Patient experiences of left-sided colorectal resection by robotic, conventional laparoscopic and open approaches: a qualitative study.

BACKGROUND: Robotic surgery (RS) is increasingly employed in colorectal surgical practice, widening the range of surgical techniques offered to patients. We investigated the perceptions of patients with colorectal cancer in relation to RS, open surgery (OS) and conventional laparoscopic surgery (CLS), to identify ideas or assumptions which, in the context of shared surgeon-patient decision-making, may affect the resultant choice of surgical technique. We also investigated salient factors affecting patients' perioperative experience, including those of RS patients, to guide improvements in care and preoperative patient preparation. METHODS: This study was conducted on patients who underwent resection of left-sided colorectal cancer at a large UK teaching hospital from November 2020 to July 2021. Purposive sampling was used to ensure a roughly equal proportion of patients who underwent RS, CLS and OS. The patients included in the study participated in semi-structured interviews six weeks postoperatively. The interview schedule allowed discussion around patients' experience of their surgery and postoperative recovery, and their perceptions of surgical techniques. Interview transcripts were coded manually using inductive thematic analysis, and analyst triangulation was employed to refine coding schemes and ensure reliability of emerging themes. RESULTS: Twenty-seven patients were recruited to the study; RS n = 9 (median age 69 [range 60-80] years); CLS n = 10 (median age 72 [range 32-82] years; OS n = 8 (median age 71 [range 60-75] years). Patients understood the technological benefits of RS but were concerned by a risk of technological failure causing patient harm. OS was understood to be associated with more pain and longer recovery than RS or CLS. Patients perceived CLS to be more technically challenging compared with OS. Less pain and smaller wounds than expected were significant positive factors in the experience of RS and CLS patients specifically. Complications and emotional impact were significant factors in the experience of all groups, for which many patients felt underprepared. CONCLUSIONS: Patients generally have a positive view of RS and technical innovation in surgery. Concerns mostly centred around failure of technology. Many patients felt unprepared for significant factors in their perioperative experience. Surgeons and healthcare providers should be prepared to address patients' perceptions and expectations of colorectal surgery preoperatively.

Proteomic data in meningiomas: post-proteomic analysis can reveal novel pathophysiological pathways.

Meningiomas account for approximately 20% of adult primary intracranial tumours. WHO I meningiomas are the most common and are generally benign, but can progress, recur or transform to WHO II or WHO III grades over many years. A systematic review of multiple independent shotgun proteomic analyses of meningioma was performed to provide insight into underlying disease pathways. Shotgun proteomics has been conducted in seven meningioma related studies but there is considerable variation in aims, methodology, statistical power and the use of control tissue between these studies. Fifteen proteins which are different between WHO I and WHO II meningiomas and nine proteins which are different between WHO II and WHO III meningiomas have been described but without a view of their biological significance. Network analysis of proteins different between WHO I and WHO II meningiomas provided a coherent hypothesis for the involvement of these proteins in meningioma. Western blot analyses of meningioma tissue provided a measure of support for a core component in the network (involving VDAC2, APOA1 and HNF4α) but highlighted intrinsic difficulty of proteomic and biochemical analysis of meningiomas (as a consequence of gross alterations in tissue composition). Systematic review of shotgun proteomics and network analysis provides insight into meningioma pathophysiology despite the many barriers and difficulties that are inherent to this type of study.

Retina-dependent activation by apomorphine of metabolic activity in the superficial layer of the superior colliculus.

Studies of the effect of the dopamine agonist apomorphine on local cerebral glucose utilization by means of the carbon-14-labeled deoxyglucose method demonstrate a dose-dependent metabolic activation in the superficial layer of the superior colliculus in the rat. Apomorphine stimulated glucose utilization in a number of other cerebral structures, but only the effect in the superficial layer of the superior colliculus depended on an intact retinal input. This effect was present with the animal in the light or in the dark, but was abolished by enucleation, which left the effects in other cerebral structures unimpaired. Activation of the superificial layer of the superior colliculus appears, therefore, to be secondary to an action of apomorphine on dopaminergic systems within the retina.

Molecular characterisation of Staphylococcus aureus strains isolated from small and large ruminants reveals a host rather than tissue specificity.

