Can degenerative aortic valve stenosis be related to persistent Chlamydia pneumoniae infection?

BACKGROUND: The cause of age-related degenerative (tricuspid) aortic valve calcification is largely unknown, but one typical characteristic is an active inflammatory process. The presence of Chlamydia pneumoniae in aortic valve stenosis was recently shown. OBJECTIVE: To test the hypothesis that if persistent C. pneumoniae infection plays an active role in the development of aortic stenosis, the organism can be detected in the healthy aortic valves of young persons. DESIGN: A cadaver study. SETTING: Oulu University Hospital, Oulu, Finland. SUBJECTS: 46 consecutive cadavers undergoing autopsy. MEASUREMENTS: Macroscopic and histologic pathology of aortic valves was determined. The presence of C. pneumoniae was determined by immunohistochemistry. RESULTS: 34 of 46 valves were macroscopically normal. Early lesions of aortic valve disease were found in 12 valves (no lesions in valves from persons 20 to 40 years of age [n = 15], 4 lesions in valves from persons 41 to 60 years of age [n = 16], and 8 lesions in valves from persons older than 60 years of age [n = 15]; P = 0.004). Fifteen of 34 normal valves (44%) and 10 of 12 valves with early lesions (83%) had positive results on staining for C. pneumoniae (P = 0.02). In persons older than 60 years of age, the chance of an early lesion was higher if the valve tested positive for C. pneumoniae (7 of 8 valves with C. pneumoniae infection compared with 1 of 7 valves without C. pneumoniae infection; P = 0.01). CONCLUSIONS: Chlamydia pneumoniae is frequently present in aortic valves and is associated with early lesions of aortic valve stenosis in elderly persons.

Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/CA IX, with potential value as a marker of cell proliferation.

Carbonic anhydrase isoenzyme IX, MN/CA IX, is a recently discovered member of the carbonic anhydrase (CA) gene family with a suggested function in acid-base balance, intercellular communication, and cell proliferation. Increased expression of MN/CA IX has been observed with certain epithelial tumors. We investigated the expression of MN/CA IX in 69 colorectal neoplasms, consisting of 1 juvenile polyp, 8 hyperplastic polyps, 39 adenomatous lesions, 21 carcinomas, and 7 metastases. Tissue sections were immunostained with a monoclonal antibody specific to MN/CA IX. The proliferative activity of the tumor cells was evaluated by Ki-67 antigen immunoreactivity. The hyperplastic polyps showed a weak or moderate reaction for MN/CA IX only in the cryptal epithelium, as did the normal intestinal mucosa. The adenomas showed immunoreactivity mainly in the superficial part of the mucosa, whereas the distribution in the carcinomas and metastases was more diffuse. Comparative immunostaining of serial sections for Ki-67, a well established marker of cell proliferation, confirmed that MN/CA IX is expressed in areas with high proliferative capacity. Our results show abnormal MN/CA IX expression in colorectal neoplasms, suggesting its involvement in their pathogenesis. The co-occurrence of MN/CA IX and Ki-67 in the same tumor cells indicates its potential for use as a marker of increased proliferation in the colorectal mucosa.

Immunohistochemistry of carbonic anhydrase isozyme IX (MN/CA IX) in human gut reveals polarized expression in the epithelial cells with the highest proliferative capacity.

MN/CA IX is a recently discovered member of the carbonic anhydrase (CA) gene family that has been identified in the plasma membranes of certain tumor and epithelial cells and found to promote cell proliferation when transfected into NIH3T3 cells. This study presents localization of MN/CA IX in human gut and compares its distribution to those of CA I, II, and IV, which are known to be expressed in the intestinal epithelium. The specificity of the monoclonal antibody for MN/CA IX was confirmed by Western blots and immunostaining of COS-7 cells transfected with MN/CA IX cDNA. Immunohistochemical stainings of human gut revealed prominent polarized staining for MN/CA IX in the basolateral surfaces of the enterocytes of duodenum and jejunum, the reaction being most intense in the crypts. A moderate reaction was also seen in the crypts of ileal mucosa, whereas the staining became generally weaker in the large intestine. The results indicate isozyme-specific regulation of MN/CA IX expression along the cranial-caudal axis of the human gut and place the protein at the sites of rapid cell proliferation. The unique localization of MN/CA IX on the basolateral surfaces of proliferating crypt enterocytes suggests that it might serve as a ligand or a receptor for another protein that regulates intercellular communication or cell proliferation. Furthermore, MN/CA IX has a completely conserved active site domain of CAs suggesting that it could also participate in carbon dioxide/bicarbonate homeostasis.

