Biomedical subjects
M Fried
Publications and source records attributed to M Fried.
[Acute pancreatitis--the need for an active approach. Experience in our department].
The authors draw attention to the rising incidence of acute pancreatitis, based on their own observations. They present very briefly the last version of the classification of acute pancreatitis, the so-called Atlanta classification of 1992. They summarise methods of conservative treatment of acute pancreatitis which they used as a basis for elaborating their own therapeutic pattern. In the presented group in 1995 19 patients with the diagnosis of acute pancreatitis were treated which was diagnosed based on the clinical condition, biochemical results, US and CT examination of the pancreas. CT examination is considered most important. In three instances acute non-complicated pancreatitis was involved, seven times acute accumulation of fluid in the pancreas and eight times acute necrosis of the pancreas. In 13 men and 6 women the mean age was 54.3 years. As to the aetiology, acute pancreatitis was 9 times of biliary origin, 6 times due to alcohol abuse, twice due to ERCP, once after chemotherapy and in one case the cause was not revealed. All patients with acute necrosis of the pancreas were operate by laparostomy, zip closure was used and repeated surgical revisions were made. Of 19 patients 8 died (all with acute necrosis of the pancreas). In antibiotic prevention of secondary infection of the pancreas in acute pancreatitis cefazoline proved most useful. Aprotinine administration to inhibit proteases is according to the authors effective only during the first 48 hours after the onset of the disease.
[Reoperation in iatrogenic injuries in the biliary tract].
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Tissue-specific processing of the Surf-5 and Surf-4 mRNAs.
The mouse surfeit locus is an unusually tight cluster of at least six "housekeeping" genes that do not share any sequence homology and whose gene organization may play a role in gene expression. The transcription of each of the five well-characterized genes (Surf-1 to -5) alternates with respect to its neighbor(s) and no more than 159 bp separates any two adjacent genes with the Surf-4 and Surf-2 genes overlapping at their 3' ends by 133 bp. In this work, the expression of the Surf-5 and Surf-4 genes has been examined in various mouse tissues. In addition to the ubiquitously expressed 3.5-kb Surf-5 mRNA, a second alternatively spliced Surf-5 mRNA, Surf-5b, was discovered that was highly expressed in the brain, heart, testis, and skeletal muscle. The alternative splice donor site of the Surf-5b mRNA is similar to splice donor sites found in neuron-specific mRNAs. Surf-5b encodes a unique protein, which, like the ubiquitous Surf-5 protein, has been found to be primarily located in the soluble fraction of the cytoplasm. The expression of the Surf-5b protein was also found to increase in embryonal carcinoma cells differentiated into neuronal cultures. Although the Surf-5 gene is highly conserved through evolution, the presence of the Surf-5b alternative splice may be restricted to higher vertebrates. The Surf-4 gene was ubiquitously expressed in eight different mouse tissues; however, the ratios of the three previously reported Surf-4 mRNAs (two of which are known to derive from different sites of polyadenylation) altered dramatically between tissues. The use of different forms of mRNA processing for regulation of tissue-specific expression of ubiquitously expressed genes is discussed.
[Results of surgical treatment of pancreatic carcinoma].
Experiences in pancreatic surgery revealed substantial mortality decrease in pancreatic resections and these procedure became treatment of the first choice for resectable pancreatic tumors in last ten years. Our results support this experience, we performed pancreatic resections in 51% of 155 patients we operated on in last five years, with mortality rate not exceeding 5%. Morbidity of pancreatic resections remains low in comparison with palliative procedures and resections provide better quality of life even in advanced disease. Together with adjuvant chemotherapy there is a possibility to offer an acceptable treatment for pancreatic tumors.
Surf5: a gene in the tightly clustered mouse surfeit locus is highly conserved and transcribed divergently from the rpL7A (Surf3) gene.
The four previously characterized genes (Surf1 to 4) of the mouse Surfeit locus do not share any sequence homology, and the transcription of each gene alternates with respect to its neighbor(s). Adjacent Surfeit genes are separated by very small distances, and two of the genes overlap at their 3' ends. In this work we have further defined the Surfeit gene cluster by the isolation of Surf5, a fifth gene of the locus, and determination of its relationship to the other Surfeit genes. Surft5 does not share any sequence homology with the four cloned Surfeit genes. The transcription of Surf5 is divergent with respect to its neighbor the Surf3 gene, and the 5' ends of Surf5 and Surf3 are separated by only 159 bp, suggesting the presence of a second bidirectional promoter in the locus. The 3' end of Surf5 maps only 68 bp away from the processed 3' end of a pseudogene. The human and partial chicken Surf5 coding regions show greater than 95% identity, and a Caenorhabditis elegans homologue shows 38% identity and 56% similarity with the mouse Surf5 amino acid sequence. The 3.5-kb transcript of Surf5 encodes a small hydrophilic protein of 140 amino acid residues, which differs from the ribosomal protein L7a encoded by the Surf3 gene or the integral membrane protein encoded by the Surf4 gene. Subcellular fractionation located the Surf5 protein to the soluble fraction of the cytoplasm. The surfeit locus appears to represent a novel type of gene cluster in which the genes are unrelated by sequence or function; however, their organization may play a role in their gene expression.