Staphylococcus aureus is an important pathogen in domestic ruminants. The main objective of this study was to determine the similarity of epidemiologically unrelated S. aureus isolates from bovine, ovine, and caprine hosts regardless the locus of isolation (nares and udder). By pulsed-field gel electrophoresis, seven major pulsotypes were identified among 153 isolates recovered from 12 different regions of France as well as from Brazil, the USA and Belgium. Typing of the accessory gene regulator (agr) and capsular (cap) serotype was carried out on all the isolates and revealed the predominance of agr I and III and of cap8 regardless the ruminant host species. Screening for methicilin-resistant S. aureus (MRSA) was carried out by disk diffusion and revealed a prevalence of only 3.2% of MRSA among the strains tested. These results suggest the existence of a host rather than tissue specificity among S. aureus isolates colonising the ruminant species and suggest a limited transmission of those isolates between large (bovine) and small (ovine-caprine) ruminants. The agr class and cap types correlated with pulsotype clusters rather than with a specific host species. Antimicrobial resistance appears not to have contributed to the predominance of any given genotypes, and MRSA prevalence appears very low in ruminant isolates.

Impact of mutations in hVISA isolates on decreased susceptibility to vancomycin, through population analyses profile - area under curve (PAP-AUC).

We analyzed sequences of graSR, vraSR, walKR and rpoB genes in hVISA from Brazil. Five isolates showed mutations in at least one gene. rpoB H481N and graS T224I were the most frequent mutations, followed by graR D148Q and walK A468T. Our study reinforces the heterogeneity of genetic patterns among hVISA.

Nucleophosmin is a novel Bax chaperone that regulates apoptotic cell death.

The proapoptotic B-cell lymphoma-2 family protein Bax is a key regulatory point in the intrinsic apoptotic pathway. However, the factors controlling the process of Bax activation and translocation to mitochondria have yet to be fully identified and characterized. We performed affinity chromatography using peptides corresponding to the mitochondrial-targeting region of Bax, which is normally sequestered within the inactive structure. The molecular chaperone nucleophosmin was identified as a novel Bax-binding protein by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Reciprocal co-immunoprecipitation and proximity assays confirmed the Bax-nucleophosmin protein-protein interaction and verified that nucleophosmin only bound to activated conformationally altered Bax. Confocal microscopy in a cell-based apoptosis model, demonstrated that nucleophosmin translocation from nucleolus to cytosol preceded Bax movement. Specific knockdown of nucleophosmin expression using RNAi attenuated apoptosis as measured by mitochondrial cytochrome c release and activation of the caspase cascade. In a mouse model of ischaemic stroke, subcellular fractionation studies verified that nucleophosmin translocation occurred within 3 h, at a time before Bax translocation but after Bax conformational changes have occurred. Thus, we have elucidated a novel molecular mechanism whereby Bax becomes activated and translocates to the mitochondria to orchestrate mitochondrial dysfunction and apoptotic cell death, which opens new avenues for therapeutic intervention.

Reversible neural inactivation reveals hippocampal participation in several memory processes.

Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes-encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage.

Focal cerebral ischaemia induces corticotropin releasing factor (CRF) vascular immunoreactivity in rat occluded hemisphere.

Corticotropin-releasing factor (CRF) induces the dilatation of cerebral blood vessels and increases cerebral blood flow (CBF). CRF receptor antagonists reduce ischaemic damage in the rat. In the present study, the expression of CRF around cerebral vessels has been investigated in the rat. No CRF immunoreactivity was identified around pial or intracerebral vessels in the absence of cerebral ischaemia. Four hours after middle cerebral artery occlusion (MCAo), intensely CRF-positive blood vessels were evident on the ischaemic cortical surface and in the peri-infarct and infarct zone. Increased CRF immunoreactivity was also detected in swollen axons in subcortical white matter, caudate nucleus and lateral olfactory tract of the ipsilateral hemisphere, consistent with the failure of axonal transport. These data provide morphologic support for a role of CRF in the pathophysiology of cerebral ischaemia.

Control of carbapenemase-producing Enterobacteriaceae outbreaks in acute settings: an evidence review.

