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Biomedical subjects

J Ward

Publications and source records attributed to J Ward.

At least 73 records · Page 4Linked to original sources
PubMed2000

Calcium-dependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells.

The pancreatic acinar cell produces powerful digestive enzymes packaged in zymogen granules in the apical pole. Ca(2+) signals elicited by acetylcholine or cholecystokinin (CCK) initiate enzyme secretion by exocytosis through the apical membrane. Intracellular enzyme activation is normally kept to a minimum, but in the often-fatal human disease acute pancreatitis, autodigestion occurs. How the enzymes become inappropriately activated is unknown. We monitored the cytosolic Ca(2+) concentration ([Ca(2+)](i)), intracellular trypsin activation, and its localization in isolated living cells with specific fluorescent probes and studied intracellular vacuole formation by electron microscopy as well as quantitative image analysis (light microscopy). A physiological CCK level (10 pM) eliciting regular Ca(2+) spiking did not evoke intracellular trypsin activation or vacuole formation. However, stimulation with 10 nM CCK, evoking a sustained rise in [Ca(2+)](i), induced pronounced trypsin activation and extensive vacuole formation, both localized in the apical pole. Both processes were abolished by preventing abnormal [Ca(2+)](i) elevation, either by preincubation with the specific Ca(2+) chelator 1, 2-bis(O-aminophenoxy)ethane-N,N-N',N'-tetraacetic acid (BAPTA) or by removal of external Ca(2+). CCK hyperstimulation evokes intracellular trypsin activation and vacuole formation in the apical granular pole. Both of these processes are mediated by an abnormal sustained rise in [Ca(2+)](i).

Animals↗
PubMed2000

Universal maternal screening for neonatal group B streptococcal disease.

Group B streptococcal infection is a leading cause of neonatal morbidity and mortality in the developed world. Data obtained in our region suggest that the incidence in the UK may be higher than previously reported, and together with the results of a pilot study indicate that preventive strategies based on maternal risk factors alone would prevent less than half the cases of neonatal disease.

Anti-Bacterial Agents↗
PubMed2000

Skill-mix. Seams good to us.

Greater use of GPs, both in general practice and hospitals, could reduce waiting times for hospital services. PCGs might consider developing some specialist services. The development of GP specialists should be considered. Allowing GPs with a special interest in surgery to perform some hospital surgery would reduce pressure on consultants' lists.

Clinical Competence↗
PubMed2000

Cardiovascular responses to carotid chemoreceptor stimulation in the dog: their modulation by urinary bladder distension.

Respiratory, heart rate and hindlimb vascular responses were studied in response to increasing levels of stimulation of the carotid body chemoreceptors, together with an examination of the modulation of their effects by distension of the urinary bladder in the dog anaesthetized with a mixture of chloralose and urethane. The vascularly isolated carotid bifurcation regions were perfused with blood, stimulation of the carotid bodies being carried out by three different levels of hypoxic isocapnic blood (PO2 approximately 58, 40 and 22 mmHg) obtained from a donor animal. A vascularly isolated hindlimb was autoperfused at constant blood flow through its femoral artery. In spontaneously breathing animals, increasingly intense hypoxic stimulation of the carotid bodies caused a progressive augmentation of respiratory minute volume. Superimposition of distension of the bladder increased ventilation further, by the same amount during hypoxic as during normoxic blood perfusion of the chemoreceptors. Prevention of the effects of lung stretch afferent stimulation by artificial ventilation modified the heart rate and hindlimb vascular responses to excitation of the carotid bodies by revealing or accentuating the primary cardiovascular responses, bradycardia and vasoconstriction. In contrast, no such respiratory modulation was apparent in the cardiovascular responses to bladder distension. When, under conditions of artificial ventilation and in the absence of changes in the arterial baroreceptor input, the primary cardio-inhibitory and vasoconstrictor responses to carotid chemoreceptor stimulation predominated, the heart slowed progressively as the stimulus was increased. At the same time the cardio-accelerator effects of bladder distension progressively diminished, indicating an interaction between the cardiac reflex responses evoked by the two inputs. In contrast, the reflex vascular responses resulting from stimulation of the two inputs were additive, at least for PO2 levels of carotid body perfusate down to approximately 40 mmHg. In conclusion these experiments demonstrate the differential nature of the integration of respiratory and cardiovascular responses evoked by stimulation of the carotid chemoreceptors and bladder distension.

Animals↗
PubMed2000

The impact on retention of expansion of an Australian public methadone program.

Although rapid expansion of methadone programs has occurred in many countries, there are few studies of the impact on treatment success. The one public methadone maintenance program in Canberra was expanded from 85 places in 1991 to 350 places in late 1992. While this responded to a real need, it also led to a temporary increase in drop-outs. Retention was considerably improved in 1996 when clients began to be transferred from the public program to fee-for-service primary health care, but the improvement was also not sustained. In recent years, one-quarter to one-half of clients dropped out before stabilization. Multiple entries into treatment were common and overall retention was not affected by previous treatment episodes or length of time between episodes. Methadone programs should monitor retention as part of on-going evaluation and improvement of treatment policy.

