Biomedical subjects

C P Hansen

Publications and source records attributed to C P Hansen.

At least 19 recordsLinked to original sources

PubMed2000

[Perioperative administration of recombinant human erythropoietin in colorectal cancer surgery. A prospective, randomized, double-blind placebo controlled study].

One hundred patients scheduled for elective colo-rectal cancer surgery, and with a preoperative haemoglobin level < or = 8.5 mmol/l were included. Eighty-one patients could be evaluated. Thirty-eight patients received r-HuEPO in a dose of 300 IU/kg body weight on day four before surgery and 150 IU/kg, daily, for the following seven days, and 43 patients received placebo. In addition, all patients received daily doses of 200 mg iron, orally, for four days before surgery. On the day of surgery and until discharge the haemoglobin concentration was significantly higher in the erythropoietin group compared to the placebo group. The number of blood transfusions given was significantly lower in the erythropoietin group with a mean of 0.3 units per patient (0-6) compared to 1.6 units (0-9) in the control group (p < 0.05). The clinical implications of these findings has yet to be assessed.

Adult↗

PubMed2000

The metabolism of gastrin-52 and gastrin-6 in pigs.

The kinetics and metabolism in various organs of three bioactive products of progastrin, the small sulfated and nonsulfated gastrin-6 and the large nonsulfated gastrin-52, were examined during intravenous administration in anesthetized pigs. The kidney, hindlimb, liver, head, and gut eliminated the hexapeptides efficiently, with a fractional extraction ranging from 0.50 to 0.28 (P<0.001-0.05). No metabolism was recorded in the lungs, and sulfation was without influence on the extraction of gastrin-6. Gastrin-52 was eliminated only in the kidney and the head, with a fractional extraction between 0.23 and 0.11 (P<0.01-0.05). The half-life of sulfated and nonsulfated gastrin-6 was 1.5+/-0.4 and 1.4+/-0.3 min, the metabolic clearance rate (MCR) was 80.8+/-7.6 and 116.0+/-13.5 ml x kg(-1) x min(-1) (P<0.05), and the apparent volume of distribution (V(dss)) was 199.3+/-70.1 and 231.4+/-37.3 ml/kg, respectively. The decay of gastrin-52 in plasma was biexponential. The half-lives of this biexponential after a bolus injection were 3.9+/-0.5 (T(1/2alpha)) and 25.7+/-1.4 (T(1/2beta)) min, and the MCR and V(dss) were 4.2+/-0.4 ml. kg(-1) x min(-1) and 116.2+/-16.2 ml/kg(1). We conclude that there is a differential elimination of progastrin products in splanchnic and nonsplanchnic tissue, which depends on the chain length of the peptides. Sulfation of gastrin-6 had no influence on the organ-specific extraction but reduced the MCR. Our results are in keeping with previous studies of nonsulfated gastrin-17, which is extracted in the kidney, head, limb, and gut but not in the liver.

Anesthesia↗

PubMed2000

Computed tomography for staging of oesophageal cancer.

BACKGROUND AND AIMS: Computed tomography (CT) is still widely used in the staging of patients with carcinoma of the oesophagus. The aim of the study was to evaluate the diagnostic accuracy of CT in a series of patients with carcinoma of the oesophagus or the cardia. Results were compared with findings at surgery or autopsy. MATERIAL AND METHODS: 47 consecutive patients of whom 30 underwent operation while 17 patients were not candidates for surgery due to advanced disease. RESULTS: Demonstration of tumour invasion on CT in 30 patients who underwent operation had an accuracy of 63%, a nosographic sensitivity of 10% and a specificity of 90%. Diagnosis of metastases to abdominal lymph nodes had an accuracy of 57%, and a nosographic sensitivity and specificity of respectively 37% and 90%. The assessment of tumour invasion and metastases to lymph nodes in patients not candidates for surgery was expectedly more accurate (100 and 67%, respectively, in nine autopsies). CONCLUSION: CT may provide valuable information in pretherapeutic staging of oesophageal cancer by identifying patients with advanced disease, who are not candidates for surgery. In patients without signs of dissemination on CT additional information may be obtained from endoscopic ultrasonography and laparoscopy.