BACKGROUND: In recent years, infections with carbapenemase-producing Enterobacteriaceae (CPE) have been increasing globally and present a major public health challenge. AIM: To review the international literature: (i) to describe CPE outbreaks in acute hospital settings globally; and (ii) to identify the control measures used during these outbreaks and report on their effectiveness. METHODS: A systematic search of MEDLINE and EMBASE databases, abstract lists for key conferences and reference lists of key reviews was undertaken, and information on unpublished outbreaks was sought for 2000-2015. Where relevant, risk of bias was assessed using the Newcastle-Ottawa scale. A narrative synthesis of the evidence was conducted. FINDINGS: Ninety-eight outbreaks were eligible. These occurred worldwide, with 53 reports from Europe. The number of cases (CPE infection or colonization) involved in outbreaks varied widely, from two to 803. In the vast majority of outbreaks, multi-component infection control measures were used, commonly including: patient screening; contact precautions (e.g. gowns, gloves); handwashing interventions; staff education or monitoring; enhanced environmental cleaning/decontamination; cohorting of patients and/or staff; and patient isolation. Seven studies were identified as providing the best-available evidence on the effectiveness of control measures. These demonstrated that CPE outbreaks can be controlled successfully using a range of appropriate, commonly used, infection control measures. However, risk of bias was considered relatively high for these studies. CONCLUSION: The findings indicate that CPE outbreaks can be controlled using combinations of existing measures. However, the quality of the evidence base is weak and further high-quality research is needed, particularly on the effectiveness of individual infection control measures.

Establishment and characterization of a cell line from a human gliosarcoma.

A human gliosarcoma culture was characterized from the time of inception to the time of establishment of the cell line (SF-539 BT). Immunohistochemical analysis of the original tumor showed 2 distinct regions of cells. The gliomatous regions were identified by immunostains for glial fibrillary acidic protein and the sarcomatous regions by immunostains for laminin, collagen type IV, procollagen type III, and fibronectin. In early-passage culture, both types of cells maintained their characteristic immunohistochemical profiles; however, after the fourth subcultivation in monolayer culture, no cells expressing glial fibrillary acidic protein could be identified. All cells had become morphologically uniform and expressed laminin, collagen type IV, procollagen type III, and fibronectin only. The immunostaining profile of clones grown in soft agar was similar to that of cells in monolayer culture. At establishment, SF-539 BT has a saturation density of 1.3 X 10(6) cells/25 sq cm, a doubling time of 32 h, and a plating efficiency of 22% in monolayer culture. The tumor cell line is resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea, has an abnormal karyotype, grows anchorage independently, and forms a tumor that most closely resembles a spindle cell sarcoma in athymic mice. Its ultrastructure in monolayer culture consists of large cells with an expanded rough endoplasmic reticulum and abundant multivesicular bodies; in athymic mice, extracellular collagen fiber formation is prominent. DEAE-cellulose chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cultures labeled with [3H] proline demonstrated interstitial collagen formation. We conclude that the cell line at establishment is a collagen-producing spindle cell sarcoma that resembles the sarcomatous regions of the original mixed tumor. Further cell separation and characterization studies are needed to determine the pathogenesis of mixed tumors such as gliosarcoma.

Treatment of limited small-cell lung cancer with concurrent etoposide/cisplatin and radiotherapy followed by intensification with high-dose cyclophosphamide: a Southwest Oncology Group study.

Between March 1986 and May 1988, the Southwest Oncology Group enrolled 58 previously untreated patients with limited small-cell lung cancer on a treatment program that administered high-dose cyclophosphamide (150 mg/kg) as late intensification. Treatment consisted of induction chemo-radiotherapy, (weeks 1 to 11), consolidation chemotherapy (weeks 11 to 18), and intensification (week 18). Median age was 61.5 years. Eighty-nine percent of patients had a Southwest Oncology Group (SWOG) performance status of 0-1. Twenty-one patients completed all prescribed treatments. There were seven treatment-related deaths, four as a result of intensification. Fifty-six patients are available for response analysis. Thirty-two patients achieved a complete remission (CR) (57%) and fifteen achieved a partial remission (PR) (26%). Median survival for all patients is 11.1 months. Among the 21 patients who received intensification, nine remain alive in a CR with a median survival of 27 months. This sequence of treatments was not associated with a survival advantage for the group as a whole, possibly because of the toxicity of induction and consolidation treatment and the delayed administration of high-dose cyclophosphamide.

