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Biomedical subjects

P Nuutinen

Publications and source records attributed to P Nuutinen.

At least 19 recordsLinked to original sources

Salivary matrix metalloproteinase-8 in patients with and without coronary heart disease may indicate an increased susceptibility to periodontal disease.

BACKGROUND AND OBJECTIVE: Tissue destruction caused by periodontitis may increase the number of cytokines implicated in the pathogenesis of cardiovascular diseases. We measured the concentration of the leukocyte-derived proteolytic enzyme, salivary neutrophil collagenase-2 [matrix metalloproteinase-8 (MMP-8)], as a marker of periodontal disease and assessed its relationship to coronary heart disease (CHD). Our aim was to study whether salivary MMP-8 levels were different among patients with and without CHD. The hypothesis was that patients with heart disease might present higher salivary MMP-8 levels than cardiologically healthy controls. MATERIAL AND METHODS: Saliva samples were taken from 256 patients with CHD and from 250 matched controls with known oral and general health status. The MMP-8 levels in saliva were analyzed by immunofluorometric assay, salivary albumin was assessed by enzyme-linked immunosorbent assay (ELISA) and total protein was determined using the colorimetric method. We further investigated the molecular forms and isoform distribution of salivary MMP-8 by western immunoblotting. The MMP-8 results were adjusted for the number of teeth and salivary protein concentrations. RESULTS: The adjusted logarithmic MMP-8 values were 0.145 +/- 0.245 microg/l in patients with CHD and 0.088 +/- 0.115 microg/l in controls (p < 0.01). The respective MMP-8 : total protein and MMP-8 : albumin ratios were also significantly higher in CHD patients than in non-CHD subjects. CONCLUSION: Elevated salivary MMP-8 levels seemed to associate with CHD, suggesting more tissue breakdown as a result of periodontitis among the patients with heart disease.

Analysis of Variance↗

Modulation of collagen synthesis and mRNA by continuous and intermittent use of topical hydrocortisone in human skin.

BACKGROUND: Glucocorticoids have been shown to downregulate collagen synthesis in human skin in vivo, thereby contributing to skin atrophy. OBJECTIVES: To compare the effects of continuous and intermittent use of topical hydrocortisone on skin collagen synthesis and, furthermore, to elucidate the mechanism of collagen synthesis reduction induced by hydrocortisone. METHODS: Collagen propeptides reflecting the synthesis rate of type I and III collagens were studied from suction blister fluids in nine healthy subjects after 3 weeks of continuous (twice daily) or intermittent (on three consecutive days weekly) topical hydrocortisone treatment and 2 weeks after the termination of treatment. Type I collagen mRNA was studied in the same subjects from skin biopsies by using in situ hybridization (ISH) after 3 weeks of treatment. RESULTS: Three weeks of continuous treatment decreased the types I and III collagen propeptides in suction blister fluid by 89% and 82%, respectively, while intermittent treatment resulted in a corresponding decrease of 53% and 50%. ISH studies from skin biopsies showed type I collagen mRNA to be markedly reduced in fibroblasts after continuous and intermittent steroid treatment. After a 2-week drug-free interval, the synthesis rate was completely restored in both areas, and some subjects even showed upregulation of synthesis in previously steroid-treated skin. CONCLUSIONS: Continuous hydrocortisone for 3 weeks markedly decreases collagen propeptides and corresponding mRNA in human skin. Intermittent hydrocortisone has a less marked effect on the collagen synthesis rate.

Administration, Topical↗

The growth pattern and microvasculature of pancreatic tumours induced with cultured carcinoma cells.

