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Biomedical subjects

B Nyberg

Publications and source records attributed to B Nyberg.

At least 19 recordsLinked to original sources

Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic cholesterol metabolism.

BACKGROUND: Treatment with ursodeoxycholic acid and also, to some degree, statins reduces cholesterol saturation of bile. The present study aimed [1] to study the effects of combined treatment with ursodeoxycholic acid and pravastatin on hepatic cholesterol metabolism and [2] to evaluate if the addition of pravastatin to ursodeoxycholic acid treatment has beneficial effects on the lipid composition of gallbladder bile in gallstone patients. MATERIALS AND METHODS: Nineteen patients with cholesterol gallstones were subjected to combined treatment with ursodeoxycholic acid (500 mg bid) and pravastatin (20 mg bid) for three weeks before cholecystectomy. Eleven patients received ursodeoxycholic acid only and 20 untreated gallstone patients served as controls. Gallbladder bile was collected, and for both the patients receiving combined treatment and the controls a liver biopsy was also obtained peroperatively. RESULTS: The cholesterol saturation of bile averaged 59% in the patients on combined treatment, 60% in the ursodeoxycholic acid-treated patients, and 130% in the untreated controls. In the patients receiving ursodeoxycholic acid, this bile salt constituted approximately 60% of all bile salts. The patients receiving combined treatment had reduced cholesterol synthesis, as reflected by a 45% reduction in serum lathosterol. The activity and the mRNA levels of cholesterol 7 alpha-hydroxylase and the mRNA levels for the low density lipoprotein-receptor were not significantly affected. CONCLUSIONS: Pravastatin does not further reduce the cholesterol saturation of bile in gallstone patients treated with ursodeoxycholic acid, although hepatic cholesterol synthesis is inhibited. The study supports the important concept that de novo synthesized cholesterol is not particularly important for biliary cholesterol secretion in humans.

Adult↗

Outpatient laparoscopic cholecystectomy. A prospective study with 100 consecutive patients.

One hundred patients with cholelithiasis were included in a prospective consecutive follow-up study to evaluate laparoscopic cholecystectomy in a day surgical setting. The median operating time was 70 min. In 96% of the patients, it was possible to perform peroperative cholangiography. The median time off work was 7 days and the median time to full recovery was 14 days. Five patients were admitted due to weakness/nausea. Six patients were admitted due to conversion to open surgery or choledocholithiasis. Eighty-nine patients were treated in ambulatory surgery. We conclude that laparoscopic outpatient cholecystectomy can be performed safely with a low unplanned admission rate.

Journal Article↗

Reducing blood exposures during orthopedic surgical procedures.

Surgical team members constantly are exposed to blood during procedures. Inadvertent injuries (e.g., needle sticks, cuts) and contaminations expose team members and patients to the risk of transmission of bloodborne pathogens. Injuries and contaminations can be decreased significantly for scrub people and first assistants, however, by introducing new working methods (i.e., no-touch instrument passing technique, instrument neutral zone).

Blood-Borne Pathogens↗

Introduction of herniorraphy with mesh plug and patch.

OBJECTIVE: To evaluate the introduction of the Perfix mesh plug and patch system for inguinal hernia repair. DESIGN: Prospective consecutive follow-up study. SETTING: Teaching hospital, Sweden. SUBJECTS: 139 patients with 145 hernias who were operated on for inguinal hernia with the Perfix mesh plug and patch technique during 1997. MAIN OUTCOME MEASURES: Operating time, sick leave, time to full recovery, morbidity, recurrence rate. RESULTS: The median operating time was 35 minutes (range 15-105) and the mean follow-up was 9 months (range 4-13). Office workers required a mean of 7 days off work (range 0-43) and manual workers 15 days (range 0-90). Retired patients took 21 days (0-30) to recover fully, office workers 22 days (7-70), manual workers 30 days (7-90), students 34 days (0-60) and unemployed patients 60 days (21-150). There were 17 minor complications within 30 days and 2 recurrences during the follow up period. CONCLUSION: Herniorraphy with a mesh plug and patch can easily be introduced with good short-term results.

Adolescent↗

Pool exercise combined with an education program for patients with fibromyalgia syndrome. A prospective, randomized study.

