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Biomedical subjects

R Hill

Publications and source records attributed to R Hill.

At least 37 records · Page 2Linked to original sources
PubMed2002

The effect of smoking on tumour oxygenation and treatment outcome in cervical cancer.

AIM: Tumour hypoxia is associated with an increased risk of cervical tumour recurrence and death. Because smoking is a modifiable behaviour, it is important to establish the importance of smoking as a prognostic factor. We hypothesized that there is an association between smoking and tumour hypoxia, and that smoking adversely affects radiation response and survival. METHODS: A smoking history was obtained from 100 of 115 patients with cervical cancer entered into a prospective study of tumour oxygenation. Eighty-seven of these had clinically evident disease and radiation therapy alone was the planned treatment. Patients who smoked within 2 weeks of commencing radiation therapy were considered smokers, and the amount that they smoked was recorded in packs per day. Patients who had never smoked or quit at least 2 weeks prior to radiation therapy were considered non-smokers. Tumour oxygenation was determined using the Eppendorf polarographic oxygen electrode and tumour oxygenation is represented by the hypoxic proportion HP5 (% of pO2 measurements <5 mmHg). RESULTS: There was no significant association between smoking and tumour hypoxia (P=0.3), haemoglobin (P=0.6) nor tumour size (P=0.1). Progression-free survival at 3 years was 56% for non-smokers and 44% for smokers (P=0.23). In both univariate and multivariate analysis, neither smoking status nor amount smoked were significant predictors of progression-free survival or local control. CONCLUSIONS: There was no significant association between smoking and tumour hypoxia, treatment response or survival in this study of patients with cervix cancer.

Adult↗
PubMed2002

Outcome, functional recovery and unmet needs following acute stroke. Experience of patient follow up at 6 to 9 months in a newly established stroke service.

OBJECTIVE: To assess outcome at six months post stroke and the unmet needs and adherence to the secondary prevention advice among survivors living at home. SETTING: Stroke Rehabilitation Unit (SRU), Hairmyres Hospital and patients homes. SUBJECTS: Survivors living at home who had been managed in the SRU. RESULTS: Of 572 consecutive patients with confirmed acute stroke, 301 were managed in the SRU and 179 of these were reviewed at home between 6 and 9 months post acute stroke incident. One hundred and thirty seven (76%) survivors at home were living with a carer. Sixty-eight (38%) had had no personal contact with their General Practitioner since discharge from hospital, although 83 (46%) had attended or were attending day hospital. Thirty-two individuals (18%) had resumed smoking. One hundred and forty nine survivors (83%) still required assistance with daily living tasks. One hundred and fifteen patients (64%) required medication advice. One hundred and forty one (79%) had health concerns. Eight subjects had returned to paid employment. Issues raised by survivors included a feeling of being abandoned by the healthcare system, poor access to professional psychological support and a fear of further stroke. CONCLUSION: There is a need for continuing patient education, improved support for stroke survivors and more active involvement of Primary Care Services in the care of stroke patients following hospital discharge.

Activities of Daily Living↗
PubMed2002

[Fluoride release properties of GRACs. A survey of the literature].

While numerous publications have documented the anticariogenic properties of GPACs through fluoride release measurements and artificial caries studies, considerable debate still exists concerning the fluoride release properties of these materials in terms of dissolution and diffusion mechanisms. This paper will review some of the more important aspects of GPAC fluoride release. Numerous studies have reported on the fluoride release properties of GPACs. The first point to note is that all the studies were performed on commercial materials. This approach has inherent difficulties as the main factor governing fluoride release is the GPAC composition and formulation. Traditional GPACs are two component systems, consisting essentially of a ion leachable fluoroaluminosilicate glass and a polymeric acid, especially a polycarboxylic acid; fluoride ions are of prime importance in this reaction, in that they have a major influence on the structure of the glass, its reactivity, cement formation and bioactivity. GPACs may be viewed as particle reinforced polymeric composites, in which the degraded residual glass particles with their silicious layer reinforce the polysalt matrix, improving mechanical properties.

Delayed-Action Preparations↗
PubMed2002

Practical lessons from the management of an outbreak of small round structured virus (Norwalk-like virus) gastroenteritis.

