Decreased expression of apical Na+ channels and basolateral Na+, K+-ATPase in ulcerative colitis

Impaired absorption of sodium (Na+) and water is a major factor in the pathogenesis of diarrhoea in ulcerative colitis (UC). Electrogenic Na+ absorption, present mainly in human distal colon and rectum, is defective in UC, but the molecular basis for this is unclear. The effect of UC on the expression of apical Na+ channels (ENaC) and basolateral Na+, K+-ATPase, the critical determinants of electrogenic Na+ transport, was therefore investigated in this study. Sigmoid colonic and/or proximal rectal mucosal biopsies were obtained from patients with mild to moderate UC, and patients with functional abdominal pain (controls). ENaC subunit expression was studied by immunohistochemistry, western blot analysis, and in situ hybridization, and Na+, K+-ATPase isoform expression was studied by immunohistochemistry, western blotting, and northern blot analysis. UC was associated with substantial decreases in the expression of the ENaC beta- and gamma-subunit proteins and mRNAs, whereas the decrease in ENaC alpha-subunit protein detected by immunolocalization was less marked. The levels of expression of Na+, K+-ATPase alpha1- and beta1-isoform proteins were also lower in UC patients than in controls, although there were no differences in Na+, K+-ATPase alpha1- and beta1-isoform mRNA levels between the two groups. Taken together, these results show that UC results mainly in decreased expression of the apical ENaC beta- and gamma-subunits, as well as the basolateral Na+, K+-ATPase alpha1- and beta1-isoforms. In conclusion, these changes provide a basis for the low/negligible levels of electrogenic Na+ absorption seen in the distal colon and rectum of UC patients, which contribute to the pathogenesis of diarrhoea in this disease.     

Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms

Impaired expression of the FMR1 gene is responsible for the fragile X mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein with RNA-binding properties. Its complex alternative splicing leads to several isoforms, whose abundance and specific functions in the cell are not known. We have cloned in expression vectors, cDNAs corresponding to several isoforms. Western blot comparison of the pattern of endogenous FMR1 proteins with these transfected isoforms allowed the tentative identification of the major endogenous isoform as ISO 7 and of a minor band as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other isoforms (ISO 4, ISO 5) were not expressed at detectable levels. Surprisingly, in immunofluorescence studies, the transfected splice variants that exclude exon 14 sequences (and have alternate C-terminal regions) were shown to be nuclear. Such differential localisation was however not seen in subcellular fractionation studies. Analysis of various deletion mutants suggests the presence of a cytoplasmic retention domain encoded in exon 14 and of a nuclear association domain encoded within the first eight exons that appear however to lack a typical nuclear localisation signal.      

Best practice in primary care pathology: review 1

This first best practice review examines four series of common primary care questions in laboratory medicine, namely: (i) measurement and monitoring of cholesterol and of liver and muscle enzymes in patients in the context of lipid lowering drugs, (ii) diagnosis and monitoring of vitamin B12/folate deficiency, (iii) investigation and monitoring of paraprotein bands in blood, and (iv) management of Helicobacter pylori infection. The review is presented in a question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

胰腺多房性潴留性囊肿1例

0　引言　胰腺多房性潴留性囊肿极为罕见,我科收治1例,报道如下.1　病例报告　患者,男,29岁,因发现右上腹包块11d入院,缘于11d前无明显诱因感右上腹痛,仅局限于右上腹部,无肩背部放散痛,伴间歇性发热,体温最高达38.3℃,经抗炎,对症治疗无效.并逐渐可触及右上腹有一肿块,在当地医院行穿刺检查为脓血性液体.镜检发现炎性细胞,B超示:胆囊窝下方及右肾内侧及腹腔动脉,下腔静脉外前方可见异常区,大小约9.1cm×6.6cm×7.6cm,边界清楚,形态不规则,内呈蜂窝状,可见多个大小不等的液性暗区,CT示:右上腹部上腔静脉前方6.0cm×9.0cm肿块和周围组织粘…     

玻璃体切除术治疗外伤性眼内炎62例

0　引言　外伤性眼内炎是眼外伤的常见并发症 ,对视力及眼球威协极大 .由于病原体随致伤物直接进入眼内 ,在眼内和玻璃体繁殖 ,产生剧烈炎症反应 ,对眼内组织造成严重破坏 .如不及时而有效的控制 ,终使视力丧失 ,眼球萎缩 .近年随着现代玻璃体手术的发展 ,外伤性眼内炎的治愈率明显提高 .现将我科收治的 6 2例报告如下 .1　对象和方法1 .1　对象 1 996 - 0 6 / 1 998- 0 6我院连续收治 6 2例外伤性眼内炎 ,其中男 5 0例 ,女 1 2例 ,年龄 2～ 45岁 ,平均 1 6 .5岁 .1 4岁以下儿童 38例 ,占 6 1 .3% .以致伤原因分类 :角膜穿通伤30例 ,巩膜穿…     

Prophylactic treatment of patients with esophageal varices: Is it ever indicated?