CpG methylation and the binding of YY1 and ETS proteins to the Surf-1/Surf-2 bidirectional promoter.
The divergently transcribed Surf-1 and Surf-2 genes are separated by a bi-directional, TATA-less promoter which contains three important factor-binding sites, Su1, Su2 and Su3. The transcription initiation factor YY1 binds to the Su1 site and stimulates transcription in the direction of Surf-1 and, to a lesser extent, Surf-2. Members of the ETS family of transcription factors bind to the Su2 and Su3 sites. Here we show that in transient transfection assays, transcription in both the Surf-1 and the Surf-2 direction is severely reduced by CpG methylation. Although the Su1 site contains three CpG dinucleotides, the binding of YY1 is not affected by CpG methylation. In contrast, the binding of two ETS factors (ETS-2 and PEA-3) to the Su2 site (which also contains three CpG dinucleotides) is totally abolished by CpG methylation. Finally, we show that methylation of a single C within the Su2 site is sufficient to prevent ETS factor binding.
Use of alternative polyadenylation sites by the chicken S6 ribosomal protein gene.
Two chicken ribosomal protein S6 cDNAs were isolated from a liver cDNA library and their DNA sequence determined. Each of the cDNAs was found to use a different polyadenylation signal and to be polyadenylated at a different site. This is the first observation of alternative Poly(A) site usage by a ribosmal protein gene. Northern blot analysis revealed that the chicken rpS6 transcripts can be alternatively polyadenylated in brain tissue. Southern blot analysis indicates that there is only one rpS6 gene in the chicken genome. The long open reading frame of the chicken rpS6 gene specifies 249 amino acids which show high homology with rpS6 homologues from other species. The four serine residues in rpS6 which are major sites of phosphorylation in mammals are conserved in chicken.
CpG methylation has differential effects on the binding of YY1 and ETS proteins to the bi-directional promoter of the Surf-1 and Surf-2 genes.
The divergently transcribed Surf-1 and Surf-2 housekeeping genes are separated by a bi-directional, TATA-less promoter which lies within a CpG-rich island. Here we show that CpG methylation severely reduces transcription in the direction of both Surf-1 and Surf-2. Previous work has identified three promoter elements (Su1, Su2 and Su3) which are conserved between the human and mouse Surf-1/Surf-2 promoters. These elements bind transcription factors present in human and mouse cell nuclear extracts in vitro and mutations which prevent factor binding also reduce promoter activity in vivo. Transcription initiation factor YY1 binds to the Su1 site and stimulates transcription in the direction of Surf-1 and, to a lesser extent, Surf-2. Here we show that members of the ETS family of transcription factors bind to the Su2 site. Although the Su1 factor binding site contains three CpG dinucleotides, the binding of YY1 is not affected by CpG methylation. In contrast, CpG methylation abolishes the binding of ETS proteins to the Su2 site; methylation of a single cytosine, at position 3 of the consensus ETS site, is sufficient to prevent factor binding. This direct effect on the binding of ETS proteins is, however, not in itself sufficient to explain the repression of this promoter by CpG methylation. A mutation of the Su2 site which removes the sequence CpG, but which does not prevent ETS factor binding, fails to relieve this promoter from repression by CpG methylation.
The L19 ribosomal protein gene (RPL19): gene organization, chromosomal mapping, and novel promoter region.
The intron-containing genes encoding rat and human ribosomal protein L19 (RPL19) have been cloned. The DNA sequences of the entire rat RPL19 gene and the 5' end of the human RPL19 gene have been determined. Sequence comparison of corresponding regions of the two genes reveals a striking interspecies homology in the 5' upstream region, outside the transcribed and coding regions. The transcriptional start sites of the two genes have been determined and are identical. Both rat and human RPL19 genes have 5' ends associated with CpG islands. A promoter deletion analysis of the rat RPL19 gene suggests that this promoter may differ from those of all previously characterized ribosomal protein genes in requiring far upstream sequences for efficient gene expression. By fluorescence in situ hybridization analysis, the position of the human RPL19 gene has been sublocalized to 17q11 and may be coamplified with the erbB-2 gene in human breast cancer cells. The similarities and differences between RPL19 and other previously characterized ribosomal protein genes are discussed.
Role of nutrient fat and cholecystokinin in regulation of gallbladder emptying in man.