Australia↗
PubMed2000

Prognostic value of magnetic resonance imaging in the management of fistula-in-ano.

PURPOSE: Magnetic resonance imaging of fistula-in-ano has been shown to predict surgical anatomy accurately and identify complex features. In addition, fistula complexity has been correlated with poor outcome after surgical intervention. We investigated whether preoperative magnetic resonance imaging could predict clinical outcome after surgery for fistulous disease better than clinical examination under anesthetic. METHODS: Seventy patients with clinically suspected fistula-in-ano underwent preoperative dynamic contrast-enhanced magnetic resonance imaging before surgical exploration. Outcome was assessed at a minimum of one year after surgical exploration and correlated in a blinded fashion with the surgical and magnetic resonance grading of the severity of the fistulous disease. RESULTS: Of 70 patients, 12 were not operated on and 6 were lost to follow-up, making 52 patients eligible for analysis. Assessment by dynamic contrast-enhanced magnetic resonance imaging more accurately predicted outcome than the findings at initial surgical exploration. Dynamic contrast-enhanced magnetic resonance imaging had a sensitivity of 81 percent, specificity of 73 percent, and positive predictive value of 75 percent; surgery had a sensitivity of 77 percent, specificity of 46 percent, and positive predictive value of 59 percent. Surgical assessment of apparent disease severity bore no relation to final outcome. Dynamic contrast-enhanced magnetic resonance imaging could accurately predict whether patients were likely to have a satisfactory or unsatisfactory outcome after surgery. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging better predicts clinical outcome of patients with fistula-in-ano than initial surgical exploration.

Adult↗
PubMed2000

The role of semantics in reading and spelling: evidence for the 'summation hypothesis'.

This study documents a patient, SA, with an impairment of semantic memory arising as a result of Semantic Dementia (Pick's disease). The patient is impaired at deriving semantic knowledge from both words and pictures. However, his ability to derive semantic knowledge of countries is relatively spared compared to concrete nouns and famous people. The presence of a semantic deficit was used to investigate the role of semantics in reading and spelling. Several novel cueing/priming paradigms are reported which suggest that SA is able to use partial semantic knowledge to constrain his reading and spelling. These results are broadly consistent with the 'summation hypothesis' [27] and suggest that normal reading and spelling may take place by integrating both semantic information and knowledge of direct orthography-phonology correspondences.

Atrophy↗
PubMed2000

MRI of liver: a comparison of CNR enhancement using high dose and low dose ferumoxide infusion in patients with colorectal liver metastases.

The purpose of this study was to compare the effects of high dose (HD) and low dose (LD) ferumoxides infusions on lesion-to-liver contrast-to-noise ratio (CNR) using four different T(2)-weighted MR sequences. Seventy-three patients with known colorectal liver metastases underwent T(2)-weighted fast spin echo (FSE) imaging before and after ferumoxides. After ferumoxides, T(2)-weighted dual echo (DE) and T(2)-weighted GRE FLASH images were also obtained. To evaluate the relationship between TE length and lesion-to-liver CNR, the same FLASH sequence was repeated in 18 LD patients after lengthening the TE. Ferumoxides was administered at a dose of 15 micromol/kg (HD) and 7.5 micromol/kg (LD) in 45 and 28 patients, respectively. The effects of HD and LD ferumoxides infusions were measured as the percentage signal intensity change (PSIC) in the liver and lesions, lesion-to-liver CNR and the change in lesion-to-liver CNR (DeltaCNR). In both LD and HD groups, all CNR values obtained after SPIO were significantly greater than those observed with unenhanced FSE (p < 0.01). There was no significant difference between the mean CNR values obtained with either dose for any sequence. With the FLASH sequence, CNR increased progressively with longer TE. At the longest TE of 26 ms, mean CNR was higher than that recorded with any of the other sequences. Although mean liver PSIC was significantly greater in the HD group than in the LD group (p < 0.01) because the mean lesion PSIC was also greater in the HD group, the mean DeltaCNR after ferumoxides was not significantly different in the two groups. LD SPIO enhanced MR significantly increases lesion-to-liver CNR compared with unenhanced images. At 1. 0 T, HD and LD ferumoxides infusions produce comparable lesion-to-liver CNR. Our results suggest that at 1.0 T ferumoxides may be administered at a dose of 7.5 micromol/kg without loss of image quality.

Aged↗
PubMed2000

Education and training of healthcare staff: the barriers to its success.

