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Biomedical subjects

L Marks

Publications and source records attributed to L Marks.

At least 19 recordsLinked to original sources
PubMed2006

The last deglaciation of the southeastern sector of the Scandinavian ice sheet.

The Scandinavian Ice Sheet (SIS) was an important component of the global ice sheet system during the last glaciation, but the timing of its growth to or retreat from its maximum extent remains poorly known. We used 115 cosmogenic beryllium-10 ages and 70 radiocarbon ages to constrain the timing of three substantial ice-margin fluctuations of the SIS between 25,000 and 12,000 years before the present. The age of initial deglaciation indicates that the SIS may have contributed to an abrupt rise in global sea level. Subsequent ice-margin fluctuations identify opposite mass-balance responses to North Atlantic climate change, indicating differing ice-sheet sensitivities to mean climate state.

Journal Article↗
PubMed2006

A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy.

The prognosis for patients with metastatic breast cancer remains poor. Metastatic breast cancer confined to the bones may have a better prognosis, especially hormone receptor-positive disease. We performed a prospective, randomized clinical trial to compare immediate consolidation with high-dose chemotherapy and hematopoietic support versus observation with high-dose consolidation at the time of disease progression in women with metastatic breast cancer and only bone metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil and methotrexate before randomization. In all, 85 patients were enrolled and 69 were randomized. The median follow-up is 8.1 years from randomization. The median event-free survival (EFS) for the immediate transplant arm is 12 months and for the observation arm is 4.3 months (P<0.0001). The median overall survival for the immediate transplant arm is 2.97 years and for the observation arm 1.81 years, a difference that is not statistically significant. Immediate high-dose chemotherapy and radiation therapy as consolidation offers a clinically and statistically significant improvement in EFS compared with radiation therapy alone following induction chemotherapy for women with metastatic breast cancer confined to the bones.

Adult↗
PubMed2006

Enlarged prostate: a landmark national survey of its prevalence and impact on US men and their partners.

This questionnaire-based survey evaluated the frequency and severity of lower urinary tract symptoms (LUTS) and the prevalence of enlarged prostate (EP) diagnosis and its impact on quality of life and spousal relationships among >1000 American men aged >50 years. A quarter of men suffered moderate to severe LUTS and 55% of those consulting a doctor had EP. EP negatively affected patient quality of life and caused relationship strain with spouses. These findings confirm that LUTS and EP are prevalent in the US population, affecting both patient and spouse, and may help in developing management strategies for EP.

Aged↗
PubMed2005

Load transmission through a healing tibial fracture.

BACKGROUND: Fracture healing has been linked to both the magnitude and distribution of mechanical stresses on the healing fracture tissues. However, direct clinical measurement of in vivo tibial axial loading is not possible. METHODS: Using computed tomography images, force plate data and recorded 3D interfragmentary micromovements, accurate 3D finite element models of a healing human tibial fracture were generated at 7, 10, and 16 weeks post-fracture and used to calculate longitudinal tibial forces and external fixator load-sharing during bilateral stance and walking. FINDINGS: Tibial load-sharing by the fixator decreased significantly as the fracture tissues developed even moderate stiffness, while tibial load increased steadily towards normal. INTERPRETATION: Quantitative assessment of the contribution of the external fixator is important as overloading of the callus due to insufficient support has been implicated in the retardation of the healing process.

Adult↗
PubMed2005

Dissolved oxygen concentration in culture medium: assumptions and pitfalls.

Oxygen is a key factor in the regulation of cytotrophoblast differentiation, proliferation and invasion in early pregnancy. Abnormalities in oxygen concentration have also been linked to a number of pregnancy disorders. Cell culture models have been used to study the effect of oxygen on cytotrophoblast behaviour in vitro, however, there is often little or no validation of oxygen levels in these cell culture systems. In this study, dissolved oxygen levels in culture medium maintained in standard culture conditions (18% O(2)) measured 18%. On transfer to a low oxygen environment (2% O(2)), oxygen levels decreased to 6-8% after 4h and reached 2% only after 24h in culture. Culture medium pre-gassed with nitrogen to remove dissolved oxygen quickly absorbed oxygen when exposed to ambient air during dispensing and required further incubation in a 2% oxygen environment before dissolved oxygen levels equilibrated to 2%. Thus, cultured cells placed in a low oxygen environment would be exposed to varying levels of oxygen before the desired level of oxygen exposure is reached. This study highlights the importance of validation of oxygen levels and potential problems associated with in vitro studies on the regulatory effects of oxygen.

