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Biomedical subjects

J Niinikoski

Publications and source records attributed to J Niinikoski.

At least 19 recordsLinked to original sources

Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat.

Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF-AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA-treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF-AA is effective in vitro but it is clearly less effective in vivo.

Animals

Effect of hyperbaric oxygen and surgery on experimental gas gangrene.

An experimental model of clostridial gas gangrene was developed in rats and the therapeutic value of surgical debridement alone versus a combination of surgery and hyperbaric oxygen (HBO) was assessed. The infection was produced by an intramuscular injection of Clostridium perfringens microorganisms. The mortality of untreated rats was 100%. The mortality of the rats treated only with surgery was 37.5% compared to 12.5% when HBO was added to the treatment protocol (p < 0.01). In the group treated with HBO and surgery 82.5% of the animals healed completely and were able to walk normally, whereas the corresponding figure in the rats treated with surgery alone was 12.5% (p < 0.001). In the present experimental setting HBO treatment was an important therapeutic adjunct to surgery reducing both mortality and morbidity.

Animals

Renal carnitine concentration decreases in endotoxic dogs.

BACKGROUND AND METHODS: Renal cortical and serum carnitine concentrations were studied in seven anesthetized beagle dogs in which acute circulatory collapse was induced by an iv injection of Escherichia coli endotoxin, 0.5 mg/kg given over 15 mins. Four controls received normal saline. RESULTS: The endotoxin injection resulted in cardiac depression, renal hypoperfusion, acidosis with a decrease in urinary output, and hematuria. Arterial and renal venous free carnitine concentrations increased significantly in endotoxemia during the 5-hr experiment, but remained low and unchanged in the controls. Circulating acyl-carnitine concentrations underwent no essential changes in either group. Total, free, and acyl-carnitine concentrations decreased in endotoxic renal tissue. CONCLUSIONS: These data suggest that endotoxemia decreases carnitine concentrations in the renal cortex, but increases free carnitine concentrations in the circulation.

Animals

Tumor necrosis factor alpha inhibits wound healing in the rat.

This work was undertaken to study the effects of tumor necrosis factor-alpha (TNF-alpha/cachectin) on developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the two test groups the implants were injected daily for 4 days with a solution containing either 50 or 200 ng of TNF-alpha, while the implants of the control group were treated correspondingly with phosphate-buffered saline solution only. Analyses of granulation tissue and would fluid in the sponge implants were carried out 7, 14 and 21 days after implantation. In histological specimens the ingrowth rate of granulation tissue into the sponge was significantly lower after 7 days in the group treated with 200 ng of TNF-alpha. No such an effect was observed after 14 or 21 days. After 7 days, the mean amounts of nucleic acids reflecting cellularity in the granulation tissue decreased dose-dependently, but nonsignificantly, in the groups treated with TNF-alpha. Simultaneously, the accumulation of collagen hydroxyproline of the sponge was significantly lower in the group treated with 200 ng of TNF-alpha than in the controls (-30%, one-way analysis of variance). This effect was not observed after 14 or 21 days. No significant differences were detected in the amounts of nitrogen, hexosamines and uronic acids between the groups, reflecting unchanged accumulation of glycosaminoglycans in the developing granulation tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Visceral and peripheral tissue perfusion after cardiac surgery.

Visceral and peripheral tissue perfusion and oxygenation were studied in ten patients in the early phase after coronary artery bypass grafting. Visceral perfusion was assessed indirectly, by determining gastric intramucosal pH. As parameters of peripheral tissue perfusion and oxygenation, subcutaneous tissue PO2 (PscO2), transcutaneous PO2 (PtcO2). PtcO2 index (PtcO2/PaO2), laser-Doppler skin red-cell flux (RCF) and fingertip temperature (Tft) were recorded in the upper extremity. Central haemodynamics, rectal temperature and blood gases were also measured. The inspired oxygen concentration was maintained at 30 v/v%. Gastric intramucosal pH declined progressively during the first 3 hours in the intensive care unit, reached its minimum at 5 hours and thereafter slowly increased. The peripheral vascular bed was shut down on admission to the ICU, as indicated by low values of PscO2, PtcO2, PtCO2 index, RCF and Tft. These parameters began to rise after the next 2-4 hours and peaked by the end of the 8-hour study period, indicating complete opening of the peripheral vascular bed.

Body Temperature

Internal hernias after gastric operations.

From a total of 2,146 oesophagojejunal and gastrojejunal anastomoses done between 1969 and June 1990, 7 patients (0.3%) were operated on for internal hernias. Six had developed their hernias after Billroth II gastrectomy with antecolic gastrojejunostomy and enteroanastomosis, and one patient after retrocolic Roux-en-Y reconstruction. The patients were operated on 5 days-27 years after their first operations. No patients developed internal hernias after simple gastrojejunostomy or after operations for malignant disease. Two patients died (29%) and three others developed complications. Five patients were thin. Treatment was delayed in most cases because of the nonspecific presentation of the condition. The diagnosis of internal hernia should be borne in mind in patients who develop abdominal pain with persistent nausea or vomiting after operation, so that prompt treatment may be instituted.

