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I S Roberts

Publications and source records attributed to I S Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2000

What is a natural cause of death? A survey of how coroners in England and Wales approach borderline cases.

AIM: Many deaths fall in the "grey" area between those that are clearly natural and those that are unnatural. There are no guidelines to help doctors in dealing with such cases and death certification is often arbitrary and inconsistent. In an attempt to initiate debate on these difficult areas, and with the ultimate aim of achieving national consensus, the views of coroners in England and Wales were sought. METHODS: Sixteen clinical scenarios, with causes of death, were circulated to all coroners in England and Wales. For each case they were asked to provide a verdict, with explanation. The deaths fell into three groups: (1) postoperative, (2) a combination of trauma and natural disease, and (3) infectious disease. RESULTS: Sixty four questionnaires were returned. There was near consensus (> 80% concordance) in only two of the 16 cases. In five, there was no significant agreement between coroners in the verdicts returned ("natural causes" versus "misadventure/accidental"). These included all three cases in which death resulted from a combination of trauma and natural disease (a fall after a grand mal fit; falls resulting in fractures of bones affected by metastatic carcinoma and osteoporosis), bronchopneumonia after hip replacement for osteoarthritis, and new variant Creutzfeldt-Jakob disease. The comments made for each case indicate that the variation between coroners in whether or not to hold an inquest, and the verdict arrived at, reflect the lack of a definition for natural causes, together with differences in the personal attitudes of each coroner. CONCLUSIONS: There is considerable variation in the way in which coroners approach these borderline cases, many of which are common in clinical practice. This study indicates a need for discussion, working towards a national consensus on such issues. It highlights the importance of good communication between coroners and medical staff at a local level.

Adolescent↗
PubMed2000

Small intestinal infarction: a fatal complication of systemic oxalosis.

Primary hyperoxaluria is a rare genetic disorder characterised by calcium oxalate nephrolithiasis and nephrocalcinosis leading to renal failure, often with extra-renal oxalate deposition (systemic oxalosis). Although ischaemic complications of crystal deposition in vessel walls are well recognised clinically, these usually take the form of peripheral limb or cutaneous ischaemia. This paper documents the first reported case of fatal intestinal infarction in a 49 year old woman with systemic oxalosis and advocates its consideration in the differential diagnosis of an acute abdomen in such patients.

Abdomen, Acute↗
PubMed2000

Attitudes of nursing staff to the autopsy.

We assessed the views of hospital nurses on the autopsy, using a questionnaire which was distributed by hand to all qualified nurses working at Manchester Royal Infirmary during a 48-h period. We found that many respondents (43%) had had occasion to discuss autopsy with relatives, and the majority (90%) would like to learn more about counselling the bereaved. Few (15%) clearly understood the legal distinction between coroners' and hospital autopsies. Almost all (97%) thought the main reason for autopsy was determination of the cause of death, and only 12% supported a role in clinical audit. More respondents saw benefits for doctors rather than for nurses, and only 56% perceived a benefit for relatives. In general, nursing staff have a more positive view of the autopsy than we anticipated, and we would advocate making more information about the benefits of autopsy available to nurses.

Attitude of Health Personnel↗
PubMed1999

Structure, assembly and regulation of expression of capsules in Escherichia coli.

Many Escherichia coli strains are covered in a layer of surface-associated polysaccharide called the capsule. Capsular polysaccharides represent a major surface antigen, the K antigen, and more than 80 distinct K serotypes result from structural diversity in these polymers. However, not all capsules consist of K antigen. Some are due to production of an extensive layer of a polymer structurally identical to a lipopolysaccharide O antigen, but distinguished from lipopolysaccharide by the absence of terminal lipid A-core. Recent research has provided insight into the manner in which capsules are organized on the Gram-negative cell surface, the pathways used for their assembly, and the regulatory processes used to control their expression. A limited repertoire of capsule expression systems are available, despite the fact that the producing bacteria occupy a variety of ecological niches and possess diverse physiologies. All of the known capsule assembly systems seen in Gram-negative bacteria are represented in E. coli, as are the majority of the regulatory strategies. Escherichia coli therefore provides a variety of working models on which studies in other bacteria are (or can be) based. In this review, we present an overview of the current molecular and biochemical models for capsule expression in E. coli. By taking into account the organization of capsule gene clusters, details of the assembly pathway, and regulatory features that dictate capsule expression, we provide a new classification system that separates the known capsules of E. coli into four distinct groups.

ATP-Binding Cassette Transporters↗
PubMed1999

Cytokine gene polymorphisms predict acute graft rejection following renal transplantation.

