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Biomedical subjects

B Gerdin

Publications and source records attributed to B Gerdin.

At least 55 records · Page 3Linked to original sources
PubMed1994

The influence of early postoperative intraperitoneal chemotherapy on human wound healing.

Cell ingrowth, hydroxyproline accumulation, and mRNA expression of collagen I were measured in two polytetrafluoroethylene grafts implanted subcutaneously at the time of colorectal cancer surgery to evaluate the influence of early postoperative chemotherapy on human wound healing. Eleven patients treated with intraperitoneal 5-fluorouracil and intravenous folinic acid Days 1-6 after operation were compared with 15 patients who underwent surgery alone. At 1 week, chemotherapy-treated patients had accumulated less hydroxyproline (mean 0.35 +/- 0.33 micrograms/cm) compared with untreated patients (mean 0.73 +/- 0.37 micrograms/cm, P < 0.05). By 2 weeks, the hydroxyproline content had increased sixfold in the chemotherapy group (P < 0.01) and threefold in the nonchemotherapy group (P < 0.01) and there was no difference between the groups. Cell and connective tissue ingrowth and total RNA content did not differ between the groups at any point in time, but at 1 week the mRNA expression of collagen I was higher in the chemotherapy group (P < 0.05). These results indicate that collagen accumulation in human subjects is reduced during a short course of postoperative chemotherapy and normalizes after the end of treatment.

Adult↗
PubMed1994

Prognostic predictors in colorectal cancer.

PURPOSE: Better prognostic predictors in colorectal cancer than the Dukes stage are necessary for individualized therapy and follow-up. METHODS: Survival among 212 patients operated on for colorectal cancer was examined regarding various clinical, histopathologic, cellular, and serologic tumor characteristics. RESULTS: Beside the Dukes stage, which was the most powerful variable, the erythrocyte sedimentation rate, leukocyte blood count, alkaline phosphatase, aspartate aminotransferase, six different serum tumor markers, number of small blood vessels, and age were found to be significantly associated with survival. The leukocyte blood count, alkaline phosphatase, and aspartate aminotransferase retained their significance in a multivariate model including tumor differentiation, local tumor stage, and age. Inclusion of tissue polypeptide antigen, the most powerful tumor marker in the multivariate model, showed that only the tumor stage, tissue polypeptide antigen, and age were statistically significantly correlated to survival. This was valid both for the group of patients considered as potentially curable and for those who potentially have been cured (Dukes Stages A-C). CONCLUSIONS: A great number of prognostic predictors failed to discard Dukes stage as the best one. One serum tumor marker, tissue polypeptide antigen, contains independent additional prognostic information.

Adult↗
PubMed1994

Kinetics of circulating hyaluronan in humans. 4.

The elimination of intravenously injected hyaluronan (HA) from the blood was investigated in 12 healthy volunteers. Three consecutive 30 min infusions of HA were given, separated by 90 min washout periods. Blood samples were taken before, during and after each infusion and the plasma HA concentration was determined. The deposition of HA was modelled according to a Michaelis-Menten kinetic model which included natural synthesis of HA. Km and Vmax was estimated to 0.34 +/- 0.13 microgram ml-1 and 3.48 +/- 0.97 microgram min-1 kg-1 b.w., respectively. The endogenous input was calculated to be 24 +/- 11 micrograms min-1 and was found to correlate to the age of the subjects (P < 0.05). As the baseline HA concentration was 0.031 +/- 0.21 microgram ml-1, the rate of elimination was linear in the normal concentration range. The calculated Vd was about 75% higher than a weight-estimated plasma volume. The total amount of HA excreted by the kidneys during the study period was 394 +/- 77 micrograms, which corresponded to approximately 1.7% of the total input of HA into the circulation during the experiment.

Adult↗
PubMed1994

The severity of postischemic hypoperfusion increases with duration of cerebral ischemia in rats.

Regional cerebral blood flow was studied after a period of hypotensive bilateral carotid occlusion in rats. As other studies have found, we confirm that 15 min of ischemia caused an initial brief hyperemic episode followed by severe hypoperfusion in all areas. With varying duration of ischemia from 5 to 10, 15 and 20 min, the median cerebral blood flow 60 min postischemia was 79%, 46%, 48% and 34% of control, respectively. Thus the degree of postischemic hypoperfusion increased significantly with the duration of ischemia.

