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Biomedical subjects

L Bardram

Publications and source records attributed to L Bardram.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Pain and convalescence after ambulatory inguinal herniotomy during local anesthesia].

Postoperative pain and convalescence following ambulatory inguinal herniotomy in local infiltration anesthesia was evaluated in this descriptive study. Sixty consecutive patients (median age 63 yr) were included. Per- and postoperative pain treatment were pre- and postoperative oral tenoxicam and methadone plus infiltration of the surgical field with up to 60 ml of 0.25% bupivacaine. Intraoperative pain intensity was slight and was treated with supplemental bupivacaine. Patients were totally relieved of pain at rest and during mobilisation in the first hours after surgery, but more than half of the patients had moderate pain from the first to the third postoperative day and still had light pain seven days after surgery. Normal daily activity was re-established five days postoperatively (median). Fifty-two patients were satisfied with the anesthesia and eight patients not satisfied due to fear of intraoperative pain. This study shows that inguinal herniotomy can be performed routinely as an outpatient procedure under local infiltration anesthesia. However, late postoperative pain was significant and should be improved with multi-modal analgesia.

Adult↗
PubMed1993

[Laparoscopic parietal cell vagotomy. Preliminary results].

The results from 11 laparoscopic parietal cell vagotomies are presented. The procedure could be carried out in all patients. The median day of discharge after the procedure was day 1 (range 1-16), median convalescence time 7 (range 4-50) days. One patient required re-operation due to a perforation at the lesser curvature. This complication is ascribed to the learning phase. If a sufficient reduction in gastric acid secretion can be documented in a larger series of patients, laparoscopic parietal cell vagotomy should be considered a serious alternative to conservative treatment.

Adult↗
PubMed1993

Peptide hormone processing in tumours: biogenetic and diagnostic implications.

Insight into the biogenesis of peptide hormones has grown explosively by elucidation of gene, mRNA and prohormone structures. In addition, information about prohormone processing enzymes is rapidly accumulating. Prohormones vary in size and organization from poly- to monoprotein structures. According to their structural organization and sequence homology, hormones are grouped in families. Prohormones are processed to bioactive peptides by multiple modifications during the transport from the endoplasmic reticulum to secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. By constitutive secretion, the processing is less pronounced. The same prohormone may be expressed in several cell types that process the precursor in different ways. Awareness of cell-specific processing patterns is important for understanding the tumour synthesis of peptides and for appropriate diagnosis of peptide-producing tumours. These tumours comprise not only well-known neuroendocrine neoplasias. An increasing number of common carcinomas also expresses peptide hormone genes. However, the translation and post-translational processing in tumours are generally attenuated. Consequently, the expression is often functionally and clinically silent. A new diagnostic tool, processing-independent analysis (PIA), seems promising in quantitation of hormone gene expression at peptide level irrespective of the degree of processing. Studies of progastrin expression and processing in tumours illustrate the diagnostic superiority of PIA.

DNA, Complementary↗
PubMed1992

Expression, but failing maturation of procholecystokinin in cerebellum.

The cerebellum is the only region of the central nervous system which has been found to be devoid of cholecystokinin (CCK). The assays used, however, have been directed against the alpha-amidated C-terminus of fully processed CCK peptides. Using Northern blot analysis and a library of radioimmunoassays specific for different sequences of proCCK in combination with chromatography and enzyme cleavage, we have now examined the expression and processing of proCCK in fetal, neonatal and adult cerebellar tissue from man, pig and rat. In rat cerebellum CCK mRNA was present already in the fetal state. Two weeks after birth the concentrations declined. Also proCCK was found in significant concentrations in the fetal human and rat cerebellum (approximately 20 pmol/g); but already before birth the expression began to decrease towards low concentrations in adults. The adult porcine cerebellum contained 3.2 pmol proCCK and glycine-extended processing intermediates per gram (range less than 0.1-10.4 pmol/g), and 0.8 pmol carboxyamidated CCK per gram (range 0.1-4.1 pmol/g) varying in size from CCK-58 to CCK-5. For comparison, the adult porcine cerebral cortex contained 757 pmol carboxyamidated CCK/g, 20 pmol glycine-extended CCK/g and no proCCK. We conclude that cerebellum expresses proCCK with the highest level of expression in fetal life. In comparison with other regions of the brain, the maturation to transmitter-active, carboxyamidated CCK peptides is, however, attenuated in both fetal and adult cerebellar tissue.

