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Biomedical subjects

K Walters

Publications and source records attributed to K Walters.

At least 19 recordsLinked to original sources
PubMed2002

Group formation games with reappraisal.

The formation of a social group, such as the group of individuals sharing a territory, depends on the interaction between choices made by individuals to stay or disperse. The process can be modelled as a multi-player variant of the well-known War of Attrition in evolutionary game theory, as shown by Blackwell (1997; J. Theor. Biol.189, 175-181). In this paper, we extend the set of strategies defined there by allowing reappraisal during the game. We give a formal analysis of the evolutionarily stable strategy, where one exists, and illustrate it with an example based on badger (Meles meles) territoriality. The results predict that group size will be well adapted to, and very sensitive to, the precise conditions under which the game is played, and give an indication of the potential for parent-offspring conflict.

Animals↗
PubMed2001

A comparative approach to structure-function studies of mammalian aromatases.

To date, structure--function studies of aromatase cytochrome P450 (P450arom) have been advanced by point mutation analyses utilizing almost exclusively the human enzyme, in conjunction with computer-generated models of the three-dimensional form of the enzyme based on prokaryotic cytochromes P450. Recent studies have identified duplicated isozymes of porcine P450arom, the gonadal and placental forms of which appear to differ substantially in substrate utilization and inhibitor sensitivity. We present a comparative approach to define regions of P450arom responsible for specific functional characteristics using complimentary DNAs encoding the porcine isozymes. Constructs encoding the native and chimeric porcine and human P450arom enzymes were transiently expressed and activity was assessed using the tritiated water assay. Sensitivity to inhibition by the imidazole etomidate was investigated, and P450arom expression was assessed by immunoblot analysis. All constructs yielded active P450arom, suggesting that exchanging entire structural elements does not preclude catalytic function. The activity of the gonadal isozyme was shown to be inhibited by etomidate at concentrations 185 and 300-fold lower than those required to induce a similar inhibition of the placental and human enzymes, respectively. In contrast, there was only a two-fold difference in the sensitivity of the gonadal and placental isozymes to inhibition by CGS16949A. Analysis of chimeric constructs indicated that the sensitivity to etomidate was associated with residues in the B, B' and C helices of the gonadal P450arom encompassing only one of six putative substrate recognition sites. Additionally, sensitivity to etomidate was not correlated with enzyme activity among the chimeric enzymes. Therefore, it appears that residues of the porcine gonadal P450arom that are responsible for etomidate binding may be distinct from those involved in substrate recognition and metabolism. These data support the notion that a comparative approach employing the use of chimeric enzymes provides a useful tool in directing point mutational analysis to determine residues important in inhibitor and perhaps substrate recognition of P450 enzymes such as P450arom. These studies are currently in progress.

Animals↗
PubMed2001

Immunocytochemical localization of epidermal growth factor receptor in early embryos of the Japanese medaka fish (Oryzias latipes).

This study was undertaken to localize epidermal growth factor receptor (EGFR) during early development of Japanese medaka embryos using immunocytochemistry. Specific staining was observed in all stages studied. All of the cells of the embryonic disc from the germinal disc (1 cell) through the late high blastula stages stained moderately for EGFR. Beginning with the flat blastula stage, the surface and lateral cells of the embryonic disc and the cells migrating around the yolk stained intensely for EGFR, and this continued throughout the study period. The presence of the keel at the late gastrula stage did not affect the moderate staining of the majority of the embryonic disc cells. When somites first appeared, the keel region stained less intensely than before, but scattered individual cells stained intensely for EGFR. Embryos with 12 somites had a neural tube that was lightly stained except for a few intensely stained individual cells. The neural tube, notochord and somites in 24-somite embryos lacked immunostaining. However, the surface epithelium, aorta, intestinal epithelium and pronephric duct demonstrated EGFR immunostaining. This study demonstrates that EGFR is present during medaka development and supports the hypothesis that EGFR ligands are important during cleavage, gastrulation and early organogenesis.

Animals↗
PubMed2001

An exploration of help-seeking behaviour in older people with unmet needs.