Transthyretin quaternary and tertiary structural changes facilitate misassembly into amyloid.

Human transthyretin (TTR) can be transformed into amyloid fibrils by partial acid denaturation to yield a monomeric amyloidogenic intermediate that self-associates into amyloid through quaternary structural intermediates, which are identified by sedimentation velocity methods. The monomeric amyloidogenic intermediate has substantial beta-sheet structure with a nonnative but intact tertiary structure as discerned from spectroscopic methods. Proteolysis sensitivity studies suggest that the C-strand-loop-D-strand portion of TTR becomes disordered and moves away from the core of the beta-sandwich fold upon formation of the monomeric amyloidogenic intermediate over the pH range 5.1-3.9. The single site mutations that are associated with early onset amyloid disease [familial amyloid polyneuropathy (FAP)] function by destabilizing tetrameric TTR. Under mild denaturing conditions, the FAP variants populate the monomeric amyloidogenic intermediate conformation, which assembles into amyloid, whereas wild-type TTR remains tetrameric and nonamyloidogenic. The FAP mutations do not significantly alter the native folded structure; instead, they appear to act by making the thermodynamics and perhaps the kinetics more favorable for formation of the amyloidogenic intermediate. Suppressor mutations have also been characterized that strongly stabilize tetrameric TTR and disfavor the formation of the monomeric amyloidogenic intermediate, thus inhibiting amyloid formation. The mechanistic details characterizing transthyretin amyloid fibril formation available from the biophysical studies outlined within have been utilized to develop a new therapeutic strategy for intervention in human amyloid disease. This approach features small molecules that bind with high affinity to the normal fold of transthyretin, inhibiting the quaternary and tertiary structural changes associated with the formation of the monomeric amyloidogenic intermediate that self-assembles into amyloid. Ligand binding to TTR stabilizes the native tetrameric fold, which is nonamyloidogenic.

Accidents don't happen any more: junior doctors' experience of fatal accident inquiries in Scotland.

OBJECTIVE: To determine the experience of junior doctors cited as witnesses at fatal accident inquiries (FAIs). DESIGN: Retrospective questionnaire study. SETTING AND SUBJECTS: 40 junior doctors who had been involved in FAIs from January 1998 to August 2002 were identified by the Medical Protection Society and Medical and Dental Defence Union of Scotland: 21 completed questionnaires were returned, a response rate of 52.5%. RESULTS: The process and objectives of FAIs were poorly understood. Few participants were proactive in contacting their defence union. There was a perceived lack of both formal and informal supports with respondents describing a "blame culture" within the medical profession. The experience of the FAI was generally considered stressful with respondents describing possible improvements relating to support, information, training, and the FAI procedure. CONCLUSIONS: Junior medical staff are poorly informed in this medicolegal area. There is a need for the development of mechanisms both to support junior doctors and to ensure that adverse incidents are dealt with using modern risk management techniques to minimise the risk of recurrence.

An ultrastructural and immunocytochemical analysis of leptomeningeal and meningioma cultures.

Using immunocytochemical methods, we localized several glycoproteins of the extracellular matrix to leptomeningeal cells and meningiomas in vitro. Three cell lines derived from normal human leptomeninges and seven from meningiomas were studied by indirect immunofluorescence to evaluate the cellular production of fibronectin, laminin, collagen type IV, and procollagen type III. All leptomeningeal cell lines stained intensely and uniformly for all matrix proteins; all meningioma cell cultures stained uniformly, but the intensity of staining varied considerably. After removal of the cells in culture adherent to glass with 25 mM ammonium hydroxide, indirect immunofluorescence demonstrated an exuberant residual extracellular residue enriched with fibronectin, laminin, collagen type IV, and procollagen type III. Electron microscopic examination of all leptomeningeal and meningioma cultures revealed desmosomes and dense tonofilament formation; in addition, granular, filamentous basement membrane-like material was abundant in the extracellular spaces of all cultures. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of the cell layer of two leptomeningeal and four meningioma cultures showed production of interstitial collagen types I and III; diethylaminoethyl (DEAE)-cellulose chromatography of the medium demonstrated preferential production of procollagen type I. Our findings show conclusively that normal arachnoid cells in vitro synthesize several of the collagen subtypes and may be responsible for the "fibrous response" of the leptomeninges to trauma, infection, or infiltration by tumor. The similarities between leptomeningeal cells and meningiomas demonstrated by electron microscopy and by indirect immunofluorescence support the notion that meningiomas are derived from arachnoid cells. The localization of various mesenchymal glycoproteins within the intra- and extracellular spaces and the ubiquity of specialized intercellular junctions suggest that leptomeningeal cells in culture have the potential to behave like both stromal and epithelial cells.