Aging↗
PubMed1992

Ontogeny of procholecystokinin maturation in rat duodenum, jejunum, and ileum.

Expression and processing of procholecystokinin (proCCK) in rat intestine during development were examined using sequence-specific immunoassays, cleavage with processing-like enzymes, and chromatography. Fetal proCCK concentrations were similar in duodenum, jejunum, and ileum, but the maturation to CCK followed different courses: duodenal CCK increased from 14 pmol/g in the fetus to 86 pmol/g 4 days after birth and then declined to 17 pmol/g in the adult. In jejunum, CCK varied from 34 pmol/g in the fetus to 127 pmol/g at day 7, decreased to 54 pmol/g at day 21, and increased again to 93 pmol/g in the adult. Ileal CCK decreased from 20 pmol/g in the fetus to 10 pmol/g postnatally. Whereas duodenal proCCK after birth matured completely to carboxyamidated CCK, jejunoileal proCCK matured only partially. Chromatography showed an increase of tyrosine-sulfation and proteolytic processing of N-terminal sequences. At day 7 jejunal cholecystokinin octapeptide (CCK-8) constituted only a minute fraction of the carboxyamidated CCK, of which less than half was sulfated. However, in the adult jejunum, CCK-8 constituted a significant fraction, which was completely sulfated. It is concluded that the CCK gene is well expressed at propeptide level in the fetal small intestine. Postpartum maturation of proCCK, however, is late and differs in the three parts of the small intestine. The belated maturation supports the hypothesis that factors other than CCK regulate pancreatic growth in fetal and neonatal life.

Amino Acid Sequence↗
PubMed1991

[Laparoscopic cholecystectomy--minimally invasive surgery].

In 1987, Mouret devised a technique of performing cholecystectomy through a laparoscope. When performed correctly and on the right indications, this type of minimal invasive surgery has distinct advantages for the patients. Postoperative hospitalization is reduced to a few days and most of the patients can return to work or normal activities within a week or two. In this department, laparoscopic cholecystectomy was used for treatment of symptomatic gallbladder stones in 34 patients. In three patients the procedure was converted to an open laparotomy. No mortality and no ductal injuries were observed and no re-operations were necessary. The operating time averaged 102 minutes and the postoperative stay was 2.3 days. The average duration of sick-leave was 12 days. We are convinced, that this new technique will play a dominant role in the future treatment of symptomatic cholelithiasis.

Cholecystectomy↗
PubMed1991

Ontogeny of procholecystokinin processing in rat hypothalamus.

The concentration of procholecystokinin (pro-CCK) in the fetal hypothalamus was 126 +/- 41 pmol/g (mean +/- SEM; n = 20), 22 +/- 9 pmol/g at day 7 postpartum and 3 +/- 2 pmol/g in the adult. In contrast, the concentration of bioactive carboxyamidated CCK rose from 6 +/- 2 pmol/g in the fetal hypothalamus to 52 +/- 10 pmol/g in the adult. The concentration of glycine-extended processing intermediates first decreased from 21 +/- 5 pmol/g in the fetus to 5 +/- 1 pmol/g at day 21 postpartum. Subsequently, the concentration rose to 21 +/- 4 pmol/g in the adult. The results show that the CCK gene is well expressed in the fetal hypothalamus. However, only a small fraction of pro-CCK reaches maturation before weaning. We conclude that expression of the CCK gene in the hypothalamus as bioactive peptide to a large degree is regulated at the posttranslational level.

Amino Acid Sequence↗
PubMed1991

Processing-independent analysis (PIA)--a new diagnostic tool.

Posttranslational processing is an important phase of the expression of most eucaryotic genes in terms of functional proteins. Among these, secretory proteins and peptides are of particular interest for clinical chemists, since diagnostic measurements of circulating proteins and peptides constitute a major discipline in clinical chemistry. The posttranslational covalent maturation of secretory proteins and peptides involves multiple enzymatic modifications of the corresponding proproteins along the intracellular secretory pathway. During the eighties, an increasing amount of evidence has indicated that sick secretory cells fail to process their secretory products normally. The diseased cells therefore fail to process their secretory products normally. The diseased cells therefore release also incompletely processed precursors and processing-intermediates. In order to measure the degree of disease, assays that measure proteins and peptides independent of the degree of processing are therefore desirable. We have now designed a new analytical principle, according to which secretory proteins, peptides and their precursors can be accurately quantitated irrespective of the degree of processing. This principle, named processing-independent analysis (PIA), is generally applicable to all cellular synthesized substances. The principle has been applied to and developed first for a well-defined secretory peptide system, progastrin and its products. Using this model, the results obtained so far confirm the diagnostic superiority of processing-independent analysis in comparison with conventional assays for bioactive peptides.

