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Biomedical subjects

L Berghem

Publications and source records attributed to L Berghem.

At least 19 recordsLinked to original sources

A comparison of hyaluronan and fibronectin in the healing of tympanic membrane perforations.

Fibronectin and 1% hyaluronan, two extracellular matrix components, were applied to tympanic membrane (TM) perforations, using the laboratory rat as an animal model. The perforations occupied the upper, posterior quadrant of the TM. Saline-treated and untreated perforations of equal size served as controls. Fifty percent of the perforations treated daily with hyaluronan healed prior to the first closures of the other groups. The use of fibronectin did not enhance the healing rate. The hyaluronan-treated perforations were covered initially by a sheet of keratin and hyaluronan containing abundant inflammatory cells. Within this keratin-hyaluronan cover, hyperplastic stratified keratinizing epithelium advanced and bridged the gap of the perforation ahead of the approaching connective tissue. These findings indicate that exogenously applied hyaluronan could be valuable in the clinical situation and should be tried to improve the healing of TM perforations.

Animals↗

Long-term carcinogenicity study in Syrian golden hamster of particulate emissions from coal- and oil-fired power plants.

Male Syrian golden hamsters were given 15 weekly intratracheal instillations with suspensions of coal fly ash or oil fly ash. Controls were instilled with saline containing gelatine (0.5 g/100 mL) or to check particle effects with suspensions of hematite (Fe2O3). The common weekly dose was 4.5 mg/hamster. In addition, one subgroup of hamsters was treated with oil fly ash at a weekly dose of 3.0 mg/hamster and another with coal fly ash at a weekly dose of 6.0 mg/hamster. Other groups of hamsters were treated with suspensions of benzo[a]pyrene (BaP) or with suspensions on coal fly ash, oil fly ash, or Fe2O3 coated with BaP. The mass median aerodynamic diameters of the coal and oil fly ashes were 4.4 microns and 28 microns, respectively. Hamsters treated with oil fly ash showed a higher frequency of bronchiolar-alveolar hyperplasia than hamsters in the other treatment groups. Squamous dysplasia and squamous metaplasia were most frequent in animals treated with suspensions of BaP or BaP-coated particles. The earliest appearance of a tumor, the highest incidence of tumors, and the highest incidence of malignant tumors were observed in hamsters treated with oil fly ash coated with BaP. Squamous cell carcinoma and adenosquamous carcinoma were the most frequent malignant tumors. No malignant tumors and only few benign tumors were observed in hamsters instilled with suspensions of fly ash not coated with BaP. The present study gives no indication that coal fly ash could create more serious health problems than oil fly ash.

Animals↗

Decreased fibronectin in rat liver altered foci and adenomas induced by N-2-fluorenylacetamide.

The disposition of fibronectin in N-2-fluorenylacetamide-induced rat liver lesions was studied by immunohistochemical staining. Male rats were fed the carcinogen for 7 weeks to induce hepatocellular altered foci and then given no chemical or phenobarbital in the diet for 24 weeks until adenomas developed. Regardless of the exposure conditions, the amount of extracellular fibronectin was unchanged in about 60% of the liver altered foci and decreased in about 40%. In contrast, 90% of the adenomas demonstrated a significantly decreased staining pattern for fibronectin. In some adenomas, the fibronectin staining pattern demonstrated irregular, wide, and distorted deposits. In nonlesional regions of the livers of rats exposed to N-2-fluorenylacetamide, the amount of fibronectin was decreased in the centrilobular and midlobular zones. The decrease of fibronectin in hepatocellular altered foci and adenomas demonstrates another abnormality in these lesions, which may be important in their biologic behavior. Foci with decreased fibronectin may have a greater potential to progress to adenomas.

2-Acetylaminofluorene↗

Fibronectin concentrations in lung lavage fluid after inhalation exposure to low levels of metals.

Groups of rabbits were exposed by inhalation to chlorides of cobalt, nickel, and manganese as well as to tri- and hexavalent chromium at metal concentrations ranging from 0.4 to 3.9 mg/m3 for 1-4 months (5 days/week, 6 hr/day). Fibronectin content and lysozyme (muramidase) activity in lavage fluid were measured after all treatments and in alveolar macrophages after treatment with nickel chloride. In the lavage fluid no marked changes were seen in fibronectin content and lysozyme activity after exposure to tri- or hexavalent chromium or manganese. Nickel exposure significantly decreased the lysozyme activity in the lavage fluid and in the macrophages whereas the fibronectin content was unchanged in the lavage fluid and significantly increased in the macrophages. Both fibronectin content and lysozyme activity were increased markedly in the lavage fluid after cobalt exposure.

