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Biomedical subjects

A Morton

Publications and source records attributed to A Morton.

At least 37 records · Page 2Linked to original sources

Ocular surface disease in intensive care unit patients.

PURPOSE: To assess the prevalence and natural history of ocular surface disease in patients in an intensive care unit (ICU) and to identify any predisposing factors in order to improve eye care management protocols. METHODS: The eyes of all patients admitted to an ICU between February and May 1998 were examined at least weekly. The eyelid position, presence of conjunctival oedema, degree of keratopathy and sedation score were documented at every assessment. RESULTS: Twenty-six patients in an ICU were followed throughout their stay, which ranged from 3 days to 10 weeks. Eleven patients (42%) had some degree of keratopathy, which was detected in the majority in the first week of their stay. The presence of ocular surface disease was closely correlated with the degree of lagophthalmos, which in turn is closely related to the depth of sedation or paralysis. CONCLUSIONS: In this first ever longitudinal study it was found that assessment of lid position in ICU patients is the single most important observation to be carried out. A management algorithm derived from this evidence is based on daily observation and selective lid taping and shows encouraging early results.

Adult↗

Ocular signs and symptoms and vitamin A status in patients with cystic fibrosis treated with daily vitamin A supplements.

BACKGROUND/AIMS: Patients with cystic fibrosis (CF) may have low plasma vitamin A levels from malabsorption, zinc deficiency, liver disease, or poor compliance with prescribed supplements. In view of the increasing number of adults with CF, many of whom drive cars, it is important to assess vitamin A status. In our centre an attempt has been made to achieve normal levels of fat soluble vitamins by annual estimation of plasma levels and appropriate oral supplementation. This study aimed to determine if this approach prevents vitamin A deficiency and the consequent problems with dark adaptation. METHODS: The study was conducted at the regional adult and paediatric cystic fibrosis unit and the patients were recruited from there. Dark adaptation studies were conducted at the department of ophthalmology, St James's University Hospital. All patients are regularly seen in the outpatient department by a CF specialist dietitian and have a comprehensive annual dietary assessment. 28 patients had the following investigations: serum retinol, plasma zinc, serum retinol binding protein, liver function tests, dark adaptation, contrast sensitivity, and anterior ocular surface status. 25 age and sex matched controls without CF or ocular pathology were also recruited for the dark adaptation study. RESULTS: None of the patients had vitamin A deficiency, the median value of serum retinol being 48 microg/dl, range 31-80 microg/dl (normal range 30-80 microg/dl). Dark adaptation was normal in all cases compared with the control group where the mean value was 3.4 log units of threshold luminance (95% confidence interval 2.4-4.0). None of the test group had a value of threshold luminance 2 SD above the mean value for the control group. Eight patients had reduced contrast sensitivity. The median value for serum zinc was 14.2 micromol/ l, range 13-81 micromol/l (normal range 8-23 micromol/l) and the median value for retinol binding protein was 36 mg/l, range 13-81 mg/l (normal range 35-58 mg/l). There was no correlation between dark adaptation and serum retinol, zinc, or retinol binding protein. Two patients had clinical evidence of dry eye. CONCLUSION: Regular estimates of plasma vitamin A together with appropriate supplementation and expert dietetic review can maintain normal dark adaptation in patients with cystic fibrosis. The occurrence of reduced contrast sensitivity function is well documented but remains an unexplained phenomenon and deserves further study.

Adolescent↗

Syme amputation for the treatment of fibular deficiency. An evaluation of long-term physical and psychological functional status.

