[T1-T2 disc herniation: two cases]. / Hernie discale thoracique T1-T2: à propos de 2 cas.

We report two cases of exceptional first thoracic disc herniation in a 60-year-old man and a 55-year-old woman. The man was treated surgically and the woman medically. Osteoarthritis appeared to be the predominant cause of the disc herniation in both patients. Unlike the usual calcification in the medioposterior position for middle or lower thoracic spine herniations, a soft posterolateral herniation was observed here. The symptoms are limited, as observed in both patients, to a T1 radiculopathy, to be distinguished from C8 radicopathy. Myelopathy is rare. Claude-Bernard-Horner syndrome is not constant but highly suggestive. Both of these signs were absent in our patients. T1-T2 disc herniation should be suspected in patients presenting cervico-brachial medial neuralgia. MRI provides the diagnosis. Anterior surgery can be achieved without sternotomy. Careful radiographic analysis is needed preoperatively to identify the upper limit of the sternum.

Radiolucent cage for cervical vertebral reconstruction: a prospective study of 17 cases with 2-year minimum follow-up.

In cervical spondylotic myelopathy, extended anterior spinal cord decompression necessitates subsequent stable vertebral reconstruction. Reconstruction with an iliac crest graft and screw-plate fixation gives satisfactory clinical and radiological results, but they are often compromised by morbidity involving the bone harvest. The purpose of this study was to evaluate the contribution to cervical reconstruction of a biocompatible, radiolucent cage combined with screw-plate fixation, making use of bone harvested in situ. This prospective study was performed between July 2000 and March 2001 in eight women and nine men (mean age, 55 years) operated for cervical spondylotic myelopathy. Situated between levels C3 and C6, the cage was inserted after one corporectomy in ten patients, two corporectomies in five patients, and three corporectomies in two patients. The cage consisted of a polyester mesh impregnated with poly-L-lactic acid (PLLA) conferring temporary rigidity to the cage during bony fusion. Clinical and radiological follow-up (plain films, computed tomographic reconstruction in three cases) was performed at 2 months, 6 months, 12 months, 24 months and 36 months, postoperatively, with a mean follow-up of 30 months. Functional results were evaluated according to the Japanese Orthopaedic Association's scoring system. An independent surgeon assessed the radiological evidence of anterior cervical fusion using the grades proposed by Bridwell [6]. Every patient experienced neurological recovery. At last follow-up, radiological findings were consistent with grade I (complete fusion) in five cases, grade II (probable fusion) in ten cases, grade III (radiolucent halo in favor of non fusion) in one case, and grade IV (graft lysis) in one case with persistent neck pain. In three cases there was screw breakage (two grade II, one grade IV). None of these cases required surgical revision at latest follow-up. In extensive spinal cord decompression through an anterior approach, cervical reconstruction using the present type of cage can achieve clinical results comparable to conventional techniques. The rigidity of the cage meets biomechanical imperatives. Its radiolucency permits one to monitor the course of consolidation, contrary to metal cages. The cases of probable non-fusion and screw breakage were not accompanied by signs of instability on the flexion extension films. This cage meets the biologic and biomechanical imperatives of cervical reconstruction. It obviates complications involving bone harvest.

Endoscopic therapy in primary sclerosing cholangitis: outcome of treatment and risk of cancer.