Acidosis↗
PubMed1994

Enhanced intestinal synthesis of interleukin-6 is related to the disease severity and activity in ulcerative colitis.

The concentration of interleukin-6 (IL-6) was measured in the perfusion fluid from investigated rectal and sigmoid segments in patients with ulcerative colitis (UC). The colorectal release of this substance from segments with active inflammation was greatly increased compared with that found in healthy controls and correlated to the mucosal damage defined by plasma protein leakage and endoscopic findings. The perfusate/serum ratio of IL-6 was significantly higher than the corresponding ratio of albumin, indicating that the increased amount of IL-6 detected in the perfusion fluid was synthesized in the inflamed colorectal mucosa. A strong correlation between the concentrations of IL-6 and of tumor necrosis factor-alpha in perfusion fluid suggests that macrophages/monocytes are cells of importance in the stimulated local synthesis of IL-6. The calculated total colorectal release of IL-6 was significantly correlated to the serum concentrations of C-reactive protein and alpha 1-antitrypsin, demonstrating that the acute phase response in patients with UC reflects the amount of locally produced IL-6.

Acute-Phase Reaction↗
PubMed1994

Intraoperative colonic lavage and primary anastomosis--an alternative to Hartmann procedure in emergency surgery of the left colon.

OBJECTIVE: To assess whether intraoperative lavage and primary resection with anastomosis is a safe alternative to a Hartmann procedure in emergency surgery of the left colon. DESIGN: Retrospective study. SETTING: University hospital. MATERIAL: 101 consecutive patients (39 emergency and 62 elective) who underwent a left-sided colonic resection during a 3-year-period. INTERVENTIONS: 17 of the emergency procedures comprised an intraoperative lavage followed by resection and primary anastomosis without faecal diversion; 17 were Hartmann procedures and 5 patients had primary resection without lavage. MAIN OUTCOME MEASURES: Postoperative mortality, morbidity and duration of hospital stay in these two groups compared with these after a contemporary series of elective resections. RESULTS: There were no postoperative deaths and no clinical anastomotic leaks in the lavage group. The duration of hospital stay (median 11 days) was similar in both groups (overall and sigmoid resection respectively). In the Hartmann group, there were two deaths and the postoperative stay in hospital was significantly longer. CONCLUSIONS: Primary resection with intraoperative lavage can be done successfully in patients with acute obstruction of the left colon and the duration of hospital stay and morbidity are similar to those seen in patients operated on electively.

Adult↗
PubMed1993

Intestinal distribution of hyaluronan in small bowel allografting in the rat.

Hyaluronan (hyaluronic acid; HA) was demonstrated and quantified in small bowel tissue at different times after small bowel transplantation. Semiallogeneic or semisyngeneic rat models were used to elicit either unidirectional graft rejection or graft-versus-host disease (GVHD). In normal rat small bowel, HA was present in the villous lamina propria and around medium-sized vessels in the interstitium of the crypt area. During graft rejection a cellular infiltrate and edema appeared in the lamina propria in the crypt area where an accumulation of HA was also demonstrated. There was progressive accumulation of HA in the small bowel during rejection, and on day 6 there was a threefold increase compared to the values in syngeneic grafts. The increase in tissue HA was paralleled by an increase in the total water content of the rejecting graft. In specimens from animals suffering from GVHD, no significant changes in water or HA content and distribution were observed until day 12. The data suggest that accumulation of HA might contribute to the pathophysiology of the transplantation edema and that HA might be of potential diagnostic value in differentiating between graft rejection and GVHD.

Animals↗
PubMed1993

Immunohistochemical identification of receptors for epidermal growth factor in tumor endothelium may be affected by cross-reactivity to blood group A antigen.