An outbreak of viral gastroenteritis caused illness in 92 people during October 2000. All the cases had an association with one hotel and 80% of cases identified had attended one of two buffet meals on 18th October 2000. Cohort analysis did not implicate any particular foodstuff in this outbreak. All bacteriological tests on food samples were negative. Small round structured virus (SRSV)/Norwalk-like virus (NLV) particles were seen by electron microscopy in 6 out of 27 stool samples submitted for analysis. This paper describes the outbreak and in particular the lessons learned from the management and control of it. These include practical points with regard to the outbreak control team, liaison with the microbiology laboratory, handling data, agreeing a case definition, and occupational health issues. All can be applied elsewhere by those responsible for managing outbreaks at a local level.

Caliciviridae Infections↗
PubMed2001

Tumor size and oxygenation are independent predictors of nodal diseases in patients with cervix cancer.

PURPOSE: To determine the relationships between tumor oxygenation and nodal stage in a prospective study of patients with cervix cancer, controlling for other prognostic factors. METHODS AND MATERIALS: Between 1994 and 1999, 128 eligible patients with cervix cancer were entered into a prospective study of tumor oxygenation assessed by Eppendorf oxygen electrode before primary radiation therapy. Oxygenation was evaluated using the proportion of pO(2) values < 5 mmHg (HP(5)), and tumors were classified as hypoxic if the HP(5) was > 50%. Patients were assigned to one of three groups: those with no imaging evidence of nodal (pelvic or para-aortic) or distant metastatic disease (N group; n = 67), those with equivocal findings (E group; n = 28), and those with nodal or distant metastatic disease (P group; n = 33). RESULTS: The proportion of hypoxic tumors in the P, E, and N groups were 67%, 50%, and 40%, respectively (p = 0.014), with median HP(5) values of 63%, 48%, and 36%, respectively (p = 0.0024). In a multivariate analysis including tumor size, stage, HP(5), and hemoglobin, it was found that tumor size and HP(5) were the only independently significant variables for the finding of metastatic disease (p = 0.009 and 0.017, respectively). CONCLUSION: In this patient population, there was a significantly increased risk of nodal or distant metastases in patients with hypoxic tumors, and this finding was independent of tumor size. These results are consistent with the hypothesis that tumor hypoxia is an adverse prognostic factor associated with selection for a metastatic phenotype.

Adult↗
PubMed2001

Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy.

BACKGROUND: Familial dilated cardiomyopathy (FDCM) and hypertrophic cardiomyopathy (FHCM) are the 2 most common forms of primary cardiac muscle diseases. Studies indicate that mutations in sarcomeric proteins are responsible for FHCM and suggest that mutations in cytoskeletal proteins cause FDCM. Evidence is evolving, however, that such conclusions are premature. METHODS AND RESULTS: A novel missense mutation in the cardiac troponin T gene was identified by direct sequencing and confirmed by endonuclease restriction analysis in a large family with FDCM that we had previously mapped to chromosome 1q32. The mutation substitutes tryptophan for a highly conserved amino acid, arginine, at amino acid residue 141 (Arg141Trp). The mutation occurs within the tropomyosin-binding domain of cardiac troponin T and alters the charge of the residue. This mutation cosegregates with the disease, being present in all 14 living affected individuals. The mutation was not found in 100 normal control subjects. Clinical features were congestive heart failure with premature deaths. The age of onset and severity of the disease are highly variable, with incomplete penetrance. Because 15 mutations in troponin T are known to cause FHCM, 219 probands with FHCM were screened, and none had the mutation. CONCLUSIONS: Thus, the novel cardiac troponin T mutation Arg141Trp is responsible for FDCM in our family. Because several mutations in troponin T have already been recognized to be responsible for FHCM, it appears that the phenotype, whether it be hypertrophy or dilatation, is determined by the specific mutation rather than the gene.

Adult↗
PubMed2001

Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements.

