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Biomedical subjects

S Walsh

Publications and source records attributed to S Walsh.

At least 55 records · Page 3Linked to original sources
PubMed2000

Surgical management of chronic parotid disease.

This is a retrospective review of a single surgeon's experience over a 20-year period, and covers the presentation, investigation, histology, management and complications of the surgical treatment of chronic parotid disease. There were 46 superficial parotidectomies (23 with ductal ligation); 3 required removal of calculi and there was one ductoplasty and one total parotidectomy. There were 28 cases of temporary palsy of the VIIth cranial nerve (55%, mean duration 4 months) and this was predominantly panfacial (79%). There were no cases of permanent palsy. Five patients who initially had a superficial parotidectomy required subsequent total parotidectomy for recurrent disease (11%). We have now adopted a policy of near total parotidectomy for the surgical treatment of chronic parotid disease.

Adolescent↗
PubMed2000

Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome.

Crouzon syndrome and Pfeiffer syndrome are both autosomal dominant craniosynostotic disorders that can be caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. To determine the parental origin of these FGFR2 mutations, the amplification refractory mutation system (ARMS) was used. ARMS PCR primers were developed to recognize polymorphisms that could distinguish maternal and paternal alleles. A total of 4,374 bases between introns IIIa and 11 of the FGFR2 gene were sequenced and were assayed by heteroduplex analysis, to identify polymorphisms. Two polymorphisms (1333TA/TATA and 2710 C/T) were found and were used with two previously described polymorphisms, to screen a total of 41 families. Twenty-two of these families were shown to be informative (11 for Crouzon syndrome and 11 for Pfeiffer syndrome). Eleven different mutations in the 22 families were detected by either restriction digest or allele-specific oligonucleotide hybridization of ARMS PCR products. We molecularly proved the origin of these different mutations to be paternal for all informative cases analyzed (P=2. 4x10-7; 95% confidence limits 87%-100%). Advanced paternal age was noted for the fathers of patients with Crouzon syndrome or Pfeiffer syndrome, compared with the fathers of control individuals (34. 50+/-7.65 years vs. 30.45+/-1.28 years, P<.01). Our data on advanced paternal age corroborates and extends previous clinical evidence based on statistical analyses as well as additional reports of advanced paternal age associated with paternal origin of three sporadic mutations causing Apert syndrome (FGFR2) and achondroplasia (FGFR3). Our results suggest that older men either have accumulated or are more susceptible to a variety of germline mutations.

Acrocephalosyndactylia↗
PubMed2000

Effects of high-intensity resistance training on untrained older men. II. Muscle fiber characteristics and nucleo-cytoplasmic relationships.

During growth and repair of skeletal muscle fibers, satellite cells become activated, undergo mitosis, and a daughter nucleus becomes incorporated into the muscle fiber to increase myonuclear numbers. An increase in myonuclei appears to be required for this postnatal growth. This study examined whether muscle fibers of elderly men can hypertrophy with strength training and, if so, whether they have the capacity to incorporate nuclei into the fibers. The sarcoplasmic area associated with each myonucleus was calculated in nine elderly men before and after 16 weeks of strength training, and compared to nine elderly control men. Muscle fiber type changes and myosin heavy chain composition were also compared. All major fiber types (I, IIA, IIB) became significantly larger after training, and a transition of type IIB fibers to IIA occurred with training. The area occupied by each fiber type correlated with myosin heavy chain percentage, and both of these changed similarly with strength training. The cytoplasm-to-myonucleus ratio increased, but not significantly (p = .07), with muscle fiber hypertrophy. Number of myonuclei per fiber and myonuclei per unit length of muscle fiber increased, but not significantly. Cross-sectional areas of the muscle fibers in untrained elderly men were much smaller than in untrained young men (when compared with our earlier studies). Training increased the sizes of the elderly muscle fibers to that of the untrained young men. This hypertrophy of muscle fibers by 30% with training resulted in no change in the cytoplasm-to-myonucleus ratio. This suggests that the myonuclear population continues to adapt to growth stimuli in the elderly muscles.

