Intrapericardial neuroendocrine tumour in a dog.

An 11-year-old neutered male Border Terrier presented for pericardiectomy after a nine-month history of tricavitary effusion, dyspnoea and lethargy. Transthoracic echocardiography revealed a fluid-filled structure at the heart base, starting at the mid-right ventricle and extending to the middle of the right atrium. Almost complete compression of the right atrium and the cranial vena cava was noted. Thoracic computed tomography revealed a heterogeneously enhancing and poorly marginated mass within the cranial aspect of the pericardium. A median sternotomy and subtotal pericardiectomy were performed. A non-distinct fluid-filled structure within the pericardium adhered to the epicardium was visualised. The structure was removed via marsupialisation along with extirpation of enlarged sternal lymph nodes. Histopathological examination of the sternal lymph nodes revealed expansile, well-demarcated, unencapsulated nodules of neoplastic cells consistent with a neuroendocrine tumour suspected to be thyroid in origin. After surgery, intractable pleural effusion resulted in euthanasia. Intrapericardial ectopic thyroid tumours are rarely reported in animals. The location of the mass and unusual presentation may have made it challenging for echocardiography to identify this neoplasia. Thoracic computed tomography at an earlier stage may have identified the neoplasia and potentially allowed for surgical intervention.

Emergency Laparotomy Follow-Up Study (ELFUS): prospective feasibility investigation into postoperative complications and quality of life using patient-reported outcome measures up to a year after emergency laparotomy.

BACKGROUND: Emergency laparotomy carries a significant risk profile around the time of surgery. This research aimed to establish the feasibility of recruitment to a study using validated scoring tools to assess complications after surgery; and patient-reported outcome measures (PROMs) to assess quality of life and quality of recovery up to a year following emergency laparotomy (EL). METHODS: We used our local National Emergency Laparotomy Audit (NELA) register to identify potential participants at a single NHS centre in England. Complications were assessed at 5, 10 and 30 days after EL. Patient-reported outcome measures were collected at 1, 3, 6 and 12 months after surgery using EQ5D and WHODAS 2.0 questionnaires. RESULTS: Seventy of 129 consecutive patients (54%) agreed to take part in the study. Post-operative morbidity survey data was recorded from 63 and 37 patients at postoperative day 5 and day 10. Accordion Complication Severity Grading data was obtained from 70 patients. Patient-reported outcome measures were obtained from patients at baseline and 1, 3, 6 and 12 months after surgery from 70, 59, 51, 48, to 42 patients (100%, 87%, 77%, 75% and 69% of survivors), respectively. CONCLUSIONS: This study affirms the feasibility of collecting PROMs and morbidity data successfully at various time points following emergency laparotomy, and is the first longitudinal study to describe quality of life up to a year after surgery. This finding is important in the design of a larger observational study into quality of life and recovery after EL.

A profile of the belief system and attitudes to end-of-life decisions of senior clinicians working in a National Health Service Hospital in the United Kingdom.

There is evidence from outside the United Kingdom to show that physicians' religious beliefs influence their decision making at the end of life. This UK study explores the belief system of consultants, nurse key workers and specialist registrars and their attitudes to decisions which commonly must be taken when caring for individuals who are dying. All consultants (N = 119), nurse key workers (N = 36) and specialist registrars (N = 44) working in an acute hospital in the north-east of England were asked to complete a postal questionnaire. In all, 65% of consultants, 67% of nurse key workers and 41% of specialist registrars responded. Results showed that consultants' religion and belief systems differed from those of nurses and the population they served. Consultants and nurses had statistically significant differences in their attitudes to common end of life decisions with consultants more likely to continue hydration and not withdraw treatment. Nurses were more sympathetic to the idea of physician-assisted suicide for unbearable suffering. This study shows the variability in belief system and attitudes to end of life decision making both within and between clinical groups. This may have practical implications for the clinical care given and the place of care. The personal belief system of consultants was not shown to affect their overall attitudes to withdrawing life-sustaining treatment or physician-assisted suicide.

