis during her treatment. Post-mortem examination showed complete thrombosis of the internal carotid artery leading to infarction in the territory of the middle and anterior cerebral arteries. Microscopic examination of the brain showed involvement of intra-cranial vessel walls and brain parenchyma by mucormyces, with no evidence of systemic mucormycosis. Isolated cerebral mucormycosis is a rare occurrence, more commonly found in intravenous drug abusers, but can occur in patients with haematological malignancy.

Central Nervous System Fungal Infections↗

C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

BACKGROUND: There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease. METHODS: Plasma specimens collected during 1979-83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations. RESULTS: There was a positive association between C-reactive protein and incident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002). There was also a positive association with all-cause mortality (P<0.0001). C-reactive protein was significantly associated with a number of non-circulating risk factors including body mass index (P<0.0001), smoking (P<0.0001), low forced expiratory volume in 1 s (P<0.0001), height (P=0.025), low childhood social class (P=0.014) and age (P=0.036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0.033). Further adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. CONCLUSION: C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.

Biomarkers↗

Development and implementation of the MTutor on-line tutorial system for diploma level research students.

This study describes the development, implementation and evaluation of MTutor, a web-based tutorial system, which was developed for students undertaking a diploma level research module. The aim of the study was to evaluate the feasibility of using a problem solving approach through an on-line system, to provide additional academic support for health care students undertaking a research module. The extent to which students found it a useful approach and resource for reinforcing learning and for developing their computer and information technology skills was also evaluated. The tutorial was developed around a single researchable problem related to communication skills and nurse-patient interactions. It was based on an experimental design and consisted of four sub-problems supported by a variety of text-based resources relevant to the sub-problems. A series of multiple-choice questions accompanied each sub-problem and an evaluation questionnaire at the end of the tutorial was used to obtain formal feedback on the system. The evaluation questionnaire revealed that students found the system to be easy to use and that the on-line resources provided sufficient information with which to answer the tutorial problems. Students felt that the tutorial reinforced the taught sessions in the module and that working through the problems enhanced their understanding of research design. Further piloting of the system is planned to obtain feedback from an additional cohort of students as well as lecturers teaching the diploma level research module.

Computer-Assisted Instruction↗

Palliative care in advanced dementia: a randomized controlled trial and descriptive analysis.

BACKGROUND: Few patients with end-stage dementia are enrolled in hospice care. A palliative care approach would nonetheless seem to be appropriate in various care settings, including the acute care hospital. METHODS: We conducted a randomized controlled trial of palliative care in patients with advanced dementia (Functional Assessment Staging Tool [FAST] stage 6d-7f) who were hospitalized with acute illness. Intervention patients received recommendations by a palliative care team with the goal of enhancing patient comfort; control patients received usual care without these recommendations. RESULTS: Among 99 patients enrolled over 3 years, groups were comparable at baseline in terms of gender, age, race, dementia stage, and advance directive status. Outcomes were similar in terms of mean number of hospitalizations, average length of stay, and mortality. Intervention patients were more likely than control patients to receive a palliative care plan (23% versus 4%; p = 0.008), usually on discharge, and more decisions were made to forgo certain medical treatments but the numbers were small. Fewer patients in the intervention group received intravenous therapy throughout the admission (66% vs. 81%, p = 0.025). Overall, additional interventions included daily phlebotomy for at least half of the admission (41%), systemic antibiotics (75%), and new feeding tubes (44%). Including tubes present at the time of randomization, a total of 69% received long-term enteral feeding. CONCLUSION: It was difficult for a palliative care research team to influence the care of advanced dementia patients in the acute hospital setting. When patients have advanced dementia, there may be unique barriers, including perceived prognostic uncertainty, difficulty assessing comfort level, and perceptions about tube feeding. There must be a reexamination of treatment approaches for this severely impaired group of patients. Further study should attempt to identify patients prior to the need for acute hospitalization so goals can be established when there is less urgency to make life and death decisions.

Journal Article↗

Serum inhibin A and activin A are elevated prior to the onset of pre-eclampsia.

Serum inhibin A and activin A concentrations increase in pre-eclampsia. We investigated the time courses of the changes in relation to the onset of the maternal syndrome and if their measurement could be useful for clinical prediction particularly in relation to early onset disease, the most severe of the clinical presentations. Serial samples were taken from 1496 healthy nulliparae. Changes in activin A and inhibin A were analysed in women with: early onset pre-eclampsia (n = 11), pre-eclampsia delivering at 34-36 weeks (n = 14), term pre-eclampsia (n = 25) and gestational hypertension (n = 25); and in a subset with uncomplicated pregnancies (n = 25). Serum inhibin A and activin A were increased in all groups prior to pre-eclampsia, before 20 weeks in those with early onset pre-eclampsia. Screening efficacy was determined at 15-19 and 21-25 weeks in all women who developed pre-eclampsia (n = 70) and randomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for early onset pre-eclampsia: 67 and 44% at 15-19 weeks and 89 and 89% at 21-25 weeks for inhibin A and activin A respectively. Hence, serum inhibin A and activin A concentrations increase before the onset of pre-eclampsia at gestational ages that depend on when pre-eclampsia develops. On their own such measures are unlikely to prove efficient for screening.

Activins↗