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Biomedical subjects

J Myhre

Publications and source records attributed to J Myhre.

14 recordsLinked to original sources
PubMed1998

BEAM+autologous stem cell transplantation in malignant lymphoma: 100 consecutive transplants in a single centre. Efficacy, toxicity and engraftment in relation to stem-cell source and previous treatment.

One hundred consecutive patients with malignant lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation, followed at least 1 yr post-transplant, are reported, 68 with non-Hodgkin's lymphoma and 32 with Hodgkin's disease. At transplant, 23 patients were in first remission, 69 in later chemosensitive disease and 8 were chemotherapy resistant. Based on previous treatment and stem-cell source, the patients were subdivided into 3 cohorts: BMT1: bone-marrow harvest and transplant after > or =3 treatment regimens (38 patients); BMT2: bone marrow harvest and transplant after less than 3 treatment regimens (24 patients); PBSCT: peripheral-blood stem cell transplant (38 patients, 5 of these with CD34+ cell selected PBSC). The 4-yr survival and progression-free survival of all patients was 45 and 40%, respectively. Forty-one patients have died, 27 of lymphoma, evenly distributed in the cohorts. Fourteen treatment-related deaths occurred, 13 of these in the BMT1 cohort, significantly more than in the other cohorts (p=0.001). In univariate survival analysis cohort, age, disease status at transplant and number of previous treatment regimens were significant. In multivariate survival analysis cohort, age and sex were independently significant, women having a shorter survival. The patients transplanted with unselected PBSC had significantly shorter duration of pancytopenia and hospital stay than the otherwise comparable BMT2 patients, but their progression-free survival was identical. We confirm that high-dose therapy with autologous stem cell transplant from blood or bone marrow in not-too-heavily pretreated patients is a safe procedure but will cure only half the patients.

Adult↗
PubMed1997

High risk of therapy-related leukemia after BEAM chemotherapy and autologous stem cell transplantation for previously treated lymphomas is mainly related to primary chemotherapy and not to the BEAM-transplantation procedure.

A cohort of 76 patients with previous chemotherapy for Hodgkin's disease and non-Hodgkin lymphomas received high-dose carmustine, etoposide, cytosine-arabinoside and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) and was followed for relapse and development of leukemic complications. Six patients, four with Hodgkin's disease and two with non-Hodgkin lymphomas, developed leukemic complications, myelodysplasia (MDS) in four cases and overt acute myeloid leukemia (AML) in two. All six showed an abnormal karyotype, in four of them highly characteristic of therapy-related MDS (t-MDS) and therapy-related AML (t-AML). The cumulative risk of t-MDS and t-AML increased from 16 months after start of the primary chemotherapy for lymphoma and reached 17.3% (s.e. 8.5%) after 74 months. If calculated from start of BEAM and ASCT, the cumulative risk increased as early as 4 months and reached 24.3% (s.e. 12.9%) after 43 months. For the whole course of the disease, the relative risk (RR) of AML was 357 (95% CI: 43-1290), as two overt leukemias were observed vs 0.0056 expected cases of de novo AML. In the present cohort the risk of t-MDS and t-AML although high, did not differ from our previous experience in patients treated conventionally for Hodgkin's disease and non-Hodgkin lymphomas, and did not differ for patients receiving stem cells isolated from the bone marrow as compared to patients receiving stem cells isolated from peripheral blood. Antecedent chemotherapy seems to be the critical factor for the development of t-MDS and t-AML rather than the BEAM and ASCT regimen, which however may accelerate the evolution of the disease.

Acute Disease↗
PubMed1993

Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man.

We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78-107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110 +/- 14 pmol/liter (mean +/- SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43 +/- 11% in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16 +/- 2 min to 30 +/- 5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47 +/- 17% and 40 +/- 9% during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 +/- 0.2 versus 3.7 +/- 0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.

Adult↗
PubMed1992

The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans.

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.

Adult↗
PubMed1991

[Pulmonary sarcoidosis or intrathoracic malignant lymphoma--the significance of a histological diagnosis].

The clinical appearance of sarcoidosis and the changes seen on x-ray of the thorax are often typical. However, several other conditions may present the same symptoms and identical x-ray findings. The present case report emphasizes the importance of an invasive approach and of histological investigation in patients in whom carcoidosis is suspected. For almost one year, a man aged 29 years was considered to be suffering from sarcoidosis on account of the clinical symptoms and bilateral hilar adenitis on x-ray op the thorax. He was treated with steroid for several months with clinical and radiological response. After the illness has lasted for one year, bronchoscopy was performed and bronchial biopsies revealed the diagnosis of malignant lymphoma.

Adult↗
PubMed1990

The relationship between some beta-adrenergic mediated responses and plasma concentrations of adrenaline and cyclic AMP in man.

To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the agonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed in 8 healthy subjects with and without concomitant beta-adrenoceptor blockade by iv propranolol. A significant correlation was found between increments in plasma adrenaline and plasma cyclic AMP in the experiments without beta-blockade; during concomitant beta-blockade the increase in plasma cyclic AMP concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and beta hydroxybutyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man.