OBJECTIVE: To evaluate the effects of 6 months of pool exercise combined with a 6 session education program for patients with fibromyalgia syndrome (FM). METHODS: The study population comprised 58 patients, randomized to a treatment or a control group. Patients were instructed to match the pool exercises to their threshold of pain and fatigue. The education focused on strategies for coping with symptoms and encouragement of physical activity. The primary outcome measurements were the total score of the Fibromyalgia Impact Questionnaire (FIQ) and the 6 min walk test, recorded at study start and after 6 mo. Several other tests and instruments assessing functional limitations, severity of symptoms, disabilities, and quality of life were also applied. RESULTS: Significant differences between the treatment group and the control group were found for the FIQ total score (p = 0.017) and the 6 min walk test (p < 0.0001). Significant differences were also found for physical function, grip strength, pain severity, social functioning, psychological distress, and quality of life. CONCLUSION: The results suggest that a 6 month program of exercises in a temperate pool combined with education will improve the consequences of FM.

Adult↗

Deoxycholic acid treatment in patients with cholesterol gallstones: failure to detect a suppression of cholesterol 7alpha-hydroxylase activity.

UNLABELLED: Hillebrant C-G, Nyberg B, Angelin B, Axelson M, Björkhem I, Rudling M, Einarsson C (Huddinge University Hospital and Karolinska Hospital, Karolinska Institute, Stockholm, Sweden). Deoxycholic acid treatment in patients with cholesterol gallstones: failure to detect a suppression of cholesterol 7alpha-hydroxylase activity. J Intern Med 1999; 246: 399-407. OBJECTIVES: Based on animal studies, hydrophobic bile acids have been postulated to be particularly strong inhibitors of bile acid synthesis. The present study was undertaken to characterize in humans the effects of one of the most hydrophobic of the common bile acids, deoxycholic acid (DCA), on the transcriptional regulation and activity of the cholesterol 7alpha-hydroxylase, on hepatic cholesterol metabolism and on biliary lipid metabolism and plasma lipids. DESIGN, SUBJECTS AND SETTINGS: Thirteen patients with cholesterol gallstone disease were treated with DCA (750 mg day-1) for 3 weeks prior to cholecystectomy. Blood samples were collected before and during treatment. At operation, a liver biopsy and gallbladder bile were obtained. Twenty-eight untreated gallstone patients undergoing cholecystectomy served as controls. The study was carried out at a university hospital. RESULTS: Deoxycholic acid comprised 72 +/- 6% (mean +/- SEM) of total biliary bile acids in DCA-treated patients (n = 8), and 21 +/- 2% in the controls (n = 16; P < 0.001). Cholesterol saturation of gallbladder bile averaged 102% in both treated (n = 7) and untreated (n = 16) patients. Cholesterol 7alpha-hydroxylase and HMG CoA reductase activities and mRNA levels were not different between DCA-treated and untreated gallstone patients. The LDL receptor mRNA levels were similar in both groups of patients. Plasma levels of total cholesterol were lowered by 10% upon DCA treatment (P < 0.05). CONCLUSIONS: Treatment with DCA did not significantly affect mRNA levels and activity of hepatic cholesterol 7alpha-hydroxylase or HMG CoA reductase in patients with cholesterol gallstones. There was no effect on the saturation of gallbladder bile, Thus, the present study could not verify that the hydrophobicity of the bile acid pool is a major factor regulating human hepatic cholesterol 7alpha-hydroxylase activity.

Adult↗

Depression of liver protein synthesis during surgery is prevented by growth hormone.

This study was undertaken to elucidate the specific effects of growth hormone (GH) on liver protein metabolism in humans during surgery. Otherwise healthy patients scheduled for elective laparoscopic cholecystectomy were randomized into controls (n = 9) or pretreatment with 12 units of GH for 1 day (GH 1, n = 9) or daily for 5 days (GH 5, n = 10). The fractional synthesis rate of liver proteins, as assessed by flooding with [2H5]phenylalanine, was higher in the GH 5 group (22.0 +/- 6.9%/day, mean +/- SD, P < 0.05) than in the control (16.1 +/- 3.1%/day) and GH 1 (16.5 +/- 5.5%/day) groups. During surgery, the fraction of polyribosomes in the liver, as assessed by ribosome analysis, decreased in the control group by approximately 12% (P < 0.01) but did not decrease in the GH-treated groups. In addition, the concentrations of the essential amino acids and aspartate in the liver decreased in response to GH treatment. In conclusion, GH pretreatment decreases hepatic free amino acid concentrations and preserves liver protein synthesis during surgery.