Adenosine Triphosphatases↗
PubMed2000

Pulled elbow.

Explore the source record for details and available documents.

Child↗
PubMed2000

Human junction adhesion molecule regulates tight junction resealing in epithelia.

Epithelial cells form a highly selective barrier and line many organs. The epithelial barrier is maintained by closely apposed cell-cell contacts containing tight junctions, the regulation of which is incompletely understood. Here we report the cloning, tissue localization and evidence for a role in epithelial barrier regulation of an immunoglobulin superfamily member that likely represents the human homolog of murine junction adhesion molecule (JAM). Analysis of the primary structure of human JAM, cloned from T84 epithelial cells, predicts a transmembrane protein with an extracellular domain that contains two IgV loops. Monoclonal antibodies generated against the putative extracellular domain were reactive with a 35-39 kDa protein from both T84 epithelial cells and human neutrophils. By immunofluorescence, JAM mAbs labeled epithelial cells from intestine, lung, and kidney, prominently in the region of tight junctions (co-localization with occludin) and also along lateral cell membranes below the tight junctions. Flow cytometric studies confirmed predominant JAM expression in epithelial cells but also revealed expression on endothelial and hematopoietic cells of all lineages. Functional studies demonstrated that JAM specific mAbs markedly inhibited transepithelial resistance recovery of T84 monolayers after disruption of intercellular junctions (including tight junctions) by transient calcium depletion. Morphologic analysis revealed that, after disassembly of cell-cell junctions, anti-JAM inhibition of barrier function recovery correlated with a loss of both occludin and JAM, but not ZO-1, in reassembling tight junction structure. Reassembly of the major adherens junction component E-cadherin was not affected by JAM specific mAbs. Our findings suggest that JAM plays an important role in the regulation of tight junction assembly in epithelia. Furthermore, these JAM-mediated effects may occur by either direct, or indirect interactions with occludin.

Amino Acid Sequence↗
PubMed2000

Rescuer and rescued: applying a cognitive analytic perspective to explore the 'mis-management' of asthma.

Asthma is a life-threatening and disabling condition in which medication is the major form of management. However, there is widespread evidence that asthmatic patients do not comply with their medical regimens which increases the likelihood of relapse, crisis, hospital admission and can represent a threat to the patient's life. A phenomenological qualitative study was designed which integrated the framework of cognitive analytic therapy. The aim was to explore those factors that influenced the self-care regimens of asthma sufferers. Thirty-five patients were interviewed and three patterns of 'non-compliance' were identified. The clinical implications are discussed. The paper concludes with comments on the contribution of psychotherapeutic tools as a means of understanding 'risky' patient behaviours.

Adult↗
PubMed2000

Cerebral oxygenation at high altitude and the response to carbon dioxide, hyperventilation and oxygen. The Birmingham Medical Research Expeditionary Society.

Cerebral oxygenation is likely to be of critical importance in determining function at high altitude. The present study has used the technique of near-IR spectroscopy to monitor changes in cerebral regional oxygenation in response to inhaled carbon dioxide, hyperventilation and supplementary oxygen on ascent to 4680 m over 3 days. At sea level, inhaled CO(2) resulted in a significant rise in cerebral regional oxygenation [from mean 69.6% (S.D. 2.4% to 71. 1+/-2.3%; means+/-S.D.; P<0.001). At 4680 m, CO(2) increased regional cerebral oxygenation (63.8+/-2.5% to 65.9+/-2.2%; P<0.001) and also increased peripheral oxygen saturation (75.1+/-6.1% to 83. 6+/-4.0%; P<0.001). Voluntary hyperventilation resulted in improved peripheral oxygen saturation at 2770 m, 3650 m and 4680 m, whereas cerebral regional oxygenation was reduced at sea level and at 2770 m, unchanged at 3650 m and increased at 4680 m. Supplementary oxygen (6 1itres/min) at 4680 m resulted in greater improvements in peripheral oxygen saturation (76.7+/-7.9% to 98.1+/-1.5%; P<0.001) and cerebral regional oxygenation (64.6+/-3.3% to 70.6+/-2.9%; P<0. 001) than were found with CO(2) or hyperventilation. We conclude that attempts to increase CO(2) inhalation or ventilation at high altitude are likely to be beneficial for cerebral oxygenation in the short term.

