Development, implementation and evaluation of a new nurse-led continence service: a pilot study.

The Leicestershire Medical Research Council (MRC) Incontinence Study is a series of interrelated studies exploring the epidemiology of urinary symptoms, including incontinence, and evaluating service provision and treatment options for these symptoms. This paper describes one aspect of the Leicestershire MRC Incontinence Study, namely the development, implementation and evaluation of a new nurse-led continence service. When developing a new service it is important to determine its acceptability and suitability to the target population. The new mode of service delivery was dependent on specially trained Continence Nurse Practitioners (CNP) delivering predefined evidence-based treatment interventions. Objective and subjective outcome measures were used to evaluate the service. The service was shown to be effective in reducing urinary symptoms and led to high levels of patient satisfaction. This service is currently being evaluated in a randomized controlled trial.

Educational preparation: specialist practice in continence care.

Contributing factors to effective continence service provision include funding, organization, and expert knowledge among the individuals providing care. Expert knowledge can be gained through clinical experience and appropriate ongoing education. It has been widely reported that undergraduate education in this area for nurses, doctors and physiotherapists is limited (Brocklehurst, 1990; Swaffield, 1994; Laycock, 1995). Many nurses providing continence care have accumulated knowledge through experience and trial and error. Little is known about the effectiveness of advanced postgraduate education of 'experts' in continence care. This article outlines a continence education module developed to prepare a specialist group of nurses to provide a high standard of continence care that is both safe and effective in a clinical environment. This module was designed and evaluated specifically as part of the Leicestershire Medical Research Council (MRC) Incontinence Study. Changes in continence knowledge, attitudes to research, and acceptability of the module have been explored. When setting up a new nurse-led continence service, it is of great importance to systematically detail the components of the educational preparation of the nurses providing the service. Open discussion of any problems in the design and implementation of this module may inform future modules in this and other areas.

Negative information weighs more heavily on the brain: the negativity bias in evaluative categorizations.

Negative information tends to influence evaluations more strongly than comparably extreme positive information. To test whether this negativity bias operates at the evaluative categorization stage, the authors recorded event-related brain potentials (ERPs), which are more sensitive to the evaluative categorization than the response output stage, as participants viewed positive, negative, and neutral pictures. Results revealed larger amplitude late positive brain potentials during the evaluative categorization of (a) positive and negative stimuli as compared with neutral stimuli and (b) negative as compared with positive stimuli, even though both were equally probable, evaluatively extreme, and arousing. These results provide support for the hypothesis that the negativity bias in affective processing occurs as early as the initial categorization into valence classes.

Inhibitors of nitric oxide synthase in inflammatory arthritis.

There is considerable evidence that excessive nitric oxide (NO) synthesized from L-arginine by inducible nitric oxide synthase (iNOS) plays an important pathological role in inflammatory arthritis. Since NO synthesized by constitutive isoforms of NOS has a physiological role, a great deal of activity has been directed at identifying inhibitors of NOS that are selective for the induced isoform. The major chemical areas that have been described so far in the search for such selective iNOS inhibitors and the activity of some of these compounds in animal models of arthritis are reviewed.

Investigations of closure processes: what source-monitoring judgments suggest about what is "closing".

On many occasions, the perception of an object is based on incomplete information because portions of the object are occluded from view. Nevertheless, people are able to identify an occluded object, suggesting that the identification is mediated by the activation of completion processes which "fill in" the missing information. Although these completion processes are invoked as causal mechanisms for many phenomena, the processes mediating the "completion" have not been specified. The present experiments tested two potential explanations for closure processes. In each experiment, participants were presented with pictures, complete or incomplete in form, and, on a surprise source-monitoring task, they were then asked to remember whether pictures had been presented complete or incomplete in form. Whether viewing pictures of objects, faces, or camouflaged objects, participants showed a pronounced tendency to claim that incomplete pictures were actually presented complete in form. This bias was evident after the participants described functions for objects (Experiments 1, 1A, and 2), after they evaluated properties of faces (Experiment 4), and after they searched for objects hidden in a complex scene (Experiment 5). However, this bias was not evident after they simply named objects portrayed in pictures (Experiment 3). This bias is interpreted as evidence for the activation of implicit imaginal processing. The results of these experiments are informative in their contribution to our understanding of the bases of closure, an intuitively appealing notion frequently invoked to account for object identification, but, as yet, not fully understood.