The distribution, concentration, and toxicity of enhanced green fluorescent protein in retinal cells after genomic or somatic (virus-mediated) gene transfer.

PURPOSE: The concentration of enhanced green fluorescent protein (EGFP) in individual photoreceptor cells of live mouse retina was quantified and correlated with physiological measurements of cell function. METHODS: EGFP protein levels in the retinas of mice injected subretinally by either one of two serotypes of adeno-associated virus (AAV; AAV2/5.CMV.EGFP; AAV2/2.CMV.EGFP) were quantified with a photon-counting confocal laser scanning microscope and compared with those of transgenic mice whose retinas expressed EGFP under the beta-actin (pbetaAct) or human L/M-cone opsin (pLMCOps) promoter. Single-cell suction pipette recordings of single rods and whole-field electroretinograms (ERGs) were performed to assess retinal cell function. RESULTS: The highest levels of EGFP (680 microM) were in the retinal pigment epithelium (RPE) cells of the AAV-transduced eyes. Living photoreceptors of pbetaAct.EGFP mice contained 270 microM EGFP, while their bipolars had 440 microM. The cones of pLMCOps.EGFP mice expressed 60 microM protein. The amplitudes of the major components of ERGs were within the normal range for all transgenic animals examined, and single cell recordings from living pbetaAct.EGFP rods were indistinguishable from those of controls. CONCLUSIONS: EGFP levels in individual cells of live mouse retinas can be quantified, so that the efficacy of gene transfer methods can be quantified. Concentrations of several hundred microM are not deleterious to normal function of photoreceptors and bipolar cells. This approach can also be used to quantify levels of biologically active EGFP fusion proteins.

Deficiency of Bax and Bak protects photoreceptors from light damage in vivo.

Photoreceptors of bax(-/-)bak(-/-) but neither bax(-/-) mice nor bak(-/-) mice are protected from developmental apoptosis, suggesting that bax(-/-)bak(-/-) photoreceptors may also be protected from pathologic apoptosis. To test this possibility, we exposed bax(-/-)bak(-/-) and bax(-/-) mice to bright light, which normally induces photoreceptor death. Photoreceptors in bax(-/-)bak(-/-) mice were protected from death compared to bax(-/-) mice as indicated by a reduction in the number of TUNEL-positive photoreceptor nuclei 24 h following light damage and almost complete preservation of photoreceptors 7 days following light damage. These results provide the first in vivo evidence that combined deficiency of Bax and Bak can rescue cells from a pathologic stimulus more effectively than Bax deficiency and suggest that combined deficiency of Bax and Bak may also protect cells from other insults.

The light response of ON bipolar neurons requires G[alpha]o.

ON bipolar neurons in retina detect the glutamate released by rods and cones via metabotropic glutamate receptor 6 (mGluR6), whose cascade is unknown. The trimeric G-protein G(o) might mediate this cascade because it colocalizes with mGluR6. To test this, we studied the retina in mice negative for the alpha subunit of G(o) (Galpha(o)-/-). Retinal layering, key cell types, synaptic structure, and mGluR6 expression were all normal, as was the a-wave of the electroretinogram, which represents the rod and cone photocurrents. However, the b-wave of the electroretinogram, both rod- and cone-driven components, was entirely missing. Because the b-wave represents the massed response of ON bipolar cells, its loss in the Galpha(o) null mouse establishes that the light response of the ON bipolar cell requires G(o). This represents the first function to be defined in vivo for the alpha subunit of the most abundant G-protein of the brain.

The role of endoscopic biliary stents in palliative care.

This article reviews the role of endoscopic biliary stents in palliative care. In particular it focuses on the indications for stents, and recognition and management of possible complications. These issues are illustrated with three case reports.

An investigation of general practitioner referrals to palliative care services.