Administration, Inhalation↗

Plasma fibronectin levels during daily plasmapheresis.

Plasma fibronectin concentrations were studied in 10 patients with multiple myeloma. After plasma exchange for 3 d (2.5-3 l plasma daily) the plasma fibronectin decreased to about 50% of the initial level. Resynthesis of fibronectin seemed to increase during 3 d of plasmapheresis, and was sufficient to normalize plasma fibronectin concentration. The plasma fibronectin concentration reached the initial level within 2 d after interrupting plasmapheresis in spite of concurrent cytotoxic treatment. The patients studied showed no signs of infection.

Fibronectins↗

Effects of partial hepatectomy on plasma fibronectin concentrations in the rat.

Rats were subjected to 60% partial hepatectomy. In the immediate postoperative period, there was a small decline in plasma fibronectin concentrations, which was normalized already 12 h post-operatively. Metabolic labelling of fibronectin with 35S-methionine showed that the rate of incorporation of label was unchanged after partial hepatectomy. However, when the abdominal viscera were excluded from the circulation, no incorporation of label was found. These results show that the rate of fibronectin biosynthesis has the rapid regulation characteristics of an acute phase reactant. Peripheral tissues do not contribute significantly to the plasma fibronectin concentration. Intra- or retro-peritoneal viscera, most likely the liver, are responsible for the synthesis of rat plasma fibronectin.

Animals↗

Exogenous hyaluronic acid (Healon) accelerates the healing of experimental myringotomies.

Topical application of hyaluronic acid (Healon) onto the borders of rat tympanic membrane perforations accelerated the rate of wound healing. The closure time was roughly 60% of that of the untreated perforations. Epithelial cells fused with opposing cells slightly in advance of supporting connective tissue and thus bridged the remaining gap. It seems as if hyaluronic acid, topically applied, can serve as a supporting and orienting matrix for the proliferating squamous epithelium.

Administration, Topical↗

Plasma fibronectin is initially decreased during septicemia.

Plasma fibronectin (PFN) levels were measured by radioimmunoassay in 24 normals and serially in 24 septic patients without underlying major trauma. All patients responded promptly to antibiotic therapy and none developed signs of shock or disseminated intravascular coagulation (DIC). After an initial decrease in PFN registered in most of the septic patients, the levels were normalized within 2 weeks of antibiotic treatment. The mean nadir levels of PFN were decreased (p less than 0.001) both in patients with gram-negative and gram-positive etiologies compared to the control group. Furthermore, the mean PFN value of the gram-positive group was lower (p less than 0.05) than that of the gram-negative group. It is concluded that a transient depletion of PFN is a constant finding in septic patients with a favourable outcome and that a single low PFN level alone does not justify fibronectin replacement therapy nor does it indicate a poor prognosis.

Adult↗

Effects of long-term combination chemotherapy on the reticuloendothelial system.

The phagocytic and metabolic functions of the reticuloendothelial system (RES) were studied in 20 postoperative cancer patients undergoing long-term combination chemotherapy. Each course included vincristine, methyl-CCNU (day 1) and 5-fluorouracil (days 1-5) every sixth week. The RES-test was performed prior to each course, using 125I-labeled microaggregated human serum albumin. Total leukocytes, mononuclear cells and platelets were monitored before, during and after each treatment. A significant, initial impairment of the catabolic function of the RES was found (2P = 0.006). A similar, nonsignificant trend was observed in the phagocytic function. The normalization may mirror the large metabolic capacity of the RES. This is further demonstrated by the fact that splenectomized (N = 9) and nonsplenectomized patients did not differ. A significant decrease was also found in total leukocytes and mononuclear cells (2P less than 0.001). Combination chemotherapy induced a similar myelosuppression in both groups, but did not further reduce the mobile RES in asplenic individuals.

Adult↗

Chemical and biological characterization of emissions from coal- and oil-fired power plants.