A prospective study of urinary retention and risk of death after proximal femoral fracture.

Older age, dementia syndrome and impaired mobility are well recognized risk factors for fatality after fracture of the proximal femur. Urinary retention is recognized as a common complication of elective total hip replacement. In this investigation, we estimated the incidence of urinary retention associated with hip fracture in older women and assessed its relationship to 2-year post-operative fatality. Over a 7-month period, 309 women aged 65 and over were admitted to one trauma unit with hip fracture. Readings of post-voiding residual volume were taken on admission (pre-operative), within 24 hours of operation (post-operative) and 5-7 days post-operatively (recovery). Of the 309 patients, 244 (79%) had readings of post-voiding residual volume taken on admission; 90/244 (37%) had retention pre-operatively, 122/216 (56%) post-operatively and 40/183 (22%) in the recovery phase. One year after operation 305 patients were traced and median follow-up was 2 years. Older age, cognitive impairment, polypharmacy, impaired mobility and urinary retention on admission and during recovery were associated with a higher fatality in the first post-operative year. Pre-operative urinary retention is common among older women with proximal femoral fracture and affects over half post-operatively. Retention is one of several factors associated with higher fatality.

Scanning the structure and antigenicity of HPV-16 E6 and E7 oncoproteins using antipeptide antibodies.

The structure and antigenicity of the HPV-16 E6 and E7 oncoproteins was studied using a set of antisera against overlapping synthetic peptides. We report that antigenic, mobile regions of the native proteins, as defined by reactivity with antipeptide antisera, occur at the N-termini of both E6 and E7 proteins, corresponding to regions of known or suspected protein-protein interactions. The putative zinc finger domains were consistently non-reactive, despite computer predictions of relatively high antigenicity, suggesting that the proposed zinc finger regions are held in stable secondary structures that the peptides were not able to mimic. In E6, the linker region between the two zinc fingers was antigenic, indicating that the two zinc finger structures might be able to articulate relative to one another by a flexible linker region. The highly antigenic N-terminal region of HPV-16 E7 was also found to be antigenic in E7 of both HPV-11 and HPV-18, indicating that the E7 proteins of different HPV types have similar antigenic structures. The identification of antigenic regions of the E6 and E7 proteins should be therefore be useful in the design of site-directed antibodies against E6 and E7 for numerous HPV types.

The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat.

1. The effect of endotoxin (E. coli lipopolysaccharide) on the induction of nitric oxide synthase (NOS) and the changes in vascular permeability in the colon and jejunum over a 5 h period have been investigated in the rat. 2. Under resting conditions, a calcium-dependent constitutive NOS, determined by the conversion of radiolabelled L-arginine to citrulline, was detected in homogenates of both colonic and jejunal tissue. 3. Administration of endotoxin (3 mg kg-1, i.v.) led, after a 2 h lag period, to the appearance of calcium-independent NOS activity in the colon and jejunum ex vivo, characteristic of the inducible NOS enzyme. 4. Administration of endotoxin led to an increase in colonic and jejunal vascular permeability after a lag period of 3 h, determined by the leakage of radiolabelled albumin. 5. Pretreatment with dexamethasone (1 mg kg-1 s.c., 2 h prior to challenge) inhibited both the induction of NOS and the vascular leakage induced by endotoxin. 6. Administration of the NO synthase inhibitor NG-monomethyl-L-arginine (12.5-50 mg kg-1, s.c.) 3 h after endotoxin injection, dose-dependently reduced the subsequent increase in vascular permeability in jejunum and colon, an effect reversed by L-arginine (300 mg kg-1, s.c.). 7. These findings suggest that induction of NOS is associated with the vascular injury induced by endotoxin in the rat colon and jejunum.

Role of oxygen radicals and arachidonic acid metabolites in the reverse passive Arthus reaction and carrageenin paw oedema in the rat.