Adult↗
PubMed2000

Risk factors that may adversely modify the natural history of the pediatric pronated foot.

Flatfoot is one of the most common conditions seen in pediatric podiatry practice. There is no universally accepted definition for flatfoot. Flatfoot is a term used to describe a recognizable clinical deformity created by malalignment at several adjacent joints. Clinically, a flatfoot is one that has a low or absent longitudinal arch. Determining flexibility (physiologic) or rigidity (pathologic) is the first step in management. A flexible flat foot will have an arch that is present in open kinetic chain (off weight-bearing) and lost in closed kinetic chain (weight-bearing). A rigid flatfoot has loss of the longitudinal arch height in open and closed kinetic chain. According to Mosca, "The anatomic characteristics of a flatfoot are excessive eversion of the subtalar complex during weight-bearing with plantarflexion of the talus, plantarflexion of the calcaneus in relation to the tibia, a dorsiflexed and abducted navicular and a supinated forefoot." Normally developing infants have a flexible flatfoot and gradually develop a normal arch during the first decade of life. When evaluating an infant for a pronated condition, the examiner must also consider other risk factors that may affect the foot in its overall development. These contributing factors will play a role in the development of a treatment plan. The risk factors include ligamentous laxity, obesity, rotational deformities, tibial influence, pathological tibia varum, equinus, presence of an os tibiale externum, and tarsal coalitions. The authors realize other less significant factors exist but are not as detrimental to the foot as the primary ones discussed in depth. The primary risk factors that affect the pronated foot have been outlined. The clinician should always examine for these conditions when presented with a child exhibiting pronatory changes. A thorough explanation to the parents as to the consequential effects of these risk factors and their effects on the pediatric pronated foot is paramount to providing an acceptable comprehensive treatment program. Children often are noncompliant with such treatments as stretching and orthotic maintenance. The support of the parents is crucial to maintaining an effective treatment program continued at home.

Child↗
PubMed1999

p27 expression in inflammatory bowel disease-associated neoplasia. Further evidence of a unique molecular pathogenesis.

The cyclin-dependent kinase inhibitor p27 is a negative regulator of the transition from G1 to S phase of the cell cycle, protects against inflammatory injury and promotes epithelial differentiation. Because p27 protein has been shown to be abnormally expressed both in dysplasia associated with Barrett's esophagus and in sporadic colorectal adenomas, we used immunohistochemistry to evaluate p27 expression in inflammatory bowel disease (IBD)-associated dysplasia and carcinomas. Normal, inflamed, and transitional mucosa, sporadic adenomas, and sporadic colonic carcinomas were studied as controls. In normal colonic epithelium p27 expression was restricted to the superficial, terminally differentiated cells. In colitic and inflamed diverticular mucosa p27 was expressed in the base of the crypts in 86 and 70% of cases, respectively. Similarly, in transitional mucosa adjacent to sporadic carcinomas p27 was expressed in the base of the crypts in all cases. Strong p27 expression extended more frequently from the base of the crypts to superficial cells in IBD-associated dysplasia than in sporadic adenomas (P < 0.007). Twenty of 20 (100%) IBD-associated carcinomas showed low p27 expression (<50% nuclei positive) compared to 6 of 20 (30%) stage-matched sporadic colorectal carcinomas (P < 0.001). We conclude (i) aberrant p27 protein expression in inflamed and IBD-associated nondysplastic mucosa is indistinguishable from that found in transitional mucosa adjacent to sporadic carcinomas; (ii) p27 is overexpressed in dysplastic lesions, perhaps as an attempt to counterbalance proliferative stimuli; and (iii) IBD-associated colorectal carcinomas have significantly lower p27 expression, commonly associated with poor prognosis, than stage-matched sporadic colorectal carcinomas. These findings further substantiate the existence of divergent molecular pathogenetic pathways between these types of carcinomas and suggest an intrinsically more aggressive behavior of IBD-associated colon carcinomas compared to sporadic ones.