Aminoterminal propeptide of type III procollagen in the follow-up of patients with abdominal aortic aneurysms.

PURPOSE: We evaluate here whether serial changes in the concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum bear any relationship to the rate of abdominal aortic aneurysm (AAA) expansion and whether serum PIIINP has any predictive value with respect to the rupture event. METHODS: One hundred thirty-nine patients with asymptomatic AAAs were followed-up at intervals of 6 to 12 months by means of a clinical examination, B-mode ultrasound scan, and serum markers of collagen metabolism. Similar laboratory samples were also obtained from 18 patients who had a rupture of the AAA as their primary symptom soon after onset. RESULTS: The primary correlation between serum PIIINP and AAA diameter was 0.22 (p = 0.01), and that between serum PIIINP and the thickness of the thrombus was 0.49 (p = 0.001). Toward the end of the follow-up, however, the correlation increased to 0.55 (p = 0.002) for serum PIIINP and diameter, but remained at 0.42 (p = 0.02) for serum PIIINP and the thickness of the thrombus. Serum PIIINP values were very high among the 18 patients who had ruptured AAAs. CONCLUSIONS: Acceleration of AAA growth is reflected in serum PIIINP, and a marked elevation of serum PIIINP during follow-up of a patient with an AAA may predict an approaching rupture event.

Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms.

BACKGROUND: Seroepidemiologic studies have indicated an association between chronic Chlamydia pneumoniae infection and coronary heart disease. The organism, which is a common respiratory pathogen, has been demonstrated in atherosclerotic lesions of the aorta and coronary arteries. Abdominal aortic aneurysms are frequently associated with atherosclerosis, and inflammation may actually be an important factor in aneurysmal dilatation. Hence it could be assumed that C. pneumoniae may play a role in maintaining an inflammation and triggering the development of aortic aneurysms. METHODS AND RESULTS: Specimens from abdominal aortic aneurysm were examined for the presence of C. pneumoniae by immunohistochemical analysis, the polymerase chain reaction amplifying omp 1 gene, transmission electron microscopy, and culture methods with histologically atherosclerosis-negative human aortic tissues used as a control group. Chlamydial lipopolysaccharide and C. pneumoniae specific antigens were found by immunohistochemistry in 12 and 8 of 12 aneurysm specimens, respectively, and C. pneumoniae DNA could be demonstrated in 6 of 6 aneurysm specimens studied. Furthermore electron microscopy revealed the presence of Chlamydia-like elementary bodies in three of four aneurysm specimens tested. None of the control samples gave positive reaction in the polymerase chain reaction, and C. pneumoniae antigens were not detected in any of them. CONCLUSIONS: C. pneumoniae is frequently found in the vessel wall of abdominal aortic aneurysm. The potential etiopathogenetic role of C. pneumoniae in the development of these aneurysms remains to be studied.

Is the development of adenoma and carcinoma in proximal colon related to apolipoprotein E phenotype?