BACKGROUND/AIMS: Primary sclerosing cholangitis is a cholestatic liver disease characterized by multifocal strictures in the intra- and extrahepatic biliary tree. Dominant strictures may arise in the extrahepatic bile ducts, and in these circumstances, endoscopic therapy has been introduced to relieve cholestasis and perhaps also delay the development of liver cirrhosis. The experience of endoscopic treatment at this point in time is limited and the long-term benefit is not clear. Neoplastic transformation in primary sclerosing cholangitis is unpredictable, which is illustrated in the present study along with an evaluation of the efficacy of endoscopic treatment. METHODOLOGY: Endoscopic retrograde cholangiopancreatography was performed in 25 patients with primary sclerosing cholangitis. In 15 there were dominant strictures in the hilum of the liver and/or the distal bile duct and these patients were treated by dilation and/or endoprostheses. Four patients in the treatment group had just cholestatic biochemical test results and 11 were symptomatic. RESULTS: Endoscopic therapy was technically successful in all 15 patients. In 43 sessions, 5 patients were treated by dilation, 2 with endoprostheses, and 8 by both methods. Improvement was achieved radiologically in 12 patients, clinically in 8, and according to liver function tests in 7. Therapy was complicated by cholangitis in 5 patients. Complications were mild and there was no mortality related to the procedure. However, 6 patients in the treatment group died, 5 of cholangiocarcinoma and 1 of colon cancer. CONCLUSIONS: Endoscopic therapy in primary sclerosing cholangitis is indicated in selected patients. The cancer incidence is high, not least in patients with deteriorating disease. It is important to find techniques for identifying patients at risk in order to perform liver transplantation before malignant transformation.

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

[Therapeutic program for ascites. Recommendations from the Swedish Society of Gastroenterology and Gastrointestinal Endoscopy]. / Behandlingsprogram vid ascites. Rekommendationer från Svensk förening för gastroenterologi och gastrointestinal endoskopi.

As ascites is related to liver cirrhosis in 80% of the patients, the present therapeutic guidelines are focused on ascites in liver cirrhosis. A combination of spironolactone and furosemide is recommended as first line therapy in patients with mild to moderate ascites and is effective in 90% of patients. In patients with pronounced or tense ascites, first line treatment is total paracentesis with intravenous infusion of human albumin as colloid replacement. Maintenance therapy for the prevention of recurrent ascites is based on spironolactone with or without furosemide. The indications for peritoneovenous shunt, or transjugular intrahepatic stent-shunt (TIPSS), are limited and only recommended in strictly selected patients with refractory ascites. Ascites in liver cirrhosis is a symptom of advanced liver disease, and liver transplantation should always be considered in eligible patients.

Contigs built with fingerprints, markers, and FPC V4.7.

Contigs have been assembled, and over 2800 clones selected for sequencing for human chromosomes 9, 10 and 13. Using the FPC (FingerPrinted Contig) software, the contigs are assembled with markers and complete digest fingerprints, and the contigs are ordered and localised by a global framework. Publicly available resources have been used, such as, the 1998 International Gene Map for the framework and the GSC Human BAC fingerprint database for the majority of the fingerprints. Additional markers and fingerprints are generated in-house to supplement this data. To support the scale up of building maps, FPC V4.7 has been extended to use markers with the fingerprints for assembly of contigs, new clones and markers can be automatically added to existing contigs, and poorly assembled contigs are marked accordingly. To test the automatic assembly, a simulated complete digest of 110 Mb of concatenated human sequence was used to create datasets with varying coverage, length of clones, and types of error. When no error was introduced and a tolerance of 7 was used in assembly, the largest contig with no false positive overlaps has 9534 clones with 37 out-of-order clones, that is, the starting coordinates of adjacent clones are in the wrong order. This paper describes the new features in FPC, the scenario for building the maps of chromosomes 9, 10 and 13, and the results from the simulation.

High-resolution landmark framework for the sequence-ready mapping of Xq23-q26.1.

We have established a landmark framework map over 20-25 Mb of the long arm of the human X chromosome using yeast artificial chromosome (YAC) clones. The map has approximately one landmark per 45 kb of DNA and stretches from DXS7531 in proximal Xq23 to DXS895 in proximal Xq26, connecting to published framework maps on its proximal and distal sides. There are three gaps in the framework map resulting from the failure to obtain clone coverage from the YAC resources available. Estimates of the maximum sizes of these gaps have been obtained. The four YAC contigs have been positioned and oriented using somatic-cell hybrids and fluorescence in situ hybridization, and the largest is estimated to cover approximately 15 Mb of DNA. The framework map is being used to assemble a sequence-ready map in large-insert bacterial clones, as part of an international effort to complete the sequence of the X chromosome. PAC and BAC contigs currently cover 18 Mb of the region, and from these, 12 Mb of finished sequence is available.

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Z extensions to the RHMAPPER package.