Cell Cycle↗
PubMed1999

Evaluating recovery from anorexia nervosa and bulimia nervosa: integrating lessons learned from research and clinical practice.

The aims of this article are to critically examine the conceptualization and measurement of recovery, within the eating disorder outcome literature, and suggest possible ways of developing the clinical utility of outcome research. First, definitions and measures of recovery operationalized in outcome studies are critically reviewed, highlighting the variety of definitions and measures used in outcome research. Two important caveats in the outcome literature are identified: absence of clients' views on their recovery from outcome evaluations and dissociation of outcome research from negotiated interpersonal and organizational meanings of recovery. These caveats form the focus of the second section of the article. A need for greater integration between research and clinical perspectives on recovery is identified, and the final section of the article suggests several proposals for enhancing current research on recovery from eating disorders. These proposals particularly advocate development of methods and measures that can accommodate diversity of clients' experiences of recovery, while remaining informative to both researchers and clinicians.

Adolescent↗
PubMed1999

Interval-force relation is unaffected by the presence of cardiomyopathy or coronary artery disease in patients with atrial fibrillation.

BACKGROUND: We tested the hypothesis that cycle length-dependent cardiac contractility in atrial fibrillation is primarily governed by the negative interval-force relation in patients with normal and depressed systolic function. METHODS AND RESULTS: We performed two-dimensional guided M-mode echocardiography in 41 patients (mean age, 69 +/- 4 years; range, 48 to 92 years; 19 men, 11 women). Twelve patients had objective evidence of left ventricular systolic dysfunction (CMP; mean ejection fraction, 37% +/- 7%) in the absence of coronary artery disease (CAD), 13 patients had documented CAD (mean ejection fraction, 43% +/- 6%), and 16 patients had normal resting left ventricular systolic function (mean ejection fraction, 58% +/- 7%). Simultaneous beat-to-beat blood pressure, end-systolic and end-diastolic dimension, circumferential velocity of fiber shortening (Vcf), and end-systolic wall stress (ESWS) were calculated for all patients. All three groups showed a significant linear relation between beat-to-beat Vcf and Vcf corrected for afterload (represented as the Vcf/ESWS ratio) and preceding cycle length. There was, however, no significant difference in the relation between either of these variables and cycle length among the three groups. There was also no difference in the rate of change in either Vcf or Vcf corrected for afterload (Vcf/ESWS ratio) from beat-to-beat among the three groups. Control patients with normal systolic function showed greater Vcf at any given cycle length compared with patients with CMP or CAD. CONCLUSION: Our data show that, for each beat in atrial fibrillation, Vcf and Vcf/ESWS ratio are decreased after shorter cycle lengths and increased after long cycles, but there is no significant attenuation of this effect in patients with systolic dysfunction with or without coronary disease compared with controls. Thus, the negative interval-force relation, the predominant determinant of beat-to-beat variation in contractility in atrial fibrillation, is preserved in patients with CAD or reduced left ventricular systolic function.

Aged↗
PubMed1999

Refinement of the chromosome 5p locus for familial calcium pyrophosphate dihydrate deposition disease.