BACKGROUND: Syme amputation is an accepted treatment for fibular deficiency. With improvement in limb-lengthening procedures, there has been renewed interest in limb salvage for these patients. The purpose of the present study was to evaluate the physical and psychological results in ten young adults who had had a Syme amputation for the treatment of fibular deficiency when they were children. METHODS: The evaluation consisted of physical examination, prosthetic assessment, psychological testing, and physical performance testing of knee extension and flexion with use of a Cybex-II dynamometer. RESULTS: Five patients reported no difficulty with the involved limb since the Syme amputation, four had had minor secondary procedures (three medial distal femoral or proximal tibial hemiepiphyseodeses, one reconstruction with an autologous patellar ligament graft, one revision of the stump, and one tibial osteotomy) on the affected extremity, and one had mild instability of the knee that had been treated nonoperatively. All ten patients had an appropriate, functional Syme prosthesis, and none reported difficulty with walking or running. On psychological testing, this group generally did not differ from the norm with regard to occupational satisfaction, personal growth, relationships with family members and peers, and recreational behavior. The patients' overall assessment of self-reported quality of life and self-esteem was similar to that of normative adult samples. In general, these patients were leading active, productive lives and had always done so. CONCLUSIONS: On the basis of the results of this study, we concluded that young adults who have had a Syme amputation apparently are not limited in their ability to pursue and achieve personal goals. In order to justify recommending limb salvage rather than early Syme amputation for the treatment of fibular deficiency, the results of multistaged lengthening and reconstruction would have to match the functional, psychological, and cost-effective results for the patients whom we studied, who had had a Syme amputation.

Adolescent↗

Valuing temporary and chronic health states associated with breast screening.

The aim of this study was to derive quality of life values for the four key breast screening outcomes (true negative, false positive, true positive and false negative), including the quality of life effects of the screening and treatment processes. In doing so, methodological issues in health status measurement were explored, in particular the valuation of temporary health states. The true negative and false positive descriptions were temporary health states, lasting for short term durations (12 months) and the true positive and false negative outcomes were chronic health states lasting for long term durations (rest of life). Descriptions of breast screening outcomes were valued using the time trade-off technique and the visual analogue scale. Paired comparisons between TTO values for states with the same duration found a difference between the true negative and the false positive time trade-off values but no difference for true positive and false negative descriptions. The TTO values for the false positive were low. The study highlights several important methodological issues such as the use of the two stage procedure for valuing temporary health states, the impact of duration on values, the impact of anchor points, and the importance of qualitative analysis of respondents values. Further empirical testing of all these issues is recommended.

Adult↗

Predictors for optimal mobilization and subsequent engraftment of peripheral blood progenitor cells following intermediate dose cyclophosphamide and G-CSF.

Fifty consecutive patients undergoing cyclophosphamide/G-CSF mobilization were studied for indicators predictive for adequate harvest (CD34+ cells > 2 x 10(6)/kg, CFU-GM > 1 x 10(5)/kg). Target yields following a single leukopheresis were achieved for 66% of patients (89% with no previous alkylation chemotherapy or radiotherapy). Previous alkylation therapy, radiotherapy and low collection day platelet count were predictive of poor collection yields. Following reinfusion, the median time to platelets > 20 x 10(9)/l (PLT > 20) was 10 days and to neutrophils > 500 x 10(6)/l (ANC > 500) was 13 days. Total CD34+ cells infused was predictive of early platelet engraftment. Previous radiotherapy was inversely predictive of neutrophil engraftment. For the majority of patients not exposed to alkylation therapy or radiotherapy, adequate progenitor cells can be collected following a single leukopheresis. In patients suitable for future autologous bone marrow transplantation it would seem appropriate to avoid or minimize radiotherapy and alkylation therapy exposure in the pre-collection period.

Adolescent↗

Comparison of open and laparoscopic live donor nephrectomy.