Amino Acid Sequence↗
PubMed1991

The expression of peptide hormones in normal cells and tumour cells.

Insight in the mechanisms of peptide hormone expression has grown explosively by elucidation of gene, mRNA and preprohormone structures for most hormone systems during the 1980s. In addition, information about the structure and substrate specificity of many prohormone processing enzymes is rapidly accumulating in these years. The preprohormones vary considerably in size and organization from poly- to monoprotein structures. According to the structural organization and sequence homology the hormones are grouped in families. The prohormones are processed to bioactive peptides by multiple enzymatic modifications during the intracellular transport from the rough endoplasmatic reticulum to the mature secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. The same prohormone may be expressed in several different cell types that process the precursor in entirely different ways. Awareness of such cell-specific processing patterns is important for the understanding of ectopic synthesis in neuroendocrine tumours.

Gene Expression Regulation↗
PubMed1990

[Multiple endocrine neoplasms type I].

The patient had been treated ten years previously for acromegaly. At present he was in hypercalcaemic crisis owing to multiple hyperparathyroid adenomas. He had multiple small pancreatic glucagonomas and a malignant duodenal gastrinoma which led to recurrent episodes of duodenal and gastric ulcers with perforations and hemorrhages. The hypercalcaemia increased the hypergastrinaemia significantly and probably accelerated the ulcer diathesis. This patient illustrates well how severe and complicated the clinical situation can be in patients with MEN-1 and emphasizes the importance of being aware of the syndrome.

Adult↗
PubMed1990

Procholecystokinin processing in rat cerebral cortex during development.

Using a library of radioimmunoassays for essential sequences of procholecystokinin (proCCK), we have examined the post-translational processing in the rat cerebral cortex from fetal to adult state. The concentration of proCCK in the fetal cerebral cortex was 43 +/- 7 pmol/g tissue (wet weight; mean +/- S.E.M. (n = 20)). It remained constant until day 21 post partum, after which it decreased to undetectable levels. In contrast, the concentration of fully processed, bioactive CCK peptides (i.e. alpha-carboxyamidated CCK) rose from 2 +/- 1 pmol/g in the fetal cortex to 122 +/- 21 pmol/g in the adult. A particularly steep increase occurred from day 7 post partum (13 +/- 2 pmol/g) to day 21 (108 +/- 11 pmol/g). The concentration of glycine-extended intermediates rose gradually from 8 +/- 1 pmol/g in the fetal brain to 55 +/- 6 pmol/g in the adult. Gel chromatography of cortical extracts from day 7, 21 and 100 confirmed the variable processing at the C-terminal amidation site. The results show that the CCK gene is expressed as proCCK already in the fetal brain. However, the covalent modifications of proCCK follow different time courses so that only a small fraction reaches maturation until the first week post partum. We conclude that expression of transmitter-active CCK peptides in the brain is largely regulated at the post-translational rather than at the transcriptional level.

Aging↗
PubMed1990

Progastrin in serum from Zollinger-Ellison patients. An indicator of malignancy?

Progastrin and all of its processing products were measured in serum from 48 patients with Zollinger-Ellison syndrome, 42 patients with duodenal ulcers, and 34 normal subjects. A processing-independent gastrin analysis and a conventional radioimmunoassay for the biologically active alpha-amidated gastrins were used. In serum from normal subjects, 87% (median; range, 27%-160%) of all progastrin products were alpha-amidated gastrins, whereas they constituted only 39% (15%-130%) in serum from patients with duodenal ulcers (p less than 0.01) and 46% (16%-100%) in serum from gastrinoma patients (p less than 0.01). A significantly lower percentage of alpha-amidated gastrin was found in patients with hepatic metastases (23%) than in patients with apparently benign tumors (54%). Chromatography of serum showed that large progastrin molecules occurred mainly in patients with malignant tumors, whereas smaller glycine-extended precursors dominated in patients with benign tumors. The results indicate that the total progastrin product reflects tumor synthesis of gastrin better than conventional measurements of alpha-amidated gastrin. Moreover, the results suggest that a low degree of processing of progastrin could serve as a predictor of a malignant clinical course at an early stage of the disease.