Familial calcium pyrophosphate dihydrate deposition disease (CPPDD) is a disease of articular cartilage that is radiographically characterized by chondrocalcinosis due to the deposition of calcium-containing crystals in affected joints. We have documented the disease in an Argentinean kindred of northern Italian ancestry and in a French kindred from the Alsace region. Both families presented with a common phenotype including early age at onset and deposition of crystals of calcium pyrophosphate dihydrate in a similar pattern of affected joints. Affected family members were karyotypically normal. Linkage to the short arm of chromosome 5 was observed, consistent with a previous report of linkage of the CPPDD phenotype in a large British kindred to the 5p15 region. However, recombinants in the Argentinean kindred have enabled us to designate a region<1 cM in length between the markers D5S416 and D5S2114 as the CPPDD locus.

Calcium Pyrophosphate↗
PubMed1999

Who calls 999 and why? A survey of the emergency workload of the London Ambulance Service.

BACKGROUND: In 1996-97 there were 623,000 emergency (999) calls made to the London Ambulance Service (LAS) and this represents a 30% increase over the previous five years. The reasons for this increase, which is also observed nationally, remain unknown. It has been suggested that some callers may be using the 999 service "inappropriately" but no data are available from the ambulance service. OBJECTIVE: To describe the workload of the emergency ambulance service in London with specific reference to the nature and characteristics of 999 calls, to determine who dials 999 and why, and to establish the number and types of calls that could most appropriately be dealt with by other agencies. DESIGN: A one week census of all emergency calls responded to by the LAS. SETTING: Sixty eight LAS stations. METHODS: Collation of all routine LAS incident forms (LA4) including the classification of the crews' free text description of the incident. This was supplemented by a detailed workload questionnaire for 25% of calls. RESULTS: There were 10,921 calls responded to from 29 April to 5 May 1996. The census showed that the daily number of calls was highest on Saturday and lowest on Wednesday with about half being made during normal general practitioner (GP) working hours. Half of all calls were for women and one third were for people aged > or = 65. Accidents were the commonest type of incident (24%). The remainder comprised various medical conditions such as respiratory, cardiac, and obstetric problems. In 1.5% of calls there was no illness, injury, or assistance required and 5% were for "general assistance" and mostly concerned people aged > or = 65. The workload survey indicated that two thirds of incidents occurred at home and 70% of callers had not tried to contact a GP before dialing 999. In the professional opinion of the responding crew, 60% of calls required a 999 response, with the remainder thought more appropriately dealt with by other services such as primary care, psychiatric services, and social services. CONCLUSIONS: This study suggests that while the majority of 999 calls were "appropriate", part of the 999 workload could be dealt with by other services. More research is required to clarify why people contact the 999 service for non-emergency incidents and also to establish the views of GPs and other agencies as to the role and function of the IAS.

Emergency Medical Service Communication Systems↗
PubMed1999

Delayed expression of adeno-associated virus vector DNA.

Two previous reports indicated that recombinant adeno-associated virus (rAAV) vectors were dependent on helper adenovirus (Ad) for efficient conversion of single-stranded (ss) rAAV DNA to the double-stranded (ds) form. This finding is somewhat paradoxical, however, since during a latent infection wild-type (wt)-AAV is rapidly converted to a ds form in the absence of Ad. Our hypothesis was that the effect observed in the previous studies was due to kinetic factors, i.e. to a relative delay in conversion to ds-DNA rather than to an absolute requirement for Ad. To test this, Hela cells were infected with a rAAV-CMV-green fluorescent protein (GFP) vector either in the presence or absence of Ad. Within the first 2 days, Ad infection resulted in a 4-fold increase in AAV vector expression and an augmentation of conversion to a ds-AAV DNA. By 6 days, however, the total number of GFP-expressing cells in the Ad-free culture had exceeded the original number in the Ad co-infected cells, and the conversion to ds-DNA episomes was substantial and ongoing.

Adenoviridae↗
PubMed1999

Physical and psychological needs of patients dying from colo-rectal cancer.