BACKGROUND: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of acute rejection, while animal models suggest a role for interleukin-10 (IL-10) in promoting graft survival. It has also been shown that polymorphisms in the TNFA gene promoter (position -308) and in the IL-10 gene promoter (position -1082) correlate with differential production of these cytokines in vitro. The aim of this study was to determine whether TNF-alpha and IL-10 gene polymorphisms influence the incidence and severity of acute rejection in the first six months following renal transplantation. METHODS: The cytokine genotypes of 115 consecutive first cadaveric kidney allograft recipients and their donors were screened. The rejection episodes (REs) were defined clinically and confirmed histologically where possible and further classified according to severity (RS), namely steroid-resistant or responsive REs. The genotypes were then correlated with the REs and RS. RESULTS: The recipient TNF-alpha high producer genotype and IL-10 high producer genotype were significantly associated with multiple REs (>/=2) in human leukocyte antigen (HLA)-DR mismatched transplants (P = 0.0047 and P = 0.045, respectively), whereas only the TNF-alpha high producer genotype was associated with steroid-resistant REs (P = 0.025). When recipient cytokines were analyzed together, the TNF-alpha high/IL-10 high producer genotype had the worst prognosis, whereas TNF-alpha low/IL-10 low producer genotype was protective. CONCLUSIONS: We conclude that recipient TNF-alpha and IL-10 gene polymorphisms are determinants of REs and RS following kidney transplantation. Routine screening of these gene polymorphisms may have a clinical role in identifying patients at risk of multiple REs and severe rejections.

Cadaver↗
PubMed1999

Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome.

BACKGROUND: An uncharacterized circulating factor that increases vascular permeability has previously been described in childhood steroid-sensitive nephrotic syndrome (SSNS). The aim of this study was to determine whether this factor is vascular endothelial growth factor (VEGF), the recently described endothelial cell mitogen and enhancer of vascular permeability. METHODS: Plasma and urine VEGF levels were measured in children with SSNS in both relapse and remission and in normal age- and sex-matched controls. Semiquantitative reverse transcriptase-polymerase chain reaction studies investigating VEGF mRNA expression were performed on peripheral blood mononuclear cells isolated from children with SSNS in relapse and controls. In two experimental models (one-hour and three-day follow-up postinfusion), Sprague-Dawley rats were intravenously administered 50 microg rVEGF to determine whether this induced either proteinuria or glomerular histologic change. RESULTS: Plasma VEGF levels and urine VEGF/creatinine ratios were not elevated in SSNS relapse compared with remission and control samples. Peripheral blood mononuclear cell VEGF mRNA expression was no different in SSNS patients compared with controls. The administration of VEGF to rats induced an acute reversible fall in systemic blood pressure but did not result in the development of either proteinuria or glomerular histologic change. CONCLUSION: Increased circulating VEGF levels are not responsible for the proteinuria observed during relapses of SSNS. Further studies are warranted to investigate intrarenal VEGF expression.

Adrenal Cortex Hormones↗
PubMed1999

Banff criteria as predictors of outcome following acute renal allograft rejection.

BACKGROUND: The Banff classification of renal allograft rejection grades acute tubulointerstitial rejection (AIR) by severity of tubulitis and acute vascular rejection (AVR) by severity of arteritis. The intensity of tubulitis has not, however, been demonstrated to be of prognostic value and other features such as glomerulitis and eosinophil infiltration are of uncertain significance. This study was performed in order to determine the clinical value of this pathological classification. METHODS: Banff criteria were correlated with outcome in 134 consecutive graft recipients transplanted in our unit over a 3-year period (1994 1996) who experienced at least one biopsy-confirmed acute rejection episode. Of 197 biopsies performed for the diagnosis of rejection, 177 contained at least one artery and were suitable for Banff grading. Tissue eosinophil counts were available for 101 biopsies. Clinical severity of rejection was classified as mild (fully responsive to pulse steroid therapy), moderate (partially steroid responsive) and severe (steroid unresponsive/requiring ATG therapy). RESULTS: Graft failure ensued in 18 of 58 patients with AVR compared with 10 of 65 patients with AIR (P= < 0.05). Clinical severity of rejection correlated with the presence of arteritis, but not severity of tubulitis; rejections graded I, IIA and IIB according to the Banff' 93 classification were clinically severe in 3/68 (4%), 2/28 (7%) and 15/67 (22%) respectively (P= <0.05). The presence of glomerulitis showed no correlation with clinical severity or graft loss. Tissue eosinophilia (>10 eosinophils/mm2) was present in 18 of 33 patients who had at least one episode of AVR (v1/2), compared with 11 of 45 patients who suffered only AIR (P= <0.02). CONCLUSIONS: We conclude that: arteritis, but not severe tubulitis or glomerulitis, is an adverse prognostic factor in acute rejection and that tissue eosinophilia is associated with vascular rejection. Our findings support the 1997 revision of the Banff classification, replacing grades with types of acute rejection.

Acute Disease↗
PubMed1999

Genetic organization of the Escherichia coli K10 capsule gene cluster: identification and characterization of two conserved regions in group III capsule gene clusters encoding polysaccharide transport functions.