BACKGROUND & AIMS: Alterations in plasma lipoprotein levels and bile acid metabolism observed in patients with colorectal adenoma and carcinoma may reflect a genetic background predisposing to altered lipid metabolism and tumors. This study was designed to determine whether the polymorphism of apolipoprotein E, one of the key regulatory proteins in cholesterol metabolism, is associated with proximal or distal colonic neoplasia. METHODS: Apolipoprotein E phenotype was determined in 135 patients with colorectal adenoma, 122 patients with colorectal carcinoma, and 199 randomly selected control subjects. RESULTS: The frequency of the epsilon 4 allele of apolipoprotein E was low (0.075 and 0.073) in patients with proximal adenoma and those with carcinoma, respectively, compared with the control subjects (0.181) (P < 0.05). In patients with distal tumors, there was no alteration in epsilon 4 frequency. In all subjects with the epsilon 4 allele compared with subjects without epsilon 4, the odds ratio for proximal adenoma was 0.36 (95% confidence interval, 0.14-0.89), and the odds ratio for proximal carcinoma was 0.35 (95% confidence interval, 0.14-0.86). CONCLUSIONS: The data suggest that the epsilon 4 allele of apolipoprotein E provides protection from the development of adenoma and carcinoma of the proximal colon. These results support the theory that there are common susceptibility genes modulating the susceptibility to external carcinogenic factors.

Treatment of symptomatic congenital hepatic cysts with single-session percutaneous drainage and ethanol sclerosis: technique and outcome.

PURPOSE: To evaluate the safety and efficacy of percutaneous aspiration and ethanol sclerotherapy as the sole treatment for symptomatic, nonneoplastic, congenital hepatic cysts. PATIENTS AND METHODS: In a prospective study, 59 symptomatic, congenital hepatic cysts in 25 patients were treated with ultrasound-guided percutaneous aspiration and ethanol sclerotherapy. Eleven patients had a solitary cyst, and 14 patients had polycystic liver disease. Mean follow-up was 4 years. RESULTS: Fifty-seven (97%) of 59 sclerotherapy procedures were technically successful, and there were no recurrences. Eight cysts in six patients disappeared totally. The mean diameter of the remaining 49 cysts decreased from 9 cm to 3 cm. At the last follow-up visit, 14 patients were asymptomatic, four had milder epigastric pain than before the treatment, and seven with polycystic liver disease had recurrent symptoms due to growth of nontreated cysts. No major complications occurred. CONCLUSION: Percutaneous aspiration with ethanol sclerotherapy is a safe, effective, and minimally invasive treatment method for symptomatic congenital cysts. It is the initial treatment of choice for all patients with symptomatic congenital hepatic cysts.

Five-year follow-up after radical surgery for colorectal cancer. Results of a prospective randomized trial.

OBJECTIVE: To determine whether an intensified follow-up of patients with colorectal cancer can lead to improved reresectability and a better long-term survival. DESIGN: A prospective randomized trial of 106 patients. SETTING: Oulu University Hospital, a referral center in northern Finland. PATIENTS: A total of 106 consecutive patients who underwent radical resection for colorectal cancer, 54 of whom were randomized into a conventional follow-up group and 52 into an intensified follow-up group. MAIN OUTCOME MEASURES: After a 5-year follow-up, the time of detection of recurrence, the recurrence rates, the first method showing recurrence, the mode of recurrence, reresectability, and survival were compared between the groups. RESULTS: The recurrences were identified earlier in the intensified follow-up group than in the conventional follow-up group (mean +/- SD, 10 +/- 5 months vs 15 +/- 10 months). The overall recurrence rate was 41%, with 39% in the conventional group and 42% in the intensified group. Carcinoembryonic antigen determination was the most common method showing recurrence in both groups. Endoscopy and ultrasound were beneficial in the intensified follow-up group, but computed tomography failed to improve the diagnostics. The mode of recurrence did not differ between the groups. Radical resections were performed on 19% (8/43) of the patients, 14% (3/21) in the conventional group and 22% (5/22) in the intensified group. The cumulative 5-year survival was 54% in the conventional group and 59% in the intensified group. CONCLUSION: Earlier detection of recurrent colorectal cancer by intensified follow-up does not lead to either significantly increased reresectability or improved 5-year survival.

Injection sclerotherapy for oesophageal varices: a ten-year experience.