Emission samples were obtained from two medium-sized power plants, one fired with oil and the other with pulverized coal. Particles obtained by a miniscale plume stack gas sampler (MIPSGAS), simulating the dilution process in the plume, were subjected to detailed physical, chemical and biological characterization. Studies by scanning electron microscopy and by Coulter counter demonstrated that the particles from the oil-fired boiler were considerably larger than the particles from the coal-fired boiler. Chemical analyses revealed more organic substances and more S, Ni, V, in the oil than in the coal particles. The latter contained a larger proportion of Al, Si, Cl, K, Ca, Ti, Mn, Fe, Se, Rb, Y, Zr, Ba and Pb. Biological testing revealed a greater acute and subacute toxicity by the intratracheal route in the hamster, a greater toxicity to alveolar macrophages and a greater lung retention of BaP coated on the particles from oil combustion than on those from coal combustion. In another sampling line, employed simultaneously with the MIPSGAS-particulate sampler, the total emissions were collected, i.e., both particle and gas phase. These samples were used for chemical analyses and Ames mutagenicity test. Analyses of specific PAHs in emissions from both plants demonstrated that concentrations were below the detection limit (less than 4 ng/m3 of benzo(a)pyrene), which is in accord with an efficient combustion of the fuel. The mutagenicity of the samples were below the detection limit of the mutagenicity assay.

Air Pollutants↗

Influence of low-dose sodium and calcium heparin on the reticuloendothelial system and granulocyte function in man. An in vivo and in vitro study.

The phagocytic and catabolic functions of the reticuloendothelial system (RES) were determined in ten healthy men after subcutaneous injection of low-dose sodium- or calcium-heparin. The nitroblue tetrazolium (NBT)-reducing and the bactericidal capacity of granulocytes isolated from the men after heparin administration were also measured. No statistically significant difference was found for the two salts of heparin in any of the mentioned respects as compared with control injections of physiologic saline solution. In addition to these in vivo investigations, in vitro experiments were made for further study of the influence of sodium-heparin on various granulocyte functions. The results showed slight, but statistically significant increase in attachment and engulfment of particles when granulocytes were pre-incubated with heparin. No significant effect of heparin was detected in vitro on the chemotactic and random migration of granulocytes in tests with heparin concentrations 10 and 100 IU/ml. Preincubation of granulocytes with heparin in the same concentrations, however, resulted in a statistically significant decrease in the bactericidal capacity of the cells.

Aged↗

Fibronectin increases the motility, phagocytosis and NBT (nitroblue tetrazolium)-reduction of granulocytes.

Neutrophilic granulocytes preincubated in vitro with human plasma fibronectin (0-1.25 mg/ml) for 30 minutes showed increased spontaneous and chemotactic migration, increased uptake of fluorescein labelled yeast particles as well as higher NBT-reduction both with and without E. coli stimulation. These effects on the granulocyte functions were found to be mainly dose dependent. In control experiments, no significant effects were noted when fibronectin was replaced by human serum albumin in the same concentration range.

Bacterial Infections↗

Reticuloendothelial function in patients with alcoholic liver cirrhosis.

The phagocytic and metabolic functions of the reticuloendothelial system (RES) were tested in seven patients with advanced cirrhosis of the liver due to excessive ingestion of ethanol. 125I-labelled microaggregated human serum albumin was used as a test substance. A group of 13 volunteers served as controls. Liver and spleen scans were performed in all patients. Routine blood analyses were made, including seven different liver tests. The results show that both the phagocytic and the metabolic activity of the RES were hampered significantly in all these patients compared with the control group. The liver and spleen scan findings were all pathological, showing a good correlation with the RES function test. The blood test that correlated best with the RES function test was the prothrombin time, which was likewise abnormal in all patients. It is concluded that certain functions of the RES are hampered after prolonged ethanol ingestion and that the enhanced frequency of infections in patients with alcohol liver cirrhosis might partly be due to their impaired RES function.

Aged↗

Plasma atropine concentrations determined by radioimmunoassay after single-dose i.v. and i.m. administration.

The plasma concentrations of atropine following i.v. or i.m. administration to surgical patients were determined by radioimmunoassay. When atropine sulphate 1 mg was given i.v. there was a rapid initial removal of the drug from the circulation in the first 10 min; thereafter the plasma concentration decreased more slowly. Atropine i.m. was rapidly absorbed with peak concentrations occurring at 30 min following injection. The plasma atropine concentration then decreased slowly, probably because of uptake of atropine by muscarinic cholinergic receptors. The chronotropic effect of atropine appeared to correspond to the concentration in plasma following i.m. administration. We conclude that i.m. atropine, as a premedication, should be given not later than 30 min before induction of anaesthesia.