Adult↗

PubMed1999

Recombinant human erythropoietin and hemoglobin concentration at operation and during the postoperative period: reduced need for blood transfusions in patients undergoing colorectal surgery--prospective double-blind placebo-controlled study.

In a double-blind placebo-controlled study we investigated the effect of recombinant human erythropoietin (r-HuEPO), on the perioperative hemoglobin concentration and the use of blood transfusions in patients undergoing elective colorectal surgery with a preoperative hemoglobin level </=8.5 mmol/L. Altogether 100 were included, and 81 patients could be evaluated. A total of 38 patients received r-HuEPO in a dose of 300 IU/kg body weight on day 4 before surgery and 150 IU/kg daily for the following 7 days; 43 patients received placebo. In addition, all patients received daily doses of 200 mg iron orally for 4 days before surgery. There were no differences between the two groups with regard to sex, height, weight, serum electrolytes, and liver function tests at study entry. The preentry hemoglobin concentration was similar in the two groups, with a median value of 7.9 (range 5.3-8.5) mmol/L in the erythropoietin group and 7.6 (5.1-8.5) mmol/L in the placebo group. On the day of surgery the median hemoglobin concentration was 7.8 (5. 3-9.2) mmol/L in the erythropoietin group and 7.2 (4.6-8.5) mmol/L in the placebo group (p < 0.05). On postoperative days 3 and 7 the values were 7.2 (5.3-8.2) and 7.5 (5.4-9.4) mmol/L, respectively, in the erythropoietin group compared to 6.7 (5.2-7.8) and 6.9 (5.1-8.6) mmol/L in the placebo group (p < 0.01). At discharge the hemoglobin concentration was 7.8 (5.9-8.8) mmol/L in the erythropoietin group and 7.2 (5.4-8.6) mmol/L in the placebo group (p < 0.002). The blood loss during operation was similar in the two groups. In the erythropoietin group the median value was 280 ml (range 25-2000 ml), with the lower and upper quartiles 150 and 500 ml, respectively. In the placebo group the blood loss was median 300 ml (range 50-1800 ml), with the lower and upper quartiles 200 and 750 ml, respectively. The number of blood transfusions given was significantly lower in the erythropoietin group, with a mean of 0.3 (range 0-6) units compared to 1.6 (0-9) units in the control group (p < 0.05). In conclusion, the hemoglobin concentration at the time of surgery and during the week following surgery was significantly higher in the group of patients receiving r-HuEPO perioperatively compared to the placebo group together with a significant lower use of blood transfusions in the r-HuEPO group. However, the clinical implications of these findings has yet to be proven.

Adult↗

PubMed1999

Excretion of progastrin products in human urine.

The renal handling of carboxyamidated gastrins, NH2-terminal progastrin fragments, and glycine-extended gastrins was examined in healthy volunteers. The respective urinary clearances after a meal amounted to 0.09 +/- 0.02%, 0.17 +/- 0.04% (P < 0.05), and 0.04 +/- 0.01% (P < 0.01) of the glomerular filtration rate. During intravenous infusion of carboxyamidated gastrin-17, progastrin fragment-(1-35), and glycine-extended gastrin-17, the respective urinary clearances amounted to 0.08 +/- 0.02, 0.46 +/- 0.08, and 0. 02 +/- 0.01%, respectively, of the glomerular filtration rate. The metabolic clearance rate of the three peptides was 24.4 +/- 1.3, 6.0 +/- 0.4, and 8.6 +/- 0.7 ml. kg-1. min-1. A maximum rate for tubular transport or degradation of the peptides could not be determined, nor was a renal plasma threshold recorded. Plasma concentrations and urinary excretion rates correlated for gastrin-17 and progastrin fragment-(1-35) (r = 0.94 and 0.97, P < 0.001), whereas the excretion of glycine-extended gastrin diminished with increasing plasma concentrations. We conclude that renal excretion of progastrin products is negligible compared with renal metabolism and that renal handling of the peptides depends on their molecular structure. Hence, the kidneys exhibited a higher excretion of NH2-terminal progastrin fragments than of carboxyamidated and especially glycine-extended gastrins.