Pancreatic cancer is one of the most frustrating problems in gastroenterological surgery, since there is little we can do to improve the survival of patients with current treatment strategies. If one is to elucidate factors related to carcinogenesis, tumour biology, diagnostics and new treatment modalities of this malignant disease, then it is essential to develop a suitable animal model. In the present study we investigated rat pancreatic tumour growth after intrapancreatic injection of cultured pancreatic carcinoma cells (DSL-6A/C1), originally derived from an azaserine-induced tumour, as well as the features of tumour microcirculation using the microangiography technique. After intrapancreatic inoculation, tumours were detected in 64% of animals. A 1 cm3 tumour volume was reached within 20 weeks after inoculation. The tumours were ductal adenocarcinomas. Larger tumours showed invasive growth and spreading into the surrounding tissues, mainly into spleen and peritoneum. Microangiography revealed that the pancreatic tumours had an irregular and scanty vessel network and there were avascular areas in the center of the tumour. The area between normal pancreas and the induced tumour had dense vascularization. Intrapancreatic tumour induction with cultured pancreatic carcinoma cells produced a solid and uniformly growing tumour in Lewis rats and it thus provides a possible model for pancreatic cancer studies.

Animals↗

Phospholipase A2 activity in body fluids and pancreatic tissue in patients with acute necrotising pancreatitis.

OBJECTIVE: To measure pancreatic and non-pancreatic phospholipase A2 activity in human acute necrotising pancreatitis. DESIGN: Prospective study. SETTING: University hospital, Finland. SUBJECTS: 20 patients with acute necrotising pancreatitis. INTERVENTIONS: Serum and urine samples were taken daily for a week and fluid from peritoneal lavage for six days after admission. Samples from the pleural cavity were taken from patients in whom pleural drainage was considered necessary. Pancreatic tissue was recovered from the patients who were operated on for acute pancreatitis or for pancreatic tumour. MAIN OUTCOME MEASURES: Serum phospholipase A2, amylase, and lipase activities. RESULTS: Serum phospholipase A2 activity increased up to eightfold, 25.0 (5.4) IU/L (n = 20, range 9.0-77 IU/L) (reference value <3 IU/L) and remained high during the first week, whereas serum amylase and lipase returned to the reference range during the first four days. The maximal phospholipase A2 activity in urine was 4.5 IU/L, in the fluid from peritoneal lavage 16.9 IU/L, and in the fluid from the pleural cavity 37.0 IU/L. Phospholipase A2 activity in necrotic pancreatic tissue ranged from 0.25 to 5.70 IU/g and in normal pancreatic tissue from 9.85 to 15.0 IU/g. Preincubation at 60 degrees C showed non-pancreatic phospholipase A2 activity predominated in serum, whereas part of the enzyme activity in the fluids from pleural cavity and peritoneal lavage proved to be of pancreatic derivation. CONCLUSIONS: The results suggest a role for both pancreatic and non-pancreatic phospholipase A2 in acute pancreatitis. Preincubation at 60 degrees C proved useful in the differentiation between pancreatic and non-pancreatic phospholipase A2 activity.

Adult↗

Hyperamylasemia after cardiopulmonary bypass: pancreatic cellular injury or impaired renal excretion of amylase?

BACKGROUND: Postoperative hyperamylasemia and even acute pancreatitis are associated with coronary artery bypass grafting (CABG). The mechanism of hyperamylasemia and pancreatic acinar cell damage was studied in 20 patients undergoing CABG. METHODS: Serial blood and urine samples at eight time points before, during, and 24 hours after the CABG were collected. Salivary and pancreatic isoamylases, the fractional clearance of isoamylases (i.e., relative to creatinine clearance), pancreatic phospholipase A2 (a specific serum marker of pancreatic acinar cell injury), and cystatin C (a sensitive marker of glomerular filtration rate) were measured. RESULTS: Mild serum hyperamylasemia (300 to 1000 units/L) was found in 11 of 20 (55%) and severe (> 1000 units/L) in 6 of 20 (30%) patients with no signs of clinical acute pancreatitis. Hyperamylasemia occurred from 6 to 24 hours after the CABG and was mainly caused by pancreatic isoamylase. Serum pancreatic phospholipase A2 concentration remained unchanged, which excludes acinar cell damage. Although renal glomerular filtration was normal during CABG as measured by serum cystatin C and creatinine clearance, the fractional clearance of isoamylases decreased. CONCLUSIONS: The decreased rate of excretion into urine, rather than pancreatic cellular damage, is the major source of hyperamylasemia after CABG.

Amylases↗

[Critical thinking among nurses during unit-based quality assurance projects].