Adrenergic beta-Antagonists↗
PubMed1989

Oxyntomodulin from distal gut. Role in regulation of gastric and pancreatic functions.

We studied the effects of intravenous infusion of synthetic oxyntomodulin (proglucagon 33-69), a potential hormone from the ileal mucosa, on fasting and postprandial gastric acid secretion, gastric emptying, gastroduodenal motility, and pancreatic secretion of trypsin and lipase measured simultaneously in six normal volunteers using multilumen tubes for infusion of markers, manometry, and aspiration of gastric and duodenal contents. The infusion resulted in plasma concentrations of 203 +/- 21 pmol/liter (mean +/- SEM) of oxyntomodulin, regarded as high but not unphysiological concentrations of the peptide. Oxyntomodulin almost abolished basal acid secretion and inhibited postprandial acid secretion by 35 +/- 10%. Gastric emptying decreased significantly; the time for 50% to leave the stomach increased from 17.3 +/- 2.2 min to 34.7 +/- 8.0 min. The postprandial gastroduodenal motility was massively inhibited by oxyntomodulin. Postprandial trypsin and lipase output was significantly inhibited by 56 +/- 12% and 42 +/- 11%, respectively, during oxyntomodulin infusion. However, pancreatic enzyme output was linearly related to gastric emptying and oxyntomodulin did not influence this relationship, suggesting that oxyntomodulins effect was due to its effect on gastric emptying. Oxyntomodulin seems to play an important role in the small intestinal inhibitory control of gastropancreatic functions.

Adult↗
PubMed1989

Monitoring of celiac plexus block in chronic pancreatitis.

Pharmacological, percutaneous celiac plexus blockade is often inefficient in the treatment of pain in chronic pancreatitis. Lack of efficiency could be due to incomplete denervation of the plexus; however, a method for measuring the completeness of celiac plexus blockade is not yet available. We have, therefore, monitored the physiological completeness of pharmacological percutaneous celiac blockade with 40 ml 25% ethanol by measuring the effect of posture on heart rate, blood pressure, hepato-splanchnic vascular resistance, and pancreatic hormone concentrations before and after celiac plexus block in 6 patients with chronic pancreatitis. Blood pressure decreased and heart rate increased after the block (P less than 0.025), whereas no significant change was found in hepato-splanchnic vascular resistance nor in the change of these parameters during transition from the supine to standing position. Pancreatic hormones (C-peptide, free insulin, glucagon, pancreatic polypeptide and somatostatin) did not change in response to standing, either before or after the block. The cardiovascular variables were normalized the day after the block, and all the patients were in their habitual state regarding pain after 1 week. In conclusion, pancreatic hormone concentrations in response to standing are not useful for monitoring celiac plexus block, whereas heart rate, blood pressure and hepato-splanchnic blood flow may yield useful information. From such measurements it was concluded that permanent denervation of the celiac plexus was not achieved in our patients after injection of 40 ml 25% ethanol.

Blood Pressure↗
PubMedDate not supplied

Estimation of serum concentration of parvovirus B19 DNA by PCR in patients with chronic anaemia.

Parvovirus B19 DNA was detected in serum samples from 10 out of 42 patients with chronic anaemia, the majority of whom suffered from aplastic anaemia, haemolytic anaemia, pure red cell anaemia or myelodysplastic syndrome. Nested PCR methods with sensitivities of 0.005-0.05 fg DNA were developed. In nine patients, B19 DNA could only be detected by nested PCR. Conventional PCR with a sensitivity of 50 fg B19 DNA could only detect B19 DNA in one patient. In the majority of B19-DNA-positive patients, the DNA concentration was estimated at 0.005-0.05 fg per 5 microliters serum.

Adolescent↗
PubMedDate not supplied

Parvovirus B19 infections in patients with chronic anemia.

BACKGROUND AND OBJECTIVE: Parvovirus B19 has a marked tropism for erythroid progenitor cells and this may lead to chronic anemia in predisposed individuals. It was the purpose of the present study to investigate prospectively the frequency of parvovirus B19 infections in patients with a diagnosis of chronic anemia. METHODS AND RESULTS: Evidence of parvovirus B19 infection was found in 13/43 (30%) patients by demonstrating viral DNA and/or specific IgM antibodies through the use of PCR and ELISA techniques. Parvovirus B19 infection was established in 4 of 7 patients with hemolytic anemia, in 2 of 3 patients with pure red cell aplasia, in 2 of 9 patients with myelodysplastic syndrome, and in 2 of 10 patients with aplastic anemia. In 8 of the 13 positive patients only parvovirus B19 DNA could be detected, while 4 patients tested positive for both parvovirus B19 DNA and specific IgM. In the remaining positive patient only specific IgM could be detected. CONCLUSIONS: Since no predictive paraclinical or clinical features were observed we recommend that all cases of chronic anemia be tested for the presence of parvovirus B19 infection. Due to the discrepancies between DNA and IgM results, the diagnostic procedures should include a search for specific DNA by PCR methods if specific IgM has been found to be negative.

Adult↗