Adult↗

Inhibition of liver protein synthesis during laparoscopic surgery.

Previous studies have indicated that laparoscopic surgery is associated with a decline in liver protein synthesis. In this study, the fractional synthesis rate (FSR) of total liver protein and albumin was measured in patients undergoing elective laparoscopic cholecystectomy at different times after commencing the procedure (n = 8 + 8). Liver biopsy specimens were taken after 15 min of surgery in an "early" group and after 49 min of surgery in a "late" group. The liver FSR was higher in the early group (24.1 +/- 4.7%/day) compared with the late group (19.0 +/- 2.8%/day, P < 0.02). The fractional and absolute synthesis rates of albumin were similar in the two groups, 6.4 +/- 1.5 vs. 6.5 +/- 1.0%/day and 97 +/- 19 vs. 96 +/- 18 mg. kg(-1). day(-1) for the early and late groups, respectively. It is concluded that laparoscopic surgery was accompanied by a decrease in total liver protein synthesis rate, which developed rapidly during surgery. In contrast, no change in the synthesis rate of albumin was apparent during the course of surgery.

Adult↗

Acute and short-term effects of growth hormone on insulin-like growth factors and their binding proteins: serum levels and hepatic messenger ribonucleic acid responses in humans.

We investigated the acute (4-5 h) and short-term (5 days) effects of GH treatment on hepatic messenger RNA (mRNA) levels of the genes for the insulin-like growth factors (IGFs), insulin-like growth factor binding protein-1, -2, and -3 (IGFBPs), and the acid labile subunit (ALS), as well as serum levels of these proteins in humans. At the mRNA level, we observed an increase in IGF-1 transcription (+173%) following GH treatment in the acute group, which remained elevated in the short-term treatment group. IGFBP-2 mRNA decreased after short-term GH treatment, without changes in IGFBP-1 or -3 expression. The ALS transcript level increased after 5 days. In serum, we found increased levels of IGF-I and insulin, and decreased levels of IGF-II, in the short-term treatment group. IGFBP-1 decreased in both treatment groups, whereas IGFBP-2 was reduced after 5 days treatment. ALS increased in the short-term group. We observed increased IGFBP-3 serum levels after 5 days of GH treatment, likely due to increased formation of the ternary complex. Our results show that the metabolic effects by GH on the IGF axis are complex. In addition to a direct stimulation of IGF-I and ALS expression, GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner, possibly facilitating enhanced IGF bioavailability to target tissues.

Adult↗

Reduced gene expression of UCP2 but not UCP3 in skeletal muscle of human obese subjects.

Massive overweight is an increasing health problem and underlies several complications which in turn result in premature death. The mechanisms underlying the imbalance between energy intake and energy expenditure, that lead to obesity in humans, are still only partly understood. In rodents, heat generation and the burning of calories by the mitochondrial uncoupling protein 1 (UCP1) are important for metabolic control. However, UCP1 is exclusively expressed in brown fat which is only present in limited amounts in human adults. The recent characterization of two new uncoupling proteins, UCP2 and UCP3, may elucidate potentially important pathways for energy expenditure regulation in man. The aim of this study was to investigate whether obesity is accompanied by aberrations in UCP2 and UCP3 regulation. Expression of these two genes was examined using in situ hybridization in six lean and six obese, but otherwise healthy, men. The UCP2 expression was decreased by 28 % (p = 0.001) in the abdominal muscle of the obese subjects. No differences in UCP3 expression were observed between obese and control subjects, although there was great variation in the expression between subjects. In conclusion, these data suggest an impaired activity of the mitochondrial uncoupling protein UCP2, but probably not UCP3, in obese subjects. This may result in decreased energy expenditure and contribute to the development and maintenance of obesity.