The purposes of this study were to describe the objectives and levels of critical thinking among nurses during unit-based quality assurance projects and the meaning of the participation for their own development and nursing practice. The data were collected by interviewing ten nurses who had taken part in the quality assurance projects. The themes used in interviews were created on the basis of two open questions answered by 28 nurses. The data were analysed by using qualitative content analysis and applying the levels of reflective thinking developed by Mezirow (1981), Goodman (1984) and Järvinen (1990). The first level of critical thinking was defined as technical thinking, the second level as reflective thinking and the third level as critical reflection. The results showed that nurses reflected the structural factors of the quality assurance on the technical level. When reflecting their own quality assurance processes (process factors) nurses used their critical thinking on all levels. Very few nurses considered the outcome factors of the quality assurance, but when they focused their thinking on the outcomes the reflection reached all levels. The nurses reflected the meaning of the quality assurance projects on all three levels. According to the nurses, the quality assurance enhanced their professional abilities as well as motivation in work and self-esteem. The quality assurance projects also clarified the principles guiding nursing practice. Interaction between nurses, patients and colleagues became more open.

Attitude of Health Personnel↗

Protoporphyrin-IX distribution and photodynamic effect in rat oesophagus after aminolaevulinic acid administration.

BACKGROUND: Photodynamic therapy (PDT) is a method for local and selective tumour destruction achieved by the action of light on a photosensitizing drug. METHODS: We investigated the distribution of 5-amino-laevulinic acid (ALA)-induced protoporphyrin-IX fluorescence in rat oesophagus by fluorescence microscopic examination and then studied the effects of PDT. RESULTS: The highest level of fluorescence was achieved in the mucosa after 4 h of 300 mg/kg ALA administration. A clear difference in fluorescence between mucosa and muscularis was found in all samples except those taken 24 h after ALA administration. PDT with ALA caused destruction of the mucosal and, partly, submucosal layers of the oesophagus without damaging the muscularis layer. CONCLUSIONS: According to our results with microscopic fluorescence kinetics and the preliminary results of PDT, selective destruction of the superficial layer of the rat oesophagus is achieved with PDT after ALA administration.

Aminolevulinic Acid↗

Development of a rapid PCR method for identification of Helicobacter pylori in dental plaque and gastric biopsy specimens.

A rapid and simple polymerase chain reaction (PCR) method was developed to detect Helicobacter pylori in gastric biopsy specimens and dental plaque samples. The primers were targeted to the 16S rRNA sequence of Helicobacter pylori strain ATCC 43504. The system was found to have a theoretical detection level of 0.5 to 5 Helicobacter pylori cells in a 5 microliters sample of dental plaque. In the absence of plaque, the detection level was even better: theoretically, 0.05 to 0.5 Helicobacter pylori cells were detected in water suspension. However, this appeared to be due to the presence of free bacterial DNA in the culture used for the sensitivity determination. Thus, the actual sensitivity of the system was found to be fewer than five Helicobacter pylori cells, irrespective of the type of sample used. The method was then used to analyse 29 dental plaque and gastric biopsy specimens collected from patients with a history of recurrent peptic ulcer disease. Fourteen stomach specimens were positive for Helicobacter pylori when tested with the PCR method, while the respective figures with culture, histological examination and the urease test were 11, 12 and 9. No positive dental plaque samples were observed.

Adult↗

Oral and dental manifestations in gastroesophageal reflux disease.

One hundred seventeen patients with reflux disease were examined with respect to the severity of their disease and oral, dental, and salivary findings. Twenty-eight patients had dental erosion, whereas the remaining 89 patients did not. No mucosal changes could be observed to be linked with the reflux disease. In the mean, the patients with erosion were older (54 versus 49 years), and the mean duration of their reflux disease was longer in comparison to those without erosion (17 versus 11 years, respectively). The severity of the reflux disease was more marked among patients with erosion than in those without as assessed by esophagogastroduodenoscopy, the Maratka classification, histologic examination of gastric and esophageal biopsy specimens, and 24-hour esophageal pH monitoring. No statistically significant differences were observed between the groups in any salivary parameters studied, although the number of patients with low salivary-buffering capacity was higher among those with erosion than among those without. Patients taking beta-blocking agents or tranquilizers had more erosion than those who did not take these medications. The severity of the reflux disease was not associated with any subjective symptoms in the mouth or pharynx. The frequency of consumption of acidic drinks and foodstuffs as determined by a questionnaire did not differ between the patients with and without dental erosion. Thus severe reflux disease of long duration was found to be potentially detrimental to the teeth, whereas milder forms of the disease need not cause dental side effects.