The purpose of this study was to determine the independent prognostic significanceof interstitial fluid pressure (IFP) measurements in cervix cancer. A total of 102 patients with newly diagnosed cervix cancer were accrued to this prospective study. There were 31 International Federation of Gynecology and Obstetrics stage IB or IIA tumors, 40 IIB tumors, and 31 IIIB tumors. The median size was 5 cm (range, 2-10 cm). Pelvic lymphadenopathy was identified radiographically in 20 patients. IFP was measured at examination under anesthesia using a wick-in-needle technique. Multiple measurements were made in each tumor. The mean IFP in individual tumors ranged from -3 to 48 mm Hg, and the median for the entire cohort was 19 mm Hg. Treatment consisted of external beam and intracavitary radiation without chemotherapy. Median follow-up was 2.5 years. The 3-year disease-free survival of all of the patients was 53%. Disease-free survival was 34% in patients with IFP >19 mm Hg, and 68% in those with lower IFP (P = 0.002). To evaluate rigorously the independent prognostic significance of IFP measurements relative to established clinical factors, a multivariate model was first developed using stepwise selection of clinical covariates. Tumor size (P = 0.0003) and pelvic lymph node status (P = 0.0016) comprised the clinical model. IFP, when added to this model, provided additional independent prognostic information (P = 0.0013). IFP was also significant (P = 0.0027) when the clinical factors and hypoxic proportion as determined with the Eppendorf electrode were analyzed together. Patients with high IFP were more likely to recur both locally and at distant sites. This study is the first to document a strong, independent prognostic importance of pretreatment IFP measurements in cervix cancer. Patients with high IFP are significantly more likely than those with low IFP to recur after radiotherapy and die of progressive disease, independent of clinical prognostic factors and the results of tumor oxygen measurements.

Adult↗
PubMed2001

Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH), the clinical hallmark of familial hypertrophic cardiomyopathy (FHCM), is absent in a significant number of subjects with causal mutations. In transgenic rabbits that fully recapitulate the FHCM phenotype, reduced myocardial tissue Doppler (TD) velocities accurately identified the mutant rabbits, even in the absence of LVH. We tested whether humans with FHCM also consistently showed reduced myocardial TD velocities, irrespective of LVH. METHODS AND RESULTS: We performed 2D and Doppler echocardiography and TD imaging in 30 subjects with FHCM, 13 subjects who were positive for various mutations but did not have LVH, and 30 age- and sex-matched controls (all adults; 77% women). LV wall thickness and mass were significantly greater in FHCM subjects (P<0.01 versus those without LVH and controls). There were no significant differences in 2D echocardiographic, mitral, and pulmonary venous flow indices between mutation-positives without LVH and controls. In contrast, systolic and early diastolic TD velocities were significantly lower in both mutation-positives without LVH and in FHCM patients than in controls (P<0.001). Reduced TD velocities had a sensitivity of 100% and a specificity of 93% for identifying mutation-positives without LVH. CONCLUSIONS: Myocardial contraction and relaxation velocities, detected by TD imaging, are reduced in FHCM, including in those without LVH. Before and independently of LVH, TD imaging is an accurate and sensitive method for identifying subjects who are positive for FHCM mutations.

Adult↗
PubMed2001

Quantitative autoradiographic mapping of the ORL1, mu-, delta- and kappa-receptors in the brains of knockout mice lacking the ORL1 receptor gene.

Until recently the opioid receptor family was thought to consist of only the mu-, delta- and kappa-receptors. The cloning of opioid receptor like receptor (ORL1) and its endogenous ligand nociceptin/orphanin FQ, which displayed anti-opioid properties, has raised the issue of functional co-operativity of this system with the classical opioid system. ORL1 receptor knockout mice have been successfully developed by homologous recombination to allow the issue of potential heterogeneity of this receptor and also of compensatory changes in mu-, delta- or kappa-receptors in the absence of ORL1 to be addressed. We have carried out quantitative autoradiographic mapping of these receptors in the brains of mice that are wild-type, heterozygous and homozygous for the deletion of the ORL1 receptor. ORL1, mu-, delta- and kappa-receptors were labelled with [(3)H] leucyl-nociceptin (0.4 nM), [(3)H] DAMGO (4 nM), [(3)H] deltorphin-I (7 nM), and [(3)H] CI-977 (2.5 nM) respectively. An approximately 50% decrease in [(3)H] leucyl-nociceptin binding was seen in heterozygous ORL1 mutant mice and there was a complete absence of binding in homozygous brains indicating the single gene encodes for the ORL1 receptor and any putative subtypes. No significant gross changes in the binding to other opioid receptors were seen across genotypes in the ORL1 mutant mice demonstrating a lack of major compensation of classical opioid receptors in the absence of ORL1. There were a small number of region specific changes in the expression of classical opioid receptors that may relate to interdependent function with ORL1.