OBJECTIVE: This study compares an initial group of patients undergoing laparoscopic live donor nephrectomy to a group of patients undergoing open donor nephrectomy to assess the efficacy, morbidity, and patient recovery after the laparoscopic technique. SUMMARY BACKGROUND DATA: Recent data have shown the technical feasibility of harvesting live renal allografts using a laparoscopic approach. However, comparison of donor recovery, morbidity, and short-term graft function to open donor nephrectomy has not been performed previously. METHODS: An initial series of patients undergoing laparoscopic live donor nephrectomy were compared to historic control subjects undergoing open donor nephrectomy. The groups were matched for age, gender, race, and comorbidity. Graft function, intraoperative variables, and clinical outcome of the two groups were compared. RESULTS: Laparoscopic donor nephrectomy was attempted in 70 patients and completed successfully in 94% of cases. Graft survival was 97% versus 98% (p = 0.6191), and immediate graft function occurred in 97% versus 100% in the laparoscopic and open groups, respectively (p = 0.4961). Blood loss, length of stay, parenteral narcotic requirements, resumption of diet, and return to normal activity were significantly less in the laparoscopic group. Mean warm ischemia time was 3 minutes after laparoscopic harvest. Morbidity was 14% in the laparoscopic group and 35% in the open group. There was no mortality in either group. CONCLUSIONS: Laparoscopic live donor nephrectomy can be performed with morbidity and mortality comparable to open donor nephrectomy, with substantial improvements in patient recovery after the laparoscopic approach. Initial graft survival and function rates are equal to those of open donor nephrectomy, but longer follow-up is necessary to confirm these observations.

Adult↗

Exercise effects on bone mass in postmenopausal women are site-specific and load-dependent.

It is considered that skeletal mass in humans may respond to loading or the number of loading cycles. The aim of this study was to examine the effect of a 1 year progressive resistance training program on the bone mass of 56 postmenopausal women. Assignment was by block randomization to one of two resistance training groups: a strength trained group (3 x 8 repetition maximum) or an endurance group (3 x 20 repetition maximum). The resistance exercises were selected to stress the ipsilateral forearm and hip region. The exercising side was randomly assigned with one side exercised while the alternate side acted as the nonexercise control. Bone mineral density (BMD) was measured every 3 months at the radial forearm and four hip sites using the Hologic QDR 2000 bone densitometer. A linear regression function was fitted for each individual's bone density results, and the slope was compared for the exercise and control side using paired t-tests. The bone mass increase with the strength regimen was significantly greater at the trochanteric hip site (control -0.6 +/- 2.2%, exercise 1.7 +/- 4.1%, p < 0.01), at the intertrochanteric hip site (control -0.1 +/- 2.1%, exercise 1.5 +/- 3.0%, p < 0.05), Ward's triangle (control 0.8 +/- 5.2%, exercise 2.3 +/- 4.0%, p < 0.05), and at the ultradistal radial site (control -1.4 +/- 2.3%, exercise 2.4 +/- 4.3%, p < 0.01). There was no significant increase in BMD with the endurance regimen except at the radius midsite (control -1.0 +/- 2.3%, exercise 0.1 +/- 1.4%, p < 0.01). In both the endurance and the strength group, muscle strength, tested by a one-repetition maximum (1RM) test, increased significantly for all 10 exercises (p < 0.01) and to a similar degree in the two groups. In the strength group but not the endurance group there were significant correlations between the slope of the change in BMD and the percentage increase in strength as follows: trochanter with leg press; intertrochanter with leg press (p < 0.05); and Ward's triangle with hip extension and hip adduction (p < 0.05). Thus these results support the notion of a site-specific response of bone to maximal loading from resistance exercise in that although the trochanter and intertrochanter bone density was elevated by the resistance exercises undertaken, there was no effect on the femoral neck value. Postmenopausal bone mass can be significantly increased by a strength regimen that uses high-load low repetitions but not by an endurance regimen that uses low-load high repetitions. We conclude that the peak load is more important than the number of loading cycles in increasing bone mass in early postmenopausal women.

Adult↗

Variability of airway structure and inflammation in normal subjects and in cases of nonfatal and fatal asthma.