Adrenergic beta-Antagonists↗

Argyrophilic nucleolar organizer regions may help the differential diagnostic distinction between chronic pancreatitis and pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study was to determine whether the number of argyrophilic nucleolar organizer regions (AgNORs) could be of diagnostic significance in differentiating between chronic pancreatitis and pancreatic ductal adenocarcinoma. METHODS: The number of AgNORs was enumerated in biopsy specimens of normal pancreas, chronic pancreatitis, and pancreatic ductal adenocarcinoma. RESULTS: The number of AgNORs was lower in patients with normal pancreas than in patients with chronic pancreatitis or pancreatic adenocarcinoma. In addition, the number of AgNORs was significantly lower in chronic pancreatitis than in pancreatic ductal adenocarcinoma (p < 0.001). CONCLUSIONS: The diagnosis of pancreatic adenocarcinoma is usually clear. Difficulties can be encountered, however, in cases of chronic pancreatitis, specially when biopsy material is small. Our results suggest that the number of AgNORs may help in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma, especially in diagnostically difficult specimens.

Adenocarcinoma↗

Vascular changes of pancreatic ducts and vessels in acute necrotizing, and in chronic pancreatitis in humans.

Five patients with severe acute pancreatitis (AP) underwent subtotal pancreatectomy, and six patients with advanced chronic pancreatitis (CP) were subjected to pancreatic resection. Microangiography and histological studies were performed on the resected pancreata. All patients with AP had histologically verified necrotizing pancreatitis. Pancreatic ducts in the necrotic areas had severe inflammation in their walls and a decrease in their vascularity. The ductal walls of CP patients were indistinguishable from the surrounding fibrosis and the vascular supply of the ducts was markedly diminished. The vessels were reduced in number, and their calibers varied considerably. Ductal ischemia in connection with AP and CP is discussed.

Acute Disease↗

Prognostic factors in human pancreatic cancer, with special reference to quantitative histology.

A retrospective clinicopathologic study was done on 111 patients with a pancreatic ductal adenocarcinoma. The mean follow-up period was 6 years. By means of interactive morphometry six nuclear morphometric features were measured in biopsy specimens from the primary tumours. Volume-corrected mitotic index (M/V index) was estimated in the same sections. Histologic grading was done in accordance with the WHO. The M/V index (p = 0.002), the nuclear area of the 10 largest nuclei (NA10) (p = 0.025), the histologic grade (p = 0.0956), the nuclear area (NA) (p = 0.038), the standard deviation of the nuclear perimeter (SDPE) (p = 0.033), and the standard deviation of the nuclear area (SDNA) (p = 0.0430) predicted survival in univariate analysis. The type of surgery performed was a significant prognosticator too (p = 0.0131). A multifactor regression analysis of survival including clinical and histologic factors identified the M/V index as the most important prognosticator (p = 0.009), followed by the type of surgery performed (p = 0.022). Other histologic factors had no independent prognostic value. Our results suggest the use of morphometric features instead of the conventional histologic grading in predicting survival of pancreatic ductal adenocarcinoma.

Aged↗

Magnetic resonance imaging in detecting acute oedematous and haemorrhagic pancreatitis: an experimental study in pigs.