On-going developments in Britain's healthcare services are placing great demands on its workforce. If high quality care is to be maintained, education and training is needed to provide staff with the necessary knowledge and skills to adapt to their changing roles. A recent research project looking at the education and training needs of non-specialist staff caring for people with cancer identified a number of barriers that prevent education and training from meeting its full potential. These barriers include time, accessibility, financial issues, staff motivation and marketing and advertising and are discussed in this paper together with some possible solutions to overcome them. It is concluded that the planning and development of education and training must address these barriers if it is to be successful in increasing the knowledge and skills of staff, and thereby improve the quality of patient care.

Attitude of Health Personnel↗
PubMed2000

A general overview of the cancer education needs of non-specialist staff.

The aim of this study was to identify the cancer education needs of non-specialist staff. A qualitative design was used involving focus groups, individual and paired interviews, focusing on specialist staff, non-specialist staff and patients. Six key areas were identified where staff indicated a need for education and training. These included: (1) an overview of cancer, what it is and how it effects patients; (2) treatments and side-effects; (3) communication skills; (4) physical and practical issues; (5) care organisation, referral routes and staff roles; and (6) death and dying issues. Similarities in the views of specialists and non-specialist staff of all disciplines indicated a workforce who would benefit from support and training in cancer issues. This is important if we are to provide safe and optimal care to patients with cancer at all stages of the disease trajectory.

Attitude of Health Personnel↗
PubMed2000

Improving local services for women with breast cancer: interviews with general practitioners in central Sydney.

We conducted interviews with 85 randomly selected general practitioners (GPs) in Central Sydney to examine patterns of referral of women with breast cancer, satisfaction with local services, awareness of evidence-based guidelines and suggestions for local support. Previous experience was the most frequently cited factor influencing choice of specialist (n = 80, 94%) followed by personal knowledge of the consultant's expertise (n = 72, 85%). Only one third of respondents agreed women wanted to be more involved in choosing the specialist (n = 28, 33%). Of 79 women recently diagnosed with breast cancer, the majority (96%) had been referred to a male surgeon (n = 71, 96%). While only 35% of the GPs rated the care received by women with breast cancer in local facilities as 'excellent', significantly fewer rated communication between GPs and specialists as 'excellent' (35% v 19%, p < 0.01). Younger GPs were less likely to rate communication as 'excellent' compared with GPs aged 55 years or older (p = 0.01). Only 18% of GPs considered their patients as having been 'very well informed' about their treatment choices. Younger GPs were more likely than older GPs to recall all available breast cancer guidelines (p = 0.02). Significantly more GPs (68%) requested seminars with experts than any other types of educational support (p < 0.001). To improve outcomes for women with breast cancer, mechanisms to support communication between GPs and specialists are recommended. Seminars for GPs with experts who emphasize evidence-based guidelines should be funded and evaluated, especially for impact in meeting the needs of older GPs.

Adult↗
PubMed2000

ATP in human skin elicits a dose-related pain response which is potentiated under conditions of hyperalgesia.

Despite the considerable interest in the possibility that ATP may function as a peripheral pain mediator, there has been little quantitative study of the pain-producing effects of ATP in humans. Here we have used iontophoresis to deliver ATP to the forearm skin of volunteers who rated the magnitude of the evoked pain on a visual analogue scale. ATP consistently produced a modest burning pain, which began within 20 s of starting iontophoresis and was maintained for several minutes. Persistent iontophoresis of ATP led to desensitization within 12 min but recovery from this was almost complete 1 h later. Different doses of ATP were delivered using different iontophoretic driving currents. Iontophoresis of ATP produced a higher pain rating than saline, indicating that the pain was specifically caused by ATP. The average pain rating for ATP, but not saline, increased with increasing current. Using an 0.8 mA current, subjects reported pain averaging 27.7 +/- 2.8 (maximum possible = 100). Iontophoresis of ATP caused an increase in blood flow, as assessed using a laser Doppler flow meter. The increase in blood flow was significantly greater using ATP than saline in both the iontophoresed skin (P < 0.01) and in the surrounding skin, 3 mm outside the iontophoresed area (P < 0.05). The pain produced by ATP was dependent on capsaicin-sensitive sensory neurons, since in skin treated repeatedly with topical capsaicin pain was reduced to less than 25% of that elicited on normal skin (2.1 +/- 0.4 compared with 9.3 +/- 1.5 on normal skin). Conversely, the pain-producing effects of ATP were greatly potentiated in several models of hyperalgesia. Thus, with acute capsaicin treatment when subjects exhibited touch-evoked hyperalgesia but no ongoing pain, there was a threefold increase in the average pain rating during ATP iontophoresis (22.7 +/- 3.1) compared with pre-capsaicin treatment (7.8 +/- 2.6). Moreover, ATP iontophoresed into skin 24 h after solar simulated radiation (2 x minimal erythymic dose) resulted in double the pain rating of normal skin, increasing from 15.3 +/- 4.1 to 32.7 +/- 4.1. The pain response to saline was not significantly altered after UV irradiation at any time-point studied. We conclude that ATP produces pain by activating capsaicin-sensitive nociceptive afferents when applied to skin. The possibility that ATP activates nociceptors indirectly via its degradation products cannot be ruled out. The effects of ATP are dose-dependent and responses desensitize only slowly. In inflammatory conditions, ATP may be a potent activator of nociceptors and an endogenous mediator of pain.

