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.

[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.

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.

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.

[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.

Vasopressin and glypressin in upper gastrointestinal bleeding.

Vasopressin has been in clinical use for more than two decades in the treatment of upper gastrointestinal haemorrhage, especially bleeding oesophageal varices. However the haemostatic effect in controlled clinical trials is far from impressive, and no double-blind placebo controlled trial has shown even a trend in favour of vasopressin. These studies, the effects, side-effects, and clinical use of vasopressin and its long-acting analogue triglycylvasopressin, glypressin, are reviewed.

Endoscopic sclerotherapy of oesophageal varices. A clinical study.

Haemorrhage from oesophageal varices is a serious and feared complication of liver cirrhosis. One hundred and five patients treated for their first major variceal haemorrhage (VH) 1976-1979 were reviewed. Conventional therapy in a material with 60% Child class C patients with alcoholic cirrhosis resulted in a 50% first bleeding and a 36% readmission mortality with a one year survival of 30%. The conclusion was that the management schedule could be improved and that endoscopic sclerotherapy (ST) should be further evaluated. Conservative therapy and the addition of emergency and serial ST was compared in a prospective controlled trial in 107 unselected patients with major VH. Two-thirds belonged to Child's class C and 90% had alcoholic cirrhosis. Initial control of VH was obtained in 90% of all patients and the admission mortality was about 30%. The causes of mortality were mainly VH in 50 conservatively treated patients and hepatic failure and to VH unrelated causes in the ST-group (57 patients). Supplementary ST, a median of 6 sessions, succeeded in eradication of the varices in 34 of the 41 ST-patients discharged, failure was due to early death or continued alcoholism. Varices recurred in 5 patients during a 2-year follow-up. The number of rebleeds per observation month was overall decreased 3.6 times in the ST-group, but the survival was not prolonged. The effect of initial and serial ST on the mediastinal portalsystemic collaterals was investigated prospectively in 26 patients by repeated selective percutaneous transhepatic portography (PTP) and endoscopy. PTP was performed immediately prior to, and just after the first ST, showing reduced or inhibited contrast filling of oesophageal varices delineated on the pre-ST films in three-fourth of the patients. In 21 patients, follow-up PTP was carried out a median of 8 months later, when the varices were eradicated by serial ST. In 17 patients PTP supported the endoscopic estimation of variceal eradication, one patient was found to have residual varices. These patients were followed for a year, two patients developed recurrent varices. This study showed that submucosal oesophageal varicose veins can be efficiently eradicated by serial ST with a low recurrence rate. Oesophageal necrosis with delayed perforation intervened in 4% of our ST-patients with fatal outcome. Complications were noted in 30% of the patients treated with ST, and were major in 18%, mainly ulcerations with bleeding and transmural necrosis. Strictures encountered in 15% of the patients were easily treated. Oesophageal manometry was performed in 31 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Denver peritoneovenous shunting for malignant or cirrhotic ascites. A prospective consecutive series.

A Denver peritoneovenous (PV) shunt was inserted in 54 consecutive patients for relief of malignant (24 patients) or cirrhotic (30) refractory ascites. The median age of both groups was 58 years, and the most frequent diagnoses were gastrointestinal (15) or ovarian (7) cancers and alcoholic cirrhosis (25). Median survival time was 1.7 and 3.5 months (range, 0.1-15.5 and 0.1-50.5), and the 1-month mortality 42% and 27%, respectively. Postoperative 24-h urinary output increased by 2-31, and the 1-week weight reduction was 8 and 11 kg, respectively, compared with before shunting. Complete shunt failure was encountered early in two patients, due to catheter malposition and clotting. Four more patients experienced transient failure, for an early dysfunction rate of 11%. A shunt-related operative mortality of 6% was caused by pulmonary oedema (two patients) and sepsis (one patient). Shunt malfunction intervened in almost half (6 of 14) of the cancer patients surviving 1 month but was relieved in all but 1. In 3 of 22 cirrhotic 1-month survivors, the Denver shunt had to be removed owing to clotting or sepsis (2 patients) or revised because of blockage. Seven patients with cirrhosis are alive a median of 18 months (range, 2-51) after PV shunt surgery. Side effects were detected in 22 patients (41%): thromboembolism (9 patients), sepsis (7), initially bleeding oesophageal varices (3), DIC syndrome (2), postoperative hepatic coma (2), ascitic leakage (2), and pulmonary oedema (2). Patients with gastrointestinal cancers or severe cardiac disease did not benefit from the procedure. A history of hepatic encephalopathy or a serum bilirubin level above about 100 mumol/l was a bad prognostic sign. We could confirm the reported considerable morbidity and mortality after PV shunting, but also its efficiency in certain cases. Careful patient selection and follow-up study, timing of operation, and adherence to technical details are mandatory to improve the results.