Adolescent↗
PubMed1990

Progastrin expression in mammalian pancreas.

Expression and processing of progastrin were examined in fetal, neonatal, and adult pancreatic tissue from five mammalian species (cat, dog, man, pig, and rat). A library of sensitive, sequence-specific immunoassays for progastrin and its products was used to monitor extractions and chromatography before and after cleavage with processing-like enzymes. The results showed that progastrin and its products are expressed in the pancreas of all species in total concentrations varying from 0.3 to 58.9 pmol/g of tissue (medians). The degree of processing was age- and species-dependent. In comparison with adult pancreatic tissue the fetal or neonatal pancreas processed a higher fraction to bioactive, C-terminally amidated gastrin. Nevertheless, the pancreatic processing was always less complete than that of the adult antral mucosa. The moderate level of expression and the attenuated processing in the adult pancreas contribute to explain previous failures to detect gastrin in normal pancreatic tissue. Our results indicate that gastrin-producing tumors in the pancreas are not ectopic, but arise from cells that normally express the gastrin gene.

Aging↗
PubMed1990

Screening for multiple endocrine neoplasia type 1 in patients with recognized pituitary adenoma.

A total of 79 consecutive patients with pituitary tumours were screened for multiple endocrine neoplasia type 1 (MEN-1). The 79 patients included 21 patients with acromegaly, nine with Cushing's disease, 18 with prolactinomas, three with mixed pituitary adenomas (GH and PRL), and 28 patients with no detectable hypersecretion of hormones. The screening consisted of: (1) a family history, (2) a uniform medical history of the patient using a standard questionnaire, and (3) hormonal evaluation including measurements of the serum levels of insulin, gastrin, glucagon, somatostatin, vasoactive intestinal polypeptide and pancreatic polypeptide. Ionized calcium and glucose concentration in serum were also measured. We found no patients with the MEN-1 syndrome. In one patient, we found a transient elevation of serum concentrations of pancreatic polypeptide for which we have no explanation. In another patient, the serum gastrin concentration was elevated secondary to achlorhydria. No other endocrine disorders were found, and no patients had relatives with recognized endocrine pancreatic tumours, primary hyperparathyroidism (HPT), or pituitary adenomas.

Adenoma↗
PubMed1990

Increased amino acid clearance and urea synthesis in a patient with glucagonoma.

Fasting concentrations, clearance of exogenous infused amino acids, and lean body mass were studied in a patient with glucagonoma syndrome (fasting glucagon = 380 pmol/l, normal range 15-45 pmol). The fasting concentrations of all amino acids were reduced. The clearances of alanine, arginine, glycine, isoleucine, leucine, lysine, methionine, proline, serine, threonine, and tyrosine were increased. The urea synthesis rate during amino acid infusion was 27 mumols/kg per minute (normal range 20-24 mumols/kg per minute). The lean body mass of the patients was reduced to 59% of the expected value. It is suggested that the weight loss of patients with glucagonoma syndrome is partly due to increased hepatic conversion of amino acid nitrogen to urea nitrogen, resulting in decreased blood amino acid concentration, and secondary to this, organ protein catabolism, as shown by the decreased lean body mass.

Adenoma, Islet Cell↗
PubMed1990

Non-sulphated cholecystokinin in human medullary thyroid carcinomas.

The expression of gastrin/cholecystokinin (CCK) peptides and their precursors was examined in 16 medullary carcinomas of the human thyroid. Measurements with libraries of sequence-specific radioimmunoassays before and after enzymatic cleavage of extracts and chromatographic fractions showed that the carcinomas contained 1.7 pmol carboxyamidated CCK/g tissue (median; range 0.6-21.8 pmol/g), 0.9 pmol glycine-extended precursor/g (median; range less than 0.2-2.3 pmol/g) and 2.3 pmol further COOH-terminal-extended proCCK/g (median; range 0.9-6.2 pmol/g). Neither carboxyamidated gastrins nor any progastrins could be measured. Gel and reverse-phase chromatography revealed only small molecular forms, i.e. greater than 90% of the amidated immunoreactivity eluted like non-sulphated CCK-8 or CCK-7. The results show that human medullary thyroid carcinomas synthesize CCK peptides. The predominance of non-sulphated CCK is unusual. Taken together with earlier observations from dogs and pigs, our results raise the possibility that small non-sulphated CCK peptides modulate thyroid C-cell secretion in an autocrine manner.

Amino Acid Sequence↗