It has been reported that endothelium in malignant glioma stains with a commercial antibody raised against the receptor for epidermal growth factor (EGFr) on A431 cells (clone 29.1). In this report, this antibody was used to study the immunohistochemical expression of EGFr in benign and malignant ovarian, mid-gut carcinoid, and thyroid neoplasms using the avidin-biotin-peroxidase complex technique. Eighteen of the 37 ovarian neoplasms, 4 of the 10 thyroid neoplasms, and 14 of 28 mid-gut carcinoid tumors expressed strong and distinct endothelial staining, whereas staining results of the remaining tumors were negative. The endothelial nature of the staining was verified by staining serial sections with Ulex europaeus agglutinin-I. The staining was independent of that obtained with an antibody raised against a synthetic peptide consisting of residues 985 to 996 from the cytoplasmic domain of EGFr (clone F4). All positive staining occurred in patients determined to be of blood groups A or AB, whereas samples from patients with blood groups B or O were negative. Immunoabsorption of the antibody with centrifuged erythrocytes from a blood group A donor, but not from a blood group B donor, abolished the positive staining. The data indicate that positive staining of tumor endothelium with this antibody is due to cross-reactivity with blood group A antigen. The results obtained challenge the validity of previously performed immunohistochemical studies in which monoclonal antibodies raised against the EGFr of A431 cells have been used, and in which the epitope for the monoclonal antibody has not been determined.

ABO Blood-Group System↗
PubMed1993

Coxsackie B3 myocarditis induces a decrease in energy charge and accumulation of hyaluronan in the mouse heart.

Interstitial oedema in chronic inflammation and ischaemia is related to an accumulation of hyaluronan (hyaluronic acid; HA) in the interstitium. As interstitial oedema will affect the oxygen transport in the interstitium we have evaluated whether accumulation of HA is related to signs of myocardial energy depletion in virus induced myocarditis. Myocarditis was induced in Balb/c mice by inoculation of Coxsackie B3 virus. The extractable HA content of the myocardium increased progressively from a baseline value of 153 +/- 26 micrograms g-1 dry weight to a maximum of 286 +/- 78 micrograms g-1 dry weight at day 7, whereafter there was a slight decline. Affinity histochemistry visualized HA in the endo-perimysium in healthy myocardium. At day 5 after Coxsackie B3 inoculation there was a general widening of the endomysium, which exhibited a positive staining for HA. In conjunction with focal inflammatory infiltrates the staining for HA was even more pronounced. The energy rich adenylates were reversibly affected by the Coxsackie B3 infection. There was a slight, but significant decline in EC from 0.74 +/- 0.05 in the control group to a minimum value of 0.64 +/- 0.10 at day 5, whereafter a restitution was observed at days 7 and 10. The total adenine nucleotide pool was similarly decreased from 27.8 +/- 2.9 mumol g-1 dry weight in controls to 24.6 +/- 2.1 micrograms g-1 dry weight at day 5, and normalized at days 7 and 10. The data suggest that virus induced myocarditis is associated with a local accumulation of HA in the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Neutrophil mucosal involvement is accompanied by enhanced local production of interleukin-8 in ulcerative colitis.

The concentration of myeloperoxidase, a neutrophil granule constituent, was measured in the perfusion fluid from sigmoid and rectal segments in patients with ulcerative colitis. The concentrations of myeloperoxidase were increased severalfold in the patients with ulcerative colitis compared with healthy controls pointing to an enhanced neutrophil activity. The release of myeloperoxidase correlated to an enhanced local release of the neutrophil activating peptide interleukin-8 (IL-8). Increased values of tumour necrosis factor (TNF-alpha) were also found during intestinal perfusion of the patients and correlated with those of IL-8. The results obtained are compatible with the hypothesis that local mucosal recruitment/activation of neutrophils in ulcerative colitis is mediated by an enhanced IL-8 synthesis. TNF-alpha may be one relevant factor as a stimulus to IL-8 synthesis.

Adult↗
PubMed1993

Luminal release of hyaluronan (hyaluronic acid) in intestinal ischemia in the rat.

Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn's disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60-min period of subtotal ischemia without venous stasis (p < 0.05). In sham-operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen.

Animals↗
PubMed1993

Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans.

The expression and localization of PDGF beta receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF beta receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF beta receptor expression was minor in normal skin. An increased expression of PDGF beta receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent < or = 4 wk after surgery. There was also a concordant increase in PDGF beta receptor mRNA detected by in situ hybridization. PDGF-AB/BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB/BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF beta receptors, respectively, we performed double immunofluorescence stainings. PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colocalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43 +/- 18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF beta receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled.

Adult↗
PubMed1993

Inhibition of CD18-dependent adherence of polymorphonuclear leukocytes does not affect liver oxygen consumption in fecal peritonitis in pigs.