MOTIVATION: Extensions have been made to the RHMAPPER-1.1 package. One set of extensions computes the totally linked markers and uses the results as input to the salient RHMAPPER functions. The second set of extensions uses TKperl to provide an interactive interface for ease of querying the database and displaying maps. AVAILABILITY: The extensions can be obtained via ftp.sanger.ac.uk/pub/zmapper. SUPPLEMENTARY INFORMATION: The User's Manual can be viewed from http:/www.sanger.ac.uk/Users/cari/Z.shtml. CONTACT: cari@sanger.ac.uk

FPC: a system for building contigs from restriction fingerprinted clones.

MOTIVATION: To meet the demands of large-scale sequencing, thousands of clones must be fingerprinted and assembled into contigs. To determine the order of clones, a typical experiment is to digest the clones with one or more restriction enzymes and measure the resulting fragments. The probability of two clones overlapping is based on the similarity of their fragments. A contig contains two or more overlapping clones and a minimal tiling path of clones is selected to be sequenced. Interactive software with algorithmic support is necessary to assemble the clones into contigs quickly. RESULTS: FPC (fingerprinted contigs) is an interactive program for building contigs from restriction fingerprinted clones. FPC uses an algorithm to cluster clones into contigs based on their probability of coincidence score. For each contig, it builds a consensus band (CB) map which is similar to a restriction map; but it does not try to resolve all the errors. The CB map is used to assign coordinates to the clones based on their alignment to the map and to provide a detailed visualization of the clone overlap. FPC has editing facilities for the user to refine the coordinates and to remove poorly fingerprinted clones. Functions are available for updating an FPC database with new clones. Contigs can easily be merged, split or deleted. Markers can be added to clones and are displayed with the appropriate contig. Sequence-ready clones can be selected and their sequencing status displayed. As such, FPC is an integrated program for the assembly of sequence-ready clones for large-scale sequencing projects.

Continuous intravenous infusion of omeprazole in elderly patients with peptic ulcer bleeding. Results of a placebo-controlled multicenter study.

BACKGROUND: Does profound acid inhibition by continuous infusion of omeprazole for 72 h reduce further bleeding in elderly patients with peptic ulcer bleeding (PUB)? METHODS: Three hundred and thirty-three patients > or = 60 years old with PUB were randomized to omeprazole (80 mg + mg/h) or placebo as continuous infusion for 72 h. From day 4 to 21 all patients received 20 mg omeprazole orally once daily. RESULTS: When evaluated on day 3, the primary variable 'overall outcome' (based on an ordinal ranking scale; see Study variables) (P = 0.017) and the secondary variables, surgery (P = 0.003), degree (P = 0.004) and duration of bleeding (P = 0.003) all favored the omeprazole group. Blood transfusions, need for endoscopic treatment, and mortality were not statistically different. On follow-up, by day 21, the mortality in the group initially receiving intravenous omeprazole was 6.9%, while the intravenous placebo group showed an extremely low mortality, 0.6%. CONCLUSION: Three days' infusion of omeprazole improved overall outcome and reduced need for intervention in PUB patients.

From long range mapping to sequence-ready contigs on human chromosome 6.

Our aim is to construct physical clone maps covering those regions of chromosome 6 that are not currently extensively mapped, and use these to determine the DNA sequence of the whole chromosome. The strategy we are following involves establishing a high density framework map of the order of 15 markers per Megabase using radiation hybrid (RH) mapping. The markers are then used to identify large-insert genomic bacterial clones covering the chromosome, which are assembled into sequence-ready contigs by restriction enzyme fingerprinting and sequence tagged site (STS) content analysis. Contig gap closure is performed by walking experiments using STSs developed from the end sequences of the clone inserts.

SAM: a system for iteratively building marker maps.