The quantitative assessment of airway inflammation in patients with apparently similar clinical severity of asthma has yielded variable results. The aim of this study was to assess the variability of inflammatory cell counts and airway structure in large and small airways from subjects with and without asthma, and to calculate the number of cases required to detect significant differences between disease groups. Three serial transverse sections, 20 microns apart, were examined from cartilaginous and membranous bronchioles. Airway dimensions measured were the areas and perimeters defined by the luminal surface of the airway epithelium, basement membrane, outer border of airway smooth muscle, and surrounding border of the airway adventitia. Airway wall components measured were the areas of airway smooth muscle, mucous glands and cartilage. The numbers (per mm of basement membrane) of lymphocytes, eosinophils, neutrophils and plasma cells were counted using haematoxylin and eosin staining and mast cells were counted in sections stained with Toluidine blue. Measurements were repeated by two or three observers. The coefficient of variation (CV) was used to assess intraairway, intraobserver and interobserver variability. For airway dimensions the mean (+/- SD) CV within airways was 3.8% +/- 2.1%, within observers was 3.7% +/- 1.8% and between observers, 3.4% +/- 1.8%. For airway wall components, the CV within airways was 10.7% +/- 4.6%, and between observers was 8.8% +/- 2.2%. For cell counts, the CV within airways was 20.8% +/- 12.5%, within observers was 8.3% +/- 3.7% and between observers, 9.6% +/- 4.6%. There were no significant differences in variability between cases with and without asthma. Intra-airway variability was higher (p < 0.05) in membranous airways (5.6% +/- 1.7%) than in large cartilaginous airways (2.3% +/- 1.1%). We estimate that between 5 and 15 cases in each group would be required to detect differences of 50-100% between groups, depending on the parameter being compared. These findings suggest that airway structure and inflammatory cell numbers are uniform throughout the bronchial tree in normal and asthmatic cases, and that small samples of large or small airways are likely to be representative when comparing cases.

Adult↗

CD4+ memory T cells are the predominant population of HIV-1-infected lymphocytes in neonates and children.

BACKGROUND: CD4+ memory T cells express CD45RO and are the principal viral reservoir in HIV-infected adults. In infants and children, CD45RO T cells comprise the minority of the CD4+ T-cell population. The majority of blood CD4+ T cells are naive, expressing CD45RA. OBJECTIVE: To determine the developmental stage at which pediatric CD4+ T cells become susceptible to HIV-1 infection in vivo by determining which T-cell population harbors HIV-1 proviral DNA. DESIGN: A prospective, cross-sectional analysis of peripheral blood CD8+ T cells, CD45RA, or CD45RO CD4+ T cells obtained from 10 HIV-infected neonates and children were analysed for provirus. METHODS: Semi-quantitative polymerase chain reaction methods were used to detect HIV-1 proviral DNA within purified lymphocyte populations selected using immunoaffinity magnetic microspheres. RESULTS: CD8+ T cells harbored no detectable HIV-1, indicating that infection of common thymocytes does not contribute to the population of infected blood T cells. In five children and two of the five neonates, the CD4+ CD45RO memory T lymphocytes contained 10-100-fold greater numbers of infected cells than the CD4+ CD45RA naive T-cell population. Three neonates, who exhibited rapid disease progression, demonstrated high proviral levels in their CD4+ CD45RA T cells. The normal age-related predominance of CD4+ CD45RA T cells was preserved independent of CD4+ T-cell attrition. CONCLUSIONS: The majority of HIV-1-infected blood CD4+ T cells in infants and children are restricted to the small population of terminally differentiated CD4+ CD45RO memory T cells. Neonates with rapid CD4+ T-cell attrition display high levels of provirus in their CD4+ CD45RA T-cell population.

Adult↗

Energetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme.

To determine the constraints on interactions within the core of a folded protein, we have analyzed the binding of 91 different compounds to an internal cavity created in the interior of phage T4 lysozyme by site-directed mutagenesis [Eriksson et al. (1992a) Nature 355, 371-373]. The cavity is able to accommodate a variety of small, mainly nonpolar, ligands. Molecules which do not appear to bind include those that are very polar, those that are too large, and those that have appropriate volume and polarity but inappropriate shape. Calorimetric analysis of 16 of these ligands reveals that their free energies of binding are poorly correlated with their solvent-transfer free energies. In addition, their enthalpies of binding are much larger than expected on the basis of transfer of the ligands from an aqueous to a nonpolar liquid phase. The binding energetics were analyzed by dividing the reaction into three processes: desolvation, immobilization, and packing. This analysis indicates that all three processes contribute to binding specificity. For a subset of these ligands that are structurally related, however, packing interactions in the protein interior are well modeled by the interactions of the ligands with octanol.