We tested the hypothesis that circulating polymorphonuclear leukocytes (PMNs), adhering to endothelium of the liver vascular bed are involved in the alterations of the liver oxygen delivery (DO2) and consumption (VO2) that is a result of fecal peritonitis in pigs. Twenty-two pigs were divided into three groups. Animals in group I (n = 7) served as controls. Fecal peritonitis was induced in groups II (n = 7) and III (n = 8). Animals in group III were pretreated with IB4, a monoclonal anti-CD18 antibody inhibiting adherence of PMNs to the endothelium. Peritonitis increased liver VO2 in groups II and III in spite of decreased liver DO2. In group I, circulating PMNs increased during the experimental period. Sepsis caused a decrease in the number of circulating PMNs in group II, an effect that was fully counteracted in group III, where the number of PMNs rose to control level. Myeloperoxidase activity and morphometric determination of PMN infiltration in liver biopsies virtually paralleled the circulating PMN count. Although fecal peritonitis is followed by a CD18-dependent leukopenia that can be counteracted by pretreatment with an anti-CD18 antibodies, this treatment does not affect the alteration in liver VO2 and DO2 observed.

Animals↗
PubMed1993

Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma.

The expression of platelet-derived growth factor- beta (PDGF-beta) receptors in the microvasculature of human healing wounds and colorectal adenocarcinoma was investigated. Frozen sections were subjected to double immunofluorescence staining using monoclonal antibodies (MAbs) specific for pericytes (MAb 225.28 recognizing the high-molecular weight-melanoma-associated antigen, expressed by activated pericytes during angiogenesis), endothelial cells (MAb PAL-E), laminin, as well as PDGF-beta receptors (MAb PDGFR-B2) and its ligand PDGF-B chain (MAb PDGF 007). Stained sections were analyzed by computer-aided imaging processing that allowed for a numerical quantification of the degree of colocalization of the investigated antigens. An apparent background colocalization, varying between 23 and 35%, between markers for cells not expected to co-localize was recorded. This background could be due to limitations of camera resolution, to out-of-focus fluorescence, and to interdigitations of the investigated structures. In all six tumor specimens, co-localization of PDGF-beta receptors and PAL-E was not different from the background co-localization, whereas that of PDGF-beta receptors and high-molecular weight-melanoma-associated antigen was significantly higher with mean values between 57 and 71%. Qualitatively, the same pattern was obtained in the two investigated healing wounds. PDGF-B chain did not co-localize with either PAL-E or high-molecular weight-melanoma-associated antigen, but PDGF-B chain-expressing cells were, however, frequently found juxtaposed to the microvasculature. The expression of PDGF-beta receptors on pericytes in activated microvessels and the presence of PDGF-B chain-expressing cells in close proximity to the microvasculature of healing wounds and colorectal adenocarcinoma is compatible with a role for PDGF in the physiology of the microvasculature in these conditions.

Adenocarcinoma↗
PubMed1993

Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer.

BACKGROUND: The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear. EXPERIMENTAL DESIGN: The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively. RESULTS: All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive cells), whereas the nature of the remaining stromal cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The extent of clusters of PDGF beta-receptor expressing cells varied considerably between tumors, and its prognostic value was considered in the entire tumor material. The number of clusters did, however, not correlate to tumor differentiation, tumor stage according to Dukes', or outcome. CONCLUSIONS: The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.

Carcinoma↗
PubMed1993

Ionophoric interaction with the myocyte sarcolemma: a new insight into the pathophysiology of degenerative myocardial disease.

A certain group of compounds often derived from microbes known as ionophores function as ion channels when incorporated in biological membranes. Different ionophores have a relative specificity for certain cations such as Ca2+ or K+. When such compounds are integrated in the cell membrane of a host cell a leakage of the ion in question is induced and the physiologic ion gradient will be dissipated. This will activate ion pumps at the expense of ATP in order to restore the physiologic ion gradient. This effect is seen for a number of different viruses including Coxsackie B3. Based on own experiments we suggest that this ionophoric effect is important in the pathophysiology of myocarditis. We have shown that mice with Coxsackie B3 myocarditis have low myocardial ATP and high ADP and AMP levels. This pattern of abnormal energy metabolism is also seen in patients with Syndrome X. It is suggested that the ECG and thallium perfusion scintigram suggestive of ischemia in such patients is rather due to the effect of an ionophore leading to an extracellular potassium shift.

Adenine Nucleotides↗