The prognosis of patients who bleed from esophageal varices is dismal. Prophylactic treatment of the varix or the elevated portal venous pressure offers a possibility of improving the outlook for these patients. However, as only approximately one-third of patients with varices bleed during their lifetime, correct identification of high-risk patients is vital before embarking on prophylaxis. At present, neither European or Japanese selection criteria are perfect in this respect. The documented incidence of initial variceal bleeding varies between 27% and 48%, and most bleeding episodes occur within the first year after varices are diagnosed. Data from six randomized controlled trials comparing prophylactic -blockers with placebo demonstrated a decreased incidence of bleeding in propranolol-treated patients, which in large measure may depend on patient compliance and did not significantly affect survival in all but one study. Early randomized studies of prophylactic sclerotherapy have shown significant reductions in both the incidence of bleeding and mortality, but this promise has not been sustained by subsequent trials, and indeed sclerotherapy was detrimental in two studies. The impressive results in highly selected patients treated in Japan by prophylactic surgery are unlikely to be repeated in a Western setting, involving patient populations that consist predominantly of alcoholic cirrhotics. At present prophylaxis with -blockade seems to offer the best therapeutic option, but the future may lie in the development of new interventional techniques such as tranjugular intrahepatic portosystemic stent shunting (TIPS) or variceal banding, and ultimately with hepatic transplantation.

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Resumen El pronóstico de los pacientes que sangran como consecuencia de várices esofágicas es sombró. El tratamiento profiláctico de las várices o de la elevada presión portal ofrece una posibilidad de mejorar el futuro de estos pacientes.Sin embargo, como apenas aproximadamente un tercio de los pacientes con várices sangran en el curso de su vida, la correcta identificación de los casos de alto riesgo es de vital importancia antes de embarcarse en tratamiento profiláctico.En la actualidad ni los criterios de selección europeos ni los japoneses pueden considerarse como perfectos a este respecto. La frecuencia del sangrado varicoso inicial oscila entre 27% y 48%, y la mayoría de los episodios hemorrágicos ocurren dentro del primer año después de establecido el diagnóstico de las várices. Los resultados de seis (6) ensayos clinicos randomizados en que compararon los beta-bloqueadores con placebeo demuestran una disminución en la incidencia de sangrado en los pacientes tratados con propranolol, lo cual en gran parte depende de la obediencia del paciente, pero afectó en forma significativa la sobrevida, excepto en uno de los estudios.Anteriores estudios randomizados sobre escleroterapia profiláctica han demostrado reducciones significativas tanto en la incidencia de sangrado como en la mortalidad, pero ésto no ha sido reproducido en ensayos clínicos subsiguientes, y en realidad la escleroterapia pareció ser nociva en dos estudios. Los impresionantes resultados en pacientes altamente seleccionados logrados en el Japón con la cirugía profiláctica muy probablemente no lograrán ser reproducidos en Occidente, donde las poblaciones de pacientes están conformadas predominantemente por cirróticos alcohólicos. En el momento actual la profilaxis con beta-bloqueadores parece ser la mejor opción terapéutica, pero el futuro puede bien ser el desarrollo de nuevas técnicas intervencionistas tales como shunts transyugulares intrahepáticos (TIPS) o la ligadura endoscópica de las várices y, por último, el trasplante de hígado.

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Résumé Le pronostic des patients ayant saigné de varices oesophagiennes est médiocre. Le traitement prophylactique des varices ou d'une hypertension portale permet une amélioration potentielle du pronostic de ces patients. Cependant, comme seulement un tiers des patients avec des varices saignent pendant leur vie, l'identification correcte des patients à risque élevé est capitale avant d'envisager une politique prophylactique généralisée. Actuellement, ni les critères européens ni les critères japonais ne sont suffisants pour déterminer cette population à risque. L'incidence d'hémorragie par rupture des varices initiale va de 27% à 48% dans la littérature et la plupart des hémorragies se produisent pendant la première année après le diagnostic de varices oesophagiennes. Les résultats provenant de six études comparant les béta bloqueurs à un placebo ont démontré une baisse de l'incidence de l'hémorragie chez les patients traités par le propranol. Ce résultat peut certes être attribué à une différence de coopération parmi les patients: la survie n'est pas différente d'une étude à l'autre sauf une. Les études randomisées de sclérothérapie prophylactique ont démontré une réduction significative dans l'incidence d'hémorragie et de la mortalité, mais cet espoir n'a pas été retrouvé par les essais suivants et la sclérothérapie a été néfaste dans deux de ces essais. Il est peu probable que les résultats impressionnants recueillis au Japon puissent être reproduits en Occident où la population est composée en grand majorité par des cirrhotiques d'origine alcoolique. Actuellement, la prophylaxie par béta-bloqueurs semble être le meilleur des traitements mais à l'avenir, la meilleure option thérapeutique pourrait être le shunt intrahépatique transjugulaire ou le wrapping périoesophagien et ultérieurement la transplantation hépatique.