Adult↗

Effects of short-term treatment with pravastatin on the hepatic synthesis of cholesterol and bile acids in gallstone patients.

BACKGROUND: HMG-CoA reductase inhibitors are now the therapy of choice in the treatment of hypercholesterolaemia. The effects of long-term treatment with these substances on plasma lipoproteins, cholesterol metabolism and biliary secretion of lipids have been extensively studied in humans. Much less is known about the effects of short-term treatment. The aim of this study was to determine the time course of the effects of HMG-CoA reductase inhibitors on plasma lipoprotein levels as well as cholesterol and bile acid synthesis in gallstone patients. METHODS: Thirty-six patients undergoing elective cholecystectomy were included in the study. Except for the gallstone disease, these patients were otherwise healthy. Four groups of subjects were treated with the HMG-CoA reductase inhibitor pravastatin (Pravachol), 20 mg twice daily for 12, 24, 48 and 72 h preoperatively. Plasma lipoproteins and plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one were determined before initiation of pravastatin treatment and on the morning of the day of the operation, lathosterol reflecting hepatic HMG-CoA reductase activity and 7 alpha-hydroxy-4-cholesten-3-one the activity of cholesterol 7 alpha-hydroxylase, the rate-determining enzyme in bile acid synthesis. RESULTS: All treatment groups displayed a significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol, by about 12% and 17% respectively. Lathosterol was reduced by about 50% in all treatment groups. Of great interest was the finding that 7 alpha-hydroxy-4-cholesten-3-one was unaffected in all treatment groups. CONCLUSION: The results show that short-term pravastatin treatment in gallstone patients rapidly inhibits cholesterol synthesis and lowers plasma LDL-cholesterol levels without effects on bile acid synthesis.

Adult↗

The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in humans.

Although the metabolism of liver-derived plasma proteins such as albumin has been extensively studied, human hepatic protein synthesis as a whole has not been well characterized, because a reproducible model for obtaining human liver tissue has not been available. In this study, the fractional synthesis rates of total liver protein and albumin in vivo were determined simultaneously in nine subjects undergoing elective laparoscopic cholecystectomy. L-[2H5]phenylalanine (45 mg/kg body wt) was administered for 10 minutes intravenously. Blood samples were collected at regular intervals for 90 minutes and a liver biopsy specimen was taken at 35 +/- 7 minutes. The enrichments of plasma free phenylalanine, plasma albumin, and total liver protein were measured with gas chromatography mass spectrometry (GC-MS). The fractional synthesis rate (FSR) of total liver protein was 24.7 +/- 3.1 %/d (mean +/- SD), and that of albumin was 5.9 +/-1.2%/d. The amount of albumin synthesized per day (absolute synthesis rate, ASR) was 109 +/- 21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of albumin was found. It is concluded that the technique of obtaining liver tissue specimens during laparoscopic surgery may serve as a human in vivo model to study total liver protein synthesis. The fractional synthesis rate of total liver proteins (stationary and exported), equals approximately 25% of the liver protein content daily. Within the range of values of this study, the absolute synthesis rate of albumin was not correlated to the fractional synthesis rate of total liver protein.

Adult↗

The effect of plasma low density lipoprotein apheresis on the hepatic secretion of biliary lipids in humans.