BACKGROUND: Despite decades of research showing high rates of unmet need in older people, there currently is little understanding of why these needs remain unmet. This study was performed as part of a larger feasibility study of a multidisciplinary needs assessment tool in primary care. OBJECTIVE: The aim of the present study was to explore patients' and carers' help-seeking behaviour and perceived barriers to meeting unmet needs. METHOD: Four general practices were selected purposefully in inner city and suburban London A random sample of 1 in 20 people aged 75 years and over registered with each practice was selected for a multidisciplinary needs assessment using the 'Camberwell Assessment of Need for the Elderly' (CANE) schedule and unmet needs identified by patients and their informal carers. For each unmet need, a further semi-structured interview was used to explore the help-seeking behaviour and perceived barriers to meeting their needs. Responses were recorded verbatim contemporaneously and a thematic analysis performed on perceived barriers following completion of all interviews. RESULTS: A total of 55/84 (65.5%) of patients and 15/17 (88%) of carers completed the initial needs assessment. For 104 unmet needs identified by 31 patients and 11 carers, a further interview was completed on the barriers to meeting that need. Help had been sought for only 25/104 (24%) of unmet needs and it had been offered in only 19/104 (18%). In those not seeking help, withdrawal, resignation and low expectations were dominant themes. In those that had sought help, there were issues of perceived failure of service delivery and rationing, with themes of resignation and withdrawal again emerging in those declining help offered. CONCLUSION: The majority of older people and their carers do not appear to seek help for their unmet needs for a range of complex reasons, often involving issues of withdrawal, resignation and low expectations. This complexity has implications for the commissioning of services for older people.

Activities of Daily Living↗
PubMed2000

Assessing needs from patient, carer and professional perspectives: the Camberwell Assessment of need for Elderly people in primary care.

BACKGROUND: despite evidence that needs assessment of older people can improve survival and function when linked to effective long-term management, there is no structured needs assessment tool in widespread use. The Camberwell Assessment of Need for the Elderly is a new tool not previously evaluated in primary care. It includes the views of patients, carers and health professionals, enabling a direct comparison of their perspectives. AIM: to conduct a feasibility study of Camberwell Assessment of Need for the Elderly in primary care and to compare the needs identified by patients, carers and health professionals. METHODS: we selected a random sample of 1:20 of all people aged 75 and over from four general practices in inner-city and suburban north-west London. We interviewed the patients, their informal carers and lead health professionals using the Camberwell Assessment of Need for the Elderly schedule. RESULTS: 55 (65.5%) of 84 patients, 15 (88.2%) of 17 carers and all of 55 health professionals completed interviews. The patients' three most frequently identified unmet needs were with 'eyesight/hearing', 'psychological distress' and 'incontinence'. The carers' three most frequently identified unmet needs were with 'mobility', 'eyesight/hearing' and 'accommodation' and the health professionals' were with 'daytime activities', 'accommodation' and 'mobility'. Kappa tests comparing patient and health professional assessments showed poor or fair agreement with 18 of the 24 variables and moderate or good agreement with six. None showed very good agreement. CONCLUSION: the Camberwell Assessment of Need for the Elderly schedule is feasible to use in primary care and can identify perceived needs not previously known about by health professionals. A shorter version of Camberwell Assessment of Need for the Elderly focusing on areas of poor agreement and high levels of need might be useful in the assessment of needs in older people in primary care.

Aged↗
PubMed1998

Ribavirin and interferon alfa-2b in chronic hepatitis C: assessment of possible pharmacokinetic and pharmacodynamic interactions.