Analgesics, Opioid↗
PubMed2001

Ion channels of importance for the locomotor pattern generation in the lamprey brainstem-spinal cord.

The intrinsic function of the spinal network that generates locomotion can be studied in the isolated brainstem-spinal cord of the lamprey, a lower vertebrate. The motor pattern underlying locomotion can be elicited in the isolated spinal cord. The network consists of excitatory glutamatergic and inhibitory glycinergic interneurones with known connectivity. The current review addresses the different subtypes of ion channels that are present in the cell types that constitute the network. In particular the roles of the different subtypes of Ca2+ channels and potassium channels that regulate integrated neuronal functions, like frequency regulation, spike frequency adaptation and properties that are important for generating features of the motor pattern (e.g. burst termination), are reviewed. By knowing the role of an ion channel at the cellular level, we also, based on previous knowledge of network connectivity, can understand which effect a given ion channel may exert at the different levels from molecule and cell to network and behaviour.

Animals↗
PubMed2001

The influence of calcium to phosphate ratio on the nucleation and crystallization of apatite glass-ceramics.

The nucleation and crystallization behavior of a series of glasses based on 4.5SiO2-3Al2O3-YP2O5-3CaO-1.51CaF2 was studied. The parameter Y was varied to give calcium to phosphate ratios between one and two. All of the glasses studied crystallized firstly to fluorapatite (Ca5PO4)3F). The glass with a calcium to phosphate ratio of 1.67, corresponding to apatite, bulk nucleated to give fluorapatite (FAP). The glasses with calcium : phosphate ratios either less than that of apatite, or greater than that of apatite all exhibited surface nucleation of FAP. However, following a nucleation hold of one hour at approximately 50 K above the glass transition temperature these glasses exhibited bulk nucleation of FAP.

Journal Article↗
PubMed2001

A psychophysiological marker of attention deficit/hyperactivity disorder (ADHD)--defining the EEG consistency index.

This study continues our research to further validate the idea that ADHD (Attention Deficit/Hyperactivity Disorder) interferes with transition from one task to another and this interference can be quantified by a Consistency Index (CI) derived from a specific mathematical representation of EEG data. We reanalyze 32 previously reported data sets present new data for 35 boys and girls, ages 7-12, ADHD or control. Each data set contains EEG, recorded and digitized while participants perform consecutive 10-min tasks: video, reading, and math. For boys, the CI in ADHD was four times lower than in controls, p < .005, for girls this difference was two times, p < .05. ADHD/control classification based on the CI coincided with the DSM-IV criteria for 88% of the boys and for 67% of the girls. Post hoc analysis indicated that the classification utility of the CI diminished with age. A CI below 40% could be a discriminating, reliable, and reproducible marker of ADHD in young boys.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

The Raynaud's Treatment Study: biofeedback protocols and acquisition of temperature biofeedback skills.

The Raynaud's Treatment Study (RTS) compared temperature biofeedback training and a behavioral control procedure (frontalis EMG biofeedback) with nifedipine-XL and a medication placebo for treatment of primary Raynaud's phenomenon (RP) in a large (N = 313) multicenter trial. The present study describes the RTS biofeedback protocols and presents data on the acquisition of digital skin temperature and frontalis EMG responses in the RTS. The findings point to substantial problems with acquisition of physiological self-regulation skills in the RTS. Only 34.6% of the Temperature Biofeedback group (N = 81) and 55.4% of the EMG Biofeedback group (N = 74) successfully learned the desired physiological response. In contrast, 67.4% of a Normal Temperature Biofeedback group (N = 46) learned hand warming. Multivariate analysis found that coping strategies, anxiety, gender, and clinic site predicted acquisition of hand-warming skills whereas variables related to RP disease severity did not. Physiological data showed vasoconstriction in response to the onset of biofeedback and also found that performance in the initial sessions was critical for successful acquisition. These findings indicate that attention to the emotional and cognitive aspects of biofeedback training, and a degree of success in the initial biofeedback sessions, are important for acquisition.

Adult↗
PubMed2001

Colocalization of CGRP with 5-HT1B/1D receptors and substance P in trigeminal ganglion neurons in rats.