Analysis of the Escherichia coli K10 capsule gene cluster identified two regions, regions 1 and 3, conserved between different group III capsule gene clusters. Region 1 encodes homologues of KpsD, KpsM, KpsT, and KpsE proteins, and region 3 encodes homologues of the KpsC and KpsS proteins. An rfaH mutation abolished K10 capsule production, suggesting that expression of the K10 capsule was regulated by RfaH in a manner analogous to group II capsule gene clusters. An IS3 element and a phiR73-like prophage, both of which may have played a role in the acquisition of group III capsule gene clusters, were detected flanking the K10 capsule genes.

Amino Acid Sequence↗
PubMed1998

Characterization of the glycosyltransferase enzyme from the Escherichia coli K5 capsule gene cluster and identification and characterization of the glucuronyl active site.

Bacterial capsular polysaccharides play an important role in virulence and survival. The Escherichia coli K5 capsule consists of a repeat structure of -4)GlcA-beta(1,4)-GlcNAc alpha(1-, identical to N-acetylheparosan. A 60-kDa protein, KfiC, has been identified as a bifunctional glycosyltransferase, responsible for the alternating alpha and beta addition of each UDP-sugar to the nonreducing end of the polysaccharide chain. Using hydrophobic cluster analysis, a conserved secondary structure motif characteristic of beta-glycosyltransferases was identified along with two highly conserved aspartic acid residues at positions 301 and 352 within the KfiC protein. Site-directed mutagenesis was used to identify catalytically active amino acids within domain A of the KfiC protein. The conserved aspartic acid residues at 301 and 352 were shown to be critical for the beta addition of UDP-GlcA (uridine diphosphoglucuronic acid) to defined nonreducing end oligosaccharide acceptors, suggesting that these conserved aspartic acid residues are catalytically important for beta-glycosyltransferase activity. A deleted derivative of the kfiC gene was generated, which encoded for a truncated KfiC (kfiC') protein. This protein lacked 139 amino acids at the C terminus. This enzyme had no UDP-GlcA transferase activity but still retained UDP-GlcNAc transferase activity, indicating that two separate active sites are present within the KfiC protein.

Amino Acid Sequence↗
PubMed1998

Sclerosing epithelioid fibrosarcoma: a study of five cases emphasizing diagnostic criteria.

AIMS: To study the clinical and histopathological features of sclerosing epithelioid fibrosarcoma, and to define diagnostic criteria for this uncommon soft-tissue tumour. METHODS AND RESULTS: Standard histological, immunohistochemical and ultrastructural techniques were applied to five tumours from head and neck, chest wall and groin. Tumours consisted of groups of monomorphic rounded/epithelioid cells surrounded by a prominent collagenous stroma. Tumour cells showed positive vimentin staining but were negative for other markers. They contained prominent rough endoplasmic reticulum and a large Golgi apparatus which in one case was producing collagen secretion granules, an ultrastructural marker for collagen production. Three patients had medium to long-term survival (3-7 years). Of these, one was disease-free for 3 years, and two experienced multiple recurrences: one of the latter died of metastatic disease. CONCLUSION: Criteria for diagnosing this uncommon tumour include: small to medium cell size, clear or pale cytoplasm, cellular arrangement in cords and strands, dense collagenous stroma; vimentin staining; rough endoplasmic reticulum and a Golgi apparatus producing, in well preserved examples, collagen secretion granules. The paper emphasizes the value of electron microscopy, supporting an appropriate histological picture and immunophenotype, in identifying these relatively low-grade sarcomas.

Adult↗
PubMed1997

Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic mice reveals essential roles for TGF-beta in regulation of growth and differentiation in the exocrine pancreas.

Using a dominant-negative mutant receptor (DNR) approach in transgenic mice, we have functionally inactivated transforming growth factor-beta (TGF-beta) signaling in select epithelial cells. The dominant-negative mutant type II TGF-beta receptor blocked signaling by all three TGF-beta isoforms in primary hepatocyte and pancreatic acinar cell cultures generated from transgenic mice, as demonstrated by the loss of growth inhibitory and gene induction responses. However, it had no effect on signaling by activin, the closest TGF-beta family member. DNR transgenic mice showed increased proliferation of pancreatic acinar cells and severely perturbed acinar differentiation. These results indicate that TGF-beta negatively controls growth of acinar cells and is essential for the maintenance of a differentiated acinar phenotype in the exocrine pancreas in vivo. In contrast, such abnormalities were not observed in the liver. Additional abnormalities in the pancreas included fibrosis, neoangiogenesis and mild macrophage infiltration, and these were associated with a marked up-regulation of TGF-beta expression in transgenic acinar cells. This transgenic model of targeted functional inactivation of TGF-beta signaling provides insights into mechanisms whereby loss of TGF-beta responsiveness might promote the carcinogenic process, both through direct effects on cell proliferation, and indirectly through up-regulation of TGF-betas with associated paracrine effects on stromal compartments.

Animals↗