AIMS: The primary objective of this study was to determine whether pharmacokinetic interactions occurred between interferon alpha-2b (IFN) and ribavirin in patients with chronic hepatitis C infections. Additionally this study assessed the single and multiple-dose pharmacokinetics of ribavirin and IFN, and compared the safety, tolerability and antiviral pharmacodynamics of IFN plus ribavirin compared with either drug alone. METHODS: In this open label parallel group study, patients with chronic hepatitis C were randomized to receive IFN 3 million IU thrice weekly s.c. alone, ribavirin 600 mg twice daily p.o. alone or both drugs in combination over 6 weeks. Single and multiple dose pharmacokinetics and indices of antiviral pharmacodynamics were assessed during weeks 1 and 6, along with safety assessments during the study. RESULTS: The range of mean ribavirin terminal phase half-lives after single doses was 44-49 h. Comparison of week 1 and week 6 AUC(0,12h) values showed accumulation in plasma of approximately 6-fold. The range of mean washout half-lives after week 6 was 274-298 h, reflecting release of ribavirin from deep compartment stores. The range of single and multiple dose IFN terminal phase half-lives was 5-7 h. IFN demonstrated an increase in bioavailability (approximately 2-fold) upon multiple dose administration. Ribavirin and IFN pharmacokinetic parameters for combined ribavirin and IFN were similar to those during monotherapy with either compound, although the power of this study to detect differences was low. Serum HCV-RNA titers and ALT concentrations were reduced by IFN alone, ribavirin alone reduced ALT concentrations only, and combined IFN plus ribavirin produced numerically greater falls in both measurements than either treatment alone. Serum concentrations of neopterin and activity of 2',5'-oligoadenylate synthetase (2'5'-OAS) were increased by IFN alone and in combination with ribavirin, whereas serum 2'5'-OAS activity was decreased and neopterin concentrations unaltered by ribavirin monotherapy. IFN and ribavirin monotherapy produced characteristic changes in safety laboratory tests (IFN--reductions in white cells, neutrophils and platelets; ribavirin--reduced haemoglobin) and characteristic adverse event profiles (IFN--headache, flu-like symptoms, fatigue, anorexia, nausea, myalgia, and insomnia; ribavirin--headache, fatigue, myalgia, and pruritus). There was no additive effect of combination therapy on safety laboratory tests or reported adverse events. All changes were fully reversible upon treatment cessation. CONCLUSIONS: There was no evidence of pharmacokinetic interactions between IFN and ribavirin in this study. There were numerical trends indicating that the combination of IFN and ribavirin reduced titers of HCV-RNA to a greater extent than did either treatment alone, and the safety profile of combination therapy was similar to those of both monotherapy treatments.

Adolescent↗
PubMed1995

Propofol blood concentration and the Bispectral Index predict suppression of learning during propofol/epidural anesthesia in volunteers.

Propofol is often used for sedation during regional anesthesia. We tested the hypothesis that propofol blood concentration, the Bispectral Index and the 95% spectral edge frequency predict suppression of learning during propofol/epidural anesthesia in volunteers. In addition, we tested the hypothesis that the Bispectral Index is linearly related to propofol blood concentration. Fourteen healthy, male volunteers were studied on three randomly ordered days: no propofol, target propofol blood concentration 1 microgram/mL, and target propofol blood concentration 2 micrograms/mL. Each day, epidural anesthesia (approximately T11 level) was induced using 2% 2-chloroprocaine. Propofol was infused by a computer-controlled pump, and propofol concentration measured in central venous blood. We administered a Trivial Pursuit-type question task on all 3 days. The electroencephalogram was monitored continuously (Fp1, Fp2; reference, Cz; ground, mastoid). Propofol caused concentration-related impairment of learning. The propofol blood concentration suppressing learning by 50% was 0.66 +/- 0.1 microgram/mL. The Bispectral Index value when learning was suppressed by 50% was 91 +/- 1. In contrast, the 95% spectral edge frequency did not correlate well with learning. The Bispectral Index decreased linearly as propofol blood concentration increased (Bispectral Index = -7.4.[propofol] + 90; r2 = 0.47, n = 278). There was no significant correlation between the 95% spectral edge frequency and propofol concentration. In order to suppress learning, propofol blood concentrations reported to produce amnesia may be targeted. Alternatively, the Bispectral Index may be used to predict anesthetic effect during propofol sedation.

Adult↗
PubMed1995

Increased neuronal excitability conferred by a mutation in the Drosophila bemused gene.