The present study was undertaken to evaluate the role of magnetic resonance imaging (MRI) in the diagnosis of pancreatic inflammation. It was focused on the use of ultra-low- and low-field MRI imagers because of the good results achieved with them in detecting intracranial oedema and haemorrhage. In addition, there are 16 ultra-low-field MRI imagers in clinical use in the world. Nineteen piglets were examined by computed tomography (CT) and then by two MRI prototype imagers operating at 0.02 and 0.17 T. The level of the pancreas was selected on CT. Oedematous pancreatitis was induced in 9 animals by intraductal injection of autologous bile and haemorrhagic form in 7 animals by intraductal injection of 15% Na-taurocholate-trypsin with simultaneous intravenous secretin injection. After 6 or 24 h the animals were re-examined by both CT and MRI. The results show that haemorrhagic-necrotizing pancreatitis can well be differentiated from oedematous pancreatitis by CT. On MRI using an ultra-low or low magnetic field the pancreas was difficult to identify and the different forms of pancreatitis could not be differentiated. Thus, at present CT with or without contrast enhancement is superior to ultra-low-field MRI in detecting and estimating the severity of acute pancreatitis. Further progress in the MRI techniques probably improves the results in the future.

Acute Disease↗

Contrast-enhanced computed tomography and microangiography of the pancreas in acute human hemorrhagic/necrotizing pancreatitis.

Five patients with severe acute pancreatitis had a low contrast enhancement (CE) of the pancreas in computed tomography (CT) and underwent subtotal pancreatectomy. Microangiography and histologic studies were performed on the resected pancreases, and the findings were related to those of CE. All patients had histologically documented hemorrhagic/necrotizing pancreatitis. The more disturbed the vascular anatomy in microangiography, the more hemorrhages and necroses were found in histology. The microangiographic and histologic findings corresponded closely to the low contrast-enhanced CT of the diseased pancreas in each patient. Thus, in the early phase of severe acute pancreatitis, one can detect by noninvasive means which areas of the gland are necrotic and which edematous by a dynamic study of contrast-enhanced CT of the pancreas.

Acute Disease↗

Effect of pancreatitis on the absorption of contrast medium from the pancreatic duct.

The absorption of contrast medium (CM) from the pancreatic duct into blood and lymph was studied in piglets with oedematous (n = 5), haemorrhagic (n = 6) and chronic (n = 7) pancreatitis. Six healthy animals served as controls. In piglets with oedematous pancreatitis, lymphatic absorption was found to be delayed, whereas venous absorption remained almost normal. Haemorrhagic pancreatitis severely delayed both venous and lymphatic absorption, due to microvascular damage. CM absorption was also delayed in chronic pancreatitis. Absorption from the pancreatic interstitium was rapid in healthy and oedematously inflamed pancreas. The slow absorption during haemorrhagic pancreatitis means that the parenchyma is exposed to the effects of CM for a longer period.

Absorption↗

Blood circulation in the urethra during hypovolemia--an experimental study.

The changes in urethral blood circulation caused by hypovolemia were studied in male piglets to simulate the hemodynamic changes during extracorporeal perfusion used in open-heart surgery. Changes caused by mild pancreatitis were studied which produced a similar reduction in urethral blood flow measured by microspheres comparable to a 34% hemorrhage of the circulating blood volume. According to this study the urethral mucosa is very sensitive to hemodynamic changes. It may be the case that catheter toxicity is more significant when the urethral blood flow is diminished.

Animals↗

The effect of peritoneal exudate on peritoneal morphology in experimental acute pancreatitis. A histologic and scanning electron microscopic study.

Changes in peritoneal morphology were examined histologically and by scanning electron microscopy during porcine acute hemorrhagic (n = 8) and edematous (n = 9) pancreatitis and after intraperitoneal installation of hemorrhagic pancreatitis-associated peritoneal exudate in healthy piglets (n = 3). In all experimental groups peritoneal inflammatory changes with mesothelial damage were evident already 1 h after the induction of the disease, and increased with time. Hemorrhagic pancreatitis caused desquamation of mesothelial cells and denudation of the basal membrane. Intraperitoneal installation of hemorrhagic pancreatitis-associated peritoneal exudate in healthy piglets caused similar changes, whereas the changes in edematous pancreatitis were much less extensive. Peritoneal exudate accumulating in the peritoneal cavity during hemorrhagic pancreatitis caused early chemical peritonitis characterized by severe inflammation of the peritoneum with destruction of the mesothelial cell layer, leading to denudation of the underlying connective tissue. The significance of these changes in the pathophysiology of acute fulminant pancreatitis remains to be further studied.

Acute Disease↗