Overexpressed nitric oxide synthase in portal-hypertensive stomach of rat: A key to increased susceptibility to damage?

BACKGROUND & AIMS: Portal hypertension predisposes gastric mucosa to increased injury. The aim of this study was to determine whether overexpression of constitutive nitric oxide synthase (cNOS) is responsible for increased susceptibility of portal-hypertensive (PHT) gastric mucosa to damage. METHODS: In gastric specimens from PHT and sham-operated rats, cNOS messenger RNA expression was determined by Northern blotting and cNOS protein expression by Western blotting, immunohistochemistry, and enzyme activity assay. Extent of ethanol- induced gastric mucosal necrosis, mucosal blood flow, and gastric NOS activity in PHT and sham-operated rats was determined after administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline. RESULTS: cNOS messenger RNA level, cNOS enzyme activity, and fluorescence signals for cNOS were increased significantly in PHT rats compared with controls. Inhibition of overexpressed cNOS by L-NAME (5 mg/kg) significantly reduced ethanol-induced mucosal necrosis and normalized blood flow in PHT gastric mucosa, whereas this dose of L- NAME significantly increased mucosal necrosis in sham-operated rats. CONCLUSIONS: Portal hypertension activates the cNOS gene with overexpression of cNOS protein in endothelia of gastric mucosal vessels. Excessive NO production by overexpressed cNOS may play an important role in the increased susceptibility of PHT gastric mucosa to damage. (Gastroenterology 1997 Jun;112(6):1920-30)     

Selective non-operative management of penetrating liver injuries at a UK tertiary referral centre

Introduction

Selective non-operative management (SNOM) of penetrating abdominal injuries has increasingly been applied in North America in the last decade. However, there is less acceptance of SNOM among UK surgeons and there are limited data on UK practice. We aimed to review our management of penetrating liver injuries and, specifically, the application of SNOM.

Methods

A retrospective review was performed of patients presenting with penetrating liver injuries between June 2005 and November 2013.

Results

Thirty-one patients sustained liver injuries due to penetrating trauma. The vast majority (97%) were due to stab wounds. The median injury severity score was 14 and a quarter of patients had concomitant thoracic injuries. Twelve patients (39%) underwent immediate surgery owing to haemodynamic instability, evisceration, retained weapon or diffuse peritonism. Nineteen patients were stable to undergo computed tomography (CT), ten of whom were selected subsequently for SNOM. SNOM was successful in eight cases. Both patients who failed SNOM had arterial phase contrast extravasation evident on their initial CT. Angioembolisation was not employed in either case. All major complications and the only death occurred in the operatively managed group. No significant complications of SNOM were identified and there were no transfusions in the non-operated group. Those undergoing operative management had longer lengths of stay than those undergoing SNOM (median stay 6.5 vs 3.0 days, p<0.05).

Conclusions

SNOM is a safe strategy for patients with penetrating liver injuries in a UK setting. Patient selection is critical and CT is a vital triage tool. Arterial phase contrast extravasation may predict failure of SNOM and adjunctive angioembolisation should be considered for this group.     

腹腔镜在肝局灶性结节性增生诊断及切除中的应用

目的探讨腹腔镜在肝局灶性结节性增生中的诊断及手术切除的应用价值。方法11例肝占位病人均在腹腔镜下行肝肿物切除术,术中肿物送病理学检查,病理诊断为局灶性增生结节。结果本组11例患者均成功实施腹腔镜下肝切除术,标本完整取出,切缘距肿瘤2cm,无中转开腹。术后病人均恢复良好,无并发症,出院后随访均未见复发病例。结论腹腔镜手术对于肝局灶性结节性增生的诊断和治疗有很好的价值。对肝局灶性增生结节位于肝脏边缘,且肿块非巨大的患者,行腹腔镜手术切除应被视为最佳选择。     

The polymorphous light eruption–severity assessment score does not reliably predict the results of phototesting