Postprandial gallbladder contraction is mainly regulated by cholecystokinin (CCK), but little is known about the dose-response relationship between CCK release and gallbladder contraction, in particular after meals with differing fat content. Decreased postprandial gallbladder emptying has been suggested to play a major role in the development of gallstones in man, and dietary factors may therefore be important in the pathogenesis of gallbladder stasis. We studied, in a randomized order, the effect of three isocaloric meals (250 ml) with identical osmolality on CCK release and gallbladder contraction in six healthy volunteers: (1) a pure fat meal (25 g triglycerides); (2) a mixed meal containing fat (8 g, 29% of caloric content), protein (10 g, 17%), and dextrose (32 g, 54%); and (3) a fat-free meal containing albumin (25 g, 46%) and dextrose (32 g, 54%). Gallbladder volumes and antral cross-sectional areas were determined by ultrasonography and plasma CCK and PP levels by RIA. The pure fat meal caused the highest CCK release (187 +/- 27; mean +/- SEM) and maximal (> 85% of fasting volume) gallbladder contraction (3172 +/- 361; AUC) as compared to the other two meals (P < 0.05). The mixed and the fat-free meal caused similarly low (< 50% of fasting volume) gallbladder contraction (6052 +/- 342 and 6134 +/- 500, respectively), although they induced markedly different CCK levels (157 +/- 12 and 87 +/- 13, respectively; P < 0.05). Gastric emptying rates were similar for all meals (18,500 +/- 3300, 18,600 +/- 2700 and 19,800 +/- 3100, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Conscious sedation for gastroscopy: patient tolerance and cardiorespiratory parameters.
BACKGROUND/AIMS: Most patients receive conscious sedation for gastroscopy. However, the benefit of the most often used combination of low-dose intravenous midazolam and topical lidocaine on patient tolerance remains poorly defined and has not been shown to outweigh cardiorespiratory risks. To respond to these issues, a randomized, double-blind, placebo-controlled prospective study was performed. METHODS: Two hundred outpatients undergoing diagnostic gastroscopy were assigned to receive either (1) midazolam (35 micrograms/kg) and lidocaine spray (100 mg), (2) midazolam and placebo lidocaine, (3) placebo midazolam and lidocaine, or (4) placebo midazolam and placebo lidocaine. RESULTS: Tolerance (visual analogue scale, 0-100 points; 0, excellent; 100, unbearable) improved as compared with placebo midazolam and placebo lidocaine by 23 points (95% confidence interval, 15-32) in group 1, 15 points (95% confidence interval, 7-24) in group 2, and 10 points (95% confidence interval, 2-18) in group 3. Increasing age (P < 0.001), low anxiety (P < 0.001), and male sex (P < 0.03), but not amnesia, were associated with better patient tolerance. Oxygen desaturation (< 1 minute) occurred in 8.2% and was not more frequent after midazolam treatment. Hypotension was rare (2.1%), and no adverse outcome occurred. CONCLUSIONS: Both low-dose midazolam (35 micrograms/kg) and lidocaine spray have an additive beneficial effect on patients tolerance and rarely induce significant alterations in cardiorespiratory monitoring parameters, thus supporting the widespread use of conscious sedation.
Effect of cisapride on gallbladder motility after extracorporeal shock-wave lithotripsy.
BACKGROUND/AIMS: Altered gallbladder motility is regarded as one of the important factors involved in the formation and recurrence of gallstones. Previous studies have suggested that cisapride increases postprandial gallbladder contraction and may therefore be theoretically useful in preventing stone recurrence. The aim of our study was therefore to investigate the effect of cisapride on gallbladder motility in stone-free patients after extracorporeal shock-wave lithotripsy, as compared to healthy volunteers pair-matched for age and sex. METHODS: Each subject received cisapride or placebo in a double-blind, cross-over, random order. Gallbladder volumes were measured by ultrasonography in the fasting state and after intake of a standard liquid meal. Plasma cholecystokinin levels were determined by radioimmunoassay. RESULTS: Fasting gallbladder volumes were smaller in patients as compared to volunteers (20.7 +/- 1.3 ml vs. 46.0 +/- 9.2 ml; p < 0.05) but were not modified by cisapride (21.1 +/- 1.7 ml vs. 58.6 +/- 11.3 ml). The maximal postprandial decrease in gallbladder volume was similar in patients and volunteers (64.5 +/- 12% vs. 62 +/- 10%; NS) and was not significantly altered by cisapride (59 +/- 9.4% vs. 54 +/- 9%; NS). In patients, cisapride increased integrated postprandial gallbladder volume by accelerating gallbladder refilling as compared to placebo by 37 +/- 15% (p < 0.05). Integrated cholecystokinin plasma levels were similar in patients and volunteers and were 13.4 +/- 4.7% higher after cisapride as compared to placebo (p < 0.05). CONCLUSIONS: The results of this study suggest that cisapride does not alter postprandial gallbladder contraction but accelerates gallbladder refilling in patients free from gallstones after extracorporeal shock-wave lithotripsy. This effect of cisapride is probably due to an acceleration of gastric emptying also causing a secondary enhanced cholecystokinin release.