Biotransformation↗

PubMed1997

Epididymo-orchitis and Reiter's disease. Two infrequent complications after intravesical bacillus Calmette-Guérin therapy.

Two cases of adverse reactions to intravesical treatment with bacillus Calmette-Guérin are reported. The first patient presented with a severe suppurating epididymo-orchitis three months after his last treatment. The second patient developed Reiter's disease with arthritis of one knee and conjunctivitis 1 week after the fourth instillation.

Administration, Intravesical↗

PubMed1996

Pharmacokinetics and organ metabolism of carboxyamidated and glycine-extended gastrins in pigs.

The elimination of carboxyamidated gastrin-17 and its glycine-extended precursor was studied in anesthetized pigs during constant-rate infusion. Extraction of amidated gastrin-17 was recorded in the hindlimb (42%), kidney (40%), head (32%, P < 0.001), and the gut (13%, P < 0.01). Elimination was not recorded in the liver, lungs, or heart. Extraction of glycine-extended gastrin-17 was measured in the kidney (36%), hindlimb (31%, P < 0.001), head (26%), and the gut (16%, P < 0.01), but not in the liver or the lungs. Glycine-extended gastrin-17 was not processed to amidated gastrin during infusion. The half-life, metabolic clearance rate, and apparent volume of distribution for amidated gastrin-17 were 3.5 +/- 0.4 min, 15.5 +/- 1.1 ml.kg-1.min-1, and 76.5 +/- 9.9 ml/kg, respectively, and for glycine-extended gastrin-17 were 4.3 +/- 0.6 min, 17.4 +/- 0.9 ml.kg-1.min-1, and 104.7 +/- 11.9 ml/kg, respectively. We conclude that extraction of amidated and glycine-extended gastrin-17 varies in the vascular beds, with elimination mainly confined to nonorgan tissues and the kidneys.

Animals↗

PubMed1996

Hepatic and intestinal elimination of endogenous gastrin in pigs.

The elimination of endogenous carboxyamidated and glycine-extended gastrins in liver and gut was studied before and after feeding in 14 anesthetized pigs. Before the meal, liver and gut extractions were nonsignificant. After feeding, the release rate of amidated gastrin increased from 7.5 +/- 2.6 to 21.9 +/- 5.3 pmol/min (p < 0.02), and the liver extracted significant amounts of amidated gastrin, while the intestinal extraction remained nonsignificant. The postprandial hepatic extraction ratio increased from 0.09 +/- 0.04 to 0.18 +/- 0.04 (p < 0.01). Before feeding, the hepatic and extrahepatic clearance rates were 80.0 +/- 38.7 and 232.3 +/- 77.7 ml/min. Clearance rates after feeding were 144.8 +/- 29.5 (p < 0.01) and 326.4 +/- 75.3 ml/min (NS), respectively. Portal plasma displayed a small postprandial increase in the concentration of glycine-extended gastrin, but extraction over the liver and gut remained nonsignificant. Gel chromatography of portal plasma showed that the fraction of postprandial amidated gastrin corresponded to gastrin-17. The concentration of glycine-extended gastrin was too low for chromatographic analysis. We conclude that endogenous amidated gastrin is eliminated in the liver after feeding in pigs.

Animals↗

PubMed1995

Post-poly(Glu) cleavage and degradation modified by O-sulfated tyrosine: a novel post-translational processing mechanism.

Expression of bioactive peptides requires several modifications of the primary translation product. Gastrin, a vertebrate gut hormone, occurs in multiple forms, including a bioactive fragment of the predominant gastrin-17. Gastrin-17 is, however, without known cleavage sites. In order to identify the new site, we therefore isolated, from antral mucosa, fragments of gastrin-34 and -17 monitored by monospecific immunoassays. After three steps of reverse-phase chromatography, the short gastrins were identified as hepta-, hexa- and pentapeptide amides. By far the most abundant of these was tyrosine O-sulfated gastrin-6. The near complete sulfation contrasts with the larger gastrins, of which only half are sulfated. The longest N-terminal fragment of gastrin-34 was a hexadecapeptide without complementarity to the short gastrins. Instead, the predominant N-terminal fragment of gastrin-17 was the decapeptide complementary to gastrin-7. Therefore the novel processing site is the Glu10-Ala11 bond that follows a poly(Glu6-10) sequence. Moreover, gastrin-7 is apparently trimmed, with subsequent accumulation of sulfated gastrin-6. Consequently, O-sulfated tyrosine ensures production of a new hormone which stimulates gastric acid secretion as potently as gastrin-17.