BACKGROUND: The liver is a key organ in the metabolism of cholesterol in humans. It is the only organ by which substantial amounts of cholesterol are excreted from the body, either directly as free cholesterol into the bile or after conversion to bile acids. The major part of cholesterol synthesis in the body occurs in the liver. Cholesterol is also taken up by the liver from plasma lipoproteins. The relative contributions of newly synthesised cholesterol and plasma lipoprotein cholesterol to bile acid synthesis and biliary cholesterol secretion, respectively, are not known in detail. AIMS: To determine how a rapid lowering of plasma low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol influences the biliary secretion rates of cholesterol and bile acids in patients with cholesterol gallstones and complete biliary drainage. In this model with a completely interrupted enterohepatic circulation, the secretion of bile acids equals the new synthesis of bile acids in the liver. PATIENTS: Eight patients with common bile duct stones of cholesterol type undergoing conventional cholecystectomy and choledocholithotomy. METHODS: At operation a balloon occludable Foley catheter attached to a T tube was inserted into the bile duct with the balloon placed just past the distal limb of the T tube. The T tube was allowed to drain the bile externally. One week after the operation the Foley catheter balloon was inflated, creating complete biliary drainage. Twelve hours following the inflation plasma LDL apheresis was carried out for two hours. Bile was collected for 15 minute periods starting one hour before the apheresis and ending two hours after its termination. During the collection of bile, plasma lipids were analysed on several occasions. RESULTS: The plasma level of LDL cholesterol decreased by 26% from (mean (SEM)) 2.19 (0.29) to 1.63 (0.17) mmol/l during the LDL apheresis while high density lipoprotein (HDL) cholesterol in plasma was unaffected. During LDL apheresis apolipoprotein B containing lipoproteins bind to the column, causing a significant decrease of not only plasma LDL but also of VLDL cholesterol. The secretion rate of bile acids decreased significantly by 31% from 131 (38) to 90 (16) mumol/15 minutes (p = 0.045). The output of phospholipids also decreased by 19%. The biliary secretion rate of cholesterol was not, however, affected by the plasma LDL apheresis. CONCLUSIONS: The results suggest that, in patients with cholesterol gallstones and complete biliary drainage, lowering of plasma LDL and VLDL cholesterol reduces the biliary secretion rate--synthesis--of bile acids without affecting the biliary secretion rate of cholesterol.

Adult↗

Reconstruction of the resorbed edentulous maxilla using autogenous rib grafts and osseointegrated implants.

14 patients with severely resorbed edentulous maxillae underwent reconstruction by the use of autogenous rib graft on-lays and osseointegrated Brånemark System implants in a one-stage procedure. 75 implants were installed. 16 (21.3%) failed to osseointegrate at the abutment connection. After a mean observation period of 5.2 years, 55 (73.3%) of the original implants were osseointegrated. 10 supplementary implants were inserted in 3 patients. At the end of the observation periods, 2 patients had overdentures and 12 had fixed prostheses. The mean marginal bone loss was 2.13 mm (SD 0.47 mm) the 1st year after grafting, and 2.92 mm (SD 1.27 mm) at the end of the follow-up periods. Long-term follow-up did not show any persistent donor site discomfort. The results indicate that this technique is a conceivable alternative for patients with severe maxillary resorption.

Aged↗

Changes in biliary lipid output after interruption of pravastatin treatment in humans.

The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (e.g. pravastatin) has gradually increased in the treatment of hypercholesterolaemia. By inhibiting HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) activity, cholesterol synthesis in the liver is reduced and the plasma level of cholesterol, especially low-density lipoprotein (LDL)-cholesterol, is substantially lowered. Simultaneously, inhibition of HMG CoA reductase activity is associated with increased synthesis and accumulation of larger amounts of HMG CoA reductase enzyme protein. The main purpose of this study was to determine if the cessation of pravastatin treatment causes a rapid increase in the synthesis and biliary secretion of cholesterol, a condition which might lead to a temporarily increased cholesterol saturation of bile. Nine patients undergoing surgery for stones in the common bile duct were fitted with T-tubes in the common bile duct peroperatively; the side arm of the T-tube was left open postoperatively, creating a biliary fistula. All patients were given 6 days' treatment with pravastatin (20 mg b.i.d.) following the operation. Bile was collected from the T-tube, in 12-h fractions during this period and for another 3 days after termination of the treatment. Plasma levels of lipoproteins and lathosterol--reflecting cholesterol synthesis--were determined on several occasions. After cessation of pravastatin treatment, the plasma levels of total cholesterol and LDL-cholesterol increased by 21% and 33% respectively. High-density lipoprotein (HDL)-cholesterol did not change. The plasma level of lathosterol was increased two- to fourfold. Outputs of bile acids and phospholipids were significantly increased (23% and 10% respectively) after termination of treatment, whereas the output of cholesterol was not significantly changed. Cholesterol saturation was reduced by 20%, from 175 +/- 37% to 140 +/- 19%, but this change was not significant. The results indicate that, with the present experimental model (biliary diversion), the synthesis and biliary secretion of bile acids seem to be largely dependent on the de novo synthesis of cholesterol in the liver, whereas the biliary output of cholesterol is not.