Adolescent↗

Influence of cancer chemotherapy treatment on the reticuloendothelial system in the rat.

The phagocytic function of the reticuloendothelial system (RES) in the rat has been studied after the administration of cyclophosphamide, 5-fluorouracil or a combination of these drugs and vincristine. No impairment in the elimination of 125I-labelled microaggregated human serum albumin was found. A significant reduction in relative and total spleen weight was not paralleled by a decreased splenic uptake of the RES test substance per gram tissue. A significant increase in the relative weight of the lungs was paralleled by a significant increase in the uptake of test substance on a per gram basis. No correr. A general reduction in the cell population of the haematopoietic system has to be assumed. If this reduction is more pronounced in subpopulations of T lymphocytes (suppressor T cells) has to be further tested.

Animals↗

Influence of cardiopulmonary bypass on some host defence functions in man.

Four different functions of the immune defence were studied in six men undergoing open-heart surgery with cardiopulmonary bypass (CPB). Pre-operatively, a few hours after and three days after surgery the following tests were performed: (I) in vivo phagocytic and metabolic functions of the reticuloendothelial system (RES), (II) haemolytic activity of blood monocytes, (III) nitroblue tetrazolium (NBT) reduction by granulocytes, and (IV) bactericidal capacity of granulocytes. Compared to the pre-operative values, the RES functions were unchanged postoperatively, whereas there was a significant increase in the haemolytic activity of monocytes and in the NBT reduction of granulocytes. The capacity of the granulocytes to kill bacteria was normal a few hours after surgery, but significantly increased on day 3. No infectious complications occurred and all patients recovered uneventfully. These results suggest that, at the present time, open-heart surgery under CPB is accompanied by an increased activity of granulocytes and monocytes in the early postoperative period.

Adult↗

The effect of immunosuppressive therapy on the phagocytic and metabolic functions of the reticuloendothelial system in renal transplant recipients.

The object of this study was to examine the bearing that immunosuppressive therapy may have on the phagocytic and metabolic functions of the reticuloendothelial system (RES). The phagocytic and metabolic activities of the RES were determined in renal graft recipients before transplantation and at intervals afterwards. The activities were measured as the plasma clearance rate of 125I-labelled microaggregated human serum albumin and the increase in the plasma metabolites of this test substance. The intravascular clearance of microaggregated albumin was significantly depressed at 1-12 days (P less than 0.001), 1.4 months (P less than 0.02) and 6-9 months (P less than 0.01) after transplantation compared to the levels before operation. RES phagocytosis was normal in the 1-3 year group. Furthermore, in all except the 1-4 month group the metabolic activity was significantly reduced. The significant impairment of the RES functions immediately after transplantation was probably due to administration of antilymphocyte globulin and extremely high doses of steroids. After antilymphocyte globulin had been withdrawn the phagocytic capacity of the RES was correlated to the total dose of steroids given over the 12 months prior to the test. The azathioprine regime seems to have had no influence on the RES functions.

Adult↗

Reticuloendothelial function in human renal allograft recipients.

The phagocytic and metabolic functions of the reticuloendothelial system (RES) were determined, by measuring the plasma clearance rate of 125I-labelled microaggregated human serum albumin and the increase in plasma metabolites of this test substance, in patients with chronic renal failure and in renal transplant recipients at different times after transplantation. All transplant recipients received triple immunosuppressive therapy consisting of azathioprine, corticosteroids, and antilymphocyte globulin. The intravascular clearance of microaggregated albumin was significantly depressed in patients when tested at 1 to 12 days (P less than 0.001), 1 to 4 months (P less than 0.02), and 6 to 9 months (P less than 0.001) after transplantation compared to pretransplantation. The 1- to 3-year transplant survivors had a normal RES phagocytosis. Furthermore, the metabolic RES function in all groups of transplant recipients except the group of patients tested at 1 to 4 months after transplantation was significantly impaired compared to pretransplantation. Administration of antilymphocyte globulin and extremely high daily doses of steroids were probably responsible for the significant depression in the RES functions recorded immediately post-transplantation. The further development of the phagocytic ability of the RES was shown to be correlated to the cumulative dose of steroids given over the last 12 months. The azathioprine regime seemed to have no influence on the RES functions.

Adult↗