BACKGROUND/AIM: Severe hemorrhage from oesophageal varices is one of the most serious complications in patients with liver cirrhosis and portal hypertension, affecting about 30-70% of the former. This paper reports the results of treatment of oesophageal varices by injection sclerotherapy. PATIENTS AND METHODS: 89 patients with oesophageal varices were treated with sclerotherapy in Oulu University Hospital in the period 1982-1991. The indication was acute bleeding in 74 cases and prophylaxis in 15. RESULTS: Three patients died of rebleeding before eradication of the varices and nine afterwards. Rebleeding was more common in the Child B and C groups than in Child A (p < 0.01). Rebleeding did not correlate with the amount of sclerosant used. The most common complication was oesophageal stricture, noted in 15 patients, although only two required dilatation. This correlated with the amount of sclerosant used (P < 0.05). 34% of the patients died during the follow-up, the overall mortality rate being 14% in Child A cases, 35% in Child B cases and 92% in Child C cases. Mortality was 26% among the patients receiving prophylactic sclerotherapy (4/15) and 35% among those with bleeding varices 35% (26/74). Five patients were operated on for rebleeding problems, four as emergencies and one electively. Two emergency patients died. CONCLUSION: While the number of patients in our group receiving prophylactic sclerotherapy was small, our results follow the general survival trend for bleeding varices.

Increased turnover of collagen in abdominal aortic aneurysms, demonstrated by measuring the concentration of the aminoterminal propeptide of type III procollagen in peripheral and aortal blood samples.

PURPOSE: The pathogenesis of abdominal aortic aneurysm (AAA) involves many factors; elastin degradation is believed to lead to initial dilation, whereas changes in the collagen structure predispose the aneurysm to rupture. The major collagens in the aortic wall are types I and III. We set out here to determine whether changes in serum propeptide of type III procollagen (PIIINP), a biologically relevant marker of type III collagen turnover, could be associated with the characteristics of AAA. METHODS: The aminoterminal PIIINP and the carboxyterminal propeptide of type I collagen were measured by radioimmunoassay in 87 patients with AAA and 90 control subjects with aortodistal arteriosclerosis. The samples were taken from the peripheral blood and from the abdominal aorta at the levels of the diaphragm and the common iliac artery. RESULTS: Mean PIIINP concentrations were higher in patients with AAA than in control subjects (3.47 micrograms/L vs 2.73 micrograms/L, p < 0.0001), correlating positively with aneurysm diameter in the former (r = 0.27, p = 0.04) and with the maximum thickness of the intraluminal thrombus (r = 0.39, p = 0.003). The gradient in PIIINP between the upper and lower end of the abdominal aorta was significant in the AAA group (-0.30 microgram/L, range -0.20 to -0.50 vs -0.10 micrograms/L, range -0.20 to 0.30, p = 0.002). CONCLUSIONS: These studies indicate that the turnover of type III collagen is increased in patients with AAA.

Effect of cholecystectomy on plasma lipid and lipoprotein levels.

BACKGROUND/AIM: This study was designed to elucidate the effect of cholecystectomy, a common surgical procedure, on the concentrations of plasma lipids and lipoproteins. PATIENTS AND METHODS: 19 consecutive patient with symptomatic gallstone disease and emptying gallbladder, and 16 control patients (Nissen-Rosetti fundoplication) were studied. Cholesterol, triglyceride, and protein concentrations of various lipoproteins were analysed. RESULTS: Plasma total and LDL cholesterol levels were significantly reduced in cholecystectomy patients (p = 0.0048 and p=0.0239) at day 3 after the operation, the values returning to the preoperative level thereafter. In the control patients similar trends were observed for total and LDL cholesterol levels but these changes did not reach statistical significance. In cholecystectomy patients a significant increase was noticed in the very-low-density lipoprotein and intermediate density lipoprotein apoprotein B concentration three years after surgery (p= 0.0019 and p=0.0001). CONCLUSIONS: These minor changes in plasma lipoproteins following cholecystectomy are unlikely to have any importance in the development coronary heart disease. They indicate, however, altered enterohepatic metabolism of cholesterol after the removal of the gallbladder.

Responses of type I and type III collagen synthesis after replacement of the hip joint.