Sixty-one patients suffering from terminal colo-rectal cancer were interviewed in depth by trained research nurses. The nurses used a semistructured interview, a concerns checklist and the Psychiatric Assessment Schedule to determine patients' key physical complaints, their main concerns and whether or not an affective disorder was present. The interviewers' estimates of these aspects were then compared with the assessments of 48 carers and 58 general practitioners (GPs). The congruence between patients' and carers' reports was reasonable for appetite loss (77%), nausea and vomiting (75%) and pain (72%), and the rate of false positive reporting was low. However, there was much less congruence for breathlessness (48%) and pyrexia (32%). There was even less congruence between the estimates of patients' physical symptoms and GPs' perceptions. The highest congruence was for pain (42%). The congruence was low for appetite loss (8%) and breathlessness (5%). The congruence between patients' and carers' perceptions of the patients' major concerns was low, being at best 33% for patients' concerns about their physical illness. The rate of false positive reporting by carers was high. The carers' major concerns included the patients' illness (47%), the future (33%) and the emotional demands being put on them (23%). Thirteen (22%) of the 59 patients completing a full interview were suffering from an affective disorder. This had been recognized by the GP in only five cases and six patients who had a normal mood were wrongly diagnosed as being depressed. Of the carers interviewed, 22 (46%) considered symptom control had been inadequate and 23 (48%) felt they had no relief from the burden of caring or had too little help. Sixteen (33%) had recently suffered from a major depressive illness, generalized anxiety disorder or adjustment disorder. It is concluded that it is unreliable to rely on carers' proxy reports of the symptoms experienced by terminally ill patients; more accurate personal assessments are needed where possible. It is likely that this will only be achieved by ensuring that those health professionals involved in palliative care have training in the relevant assessment skills.

Aged↗
PubMed1999

Further characterization of cells expressing STRO-1 in cultures of adult human bone marrow stromal cells.

Primitive cells of the osteoblast lineage are not well characterized but are known to be present within the STRO-1+ fraction of adult human bone and marrow. A survey of human osteosarcoma cell lines revealed that STRO-1 is expressed by MG-63 but not SaOS-2. Among murine cell lines tested, expression of STRO-1 was detected in the bipotential (adipocyte/osteoblast) line BMS-2 but not the committed osteoblast precursor MC3T3-E1. A proportion of cultured adult human bone marrow stromal cells (BMSCs) consistently expressed the STRO-1 antigen. The expression of a range of cell surface antigens was studied in relation to STRO-1 by flow cytometry and several, including the bone/liver/kidney isoform of alkaline phosphatase (ALP), were found to subtype the STRO-1+ population of BMSCs. Further, BMSCs dual-labeled with antibodies recognizing STRO-1 and ALP could be assigned to one of four fractions: STRO-1-/ALP-, STRO-1+/ALP-, STRO-1+/ALP+, and STRO-1-/ALP+. Cells from each fraction could be isolated in high purity and, when recultured, remained viable and exhibited a limited degree of phenotypic stability. Using reverse transcriptase-polymerase chain reaction, cells in the four fractions were found to express different levels of transcripts for the parathyroid hormone receptor (PTHr) and bone sialoprotein (BSP). The expression of transcripts for the nuclear transcription factor core-binding factor alpha 1/osteoblast-specific factor-2 (CBFA1/OSF2) was restricted to those fractions expressing STRO-1 and/or ALP. Treatment with 10 nM dexamethasone consistently increased the proportion of cells present in those fractions which expressed the highest levels of transcripts for PTHr and BSP (STRO-1+/ALP+ and STRO-1-/ALP+) while simultaneously decreasing the proportion present in the STRO-1+/ALP- fraction. In conclusion, the expression of STRO-1 in vitro remains a characteristic of less well differentiated cells of the osteoblast lineage; in cultures of BMSCs and in established human osteosarcoma cell lines, there is an inverse association between the expression of STRO-1 and ALP; dual labeling of BMSCs with monoclonal antibodies recognizing STRO-1 and ALP permits the identification and isolation of cells of the osteoblast lineage at different stages of differentiation.

Adult↗