We have identified a new gene in Drosophila on the basis of a mutation that affects both behavior and neuronal excitability. This mutation, called bemused (bem) is the result of a P element insertion at cytological position 85D. Flies defective at bem display greatly reduced coordination, flight ability and fertility. The bem mutation also affects synaptic transmission at the larval neuromuscular junction. In particular, bem larvae display a more rapid onset of augmentation than bem+ larvae. This effect is potentiated by the potassium channel blocking drug quinidine. The increased transmitter release that occurs in bem mutants following repetitive nerve stimulation is accompanied by the appearance of extra action potentials in the motor neuron. We conclude that the bem mutation increases neuronal excitability, possibly as a result of a defect in an ion channel structural or regulatory gene.

Animals↗
PubMed1994

Epidural anesthesia increases apparent leg temperature and decreases the shivering threshold.

BACKGROUND: Lower core temperatures than usual are required to trigger shivering during epidural and spinal anesthesia, but the etiology of this impairment remains unknown. In this investigation, we propose and test a specific mechanism by which a peripheral action of regional anesthesia might alter centrally mediated thermoregulatory responses. Conduction anesthesia blocks all thermal sensations; however, cold signals are disproportionately affected because at typical leg temperatures mostly cold receptors fire tonically. It thus seems likely that epidural and spinal anesthesia increase the leg temperature perceived by the thermoregulatory system. Because skin temperature reportedly contributes 5-20% to thermoregulatory control, increased apparent (as distinguished from actual) leg temperature would produce a complimentary decrease in the core temperature triggering thermoregulatory shivering. Accordingly, we tested the hypothesis that abnormal tolerance for hypothermia during epidural anesthesia coincides with an increase in apparent leg temperature. We defined apparent temperature as the leg-skin temperature required to induce a reduction in the shivering threshold comparable to that produced by epidural anesthesia. METHODS: Six women were studied on 4 randomly ordered days: (1) leg-skin temperature near 32 degrees C; (2) leg-skin temperature near 36 degrees C; (3) leg-skin temperature near 38 degrees C; and (4) epidural anesthesia without leg-warming (leg-skin temperature approximately 34 degrees C). At each designated leg temperature, core hypothermia sufficient to evoke shivering was induced by central venous infusion of cold fluid. Upper-body skin temperature was kept constant throughout. In each volunteer, linear regression was used to calculate the correlation between the shivering thresholds on the 3 non-epidural days and concurrent leg temperatures. The slope of these regression equations thus indicated the extent to which leg-warming increased thermoregulatory tolerance for core hypothermia, and was expressed as a percentage leg-skin and leg-tissue contribution to total thermal afferent input. The skin and tissue temperatures that would have been required to produce the observed shivering threshold during epidural anesthesia, the apparent temperatures, were then interpolated from the regression. RESULTS: There was a good linear relation between the shivering threshold and leg-skin temperature (r2 = 0.94 +/- 0.06). The contribution of leg-skin temperature to the shivering threshold was 11 +/- 3% of the total thermal input. Apparent leg-skin temperature during epidural anesthesia was 37.8 +/- 0.5 degrees C, which exceeded actual leg-skin temperature by approximately 4 degrees C. The contribution of leg-tissue temperature to the shivering threshold was 19 +/- 7% of the total. Apparent leg-tissue temperature during epidural anesthesia was 37.1 +/- 0.4 degrees C, which exceeded actual leg-skin temperature by approximately 2 degrees C. CONCLUSIONS: Because leg-skin contributed approximately 11% to the shivering threshold, it is unlikely that the entire skin surface contributes at much less than 20%. These data suggest that the shivering threshold during epidural anesthesia is reduced by a specific mechanism, namely that conduction block significantly increases apparent (as distinguished from actual) leg temperature.

Adult↗
PubMed1993

Antigenic and immunogenic properties of recombinant hepatitis A virus 14S and 70S subviral particles.

Hepatitis A virus (HAV) has an immunodominant neutralization antigenic site. By using a panel of monoclonal antibodies targeted against the HAV neutralization antigenic site, it was shown that three epitopes within this site are present on 14S subunits (pentamers of the structural unit). In contrast, two other epitopes within this site are formed upon assembly of 14S subunits into capsids. Thus, the epitopes recognized by these two monoclonal antibodies are formed either by a conformational change in the antigenic site or by the juxtaposition of epitope fragments present on different 14S subunits during assembly of 14S into 70S particles. Both 14S and 70S particles elicited HAV-neutralizing antibodies in mice; thus, these particles may be useful for HAV vaccine development.