Liberation of the carboxy-terminal propeptide of type I procollagen (PICP) and the amino-terminal propeptide of type III procollagen (PIIINP) into body fluids reflects synthesis of the respective collagen types. Here, we followed PICP and PIIINP in serum with specific radioimmunoassays after hip surgery. Preoperative median of S-PICP was 112 micrograms/liter (range 87 to 154, n = 9), the 1-day median being 58 micrograms/liter (33 to 79). The corresponding medians for S-PIIINP were 4.4 micrograms/liter (3.5 to 7.0) and 3.3 micrograms/liter (2.0 to 3.5). The medians reached their maximums 14 days after surgery, 172 micrograms/liter (122 to 440) for S-PICP and 12.4 micrograms/liter (8.0 to 15.4) for S-PIIINP, after which the preoperative values were slowly approached over several months. Comparable results were found in a greater sample (n = 50). Our results indicate that the synthesis of structural collagen is inhibited immediately after surgery, but the inhibition is soon overcome by active collagen synthesis at the site of trauma. Collagen metabolism remains activated for several months after surgery.

Polymorphisms at the apoB, apoA-I, and cholesteryl ester transfer protein gene loci in patients with gallbladder disease.

Alterations in lipoprotein levels are reported to be related to an increased risk of gallstones. Plasma lipid metabolism is regulated by a number of proteins that are polymorphic in the population. The present research was designed to investigate the association between the polymorphisms of these proteins and the presence of various gallbladder diseases. Restriction fragment length polymorphisms (RFLPs) of apolipoprotein B (XbaI, EcoRI), apolipoprotein A-I (PstI, MspI), and cholesteryl ester transfer protein (CETP) (EcoNI, TaqIA, TaqIB) genes were examined in a series of 210 cholecystectomy patients operated on for symptomatic gallbladder disease and in 92 healthy controls. The patients were categorized into four groups according to the type of gallstones and the presence or absence of cholesterolosis. The distribution of CETP TaqIB polymorphism in the patients with cholesterol gallstones differed significantly from that in the controls, with the B1B1 jects (39.7%) (P = 0.036). The patients with both cholesterol and non-cholesterol stones had lower high density lipoprotein (HDL)-cholesterol levels than the control subjects. However, the most distinct difference was found in the gallstone patients with the B2B2 genotype (P = 0.006). The frequency of the X1X1 genotype of the apolipoprotein B XbaI polymorphism was markedly higher in the patients with acalculous cholesterolosis (48.9%) or cholesterolosis with stones (58.1%) than in the gallstone patients with cholesterol stones (27.2%) or with non-cholesterol stones (34.1%) (P = 0.002). The present data suggest that CETP gene polymorphism may ba associated with cholesterol gallstone disease, probably in combination with some additional factor that reduces the plasma HDL cholesterol concentration, especially in TaqIB B2B2 genotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma of the gastric cardia.

One hundred and ninety-five patients operated on for adenocarcinoma of the gastric cardia during the years 1961-90 were analysed and the present data indicate that the more enthusiastic attitude adopted towards resective surgery led to a significant increase in operative explorations performed and in resectability rate, from 50% (44/88) and 35% (28/88) during the years 1961-75 to 84% (90/107) and 56% (60/107) during the years 1976-90, respectively. The difference between radical resections, 54% (15/28) and 67% (34/60), remained non-significant. The overall postoperative mortality and morbidity after resective surgery were 14% and 35% and these rates did not rise with time. The anastomotic leakage rate was 15%. Anastomotic leakage was, in fact, not only the most common postoperative complication but also the most common cause of death. Overall cumulative survivals at 1, 3 and 5 years were 47%, 11% and 5%. Comparison of the cumulative survival rates between the 15-year periods indicated that there were no differences in overall survival or in survival after resective surgery. We regard these results disappointing, because over half of the patients died in 1 year and because the long-term survival remained dismal.

High-activity carbonic anhydrase isoenzyme (CA II) in human gallbladder epithelium.