Amides↗

PubMed1995

Metabolism and influence of gastrin-52 on gastric acid secretion in humans.

It has been shown recently that the two largest alpha-carboxyamidated progastrin products are gastrin-71 and gastrin-52. Human gastrin-52 has now been synthesized, and the effect on gastric acid secretion and elimination from plasma was examined and compared with gastrin-17 in 12 normal subjects. The peptides were infused separately in four consecutive doses; the maximum response of gastrin-17 and gastrin-52 was 25.2 +/- 2.8 and 22.2 +/- 2.8 mmol H+/50 min, respectively (P < 0.01). This difference in efficacy was presumably related to nonequilibrium of gastrin-52 between plasma and receptor. The elimination of gastrin-17 was monoexponential with a half-life of 4.7 +/- 0.3 min; clearance and apparent volume of distribution were 16.7 +/- 1.5 ml.kg-1.min-1 and 106.0 +/- 9.2 ml/kg, respectively. The elimination of gastrin-52 was biexponential, the half-lives were 4.9 +/- 0.7 and 49.9 +/- 4.2 min, and clearance and apparent volume of distribution were 1.9 +/- 0.2 ml.kg-1.min-1 and 106.3 +/- 10.1 ml/kg, respectively. Gel chromatography of plasma samples drawn during infusion of gastrin-52 revealed that most of the immunoreactivity eluted in the position of the intact peptide. Small peaks in the positions of gastrin-34 and the NH2-terminal pentapeptide fragment of gastrin-52 indicate that a minor part of gastrin-52 is degraded to smaller peptides in vivo. It is concluded that gastrin-52 is bioactive with an efficacy close to or similar to that of gastrin-17. A minor fraction of gastrin-52 undergoes postsecretory cleavage either in plasma or after capillary transit.

Adult↗

PubMed1994

Postoperative electrolyte and mineral balance after restorative proctocolectomy with ileoanal reservoir.

Postoperative electrolyte and mineral balance was studied in nine patients with ulcerative colitis who underwent restorative proctocolectomy with ileoanal reservoir (J-pouch). The study was carried out during the first seven days of bowel function after construction of the reservoir and temporary ileostomy, and again after the ileostomy was closed and bowel continuity re-established. Stool volume and intestinal sodium excretion were reduced by respectively 40 and 45% after ileostomy was closed (p < 0.05), but potassium excretion was unchanged. The concentration of sodium was higher in ileostomy effluents, whereas the concentration of potassium was higher in stools after the ileostomy was closed (p < 0.05). Significant changes in blood and urinary electrolytes or minerals were not recorded. It is concluded that a major reduction in stool volume and intestinal excretion of sodium is already present in the early postoperative period after bowel continuity has been re-established.

Adult↗

PubMed1994

Leiomyosarcomas of the gastrointestinal tract.

Nine men and four women (median 69 years, range 38-86 years) with gastrointestinal leiomyosarcomas were treated from 1981 to 1991. Tumours arose from the stomach (5), the small intestine (6) and the rectum (2). Nearly half of all patients were surgical emergencies: one patient had perforation of the stomach and two of the small intestine from tumour ulceration, three cases presented with life-threatening bleeding from leiomyosarcomas of the small intestine. All patients were operated on, but only seven for cure. At follow-up one patient had emigrated and four had died, two from leiomyosarcoma after 13 and 36 months and two from unrelated causes after seven and 48 months. Two patients are still alive 24 and 78 months after surgery without recurrence. Patients and amenable to a curative operation died within nine months.