Background Polymorphous light eruption (PLE) is a very common photodermatosis in which patient history is highly specific. Phototesting is used to confirm the diagnosis and to determine the action spectrum and the severity of this disease. In daily practice and in research studies, it would be convenient to assess disease severity by patient history only. Objectives This study aims to assess PLE disease severity via patient history and compares this with severity assessment via phototesting. Patients and methods Sixty‐one patients with PLE were asked 10 standard questions and all were phototested. The answers to the standard questions were coded with linear scores ranging from 0 to 10. The score of each question was plotted as independent variable in a multiple linear regression model against the score of the phototest (minimal number of irradiations necessary to elicit a positive skin lesion, with a maximum of 6 irradiations) as dependent variable using an enter approach. Furthermore, the scores of the separate questions were added to form a total score, the PLE–severity assessment score (PLE‐SAS). The medians of these PLE‐SASs were compared with the result scores obtained by phototesting. Phototesting was done with ultraviolet A and ultraviolet B irradiation. Results Fifty‐seven of the 61 patients had a positive test result (93%). Using the multiple linear regression model, the severity assessment by patient history (PLE‐SAS) compared with the result of phototesting showed two significant contributing questions (adjusted PLE‐SAS) (P < 0.05) but with a regression coefficient of 0.2. A significant difference in median scores with the severity assessment (PLE‐SAS and adjusted PLE‐SAS) between patients testing positive after 1–3 irradiations compared with those testing positive after 4–6 irradiations was present (P < 0.05). However, the overlap quartile range between both groups was such that the PLE‐SAS and the adjusted PLE‐SAS have little predictive value in individual patients. Conclusions We showed that in PLE, disease severity as determined using the PLE‐SAS or adjusted PLE‐SAS did not reliably predict severity as assessed by phototesting. Two significant contributing questions were not discriminating enough to be used as predicting questions to assess severity. Accurate patient history proved to be a reliable method to diagnose PLE. Phototesting is useful to determine the responsible ultraviolet action spectrum and to exclude differential diagnoses like photosensitive eczema, lupus erythematosus or chronic actinic dermatitis. PLE‐SAS cannot replace phototesting for determining the severity of PLE.     

Analysis of circulating tumor cells in patients with multiple myeloma during the course of high-dose therapy with peripheral blood stem cell transplantation.

In multiple myeloma (MM) circulating CD19+ cells have been considered as myeloma precursors. As these cells are also possibly a reservoir of treatment resistant disease evaluation of the CD19+ cells during the course of high-dose therapy has to be a major concern. We determined the number of tumor cells in the CD19+ as well as CD19- fractions of PB of eight patients with disease sensitive to VA[I]D chemotherapy, of 10 patients who achieved partial or complete remission post-high-dose therapy (HDT) with peripheral blood stem cell transplantation (PBSCT) and of a further seven patients with disease progression post-transplantation. CD19+ cell fractions were obtained by preparative sequential magnetic and fluorescence activated cell sorting with a median purity of 97.1%. In addition, PB samples of seven patients post-transplantation were sorted for CD20+ cells (median purity, 98.7%). The number of tumor cells in the CD19+, the CD19- and the CD20+ fractions were determined using a quantitative CDR3 PCR assay. The number of CD19+ tumor cells in patients in remission post-HDT was similar to those of the patients post-VA[I]D (median, 1.05 vs 0.92 CD19+ tumor cells/ml PB, P = 0.72) providing evidence for the persistence of this tumor cell fraction during the course of HDT. This was in contrast to the CD19- compartment, in which the number of tumor cells was significantly reduced in those patients in remission post-transplantation (median, 53 vs 0 CD19- tumor cells/ml PB; P = 0.006). In patients with progressive disease the number of tumor cells in both cell fractions was significantly higher (CD19+: median, 1.05 vs 21 tumor cells/ml PB, P = 0.05; CD19-: 0 vs 63 tumor cells/ml PB, P = 0.008). While the absolute number of CD19+ cells was reduced in the group of patients after VA[I]D treatment, a polyclonal CD19+ reconstitution had occurred in patients responding to HDT. The tumor cell content in the CD19+ fractions could be confirmed by the results obtained analyzing the CD20+ cell fractions. In conclusion, these results indicate that disease progression after PBSCT in MM is accompanied by an expansion of tumor cells in both the CD19+ and CD19- fractions. Similar numbers of CD19+ clonotypic cells post-HDT suggest that these cells persist and thus, contribute to disease dissemination and relapse.     