Bacteriophage T4↗

Specificity of ligand binding in a buried nonpolar cavity of T4 lysozyme: linkage of dynamics and structural plasticity.

To better understand the role of shape complementarity in ligand binding and protein core interactions, the structures have been determined of a set of ligands bound within a cavity-containing mutant of T4 lysozyme. The interior cavity is seen to consist of two parts that respond very differently to the binding of ligands. First, there is a relatively rigid region that does not relax significantly upon binding any ligand. Second, there is a more flexible region that moves to various extents in response to binding the different ligands. The part of the binding site that remains rigid is characterized by low temperature factors and strong protection from hydrogen exchange. This part of the site appears to be primarily responsible for discriminating between ligands of different shape (i.e., for determining specificity). The more flexible region, characterized by relatively high temperature factors and weak protection from hydrogen exchange, allows some promiscuity in binding by undergoing variable amounts of deformation at essentially the same energetic cost. This linkage between the dynamic information represented by crystallographic temperature factors and hydrogen-exchange behavior on the one hand, and structural plasticity in response to ligand binding on the other hand, suggests a way to improve our understanding of steric interactions in protein cores and protein-ligand binding sites. Ligand design and packing algorithms might take advantage of this information, requiring complementary interactions where the protein is rigid and allowing some overlap in regions where the protein is flexible.

Bacteriophage T4↗

Rapid differentiation of closely related isolates of two plant viruses by polymerase chain reaction and restriction fragment length polymorphism analysis.

Immunocapture reverse transcriptase-polymerase chain reaction (RT-PCR) followed by restriction fragment length polymorphism (RFLP) analysis of the product has been shown to be an effective procedure for discriminating serologically indistinguishable isolates of two plant viruses, raspberry bushy dwarf (RBDV) and zucchini yellow mosaic (ZYMV). For both viruses, only limited sequence information was available at the time of primer design, but most of the isolates which were tested could be amplified (the one exception being a serologically quite distinct isolate of ZYMV). Restriction endonucleases revealing diagnostic RFLPs were readily identified. Each of two isolates of ZYMV could be detected in the presence of the other and the relative proportions approximately quantified by visual estimation of the relative intensity of the appropriate bands. A range of isolates of different RBDV pathotypes were compared; isolates were grouped in ways that accorded with their known history. Computer analysis of the published sequence from which the primers had been derived showed the sequenced isolate to be identical with an isolate imported from the USSR. The PCR/RFLP procedure is rapid (it can be completed in less than 2 days), effective and will probably be generally applicable to distinguishing closely related virus isolates, even where little sequence information is available.

Base Sequence↗

Body dysmorphic disorder in patients with anxiety disorders and major depression: a comorbidity study.

OBJECTIVE: The authors evaluated the frequency of body dysmorphic disorder in patients with a primary diagnosis of anxiety disorders and major depression. METHOD: Patients with social phobia (N = 54), obsessive-compulsive disorder (N = 53), generalized anxiety disorder (N = 32), panic disorder (N = 47), and major depression (N = 42) and normal comparison subjects (N = 33) were studied. RESULTS: Body dysmorphic disorder was most common in patients with social phobia (11%) and obsessive-compulsive disorder (8%); it was less prevalent among patients with panic disorder (2%), generalized anxiety disorder (0%), and major depression (0%) and among normal subjects (0%). CONCLUSIONS: These findings suggest that body dysmorphic disorder may share etiologic elements with social phobia and obsessive-compulsive disorder.

Adolescent↗