Vasodilatation in the dura mater has been implicated in migraine pathogenesis. Anti-migraine triptan drugs block vasodilatation by binding to 5-HT1B/1D receptors localized on the peripheral sensory terminals and dural blood vessel smooth muscles. Previous studies suggest that calcitonin gene-related peptide (CGRP) released from Adelta-fibres plays a more important role than substance P (SP) released from C-fibres in inducing dural vasodilatation and that one of the antimigraine mechanisms of triptan drugs is inhibiting CGRP release. In the present study, the relationship between CGRP and 5-HT1B/1D receptors, and between CGRP and SP in the trigeminal ganglion neurons in rats was examined by double immunohistochemical staining. CGRP, 5-HT1B, 5-HT1D and SP-positive trigeminal ganglion neurons were all predominantly small and medium-sized. In the trigeminal ganglia, approximately 50% of CGRP-positive neurons were 5-HT1B positive. Similarly, approximately 55% of CGRP-positive neurons were 5-HT1D immunoreactive. Approximately 50% of CGRP-positive neurons were SP-positive, while 93% of SP-positive neurons were CGRP-positive, suggesting that nearly all SP-positive neurons also contain CGRP. The fibre types of the 5-HT1B- and 5-HT1D-positive neurons were further investigated with an antibody against the A-fibre marker 200-kDa neurofilaments (NF200). Approximately 46% of the 5-HT1B-positive and 43% of the 5-HT1D-positive trigeminal ganglion neurons were also NF200 positive, indicating that many A-fibre trigeminal neurons express 5-HT1B or 5-HT1D receptors. These results support the hypothesis that one important action of antimigraine drugs is the inhibition of CGRP release and that Adelta-fibres may play an important role in migraine pathogenesis.

Animals↗
PubMed2001

Anorexia nervosa in an elderly woman.

OBJECTIVE: To demonstrate a case of anorexia nervosa in the elderly and to highlight the need for broadening of current diagnostic criteria. CLINICAL PICTURE: First onset of anorexia nervosa in a 72-year-old woman following bereavement of her husband. TREATMENT: Nine treatments of electroconvulsive therapy. OUTCOME: Treatment resulted in remission of the depressive symptoms and improvement of eating behaviour. CONCLUSIONS: Anorexia nervosa does occur in the elderly and can be difficult to detect. Where comorbid depression exists it requires aggressive treatment.

Aged↗
PubMed2001

The importance of definitions and methods in surgical wound infection audit.

We investigated the value of a full-time audit nurse personally following up every patient from admission to 30 days postoperatively in order to obtain accurate surgical wound infection rates. Our results show that this type of audit is an effective, although time-consuming, way of collecting accurate data on wound infection rates. It enabled the early identification of problem areas in practice and facilitated the adoption of evidence based practice. As a result of the audit there was a significant reduction in the clean wound infection rate from 13.9% in November 1995 to 7.9% in March 1998 (P= 0.05).

Aftercare↗
PubMed2001

Interstitial fluid pressure in cervical cancer: guide to targeted therapy.

Interstitial fluid pressure (IFP) is elevated in most malignant tumors, mainly as a result of the abnormal tumor vasculature that develops from unregulated angiogenesis. Theoretical models predict that IFP should correlate with capillary flow resistance in tumors, and therefore also with perfusion and oxygenation. However, a prospective clinical study in patients with cervical cancer at Princess Margaret Hospital failed to demonstrate a relationship between IFP and oxygenation. Despite this, high IFP was strongly associated with inferior survival after radiotherapy independent of clinical prognostic factors and tumor oxygen status. This suggests that IFP and direct needle oxygen measurements may provide information about different aspects of tumor oxygenation, such as chronic versus intermittent hypoxia. Alternatively, IFP may reflect an aspect of tumor biology that is largely unrelated to perfusion and oxygenation. One possibility is that tumors with high pretreatment angiogenesis levels, as indicated by high IFP, may be more radioresistant because the vascular endothelium is more likely to survive during and after treatment. The mechanistic link between elevated IFP and the abnormal tumor vasculature and the strong prognostic effect of IFP in our cervix study together suggest that drugs targeted at angiogenesis, when combined with radiotherapy, may lead to improved tumor control and patient survival.

Angiogenesis Inhibitors↗