Can obstructive sleep apnoea be a complication of uvulopalatopharyngoplasty?
UNLABELLED: Polysomnography is currently used for diagnosis, evaluation and selection of therapy in patients with obstructive sleep apnoea (OSA), but clinically successful uvulopalatopharyngoplasty (UPPP) is not necessarily reflected by post-operative improvement of polysomnographic recordings. Post-operative polysomnography may suggest deterioration of pre-existing OSA or, in snorers, de-novo precipitation of OSA. Thus, if polysomnography is a reliable indicator of OSA, then OSA may be a post-operative risk of UPPP. THE AIMS OF OUR STUDY WERE: (i) to assess the possible deleterious effect of UPPP on sleep patterns; (ii) to further define the role of cardioisotope scanning in the evaluation of OSA; (iii) to assess the reliability of polysomnography given the clinical and cardiosotope scan findings. Symptoms, polysomnography and radionuclide ventriculography were prospectively compared pre- and post-operatively in 41 patients undergoing UPPP. In 12 patients (29 per cent), there were disparate results between pre- or post-operative polysomnography and the clinical and/or radionuclide ventriculography, as follows: In four of 16 patients with abnormal pre-operative ventricular performance, there was pre-operative symptomatology of severe OSA and a bedmate's reports of apnoeic episodes. This was in contrast to normal or near normal sleep apnoea recordings. In eight patients, post-operative improvement of symptoms was reported, despite deterioration of post-operative polysomnographic recordings. In these patients the post-operative improvement of symptoms was also reflected by improved ventricular performance. Worsening of ventricular performance was not demonstrated in any patient. In conclusion, UPPP does not induce OSA. Polysomnography may underestimate or even misdiagnose cases of OSA.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrical burns associated with head injuries.
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The genomic organization of the region containing the Drosophila melanogaster rpL7a (Surf-3) gene differs from those of the mammalian and avian Surfeit loci.
The Surf-3 gene of the unusually tight mouse Surfeit locus gene cluster has been identified as the highly conserved ribosomal protein gene L7a (rpL7a). The topography and juxtaposition of the Surfeit locus genes are conserved for the 600 million years of divergent evolution between mammals and birds. This suggests cis interaction and/or coregulation of the genes and suggests that, within this locus, gene organization plays an important role in gene expression. The further evolutionary conservation of the organization of the Surfeit locus was investigated. A cDNA encoding the Drosophila melanogaster homolog of the Surf-3/rpL7a gene was cloned, was shown to be present as a single copy, and was expressed constitutively at high levels throughout development. Genomic cosmid clones encompassing the gene and its surrounding DNA were isolated. The gene was determined to have five introns, of which two were located in the 5' untranslated region of the gene. The remaining three introns had splice sites at positions equivalent to those found in the Surf-3/rpL7a mammalian homologs. S1 analysis and 5' rapid amplification of cDNA ends both confirmed the start of transcription to occur in a polypyrimidine tract in the absence of a TATA box in the promoter. The genomic region around the Surf-3/rpL7a gene was analyzed by low-stringency hybridization with murine Surfeit gene probes, by partial sequence analysis, and by hybridization of fragments to Northern (RNA) blots. No homologs of other members of the Surfeit gene cluster were detected in close proximity to the D. melanogaster Surf-3/rpL7a gene. However, a gene which was detected directly 3' to the Surf-3/rpL7a gene was shown to encode a homolog of a mammalian serine-pyruvate aminotransferase.
Brainstem abscess and meningitis due to Listeria monocytogenes in an adult with juvenile chronic arthritis.
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Gastric Banding: Advantages and Complications. A 5- and 10-Year Follow-up.
BACKGROUND: Gastric banding is one of the simplest surgical procedures for the treatment of morbid obesity. We performed more than 150 'laparotomy' (open) gastric bandings and more than 50 'laparoscopic' bandings in the last 1 0 years. METHODS: In most procedures we used non-adjustable bands, but since the beginning of 1995 we have used adjustable silicone banding. RESULTS: The 5- and 10-year follow-up weight loss results are encouraging. The average long-term weight loss was 35.5 kg. Since 1993, we performed all the procedures laparoscopically, and the postoperative complications decreased from 18.5% in the 'laparotomy' group to 9.5% in the 'laparoscopic' group, with the majority being esophagus and outlet area irritation. CONCLUSION: Gastric banding itself and especially the minimally invasive laparoscopic approach is an easy technical procedure. The long-term weight loss results and the reoperation rate are acceptable for bariatric surgery criteria.