Acyl Coenzyme A↗

Modelling of the biological activity for a set of ceramic fibre materials: a QSAR study.

The objective was to develop quantitative structure-activity relationships (QSARs) for a set of nine ceramic raw materials. The samples were characterized by a chemical analysis (both X-ray fluorescence and neutron activation analysis) and the morphology was determined by electron microscopy in combination with automated image analysis. Further, the fibre samples were subjected to two biological activity assays, measuring cytotoxicity and hydroxyl radical production. To investigate the produced data structures, principal component analysis (PCA) and partial least squares (PLS) were applied together with rigorous validation techniques. Significant QSARs were found for both biological activity assays. The morphology of the fibres plays an important role for the cytotoxicity and their trace element background is related to the hydroxyl radical production.

Animals↗

The concentrations of free amino acids in human liver tissue obtained during laparoscopic surgery.

The concentrations of the free amino acids in individual tissues gives information concerning amino acid, energy and protein metabolism. In muscle and intestinal mucosa, different metabolic states are distinctly characterized by an altered free amino acid pattern. Furthermore, the patterns are quite different in individual tissues. So far, liver tissue has not been investigated systematically in this respect. The aims of this investigation were to establish a standardized sampling procedure for liver tissue during laparoscopic surgery and to characterize the free amino acid concentrations in human liver tissue. Aspartate was the most abundant amino acid in the liver, followed by taurine, glutamine, glutamate, glycine and alanine. These six, and most abundant, amino acids constitute 90% of the total hepatic amino acid concentration. In the future, liver tissue sampling during laparoscopic surgery may be used as a model for investigating the influence of nutrition and hormones on hepatic amino acid and protein metabolism in man.

Adult↗

Immunochemical determination of human cholesterol 7 alpha-hydroxylase.

To produce antibodies for determination of the protein mass of human cholesterol 7 alpha-hydroxylase, a fusion protein was prepared from an in-frame fusion gene containing the cDNA for human cholesterol 7 alpha-hydroxylase near the 3' terminus of the lacZ gene of Escherichia coli. The fusion protein was purified by (NH4)2SO4 fractionation and gel-filtration chromatography on a Sephacryl column. Rabbits were immunized with this fusion protein and antisera were obtained. IgG was prepared by submitting antisera to chromatography on protein-A--Sepharose. Antibodies directed against bacterial proteins including beta-galactosidase were removed by affinity chromatography on a column to which bacterial proteins of E. coli containing beta-galactosidase had been immobilized. Evidence that the antibodies are indeed reactive against human liver cholesterol 7 alpha-hydroxylase was obtained by immunoblot analysis with human cholesterol 7 alpha-hydroxylase expressed in COS cells from the coding region of the human cholesterol 7 alpha-hydroxylase cDNA. The antiserum inhibited the activity of cholesterol 7 alpha-hydroxylase in human liver microsomes by approximately 70%. On immunoblotting of solubilized human liver microsomes, a positive band was obtained at a position corresponding to the protein mass for human cholesterol 7 alpha-hydroxylase. When calibration was performed using the fusion protein, a linear relationship was observed between the density and the amount of protein. Proportionality was also observed between the density and the amount of protein for microsomes of COS cells transfected with the coding region of the human cholesterol 7 alpha-hydroxylase cDNA. Liver microsomes from patients treated with cholestyramine (n = 3) were shown to contain levels of cholesterol 7 alpha-hydroxylase protein approximately twofold higher than those of liver microsomes from untreated patients (n = 6; P < 0.02), whereas cholesterol 7 alpha-hydroxylase activity was approximately six-fold higher in liver microsomes from the cholestyramine-treated patients than in the corresponding preparations from the untreated patients (P < 0.02). The higher activities observed in cholestyramine-treated patients, therefore, cannot be explained only by an increased amount of protein, suggesting a posttranslational mechanism to increase the activity of human cholesterol 7 alpha-hydroxylase in addition to the transcriptional control.

Adult↗