     

Experience with Radical esophagogastric devascularization procedures (Sugiura) for variceal bleeding outside Japan

The Sugiura operation has been reported to have low operative mortality, rebleeding, and encephalopathy rates when carried out in a predominantly nonalcoholic Japanese population with good liver function. A literature review of reports of the Sugiura procedure outside Japan reveals a high complication and mortality rate when it is used as an emergency procedure in patients with advanced liver disease, especially in those with alcoholic cirrhosis. Uncontrolled studies report results that differ little from the Japanese series when the operation is confined to good-risk patients in the elective situation. Our experience with the Sugiura operation supports its role in these circumstances, especially in patients with portal vein thrombosis and normal liver function. The only good prospective controlled trial has been carried out in patients with schistosomiasis and suggests that the Sugiura operation is far superior to total shunt and may have a slight advantage over the Warren shunt because of its low incidence of postoperative encephalopathy. More controlled trials are required to establish its role in good-to moderate-risk patients with alcoholic cirrhosis.

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Resumen Se ha informado que la operación de Sugiura se asocia con bajas tasas de mortalidad, de hemorragia recurrente y de encefalopatía cuando se la ejecuta en poblaciones no alcohólicas, predominantemente japonesas y con buena función hepática. Una revisión de la literatura sobre los resultados del procedimiento por fuera del Japón, revela elevadas tasas de mortalidad y de morbilidad cuando se la practica como operación de emergencia en pacientes con enfermedad hepática avanzada, especialmente en los cirróticos alcohólicos. Estudios no controlados informan resultados que no difieren grandemente de las series japonesas cuando el uso de la operación es confinado a pacientes de buen riesgo y en condiciones electivas. Nuestra experiencia con la operación de Sugiura da apoyo al rol que quede desempeñar en estas circunstancias, especialmente en pacientes con trombosis de la vena porta y función hepática normal. El único buen ensayo prospectivo y controlado ha sido realizado en pacientes con esquistosomiasis, el cual sugiere que la operación de Sugiura es superior al shunt total y que parece tener una ligera ventaja sobre el shunt de Warren en virtud de su may baja incidencia de encefalopatía postoperatoria. Se requieren ensayos clínicos controlados adicionales para definir y dejar establecido su papel en pacientes de riesgo bueno y moderado con cirrosis alcohólica.

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Résumé L'opération de Sugiura est réputée pour avoir une mortalité opératoire, un taux de récidive hémorragique et d'encéphalopathie réduites lorsqu'il s'agit d'une population japonaise, non-alcoolique avec une bonne fonction hépatique. Une revue de la littérature sur l'opération de Sugiura en dehors du Japon montre des taux de complications et de mortalité lorsqu'elle est utilisée pour les cas opérés en urgence, chez les patients ayant une maladie hépatique avancée et surtout d'origine alcoolique. Des études non contrôlées ont rapporté des résultats qui ne diffèrent que peu des séries japonaises lorsque l'intervention est pratiquée uniquement chez les patients à bon risque et dans un climat non urgent. Notre expérience de l'opération de Sugiura soutient ces notions, surtout lorsqu'il s'agit de patients ayant une thrombose portale et une bonne fonction hépatique. Par ailleurs, dans la seule étude prospective et contrôlée accomplie jusqu'à présent chez le patient ayant une bilharziose, il a été démontré que l'opération de Suguira était très supérieure à l'anastomose portocave complète et pourrait être même supérieure à celle de Warren en raison d'une incidence extrêmement basse d'encéphalopathie postopératoire. D'autres études contrôlées sont nécessaires pour établir son rôle chez le patient cirrhotique et alcoolique, à risque opératoire modéré.

     

IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR TEETH ON THE SAME SIDE (A Case Report)

A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition