Salivary immunoglobulins and prevalent coronary artery disease.

Previous studies examined the serum immunoglobulin levels in relation to coronary artery disease (CAD). We hypothesized that the salivary immunoglobulins might better estimate oral infections in this relationship. Multivariate logistic regression analyses utilizing the data from 256 angiographically confirmed CAD patients and 250 non-CAD individuals that controlled for age, sex, smoking, diabetes, total/HDL cholesterol ratio, hypertension, and education revealed the trends that salivary IgA was positively and salivary IgG was inversely associated with CAD. The odds ratios (OR) of each increasing quartile of salivary IgA were 1.00 (first and second quartiles combined), 1.97, and 1.37 (p-value for trend = 0.06), while those for salivary IgG were 1.00, 0.77, 0.60, and 0.51 (p-value for trend = 0.02). Additionally, salivary IgA correlated positively with C-reactive protein and Asymptotic Dental Score (dental infection score), while IgG was inversely associated with these inflammation markers. Salivary IgA warrants further studies to confirm its role in the risk assessment of CAD.

Salivary lysozyme and prevalent hypertension.

Although the etiology of essential hypertension is not clearly understood, endothelial dysfunction from chronic infection and/or impaired glucose metabolism may be involved. We hypothesized that salivary lysozyme, a marker for oral infection and hyperglycemia, might display a significant relationship with hypertension, an early stage of cardiovascular disease. Logistic regression analyses of the Kuopio Oral Health and Heart Study demonstrated that persons with higher lysozyme levels were more likely to have hypertension, after adjustment for age, gender, smoking, BMI, diabetes, the ratio of total cholesterol to HDL cholesterol, and C-reactive protein. The exposure to increasing quartiles of lysozyme was associated with adjusted Odds Ratios for the outcome, hypertension, 1.00 (referent), 1.25, 1.42, and 2.56 (linear trend p < 0.003). When we restricted the sample to the individuals without heart disease (N = 250), we observed a non-significant trend for increasing odds. Our hypothesis--"high salivary lysozyme levels are associated with the odds of hypertension"--was confirmed.

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.

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.

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.

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.

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.

[Critical thinking among nurses during unit-based quality assurance projects]. / Sairaanhoitajien kriittinen ajattelu hoitotyön laadunvarmistuksessa.

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.

Microangiopathy in acute acalculous cholecystitis.

BACKGROUND: Acute acalculous cholecystitis is a well recognized complication of many acute illnesses. Ischaemia of the gallbladder seems to have an important role in its pathogenesis. METHODS: Microangiography was performed in 15 gallbladders immediately after cholecystectomy by infusing 10 per cent barium sulphate into the specimen. Five patients had symptomatic gallstone disease, five had acute gallstone-associated cholecystitis and five had acalculous cholecystitis. Sections for histological examination were taken from adjacent sides of the microangiography section. Filling of the vessels by contrast medium was compared with histological findings. RESULTS: Microangiography of the gallbladder in acute gallstone-associated cholecystitis showed strongly dilated arterioles and regular filling of the capillary network, whereas in acalculous cholecystitis the capillary filling was poor and irregular. CONCLUSION: Disturbed microcirculation may play an important role in the pathogenesis of acute acalculous cholecystitis.

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.

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.

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.

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.

Sapphire probe versus bare fiber in interstitial laser hyperthermia (ILH). An experimental study with Wistar rats.

The aim of this study was to compare the effects of a bare laser fiber and a contact sapphire probe on normal Wistar rat liver in interstitial laser hyperthermia (ILH). We used two different powers (1W and 2W) and eight different exposure times (50s to 900s). The livers were examined after 3 days and in the long-term follow-up group after 2 months. The greatest necrotic lesions were achieved with 600-900J energy (2W, 300-450s) using a bare laser fiber. The diameter of the necrotic lesions plateaued with 2W power setting after 300J energy. Generally, necrotic lesions were greater using a bare fiber than a sapphire probe with equal energy levels. The lesions healed by granulation and fibrosis. No scars or necrotic lesions were found 2 months after treatment when a 1W power setting was used, whereas a power of 2W caused a clear scar in the rat liver. ILH treatment caused necrosis safely and the bare fiber produced a greater necrotic area than the sapphire probe.

Clinical evaluation of serum tumour markers CEA, CA 50 and CA 242 in colorectal cancer.

The aim of the present prospective study was to evaluate the clinical value ol serum tumour markers CEA, CA 50 and CA 242 in patients with colorectal cancer (n = 138) and patients with benign gastrointestinal disease (n = 104). The cutoff levels (90% specificity) determined for each test were 2.5 ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic sensitivity of the CEA test was 0.63, that of the CA 50 test was 0.30 and 0.30 for the CA 242 test in detecting colorectal cancer. CEA, CA 50 and CA 242 tests were tested in a multivariate analysis to find the best combination of independent predictors of colorectal cancer. The most important predictor of colorectal cancer was CEA followed by CA 242. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The sensitivity of the DS in detecting colorectal cancer was 0.47 with a specificity of 0.88 and an efficiency of 0.67. On the basis of this study, serum CEA and CA 242 seem to possess diagnostic value in preoperative evaluation of patients with colorectal cancer.

Ag-NORs related to flow cytometry, morphometry and prognosis in patients with pancreatic cancer.

The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy specimens of 73 patients with human pancreatic adenocarcinoma. The number of Ag-NORs was related to histological features, S-phase fraction (SPF), DNA ploidy, morphometric nuclear features, clinical stage and survival. Grade I tumours had on average fewer Ag-NORs (mean +/- SD, 5.2 +/- 2.0) than grade II (mean +/- SD, 5.9 +/- 1.6) or grade III (mean +/- SD, 6.6 +/- 2.6) tumours. Patients with low SPF (0-7%) values had lower mean Ag-NORs counts (5.7 +/- 1.0) than patients with a high SPF (7%) (6.6 +/- 2.0) (p = 0.05) and the number of Ag-NORs was related almost significantly to mitotic index (p = 0.09). The Ag-NORs were not related significantly to DNA ploidy or to clinical stage. In survival analysis the number of Ag-NORs predicted prognosis significantly (p = 0.03). From the results we conclude that Ag-NORs are related to several malignant features in human pancreatic adenocarcinoma and that the number of Ag-NORs predicts survival.