Acidification of bile is one of the factors that prevents calcium precipitation and thereby gallstone formation. Carbonic anhydrase II (CA II) has previously been shown to be one of the key factors in the human alimentary tract that regulates the acid-base balance. We demonstrated CA II expression in the human gallbladder epithelium using immunohistochemical techniques, elucidated the CA II content of the epithelium by digital image analysis of the immunohistochemically stained enzyme in samples from 16 patients undergoing cholecystectomy, and correlated the results with the calcium content of the gallstones. Nine patients had symptomatic gallstone disease and seven an acalculous, histologically normal gallbladder. The patients were classified into two groups on the basis of the calcium content of their gallstones: no gallstones or gallstones containing no calcium (Group 1) and gallstones with 2-87% calcium by weight (Group 2). The immunohistochemical techniques showed distinct epithelial CA II-positive staining in most of the gallbladder samples, but digital image analysis revealed distinct variations in staining intensity among them. The median staining intensity index was significantly higher in Group 1 (0.4463) than in Group 2 (0.2376; p = 0.0262). The results suggest that CA II is abundantly expressed in the normal gallbladder epithelium and that decreased expression may be associated with the formation of calcified gallstones. These findings are relevant to the pathogenesis of gallstone disease.

Characteristics of symptomatic gallbladder disease in patients with either solitary or multiple cholesterol gallstones.

Recent studies have indicated that solitary or multiple gallstones may differ with respect to the conditions favoring their formation, such as nucleation time. We examined the clinical, histological and laboratory characteristics of symptomatic gallstone disease in a series of 125 consecutive patients with either solitary (n = 33) or multiple (n = 92) cholesterol gallstones undergoing cholecystectomy. The nature of biliary pain was found to differ in the two groups. Histological diagnoses of acute cholecystitis and gallbladder cancer was more frequent in the patients with multiple stones, and cholesterolosis in those with solitary stones. Furthermore, the stone cholesterol content was higher in the solitary stone group than in the multiple stone group. Morbid complications such as cholangitis and pancreatitis were rare and occurred only in the multiple stone group. The results support the view that gallbladder disease presents histological evidence of biliary complications more often in patients with multiple cholesterol stones than in those with solitary stones.

Cost effectiveness of preoperative ultrasound in primary parathyroid surgery.

A prospective, randomized, blind study was undertaken to assess whether preoperative ultrasound (US) localization of the abnormal parathyroid glands is cost-effective in patients undergoing initial neck exploration for primary hyperparathyroidism (PHPT). Twenty-eight patients were randomly allocated into two groups. In Group I the results of preoperative US were reported to the surgeon before exploration, and in Group II he was not informed of the US results. All patients underwent bilateral neck exploration, performed by the same surgeon. The operating room time was recorded and the operating room costs calculated. They included the total costs of cervical US in Group I. The cure and morbidity rates in Group I were 100% and 14% and those in Group II 86% and 7%, respectively (P > 0.05). The mean operating room time of 97 +/- 15 min in Group I was significantly lower than that of 113 +/- 23 min in Group II (P < 0.05). The mean operating room costs, however, were almost the same in both groups being only 286 FIM higher in Group II (P > 0.4) because the costs of preoperative US, the least expensive of the localization studies, of 497 FIM negated any cost savings achieved by the reduced operating room time. We thus conclude that preoperative US before initial neck exploration for PHPT is not cost-effective.

Parathyroid re-exploration in patients with primary hyperparathyroidism.

In a prospective study fifteen consecutive patients underwent re-exploration for persistent or recurrent primary hyperparathyroidism. We aimed at definite preoperative localization of enlarged, abnormal parathyroid glands in all patients. Ultrasound guided fine needle aspirations for parathyroid hormone assay had the highest accuracy rate of 100%, those for cervical ultrasound and thallium-technetium, scintigraphy were similar, both 86%. Normocalcaemia was achieved in all patients, but five (33%) patients required more than one re-exploration. Permanent unilateral vocal cord injury occurred in two (13%) patients, but none had permanent hypocalcaemia. We conclude that the results of re-exploration are good but one third of the patients required more than one reoperation. Localization studies aiming at definite localization are mandatory before re-exploration. On the basis of our results we suggest a protocol for preoperative localization which takes into consideration both the accuracy rates and the costs of localization examinations.