SAM (system for assembling markers) is a system which supports man-machine problem solving for iteratively ordering a set of markers. SAM aids the user in partially ordering a set of markers based on incomplete and uncertain data. As data is added and modified, SAM aids the user in updating the previously assembled maps. The input is a file of clones and for each clone, a list of the markers contained within it. The objective is to order the set of markers such that the markers contained in each clone are consecutive. The user directs the map building by selecting functions to assemble a region of markers, order the clones to fit the order of the markers and position new markers within an ordered set of markers. The user can edit the input data, edit the assembled map and add clones to the map based on their marker content. The results are displayed graphically and can be saved in a solution file. Based on the partial map, the user designs new experiments or edits the existing data to fill gaps and resolve ambiguities. When a previously assembled map is loaded into SAM, it is automatically updated with the new or altered data. SAM treats all markers as points, but has special features for multiple copy and long markers so that they can be used in the map building process. This system has supported the building of a YAC map of human chromosome 22 at the Sanger Centre, where use of Alu-PCR product markers is a major component in determining clone overlap and where we have an on-going effort to accumulate data from various sources. SAM is also being used at various other laboratories.

A high-density YAC contig map of human chromosome 22.

We have constructed a high-resolution clone map of human chromosome 22 which integrates the available physical and genetic information, establishing a single consensus. The map consists of all classes of DNA landmarks ordered on 705 yeast artificial chromosomes (YACs) at an average landmark density of more than one per 70 kilobases. This map represents the practical limits of currently available YAC resources and provides the basis for determination of the entire gene content and genomic DNA sequence of human chromosome 22.

GRAM and genfragII: solving and testing the single-digest, partially ordered restriction map problem.

GRAM (Genomic Restriction map AsseMbly) takes as input single-digest restriction fragments for a set of overlapping clones and outputs one or more plausible partially ordered restriction maps. For each restriction map, GRAM shows the corresponding alignment of the input clone fragments. Due to the error and uncertainty in experimental data, this problem is computationally difficult to solve; therefore, the principle objective in the design of GRAM is to facilitate man-machine collaborative problem solving. GRAM quickly approximates a solution, as follows. (i) A clustering algorithm determines a probable set of restriction fragments. (ii) An assembly algorithm permutes the set of restriction fragments such that the maximal number of clone fragments are contiguous. The output of the GRAM algorithm is displayed for the user to query and edit. This paper describes the stochastic assembly algorithm and shows how it works with the interactive graphics to support man-machine problem solving. In order to test and verify the performance of GRAM, we have developed a program called genfragII to simulate the digestion of clones and fragments; this program is described and results are presented. GRAM is also being used for a number of genome mapping projects.

Surgical treatment of cytomegalovirus enterocolitis in severe human immunodeficiency virus infection. Report of eight cases.

PURPOSE: The aim of this study was to describe our experiences of surgical removal of inflamed bowel in cytomegalovirus enterocolitis. METHODS: Eight homosexual males with a mean age of 41 years (range, 29-59 years) and a mean CD4 count of 21 x 10(6)/l (1-60 x 10(6)/l) with advanced human immunodeficiency virus infection and severe cytomegalovirus enterocolitis were treated with ileocecal resection (4 patients) or right-sided hemicolectomy (4 patients). Symptoms were lower abdominal pain, severe diarrhea, fever, and weight loss, unrelieved by anticytomegalovirus therapy. Radiologic examination showed that ulcerative inflammation was limited to the right colon and terminal ileum. Microscopic examination confirmed the cytomegalovirus enterocolitis. Intermittent cytomegalovirus treatment, usually with foscarnet for 10 to 14 days every 4 to 6 weeks was given postoperatively. RESULTS: Two minor postoperative complications occurred: a lesser wound infection and a moderate bleeding from the abdominal wound edges. One patient died after three weeks because of gastrointestinal bleeding from an ulcerating Kaposi's sarcoma lesion and another patient died from unrelated causes three weeks after discharge from the hospital. The remaining 6 patients experienced complete or partial palliation of the abdominal symptoms for a mean of 14 months (range, 5-35 months) until death or the end of observation time. One patient is still alive two years after the operation. The overall mean survival was 12 months (range, 0.5-35 months). Recurrent or persistent symptoms and/or signs of cytomegalovirus enterocolitis occurred in four patients after a mean of seven months. CONCLUSION: Resection of inflamed bowel combined with postoperative anticytomegalovirus treatment leads to excellent palliation and a relatively favorable survival in AIDS patients with cytomegalovirus enterocolitis.