1. The role of arachidonic acid metabolites and oxygen radicals in carrageenin-induced rat paw oedema and dermal reverse passive Arthus reaction (RPA) have been investigated. 2. Indomethacin (10 mg kg-1, p.o.) inhibited carrageenin paw oedema when administered 30 min before, but not 2 h after carrageenin. BWB70C (10 mg kg-1, p.o.), a selective inhibitor of 5-lipoxygenase, had no effect whether administered before or after carrageenin. Administration of both indomethacin and BWB70C had no greater anti-inflammatory effect than indomethacin alone. 3. BW755C (20 mg kg-1, p.o.), which inhibits the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, or superoxide dismutase-polyethylene glycol conjugate (SOD-PEG, 3000 u, i.v.) inhibited carrageenin paw oedema whether administered either 30 min before, or 2 h after carrageenin. 4. Pretreatment with dexamethasone (0.1 mg kg-1) or colchicine (2 mg kg-1), likewise suppressed carrageenin paw oedema. 5. BW755C (25-100 mg kg-1, p.o.) dose-dependently reduced plasma leakage in the RPA, whereas indomethacin (5 mg kg-1, p.o.) or BWB70C either alone or in combination, did not. 6. SOD-PEG (300-3000 u, i.v.) dose-dependently inhibited plasma leakage in the RPA. In addition, the iron chelator and peroxyl radical scavenger, desferrioxamine (200 mg kg-1, s.c.) also inhibited plasma leakage. 7. Pretreatment with dexamethasone (0.1 mg kg-1) or colchicine (1 mg kg-1) reduced the plasma leakage in RPA, whereas MK-886 (10 mg kg-1) had no effect. 8. These results indicate an important role for oxygen radicals but not arachidonic acid metabolites in the maintenance of carrageenin paw oedema and the plasma leakage in RPA. Furthermore, the results suggest that the anti-inflammatory actions of BW755C can be dissociated from its effects on arachidonic acid metabolism and are attributed to its anti-oxidant activity.

Nitric oxide synthase activity in ulcerative colitis and Crohn's disease.

Excessive nitric oxide (NO) production by an isoform of NO synthase that can be induced by inflammatory stimuli leads to changes in vascular permeability and to tissue injury. We measured NO synthase activities in mucosa and muscle from the colons of control patients (n = 11) and patients with ulcerative colitis (6) or Crohn's disease (4). NO synthase activity in colonic mucosa of ulcerative colitis patients was 0.55 (median interquartile range 0.32-0.57) nmol/min per g tissue, which was about eightfold higher than the value in control mucosa, with no individual overlap (p < 0.001). With colonic muscle there was no difference in NO synthase activity between ulcerative colitis patients and controls. In the patients with Crohn's disease, mucosal NO synthase activity did not differ from control values and activity in the colonic muscle was low. Thus, induction of colonic NO synthase may be involved in the mucosal vasodilation and increased vascular permeability of active ulcerative colitis, and could also contribute to the impaired motility that accompanies toxic dilation.

A phase I study of recombinant human interleukin-4 administered by the intravenous and subcutaneous route in patients with advanced cancer: immunological studies.

The effects of recombinant human interleukin-4 (rhu IL-4) on immunological parameters in patients receiving increasing doses of IL-4 in a Phase I trial were investigated. Peripheral blood mononuclear cells were phenotyped for a variety of lymphocyte markers, but no consistent effects were observed. However, increases in HLA Class II expression on monocytes were detected in four patients. NK and LAK activity were neither induced nor augmented by IL-4 treatment. Slight increases in proliferative responses to mitogens and cytokines were observed in some patients. The latter observations and other clinical studies suggest that a combination of IL-4 with IL-2 may be more effective in Phase II clinical trials.

Serological response to HPV 16 in cervical dysplasia and neoplasia: correlation of antibodies to E6 with cervical cancer.

Sera from patients with cervical cancer, cervical intraepithelial neoplasia (CIN) and non-genital cancers, and from healthy individuals, were investigated for antibodies to human papilloma virus (HPV) early proteins E4, E6 and E7 and the major capsid protein LI by Western blot analysis of recombinant HPV proteins. There was a significantly higher prevalence of sera with antibodies to E6 in cervical cancer patients than in healthy individuals or in CIN or non-genital-cancer patients. Antibodies to E7 were detected in 25% of cervical-cancer patients, which is significantly higher than in HPV-associated cervical lesions or in control populations, but not significantly different from the incidence in patients with non-genital cancers. Antibodies to LI were found more frequently in CIN, while antibodies to E4 had a similar prevalence in cervical-cancer, cervical-dysplasia and non-genital-cancer groups, with 24% in the controls. The inability to detect antibodies to E6 and E7 in the majority of cervical-cancer patients limits the application of this methodology to the monitoring of HPV infection and the development of cervical cancer. However, the latter approach may be useful in combination with other assay systems which allow detection of different, including conformational, epitopes of HPV E6 and/or E7 recombinant proteins.