Aged

Diagnostic factors for postoperative candidosis in abdominal surgery.

Abdominal surgery patients with postoperative septicaemia and a deep septic focus were analyzed in an attempt to identify characteristics typical of postoperative candidosis. There were 36 patients, 10 with candidosis and 26 with bacterial septicaemia. Typical for candidosis when the septic signs appeared was a history of prolonged antibiotic treatment before the operation (10/10), long courses of antibiotics (7/10), and therapy with combinations containing aminoglycoside (7/10). Operations on the small intestine were characteristic of candidosis patients (4/10). A poor clinical condition (9/10) on admission to the hospital, late onset of septicaemic symptoms postoperatively (7/10), long hospitalization (9/10), parenteral nutrition (10/10) and reoperations (9/10) were also features associated with the development of candidosis. Patients with postoperative candidosis have several characteristics on the basis of which the developing serious infection can be suspected and empirical therapy started. It may be appropriate to initiate antifungal prophylaxis in connection with operations when necrotic intestine is resected. Avoiding long courses of postoperative antibiotics could also be a measure to diminish the incidence of postoperative candidosis.

Abscess

Renal uptake of fats and glycerol in endotoxin shock in dogs.

Circulatory changes and renal uptake of free fatty acids (FFA), glycerol and triglycerides were studied in ten adult beagle dogs during pentobarbital anesthesia. Six dogs were injected intravenously with E. coli endotoxin 0.5 mg/kg over 15 min and four control dogs received saline. Cardiac depression, hypotension, renal hypoperfusion and acidosis resulted in endotoxin shock. Arterial FFA concentrations increased significantly 2 hours after onset of shock whereas renal venous FFA levels remained rather stationary during the 5-hour study. Arterial and renal venous glycerol levels increased during the first two hours and decreased thereafter. Unchanged triglyceride levels were observed in endotoxin shock. The renal uptake of FFA increased with increasing arterial FFA concentrations. Net renal uptake of glycerol and triglycerides were observed as well. Blood concentrations and renal uptake of fats and glycerol remained relatively stationary in the control animals through the observation period. These data suggest renal ability to consume FFA, glycerol and triglycerides during endotoxin shock.

Animals

Epidermal growth factor (EGF) prevents methylprednisolone-induced inhibition of wound healing.

Subcutaneously implanted cylindrical hollow viscose cellulose sponges were used to study the effect of locally applied epidermal growth factor (EGF) on methylprednisolone-induced inhibition of granulation tissue formation in rats. In in vivo studies the sponges were treated immediately after implantation with a single injection of 2 mg (approximately 1.7 x 10(-3) M) of depot methylprednisolone or with its carrier solution only. Thereafter the implants were injected daily with 5 micrograms of EGF or with its carrier solution 0.1% albumin for 7 days. Methylprednisolone treatment decreased the accumulation of nucleic acids, collagen, and glycosaminoglycans in the developing granulation tissue. After daily injections of EGF the concentrations of these tissue components returned close to the control values. In cultures of rat granulation tissue fibroblasts, 10(-4) M and 10(-3)M methylprednisolone decreased collagen synthesis by 41 and 81% from the control level, respectively. In the presence of methylprednisolone EGF treatment could not increase collagen synthesis of fibroblasts. Methylprednisolone treatment resulted in a dose-dependent reduction in pro alpha 1(I) collagen mRNA levels, which was partially inhibited by low EGF concentrations (1 and 10 ng/ml). In the presence of methylprednisolone all concentrations of EGF increased fibronectin mRNA levels in a dose-dependent manner. It is concluded that EGF treatment can prevent the inhibitory effect of methylprednisolone on wound healing by stimulating fibroblast proliferation but does not stimulate collagen synthesis per cell.

Animals

Peripheral perfusion after cardiac surgery.

Postoperative peripheral perfusion was studied in eight male patients undergoing coronary arterial bypass grafting. Transcutaneous PO2 (PtcO2), subcutaneous tissue PO2 (PscO2) and skin red cell flux (RCF) were recorded continuously in the upper extremity. In addition, peripheral and core temperatures, as well as central hemodynamic and some metabolic variables, were determined. The FIO2 was maintained at 0.3. Complete opening of peripheral circulation occurred within a mean of 7 h after transferring the patients to the ICU. As the fingertip temperature rose, the PtcO2 index, PscO2, and RCF underwent simultaneous increases, thereby reflecting reperfusion of the peripheral vascular bed.

Blood Circulation

Renal oxygenation in endotoxin shock in dogs.