Adenosine Triphosphate↗
PubMed2000

Insight into the physiological function(s) of uteroglobin by gene-knockout and antisense-transgenic approaches.

To determine the physiological function(s) of uteroglobin (UG), a steroid-inducible, homodimeric, secreted protein, we have generated transgenic mice that either are completely UG-deficient due to UG gene-knockout (UG-KO) or are partially UG-deficient due to the expression of UG antisense RNA (UG-AS). Both the UG-KO and UG-AS mice develop immunoglobulin A (IgA) nephropathy (IgAN), characterized by microhematuria, albuminuria, and renal glomerular deposition of IgA, fibronectin (Fn), collagen, and C3 complement. This phenotype of both UG-KO and UG-AS mice is virtually identical to that of human IgAN, the most common primary glomerulopathy worldwide. The molecular mechanism by which UG prevents this disease in mice appears to center around UG's interaction with Fn. Since Fn, IgA, and UG are present in circulation and high plasma levels of IgA-Fn complex have been reported in human IgAN, we sought to determine whether UG interacts with Fn and prevents Fn-Fn and/or IgA-Fn interactions, essential for abnormal tissue deposition of Fn and IgA. Our coimmunoprecipitation studies uncovered the formation of Fn-UG heteromers in vitro and these heteromers are detectable in the plasma of normal mice, but not UG-KO mice. Further, high plasma levels of IgA-Fn complex, a characteristic of human IgAN patients, were also found in UG-KO mice. Finally, coadministration of UG + Fn or UG + IgA to UG-KO mice prevented glomerular deposition of Fn and IgA, respectively. Our results define a possible molecular mechanism of IgAN and provide insight into at least one important physiological function of UG in maintaining normal renal function in mice.

Animals↗
PubMed2000

Maximizing response rates to a survey of dentists: a randomized trial.

Dentists currently practising within the Central Sydney Area were surveyed (n = 179). A randomized controlled trial was conducted to evaluate the effect of an advance telephone prompt (intervention group) compared with an advance letter prompt only (control group) in maximizing the response rate to a self-administered questionnaire. While the overall response rate was 83 per cent, the final response rate (89 per cent) from dentists in the intervention group was significantly higher than that from dentists in the control group (78 per cent) (chi 2 = 4.14, df = 1, p = 0.04). Advance telephone prompts are effective in maximizing the response rates from dentists and are recommended in future surveys of this professional group.

Attitude of Health Personnel↗
PubMed2000

Hepatic lesion detection after superparamagnetic iron oxide enhancement: comparison of five T2-weighted sequences at 1.0 T by using alternative-free response receiver operating characteristic analysis.

PURPOSE: To compare the accuracy of five T2-weighted sequences in the detection of liver lesion at magnetic resonance (MR) imaging after superparamagnetic iron oxide (SPIO) enhancement. MATERIALS AND METHODS: Forty-nine candidates for hepatic resection with known coloretal metastases were examined. Before SPIO enhancement, fast spin-echo (SE) images were obtained. After enhancement, the same fast SE sequence and long; TR/short TE, short TE, long TR/TE, and T2-weighted fast low-angle shot (FLASH) sequences were used. All images were viewed independently by four observers who were blinded to the results of the other imaging sequences, the results of the other observers, and the findings at surgery and histopathologic examination. Four weeks after the initial reading, the combined long TR/short TE and long TR/TE dual-echo images were also viewed as an additional set. The alternative free response receiver operating characteristic (ROC) method was used to analyze the results, which were correlated with findings at surgery, intraoperative ultrasonography, and histopathologic examination. RESULTS: Irrespective of lesion size, the accuracy of all sequences after enhancement was significantly greater than that of the nonenhanced fast SE sequence (P < .01). Dual-echo and FLASH sequences were significantly more accurate than the enhanced fast SE sequence (P < .03 or P < .02, respectively). For all lesions, lesions smaller than 1 cm, and lesions 1 cm or larger, mean accuracies were as follows: dual-echo, 0.75, 0.54, and 0.93; FLASH, 0.75, 0.54, and 0.95; and enhanced fast SE, 0.72, 0.49, and 0.92. CONCLUSION: At 1.0 T, dual-echo and FLASH sequences are the most accurate pulse sequences after SPIO enhancement.

Aged↗