Absorption↗
PubMed2005

A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing.

INTRODUCTION: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 (MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1-like conditions. RESULTS: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. DISCUSSION: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. CONCLUSIONS: We therefore suggest that routine germline MEN1 mutation testing of all cases of "classical" MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 (Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients <30 years old with sporadic hyperparathyroidism and multigland hyperplasia.

Australia↗
PubMed2004

Stromal-epithelial measurements of prostate cancer in native Japanese and Japanese-American men.

We measured the histologic stromal and epithelial tissue components of the benign (normal) and malignant tissue compartments of Japanese-Americans (J-A) and native Japanese (NJ) men living in Japan. The patient cohort included 25 NJ men undergoing radical prostatectomy (RP) in Nagoya, Japan and 25 J-A (second or third generation US born). We conducted tissue image quantitation (in-house image software) of the stromal and epithelial compartments in malignant and adjacent normal tissue areas from a tissue microarray (TMA) selected from radical prostatectomy (RP) blocks. Stromal-epithelial (S-E) areas were determined using immunohistochemical stains for CAM-5.2 epithelial cytokeratin marker and the Masson trichrome stain to measure the stroma component. We observed differences in the volumes of normal and cancer epithelium and stroma within both the J-A and NJ study populations (P<0.01). Only the individual average cancer epithelium (CE) volume (JA=24.1 vs NJ=29.9) differed significantly between the NJ and J-A study populations (P=0.03). Consequently, the S-E ratio in NJ group was significantly different from that of J-A population (P=0.05). The decrease in S-E ratio noted in the malignant tissues of NJ prostate tissue may provide a biological marker for differentiation of the two groups and suggests a need for further investigations into the molecular basis for these histologic differences.

Aged↗
PubMed2003

Return to work after lower limb amputation.

This study investigated the proportion of patients who returned to work following amputation and the factors that influenced a positive or negative outcome. One hundred patients of working age who had sustained unilateral lower limb amputation at least 1 year previously and who were established prosthesis users participated in the study. A specially designed questionnaire similar to a guided interview was administered by the rehabilitation physician at the patients' routine follow-ups. The questionnaire yielded a unique score dependent on whether return to work (or a different or preferred occupation) had been achieved with good or reduced productivity. All patients were eligible for mobility benefit, including schemes to purchase suitably adapted vehicles if necessary. However, no vocational rehabilitation was available. Sixty-six per cent of patients returned to employment and this was related to mobility, time since amputation and Handicap Scale scores. Age, socket comfort, level and cause of amputation, type of previous work or the presence of other medical problems did not differ between those who did and did not return to work. The Employment Questionnaire showed good correspondence with the London Handicap Scale, indicating some concurrent validity, although future development might include consideration of psychological factors, which could explain more of the reasons for continued unemployment.

Adult↗
PubMed2001

Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy.

PURPOSE: Weight gain is a common problem among breast cancer patients who receive adjuvant chemotherapy (CT). We undertook a study to determine the causes of this energy imbalance. PATIENTS AND METHODS: Factors related to energy balance were assessed at baseline (within 3 weeks of diagnosis) and throughout 1 year postdiagnosis among 53 premenopausal women with operable breast carcinoma. Thirty-six patients received CT and 17 received only localized treatment (LT). Measures included body composition (dual energy x-ray absorptiometry), resting energy expenditure (REE; indirect calorimetry), dietary intake (2-day dietary recalls and food frequency questionnaires) and physical activity (physical activity records). RESULTS: Mean weight gain in the LT patients was 1.0 kg versus 2.1 kg in the CT group (P =.02). No significant differences between groups in trend over time were observed for REE and energy intake; however, a significant difference was noted for physical activity (P =.01). Several differences between groups in 1-year change scores were detected. The mean change (+/- SE) in LT versus CT groups and P values for uncontrolled/controlled (age, race, radiation therapy, baseline body mass index, and end point under consideration) analysis are as follows: percentage of body fat (-0.1 +/- 0.4 v +2.2 +/- 0.6%; P =.001/0.04); fat mass (+0.1 +/- 0.3 v +2.3 +/- 0.7 kg; P =.002/0.04); lean body mass (+0.8 +/- 0.2 v -0.4 +/- 0.3 kg; P =.02/0.30); and leg lean mass (+0.5 +/- 0.1 v -0.2 +/- 0.1 kg; P =.01/0.11). CONCLUSION: These data do not support overeating as a cause of weight gain among breast cancer patients who receive CT. The data suggest, however, that CT-induced weight gain is distinctive and indicative of sarcopenic obesity (weight gain in the presence of lean tissue loss or absence of lean tissue gain). The development of sarcopenic obesity with evidence of reduced physical activity supports the need for interventions focused on exercise, especially resistance training in the lower body, to prevent weight gain.