From the Cover: Global distribution of microbial abundance and biomass in subseafloor sediment

The global geographic distribution of subseafloor sedimentary microbes and the cause(s) of that distribution are largely unexplored. Here, we show that total microbial cell abundance in subseafloor sediment varies between sites by ca. five orders of magnitude. This variation is strongly correlated with mean sedimentation rate and distance from land. Based on these correlations, we estimate global subseafloor sedimentary microbial abundance to be 2.9⋅10²⁹ cells [corresponding to 4.1 petagram (Pg) C and ∼0.6% of Earth’s total living biomass]. This estimate of subseafloor sedimentary microbial abundance is roughly equal to previous estimates of total microbial abundance in seawater and total microbial abundance in soil. It is much lower than previous estimates of subseafloor sedimentary microbial abundance. In consequence, we estimate Earth’s total number of microbes and total living biomass to be, respectively, 50–78% and 10–45% lower than previous estimates.     

Visual pathway glioma: an erratic tumour with therapeutic dilemmas

OBJECTIVE: Our experience in children with visual pathway glioma (VPG) was reviewed to delineate its clinical characteristics. DESIGN: The charts and imaging studies of 21 children with VPG who were followed up in our centre during the last 12 years were reviewed and summarised. RESULTS: VPG accounted for 13.1% of all brain tumours treated during this period. Sixty two per cent of the children with VPG had neurofibromatosis type 1 (NF-1). Among these, more than 60% were detected as part of routine work up. In some cases decreasing visual function preceded the appearance of the VPG on imaging studies. Tumour growth rate was markedly unpredictable. All treatment modalities employed led to tumour shrinkage and stabilisation for a variable period, but none was successful in totally eradicating the tumour. Complications were less severe after chemotherapy compared with radiotherapy. Three children died, none with NF-1, with a globular hypothalamic/chiasmatic tumour and accompanying electrolyte abnormalities. CONCLUSIONS: NF-1 is a favourable prognostic marker for VPG. Whenever possible a period of observation is necessary before treatment is initiated, during which time tumour size and visual function should be closely followed up; an untoward change in either of these is an indication for the start of treatment, preferably chemotherapy first. The combination of a globular hypothalamic/chiasmatic glioma and electrolyte abnormalities in a child without NF-1 are related to a poor prognosis.     

Parental and professional perception of need for emergency admission to hospital: prospective questionnaire based study

AIM: To compare views of parents, consultants, and general practitioners on severity of acute illness and need for admission, and to explore views on alternative services. METHOD: Prospective questionnaire based study of 887 consecutive emergency paediatric admissions over two separate three week periods in summer and winter of five Yorkshire hospitals, combined with a further questionnaire on a subsample. OUTCOME MEASURES: Parental scores of need for admission and parent and consultant illness severity scores out of 10. Consultant judgment of need for admission. Alternatives to admission considered by consultants and, for a subsample, by parents and family GP. RESULTS: Ninety nine per cent of parents thought admission was needed. Parents scored need for admission more highly than severity of illness with no association observed between severity and presenting problem or diagnosis. High parental need score was associated with a fit, past illness, and length of stay. Consultant illness severity scores were skewed to the lower range. Consultants considered admission necessary in 71%, especially for children aged over 1 year, presentation with breathing difficulty or fit, and after a longer stay. More admissions in the evening were considered unnecessary as were admissions after longer preadmission illness, gastroenteritis, or upper respiratory tract infection. Of a subsample of parents, 81% preferred admission during the acute stage of illness even if home nursing had been available. Similar responses were obtained from GPs. Alternative services could have avoided admission for 19% of children, saving 15.6% of bed days used. CONCLUSIONS: Medical professionals and parents differ in their views about admission for acute illnesses. More information is needed on children not admitted. Alternative services should take account of patterns of illness and should be acceptable to parents and professionals; cost savings may be marginal.