Adult↗

PubMed1993

Small and intermediate conductance chloride channels in HT29 cells.

Recently, it has been shown that intermediate conductance outwardly rectifying chloride channels (ICOR) are blocked by cytosolic inhibitor (C. I.) found in the cytosol of human placenta and epithelial cells. C. I. also reduced the baseline current in excised membrane patches of HT29 cells. In the present study, this effect of C. I. was characterized further. Heat treated human placental cytosol was extracted in organic solvents and dissolved in different electrolyte solutions. It is shown that the reduction of baseline conductance (g(o)) is caused by inhibition of small non-resolvable channels, which are impermeable to Na+ and SO4(2-), but permeable to Cl-. The regulation of these small Cl(-)-conducting channels (g(o)) and of ICOR was examined further. First, no activating effects of protein kinase A (PKA) on the open probability (Po) of the ICOR or on the g(o)) were observed. The Po of the ICOR was reduced by 22% in a Ca(2+)-free solution. g(o) was insensitive to changes in the Ca2+ activity. The effects of C. I. from a cystic fibrosis (CF) placenta and the CF pancreatic duct cell line CFPAC-1 were compared with the effects of corresponding control cytosols, and no significant differences between CF and control cytosols were found. We conclude that the excised patches of HT29 cells contain ICOR and small non-resolvable Cl(-)-conducting channels which are similarly inhibited by C. I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1992

Anorectal abscesses in immunosuppressed patients.

The results of surgery in 14 immunosuppressed patients with 17 anorectal abscesses are presented. Abscess incision was followed by almost immediate relief of pain. Healing was obtained in 15 cases, but two patients died of causes unrelated to surgery. Symptoms, therapeutic possibilities and prognosis are discussed. The authors conclude that surgery should be performed in all cases to prevent development of septicemia. Fluctuation should not be awaited, but surgery should be minimized if granulocyte and platelet counts are low. Each patient must be managed individually, according to the nature of malignant disease, general state of health and degree of immunosuppression. Antibiotic cover is important, and primary closure of the abscess cavity should never be attempted.

Abscess↗

PubMed1992

Thromboembolectomy in geriatric patients from long-stay wards.

The results of arterial embolectomy with the Fogarty balloon catheter in patients over 70 years of age with acute ischaemia of the lower limbs were evaluated. Twenty-three geriatric patients from long-stay wards, median age 81 years, range 70-92, were compared with 45 independent patients, median age 81 years, range 70-91, living in their own homes. The period of ischaemic symptoms before admission was on average shorter for patients coming from long-stay wards, but the outcome was less successful. Recurrent occlusion during the first postoperative month took place in 12 patients (52%) from long-stay wards as compared to eight (18%) among independent patients (p < 0.01). The mortality was 35% and 18% respectively (p > 0.2). After six months, only 35% of patients from geriatric institutions were alive with a functional extremity as compared to 62% in the independent group (p > 0.01).

Aged↗

PubMed1992

Pulmonary hamartoma.

Eighty-nine cases of pulmonary hamartoma were studied. There were 51 men and 38 women, with a mean age of 57.5 years (range 14 to 76 years). A histologic diagnosis from examination of the resection specimens was obtained in all patients who had operations. Moreover, transthoracic needle aspiration biopsies were performed in 40 patients, with a diagnostic result in 34 (85%). The hamartomas were equally distributed in the pulmonary lobes; mean transverse diameter at the time of diagnosis was 21.7 +/- 16.2 mm. Tumor size was independent of the anatomic localization, but it correlated with the age of the patients (p less than 0.01). Tumor growth was recorded in 15 of 31 patients who had follow-up (45%); mean expansion in transverse diameter was 3.2 +/- 2.6 mm per year during an average observation time of 4.1 years (range 1 to 20 years). Pulmonary symptoms were present in 35 patients (39%). Seventy-five patients underwent operations as follows: enucleation (54), resection (11), lobectomy (5), pneumonectomy (4), and bronchoscopic removal (1). Since most pulmonary hamartomas are nonexpanding or slowly growing neoplasms, it is concluded that operation is necessary only when expansion is recorded in young or middle-aged patients and in patients with pulmonary symptoms.