Adult↗
PubMed2001

Characterization of the microglial response to cerebral ischemia in the stroke-prone spontaneously hypertensive rat.

Stroke-prone spontaneously hypertensive rats (SHRSP) sustain more ischemic damage after middle cerebral artery occlusion than do their reference strain, the Wistar-Kyoto rat (WKY). The cause of increased stroke sensitivity is still under investigation. In general, SHRSP display a greater response to inflammatory stimuli than do WKY. Because inflammatory cells may influence the extent of damage in experimental stroke, this study has investigated the acute inflammatory response to focal ischemia in SHRSP and WKY. Adult male SHRSP (n=5) and WKY (n=5) were anesthetized and underwent distal middle cerebral artery occlusion. After 24 hours of recovery, infarct volume, neutrophil counts, and activated microglia counts were performed. SHRSP displayed more ischemic damage than did WKY (135+/-4.7 versus 102+/-4.7 mm(3) [mean+/-SEM], P<0.005). Brain neutrophil counts were extremely low in both strains. SHRSP displayed significantly more activated microglia than did WKY in the ipsilateral hemisphere (respective SHRSP versus WKY values [mean+/-SEM] were 88+/-3.6 versus 51+/-3.4 per mm(2) for the cortical peri-infarct region [P<0.005] and 183+/-7.9 versus 156+/-3.7 per mm(2) for the infarct core [P<0.05]) and in the contralateral hemisphere (eg, respective SHRSP versus WKY values were 102+/-3.2 versus 50+/-3.1 per mm(2) for the sensorimotor cortex [P<0.0001]). No neutrophils and very few activated microglia were found within the brains of naive rats. However naive SHRSP possessed more microglia (resting and activated) than did naive WKY. This study demonstrates a more pronounced microglial response to focal ischemia in SHRSP compared with WKY and provides evidence of a potential role for inflammatory processes in response to ischemic damage.

Animals↗
PubMed2001

Drooling in Parkinson's disease: a novel speech and language therapy intervention.

Drooling and difficulty swallowing saliva are commonly reported in people with Parkinson's disease (PD). Drooling in PD is the result of swallowing difficulties rather than excessive saliva production. Currently, there is little research into the effectiveness of treatments to reduce drooling. The aims of the study were to develop objective measures of saliva volume and drooling for PD and to assess the efficacy of two therapeutic strategies to control drooling, i.e. specific speech and language therapy (SLT) including a portable metronome brooch to cue swallowing and injections of botulinum toxin into both parotid glands to reduce the amount of saliva produced. This paper will describe the assessments used, including the measurement of saliva, swallowing and drooling. The main focus will be the strategies used in the SLT intervention. The preliminary results are presented.

Aged↗
PubMed2001

Drooling in Parkinson's disease: a novel tool for assessment of swallow frequency.

A non-invasive way to obtain objective measurements of swallowing frequency and thus indirectly, drooling was required as part of the study 'Drooling in Parkinson's disease: objective measurement and response to therapy'. A hard disk, digital recorder was developed, for use on a laptop computer, which was capable of collecting large quantities of swallowing data from an anticipated 40 patients and 10 controls. An electric microphone was taped to the subjects' larynx for recording the swallow sounds when drinking 150 ml of water and at rest for 30 minutes. The software provides an accurate visual display of the audio-signal allowing the researcher easy access to any segment of the recording and to mark and extract the swallow events, so that swallow frequency may be efficiently and accurately ascertained. Preliminary results are presented.

Case-Control Studies↗
PubMed2001

Safe swallowing?--an opportunity for students working with dysphagic clients.

The challenges of providing student speech and language therapists (SLTs) with clinical experience in acute hospital settings are outlined. An innovative model of student clinical placement will be described which takes advantage of the recent change in policy by the Royal College of Speech and Language Therapists (RCSLT) in respect of student involvement in work with dysphagic clients.

Deglutition Disorders↗
PubMed2000

The influence of mechanical stimulus on the pattern of tissue differentiation in a long bone fracture--an FEM study.