A cross-sectional interview study designed to elicit general practitioners' reasons for referral to palliative care services was conducted. Three groups of general practitioners (GPs) were sampled: frequent referrers, non-referrers and nurse referrers. Fifteen GPs from each group were interviewed. A structured interview was carried out either face-to-face or over the telephone. The results showed significant differences between groups of GPs relating to why they did and did not refer patients to palliative care services. The main difference was that the GPs who frequently referred did so most often for 'nursing support', while those in the non-referring group most commonly mentioned 'symptom control'. Fifty-three per cent of both frequent and non-referring GPs gave 'the carers coping well' as the commonest reason for not referring patients. Significant differences were also shown in what the GPs perceived was the most important thing they could offer cancer patients, with 60% of the GPs who had referred no patients answering 'my time'. The results also provided evidence that the majority of the GPs characterised a 'good death' as being 'pain free', and that they perceived themselves to have an important role in providing palliative care for their terminally ill patients.

G-protein cascades: gain and kinetics.

G-protein cascades provide amplification in a wide variety of biological signal transducers--from hormonal and synaptic systems to the receptor cells of vision and olfaction. Through recent understanding of the molecular mechanisms involved, it is possible to construct a quantitative description of the amplification and speed of response of the cascade. The gain and kinetics can now be described in terms of physical parameters, such as enzyme activities and the densities and lateral diffusion coefficients of the proteins involved.

Calcium dependence of the activation and inactivation kinetics of the light-activated phosphodiesterase of retinal rods.

The Ca2+ dependence of the kinetics and light sensitivity of light-activated phosphodiesterase was studied with a pH assay in toad and bovine rod disk membranes (RDM), and in a reconstituted system containing GTP-binding protein, phosphodiesterase and rhodopsin kinase. Three statistics, peak hydrolytic velocity, turnoff time, and time to peak velocity, were measured. ATP decreased phosphodiesterase light sensitivity nearly 10-fold and accelerated the dim-flash kinetics of cGMP hydrolysis when compared to those with GTP alone. CA2+ reversed all of the effects of ATP, Ca2+ increased peak velocity, turnoff time, and time to peak velocity, to the values obtained with GTP alone. The Ca2+ dependence of peak velocity and turnoff time can be characterized as hyperbolic saturation functions with a K0.5 for Ca2+ of 1.0-1.5 mM in toad RDM. In bovine RDM the Ca2+ dependence of peak velocity and turnoff time has a K0.5 of 0.1 mM Ca2+. The Ca2+ dependence in the reconstituted system is similar to that in bovine RDM for peak velocity (K0.5 = 0.1 mM Ca2+) but differs for turnoff time (K0.5 = 2.5 mM Ca2+). We tested the hypothesis that a soluble modulator, normally required to confer submicromolar Ca2+ sensitivity, was too dilute in our assay by comparing data obtained at one RDM concentration with those obtained at 10-fold higher RDM, and therefore a constituent protein, concentration. We observe no difference and present a formal analysis of these data that excludes the hypothesis that the soluble modulator binds its target protein with Kd less than 5 microM. The lack of submicromolar Ca2+ dependence of any of the steps in the cGMP cascade that underlie cGMP phosphodiesterase activation and inactivation in vitro argues against Ca2+ regulation of these steps having a significant role in the light adaptation of the intact rod.

A census of patients waiting for treatment or consultation in surgical specialties in an English health region.

A census of waiting lists in five surgical specialties within the Northern Region has been carried out. In addition to enumerating those patients waiting for inpatient treatment and outpatient consultation, the census characterized lists in terms of the age and sex structure of those waiting; the length of time people had waited; their district of residence and (for inpatients only) the numbers waiting for certain specified operations or procedures. Patients waiting for inpatient treatment were older, overall, than the general population and, within specialties, ophthalmology lists contained a higher proportion of the very elderly whilst ear, nose and throat surgery lists had a younger age-structure. Three-quarters of ophthalmology inpatient lists were made up of patients waiting for cataract surgery, 14 per cent of patients awaiting orthopaedic inpatient treatment were waiting for hip joint replacement and 32 per cent of gynaecology lists comprised women needing sterilization. These data on age-structure and case composition are broadly similar to recent work carried out by Yates's group who restricted their study to longer waiting lists in the West Midlands Region and Wales. When data in the present study were related to the population from which the cases arose, it was found that the prevalence of outpatient waiting was greater than inpatient waiting except for general surgery (where a higher proportion of the population was awaiting inpatient treatment) and in gynaecology (where outpatient and inpatient waiting was equally common).2+ Standardized waiting list ratios (SWLRs) have been calculated to allow comparisons between districts and specialties, free of distortions produced by differing age-structure of populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Gain, speed and sensitivity of GTP binding vs PDE activation in visual excitation.