Antibodies, Monoclonal↗
PubMed1993

Primary care, quality improvement, and health systems change.

In this article, we have examined evidence that supports inferences regarding the critical role of primary care in determining the ultimate quality and success of our health care system as a whole. It seems clear that this nation has a critical need to correct the rapidly eroding structure and impact of our primary care system. We have suggested several strategies necessary to improve the United States primary care system. We need to correct the numeric imbalance of generalists to specialists by enhancing motivation to enter this career field. To enhance primary care as a career choice, we must increase the status, contribution, and rewards of primary practitioners. Finally, to facilitate future growth and success, we must enhance the scholarly base of knowledge in this field, particularly as related to quality improvement technology and managed health care.

Delivery of Health Care↗
PubMed1992

The 3-M syndrome: risk of intracerebral aneurysm?

We describe a child with typical features of the 3-M syndrome who presented with acute hydrocephalus owing to haemorrhage from one of two intracranial cerebral vascular aneurysms. We suggest that other children with this disorder should be screened for similar complications.

Cerebral Angiography↗
PubMed1990

Developing staff into clinical practitioners.

Developing clinical skills in pharmacy staff is a process that can enhance the services of a pharmacy department and improve the professional development and interest of the staff. Staff should be included in the development of a clinical philosophy and a training and ongoing development program that will achieve the desired goals should be planned. An MBO process may help to track the individual pharmacist's progress. Knowledgeable, motivated staff are the key ingredient in achieving success in providing pharmacy services.

Clinical Competence↗
PubMed1986

Gastrointestinal bleeding in patients with acute spinal injuries.

439 acute, male, spinal injury patients were admitted over an 11-year period at the National Spinal Injuries Centre: 206 cervical, 182 dorsal, and 51 lumbar cord injuries. 27 patients had gastrointestinal bleeds; 20 bled on one occasion, 7 had more than one episode; 22 bled within 4 weeks of injury. The mean was 22.5 days. The presentation was mostly malaena. A diagnosis was made in 19 cases; 12 had duodenal ulcers, 4 gastric ulcers, 1 had gastritis, 1 had a gastric carcinoma, 1 had oesophagitis with a possible Mallory-Weiss tear; 4 died. The incidence was higher in cervical patients. Causation was thought to be due to patients being sick from severe intercurrent illnesses and injuries. Implications for further research are discussed.

Acute Disease↗
PubMed1986

Systemic lupus erythematosus--a medical and social profile.

The social functioning of 120 patients (114 women) with systemic lupus erythematosus (SLE) was studied. The proportion of Chinese, Japanese and Native Indians was greater than expected. Familial incidences of SLE (12.5%) and rheumatoid arthritis (17.5%) were high. Sixty-one women had 76 pregnancies after the onset of SLE; although fetal wastage was common, outcomes were otherwise satisfactory. Social difficulties worsened with disease exacerbations, drug reactions and delay in diagnosis. Thirty-three percent completed their education after the onset of SLE. Sixty-three percent with a work history were employed and 52% were totally or partially self-supporting. Patients experienced problems with self-image (20%), sexual functioning (4%) and lifestyle (17%). SLE was not a barrier to marriage or a primary cause of divorce: 40% married after the onset of SLE and 12.5% had a history of divorce. In summary, SLE patients can function well socially; it is imperative to recognize the difficulties and provide support.

Adolescent↗
PubMed1982

Juvenile dermatomyositis: medical, social and economic status in adulthood.

Eighteen adults were studied an average of 18.5 years after the diagnosis of juvenile dermatomyositis had been made. Persistent weakness was found in six patients and recurrent rash in the classic distribution in seven. Other clinical features present were Raynaud's phenomenon, arthritis and subcutaneous nodules. Minor increases in the serum creatine phosphokinase level were noted in seven patients and did not correlate with the presence of weakness or rash. Educational achievement and employment status were better in this group than in a group of adults with juvenile rheumatoid arthritis or the general adult population of British Columbia. Significant residual disability related to calcinosis and flexion contractures was present in only three of the patients.

Adolescent↗