2D, coronal plane, finite elements models (FEMs) were developed from orthogonal radiographs of a diaphyseal tibial fracture and its reparative tissue at four different time points during healing. Each callus was separated into regions of common tissue histology by computerised radiographic analysis. Starting point values of tissue material properties from the literature were refined by the model to simulate exactly the mechanical behaviour of the subject's callus and bone during loading. This was achieved by matching measured inter-fragmentary displacements with calculated inter-fragmentary forces. Stress and strain distributions in the callus and bone were calculated from peak inter-fragmentary displacements measured during natural walking activity, and were correlated with the subsequently observed pattern of tissue differentiation and maturation of the callus. The growth and stiffening of the external callus progressively reduced the inter-fragmentary gap strain. Partial maturation of the gap tissue was apparent only one week before fixator removal. Principal stresses in the callus were compared with 'yield stresses' in corresponding tissue from the literature. This indicated the presence of stress concentrations medial and lateral to the fracture gap, which probably caused tissue damage during normal activity levels. Tissue damage may also have precipitated partial structural failure of the callus, both of which were believed to have delayed healing during the middle third of the fixation period. Had the fixation device provided greater inter-fragmentary support during early healing, this may have prevented callus failure and the consequent delay in healing. A further benefit of this would have been the reduction of the initially high intra-gap tissue strains to a magnitude more conducive to earlier maturation of the bridging tissue that united the bone.

Adult↗
PubMed2000

The Assaulted Staff Action Program (ASAP) and declines in rates of assault: mixed replicated findings.

The Assaulted Staff Action Program (ASAP) is a crisis intervention program that has been associated with providing both needed support for employee victims of patient assault and declines in rates of assaults in traditional state hospital and community mental health settings. This study examined the possible role of ASAP and declines in rates of assault in three community-based services impacted by privatization and managed care approaches: community residences, an acute care rural community mental health center, and an urban intermediate/extended care facility. ASAP was associated with a statistically significant decline in the rate of assault in the intermediate/extended care facility. The community residence program was not a true test because of structural issues associated with managed care. The community mental health center appeared to be a true failed replication. The extended care facility's decline in the rate of assault was interrupted by the aftermath of one serious clinical incident during one month and then continued to decline. The implications are discussed.

Adult↗
PubMed2000

Oral hygiene in 12-year-old disabled children in Flanders, Belgium, related to manual dexterity.

As part of a larger epidemiological survey of a stratified sample of 12-year-old handicapped children in Flanders, Belgium, the present study describes gingival health, gingival hypertrophy, oral cleanliness and the presence of calculus. Statistical analysis was performed with motor skills, brushing help, the use of chemical agents, the use of anti-epileptic drugs, the knowledge of parents and educators (or caregivers) and their opinion of the oral hygiene of their children/ pupils as response variables. From this study, it became clear that mildly mentally retarded and learning-impaired children had significantly better manual dexterity skills than moderately and severely mentally retarded and physically impaired children. However, this was not reflected in improved oral hygiene. The use of chemical plaque controlling agents was found to be extremely low and, with the exception of children with gingival hyperplasia, the users of these agents did not have better oral hygiene. No difference was found between subtypes in the opinion of parents and educators on oral status. There was, however, a difference between their assessment and the clinical picture. It was concluded that there was a need for in-service training programmes in oral health care for educators as well as for parents.

Analysis of Variance↗
PubMed2000

Antisense studies in PC12 cells suggest a role for H218, a sphingosine 1-phosphate receptor, in growth-factor-induced cell-cell interaction and neurite outgrowth.

Our previous studies of H218, a sphingosine 1-phosphate (S1P) receptor and a member of the G-protein-coupled receptor superfamily, suggest that it may participate in mammalian nervous system development. Thus, brain levels of H218 mRNA are higher during early neurogenesis than postnatally. In addition, embryonic H218 immunoreactivity is preferentially localized in young neuronal cell bodies during their early stages of differentiation and in axons during their extension. This report describes the morphological effects of reducing native H218 levels in PC12 cells. Western blot analyses demonstrated that PC12 cells stably transfected with an expression vector carrying an antisense-oriented H218 cDNA contain less H218 protein than vector-transfected control cells. When differentiated with growth factors, the antisense-H218 cells display more neurite production and form less cell-cell contacts than the control cells. Therefore, these data, along with our previous H218 expression studies and a recent, independent study of H218 overexpression, support the possibility that H218 contributes to developmental processes regulating neuronal interaction and axon growth. The data are also consistent with reports that H218 is a S1P receptor, that S1P is present in serum, like that used in our PC12 cell cultures, and that it causes PC12 cell neurite retraction. Finally, and in agreement with a S1P receptor role for H218, we find that the antisense-H218 cells display less S1P-induced neurite retraction than control cells.

Animals↗