Renal hemodynamics and oxygen metabolism were studied in eight adult beagle dogs during shock induced with an iv infusion of Escherichia coli endotoxin. Renal blood flow (RBF) and renal cortical PO2 decreased profoundly during the 15-min endotoxin infusion. RBF increased sharply immediately after cessation of infusion, but soon declined and remained depressed throughout the rest of the 4-h experiment. The renal cortical PO2 remained depressed for approximately 2 h and then gradually increased toward the baseline level. Endotoxin infusion was followed by an increased renal PvO2 and a decreased renal arteriovenous oxygen difference. Renal oxygen consumption declined abruptly during endotoxin infusion, but increased toward the end of the experiment. These results suggest impaired tissue oxygenation and possibly increased oxygen shunting in the kidney during endotoxin shock.

Animals

Yeasts in blood cultures: impact of early therapy.

Patients with growth of yeast in blood cultures were analyzed during the 6-year-period 1981-1986, with special regard to predisposing factors, mortality, severity of the disease and therapy. There were 80 isolations of yeasts in blood cultures in 39 patients and Candida albicans was the most common. The majority of the patients in the material had multiple predisposing factors. The overall mortality was 58%. Patients with d disseminated disease had a mortality of 79% in contrast to 32% in patients with transient fungemia. Disseminated disease was more common in surgical patients. The prognosis of patients treated within 4 days from the onset of septic symptoms was significantly better than that of patients with a later start of therapy. On the basis of these results we emphasize the importance of early empiric therapy.

Antifungal Agents

Effect of indomethacin on peripheral tissue perfusion after coronary artery bypass surgery.

The effect of indomethacin on peripheral tissue perfusion in the early phase after coronary artery bypass grafting (CABG) was investigated in ten patients randomly allocated to receive indomethacin 25 mg i.v. or placebo 'double-blind'. The patients were coupled to a respirator with FiO2 30 v/v %. Central haemodynamics, intrapulmonary shunt and blood gases showed no significant change in either group during the 2-hour study period. The thromboxane A2 metabolite P-TXB2 decreased significantly (p less than 0.05) in the indomethacin group, but the prostacyclin metabolite P-6-K PGF1 alpha showed no significant change in either group. The PtcO2 index (transcutaneous oxygen tension/arterial PO2), measured in the upper extremity, rose (p less than 0.05) after indomethacin infusion, but was almost unchanged in the controls. The mean subcutaneous tissue oxygen tension and the laser-Doppler skin red-cell flux underwent no significant change. The data thus suggested that indomethacin administered intravenously post-CABG may exert beneficial effects on peripheral tissue perfusion and oxygenation, possibly mediated by improvements in prostacyclin-thromboxane balance and microcirculation.

Coronary Artery Bypass

Management of perineal necrotizing fasciitis (Fournier's gangrene).

Eleven cases of perineal necrotizing fasciitis were treated in the Department of Surgery, University of Turku, Finland. In 10 cases the diagnosis was made on the basis of the fulminating progression of the infection to scrotal gangrene, identification of multiple underlying pathogenic organisms and toxaemia. In one female patient a corresponding infection developed in the labia majora. Each patient suffered nonspecific symptoms before the gangrene became evident. The management included surgical debridement of the necrotic tissue with incisions and drainage of the involved areas, antibiotic therapy and hyperbaric oxygen (HBO) treatment. The infection originated from the anorectal area in 5 patients, 1 patient had sustained scrotal trauma and in 5 cases the underlying condition was unknown. Colostomy was performed in 6 patients. One patient died 2 days after the admission. All the infections proved to be multimicrobial. Hyperbaric oxygenation was employed as a therapeutic adjunct in the present series, but it should neither replace nor delay surgical intervention. The key points in the management include early diagnosis with prompt surgical debridement and antibiotic therapy. After healthy granulation has appeared, the healing time can be shortened with reconstructive surgical procedures.

Adult

Inflammatory reaction and blood flow in experimental wounds inoculated with Staphylococcus aureus.

Wound healing and granulation tissue formation can be accelerated by inoculation with live pathogenic microorganisms. For further elucidation of this phenomenon the present work was undertaken to study the effects of Staphylococcus aureus microorganisms on the inflammatory reaction and blood flow in developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In control animals 1 ml of wound fluid was withdrawn from the central dead space of the implant immediately after implantation and replaced with 1 ml of physiological saline. In experimental animals the implants were injected with live staphylococci, 10(2) or 10(5) microorganisms/ml. Wound fluid was analyzed 3, 7, 10 and 14 days after implantation, whereas measurements of local blood flow and albumin extravasation in the granulation tissue were made after 7 days. Implants inoculated with 10(5) organisms developed infection with pus formation while implants contaminated with 10(2) organisms showed no infection. In wound fluid specimens collected from the infected implants correlation between the number of polymorphonuclear leukocytes and prostaglandin E2 concentration was statistically significant. The most prominent finding in contaminated but uninfected implants was an enhanced local blood flow. This may explain some of the mechanisms leading to S. aureus-induced acceleration of wound healing.

Animals