Long-term survivors after variceal haemorrhage. Follow-up of a controlled study of endoscopic sclerotherapy versus conservative management.

In a prospective controlled trial of conservative therapy (vasopressin/balloon tamponade (control group] versus endoscopic sclerotherapy (ST) for the acute bleeding and at rebleeding, 107 cirrhotic patients with major variceal haemorrhage were studied from 1979 to 1983. The prospective follow-up study is now presented of the 51 patients surviving for more than 1 year. The present ST group (30 patients) was followed for a median of 5 years (range, 1-7.5 years), and the controls for 4 years (3-5.5 years). Variceal eradication was obtained in 22 ST patients in the 1st year after a median of 6 months and 5 ST sessions, and in 7 ST patients after 21 months and 9 ST sessions. The delay was due to alcoholic abuse. Eleven ST patients and 11 controls (NS) rebled on 30 and 45 occasions during a total follow-up time of 1364 and 696 months and 0.0220 and 0.0647 bleeds per patient-month, respectively (p = 0.098). Eight ST patients experienced 12 variceal bleeds, 11 controls had 39 haemorrhages with variceal aetiology, 0.0088 and 0.0560 bleeds per patient-month (p = 0.016), respectively. Five ST patients had recurrent varices on nine occasions with five episodes of bleeding a median of 13 months after completion of the initial serial ST. Reelimination was achieved with a median of three ST sessions during 3 months, but three patients had a second variceal recurrence 14-24 months later, successfully treated with one ST session in two of them. There was no difference in survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Variceal haemorrhage. A study of unselected patients with massive bleeding from oesophageal varices.

A series of 105 unselected patients treated at Södersjukhuset, Stockholm, Sweden 1976-1979 for massive haemorrhage from oesophageal varices is presented. Ninety per cent of the patients had alcoholic cirrhosis and 60% belonged to the poorest liver risk group on admission. The diagnosis of variceal haemorrhage was assessed by early endoscopy and/or autopsy. Treatment was mainly conservative, balloon-tamponade or vasopressin infusion. Twenty-five patients received additional therapy; Portacaval shunt surgery, percutaneous transhepatic variceal obliteration or endoscopic injection sclerotherapy. Despite this treatment along with early panendoscopy and modern intensive care facilities the mortality remained high. The hospital mortality was 50% during the first bleeding episode and 35% during recurrent variceal haemorrhage. Average hospital mortality was 44% and mean one year survival was 30%. In this study the long and short time survival after variceal bleeding relates strongly to the severity of the liver disease on admission. This must be fully taken into consideration before adopting sophisticated and costly operative techniques when simple nonoperative measures would give the same or better results.

Endoscopic sclerotherapy v. conservative management of bleeding oesophageal varices. A 5-year prospective controlled trial of emergency and long-term treatment.

A comparative trial was made of conservative therapy (balloon tamponade and/or vasopression infusion) alone (control group) or with addition of acute and serial endoscopic injection sclerotherapy (ST group). The 107 unselected patients, mainly with alcoholic cirrhosis, were randomly allocated to these groups, which were comparable as regards Child's grading and clinical and laboratory findings. For emergency ST a fibreoptic endoscope and Williams sheath were used. In initial control of index bleed and hospital mortality the two groups did not differ significantly. The median follow-up was 15 and 28 months (minimum 1 year). Supplementary ST (mainly out-patient) gave variceal eradication in 34 of 41 patients, with most failures in persistent alcoholics. A calculated risk factor for rebleeds was 3.6 times higher in the controls than in the ST group. Mortality rate showed no intergroup difference. The cause of death mainly was variceal bleeding in the controls, but not in the ST group. Major complications of treatment occurred in c. 15% of all patients.