About 2000 PDE molecules are gradually activated by one bleached rhodopsin molecule, R* on a toad disk membrane to yield a final enzyme velocity of about 2.5 x 10(6) cGMP hydrolyzed sec-1 bleached rhodopsin-1. This amplified effect of a single photon requires GTP, whose function we originally proposed (Yee and Liebman, 1978; Liebman and Pugh, 1979) to serve as a "memory" label attached to each PDE as it is contacted via lateral diffusion by R*. Thus, the binding of GTP was explicitly seen as an identically-amplified casual link in the amplified PDE activation. We have subjected our GTP-PDE coupling hypothesis to both stoichiometric and kinetic tests using radioactive GTP labelling techniques. We find agreement in principle with our original hypothesis with modifications to allow for (1) GTP binding to a separate G-protein (gamma) which activates PDE; (2) evidence that there are fewer PDE's activated than GTP's bound in response to a light flash; (3) evidence of reversible binding of gamma to PDE with incomplete activation of the latter; (4) multisecond delay of GTP binding compatible with lateral diffusionally-mediated activation of thousands of gamma's by single R*'s; (5) gain regulation by ATP that reduces both PDE activation and GTP binding.

ATP mediates rapid reversal of cyclic GMP phosphodiesterase activation in visual receptor membranes.

Weak or strong lights will activate visual receptor rod disk membrane (RDM) cyclic GMP phosphodiesterase (PDE) in the presence of GTP cofactor. A similarly activated GTPase can exhaust small amounts of initially present GTP to deactivate the PDE. However, further additions of GTP reactivate PDE without more light, and deactivation by simple GTP depletion takes minutes or more, even at GTP concentrations 100 to 1,000 times lower than physiological levels. A more rapid deactivation mechanism must exist if modulation of cytoplasmic cyclic GMP by light is to play a role on the time scale (seconds) of events in vision. We report here that ATP is essential to such rapid control and that its presence permits multiple cycles of activation-deactivation. The complete control mechanism seems to involve gamma phosphate transfer from both ATP and GTP.

Characterization of the alkyl ether species of phosphatidylcholine in bovine heart.

The molecular types of lecithin in beef heart lipids were investigated by a combination of mild hydrolytic procedures and silicic acid chromatography. The major species of sn-glycero-3-phosphorylcholine (GPC) were found to be: diacyl-GPC (57%), alk-l-enyl, acyl-GPC (39%), alkyl acyl-GPC (3%), and dialkyl-GPC ( less than 1%). No di-alk-l-enyl-GPC or alk-l-enyl alkyl-GPC were detected. The derived monoalkyl-and dialkyl-glycerols were characterized by their infrared spectra and alkyl chain compositions.

Effect of cigarette smoking on fetal breathing movements in normal pregnancies.

In 18 women with uncomplicated pregnancies smoking two cigarettes significantly reduced the proportion of the time that fetal breathing movements were present.

PIP: Among 18 women with uncomplicated pregnancies of 32-38 weeks gestation who smoked at least 5 cigarettes daily, smoking 2 cigarettes in succession significantly reduced the proportion of time that fetal breathing movements were present. Using a Smith Kline Ekoline 20 ultrasonoscope, the proportion of time that fetal chest wall movements were present was recorded for each successive 5-minute period for 90 minutes. During the control period, fetal chest movements were present an average of 65% of the time. It is difficult to determine the mechanism responsible for this reduction; it could have been due to action on the mother or the fetus, to the nicotine content of the cigarette, or to the carbon monoxide generated. It is also difficult to relate these observations on the acute effects of smoking 2 cigarettes to the long-term epidemiological reports. It is hoped these results will be of value to clinical physiologists and obstetricians who are beginning to use fetal breathing movements as an index of health.