Effects of pentobarbital on contractile responses of feline cerebral arteries.

The effects of pentobarbital on the contractile responses of isolated feline middle cerebral arteries have been examined. In the presence of pentobarbital (3 x 10(-4)M), the maximum contractions effected by potassium, noradrenaline, and prostaglandin F2 alpha were reduced by 37 +/- 3, 69 +/- 3, and 10 +/- 6%, respectively. The results caution against the use of pentobarbital as an anaesthetic agent in investigations of cerebrovascular reactivity.

Effects of MK-801 upon local cerebral glucose utilisation in conscious rats and in rats anaesthetised with halothane.

The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilisation were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilisation with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cholecystokinin octapeptide on pial arteriolar diameter.

The effects of the perivascular microapplication of sulphated cholecystokinin octapeptide (CCK-8) on pial arteriolar calibre have been examined in anaesthetised cats using a video-display image-splitting technique. The microinjection of CCK-8 (10(-7) M) in the injectate did not modify the constriction or dilatation of pial arterioles provoked by the perivascular microinjection of alkalotic (pH 7.45) or acidic (pH 6.8) artificial CSFs, respectively. Thus, although CCK-8-immunoreactive neuronal processes are known to be associated with cortical blood vessels, CCK-8 appears to have minimal vasomotor effects on pial vessels.

Failure of an endothelin antagonist to modify hypoperfusion after transient global ischaemia in the rat.

The role of endogenous endothelins in mediating postischaemic hypoperfusion after transient global ischaemia was investigated in halothane-anaesthetised rats. Pretreatment with the broad-spectrum (ET (A) and ET (B)) endothelin antagonist. Bosentan (17 micromol/kg) had minimal effect on postischaemic hypoperfusion, measured by hydrogen clearance, in the caudate nucleus and the parietal cortex in the 3 h after bilateral common carotid artery occlusion with concomitant haemorrhagic hypotension (transient global ischaemia). In a separate series of rats with CBF measured by [14C]iodoantipyrine autoradiography at 90 min after carotid occlusion with concomitant haemorrhagic hypotension, Bosentan treatment failed to significantly alter CBF in any of the 35 brain regions examined. No significant alterations in CBF, measured by hydrogen clearance, were observed after transient bilateral common carotid artery occlusion. [14C]Iodoantipyrine autoradiography at 90 min after occlusion failed to demonstrate any significant increases in CBF after transient bilateral common carotid artery occlusion in any of the 35 brain regions examined in anaesthetised rats. The failure of the broad-spectrum endothelin antagonist Bosentan, at concentrations known to inhibit the cerebrovascular effects of exogenous ET-1, provide no support for the view that endothelins have a major role in mediating acute postischaemic hypoperfusion.

Alterations in local cerebral glucose utilisation in specific thalamic nuclei following apomorphine.

The alterations in local cerebral glucose utilisation in eight discrete nuclei in the thalamus following the administration of apomorphine (0.5 mg kg-1) have been investigated with the autoradiographic 2-deoxyglucose technique in 11 conscious rats. In two thalamic nuclei (parafascicular and ventrolateral nuclei), glucose utilisation was significantly elevated following apomorphine; in two thalamic nuclei (the anterior medial and anterior ventral nuclei), glucose utilisation was significantly reduced following apomorphine; and in four nuclei (lateral geniculate, medial geniculate, mediodorsal, and lateral thalamic nuclei), glucose use was unchanged.