Adolescent↗

PubMed1991

Inhibition of epithelial chloride channels by cytosol.

Chloride channels that have an intermediate conductance and are outwardly rectifying were studied by the patch-clamp technique in cell-excised membrane patches from respiratory epithelial cells in primary culture (REC) of normal and cystic fibrosis tissue, HT29 and T84 human colon carcinoma cells and placenta trophoblast cells (PTC). Chloride channels were immediately activated by the exposure of the cytosolic side of the patch to a Ringer-type solution, which lacked cytosolic components normally inhibiting chloride channels in the "on" cell configuration. Tentatively, we labelled the cytosolic component (or components) responsible for this inhibition cytosolic inhibitor (CI). The presence of CI in cytosol derived from HT29 cells was shown by assaying crude cytosol extracts from these cells on Cl- channels from HT29 cells (n = 2) and REC from normal subjects and cystic fibrosis patients (n = 4). In order to examine CI further, PTC were used as a source of cytosol. The cytosol of PTC inhibited HT29 Cl- channels in a dose-dependent manner with a half-maximal inhibition observed at a 1:6 dilution (n = 11) of the native cytosol. CI from PTC was heat-stable (10 min at 100 degrees C, n = 8). When cytosol extract was partitioned into a chloroform phase, Cl- channel inhibition was shown for the lipophilic extract (n = 12) as well as for the aqueous phase (n = 10). The inhibitory potency of the lipid extract was slightly larger than that of the aqueous phase. Several separation procedures were used to determine the molecular size of CI. When CI was filtered through 30-kDa filters at 6000 rpm for 45 min, inhibitory potency was observed in the filtrate and the retained fraction (n = 3). The same was observed with 10-kDa filters (n = 6). When CI was dialysed through a 12-kDa membrane, inhibitory capacity was recovered from the dialysate. Similarly, gel filtration indicated that CI was less than 5 kDa (n = 13) and probably less than 1.5 kDa (n = 11), but greater than 700 kDa (n = 9). CI was exposed to bead-coupled hydrolysing enzymes (trypsin, non-specific protease, lipase, alpha-amylase, nucleotidase), but none of the enzymes used destroyed the inhibitory potency of CI. These data indicate that CI is present in HT29 as well as in PTC. It inhibits reversibly intermediate-conductance outwardly rectifying Cl- channels in REC, HT29, and PTC.(ABSTRACT TRUNCATED AT 400 WORDS)

Chloride Channels↗

PubMed1991

Pharmacokinetics of 5-aminosalicylic acid in man following administration of intravenous bolus and per os slow-release formulation.

The fate of 5-aminosalicylic acid (5-ASA), which is used in the treatment of chronic inflammatory bowel diseases, was studied in six healthy volunteers receiving doses of 100 mg and 250 mg intravenous bolus as well as 250 mg per os (slow release). Following intravenous administration, the drug was rapidly eliminated with a plasma half-life of about 40 min, mainly due to rapid metabolism. No parent drug was recovered in feces, and the total recovery following oral administration (30%) was significantly lower than following the intravenous doses (77% and 72%). Nonlinear pharmacokinetics were suggested as the 2.5-fold increase in intravenous dose was followed by a significant relative increase (greater than 2.5) in the renal elimination of 5-ASA, as well as a significant decrease (less than 2.5) in the elimination of the metabolite N-acetyl-5-ASA. There was also a trend towards a decreasing total body clearance and metabolic ratio. The present study confirms earlier findings on the pharmacokinetics of 5-ASA and suggests a possible saturation of the N-acetylating system in the dose range studied. This may be of interest in the design of controlled-release formulations and dosage regimes for the treatment of diseases of the small-bowel, where 5-ASA is easily absorbed. Further, for the first time, a marked difference in the intestinal fate compared to the systemic fate of the drug is demonstrated, suggesting alternative presystemic metabolism of 5-ASA, which may bear relevance to its mode of action. Further studies on the pharmacokinetics of 5-ASA, preferably in patients, are warranted.

Administration, Oral↗