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Endometritis is nowadays rare in developed countries and typically shows a subclinical or mild course; therefore, there are probably more cases of endometritis than diagnosed but they lack clinical relevance. In the fertile period of life it can be the reason for vaginal bleeding and infertility. The most common causes for non-specific endometritis are residual placental tissue after abortion or childbirth, intrauterine interventions, lesions within the uterine cavity, such as endometrial polyps, endometrial hyperplasia and neoplasms, intrauterine devices (IUD) and cervical stenosis. The histological detection of plasma cells in the endometrial stroma is required for the diagnosis of chronic endometritis. These can be detected immunohistochemically using anti-CD138 antibodies, which should be carried out particularly in cases of infertility with only slight inflammatory symptoms and few plasma cells. The use of an IUD containing progestin is frequently associated with an asymptomatic lymphoplasmacytic infiltration. After curettage or endometrial biopsy, an eosinophilic xanthogranulomatous or granulomatous endometritis and also a foreign body granuloma reaction can occur. Specific forms of endometritis, such as caused by tuberculosis, sarcoidosis, mycoplasma and herpes are very rare. Cytomegalovirus endometritis is associated with immunosuppression. Endometritis caused by infections with Chlamydia trachomatis is characterized by an extensive lymphoplasmacytic infiltration. The differential diagnoses of chronic endometritis include the very rare malignant lymphoma, which is usually characterized by a relatively monotonous cell infiltration.

Recent evidence suggests a causal relationship between inflammatory as well as infectious pathomechanisms and valvular degeneration. Based on the concept of chronic Chlamydia pneumoniae and cytomegalovirus (CMV) infections, and of variable stressors working on valvular microecology, the present study sought to assess the presence of the specific chlamydial heat shock protein (cHSP) 60, of CMV, of macrophages and of the human homologue hHSP60. Serial sections of high-grade degenerated native (n = 16) and prosthetic (n = 6) aortic valves were analyzed by immunohistochemistry for the presence of these determinants. Degenerated aortic valves revealed prevalence of Chlamydia pneumoniae in 41% (10 of 22) and CMV in 73% (16 of 22), while immunoreactive hHSP60 was present in 64% (14 of 22) and CD68 in 86% (19 of 22). Chlamydial HSP60, CMV and hHSP60 were predominantly found in valvular fibrosa; CMV showed a second predilection site at the ventricular luminal border. Both microorganisms revealed a strong correlation between each other (r = 0.73; p < 0.001) as well as with hHSP60 (cHSP60: r = 0.74; p < 0.001; CMV: r = 0.80; p < 0.001). Macrophage infiltration correlated with cHSP60 (r = 0.78; r < 0.001), CMV (r = 0.78; r < 0.001) and hHSP60 (r = 0.56; r = 0.007). Of note, the frequency of cHSP60, CMV and CD68 signaling was increased more than 5-fold in prosthetic valves compared to native valves (p = 0.017, p = 0.002 and p = 0.005). In summary, valvular infections of Chlamydia pneumoniae and of cytomegalovirus are frequently seen in degenerated aortic valves, irrespective of native or prosthetic origin. Colocalization of both HSP60 homologues and cytomegalovirus within macrophages in valvular fibrosa points to regional stressor effects that might be at least partly attributable to chronic persistent pathogen burden and molecular mimicry.

Background and Objective: There is an increasing number of pointers towards a causative connection between Chlamydia pneumoniae and atherosclerosis. But the pathogenetic mechanism and intimal structures that are involved remain unclear. Starting with the hypothesis of a chronic infection, as demonstrated by the presence of the chlamydial stress (heat-shock) protein 60 (HSP 60), the presence and localization of these bacterial products in coronary atheromas was investigated., Patients and Methods: Coronary atheroma tissue from primary stenoses in 42 patients (36 men, 6 women, mean age 60.2 +/- 7.3 years) was studied immunohistochemically in the course of a retrospective analysis for chlamydial HSP 60. The findings in clinically acute coronary syndrome (Braunwald's classification) present in 27 patients were compared with those in 15 patients with acute angina and evaluated in relation to expression and site of predilection., Results: An immune reaction to chlamydial HSP 60 was demonstrated in 27 of 42 atheromas (64%). Intact, non-atherosclerotic vessels, such as the mammary artery and sphenous vein, showed no such signals. Chlamydial HSP 60 was localized in maximally 23% of all plaque cells, mostly in macrophages/foam cells, more rarely in smooth muscle cells. Chlamydia in foam cells most often revealed ultrastructural patterns that pointed to the persistence of the pathogen. Sites of predilection of chlamydial HSP were predominantly foam cell areas and cell-poor regions, more rarely inflammatory infiltrates and areas of rupture. When comparing both types of lesion, signals for chlamydial HSP 60 were present in 21 of the 27 atheromas (78%) with unstable angina or acute myocardial infarction, but in only 6 of the 15 atheromas (40%) with stable angina. Within the group with the acute coronary syndrome, the prevalence of chronic chlamydial infection was independent of a previous myocardial infarction., Conclusions: Chlamydial HSP 60 can often be demonstrated in primary coronary stenosis of symptomatic patients. It is most frequently found in macrophages/foam cells and is highly prevalent in the acute coronary syndrome. In-situ findings suggest a pathogenetically relevant role of chronic persistent infection of Chlamydia pneumoniae in unstable coronary plaques.

The obligate intracellular bacterium Chlamydia pneumoniae has recently been implicated in the pathogenesis of atherosclerosis. Serological response to Chlamydia pneumoniae statistically indicates an increased risk of coronary artery disease and myocardial infarction. This surprising relation is corroborated by the presence of chlamydial structures and even viable Chlamydia pneumoniae in atherosclerotic plaques. These findings have already resulted in initial studies on the potential benefit of antimicrobial therapy in coronary heart disease. However, experimental proof of an etiological role of Chlamydia pneumoniae in arteriosclerosis has not yet been accomplished since a well established animal model and a system of genetic recombination are not yet available. In addition, clinical evaluation of patients is complicated by the lack of a useful parameter to indicate the risk of endovascular infection. Whether chlamydiae initiate atherosclerotic injury. facilitate progression of existing plaques, or merely colonize the lesions is therefore not known. Chlamydial contribution to the development of atherosclerosis is a fascinating hypothesis that may initiate a radical change of clinical practice for one of the leading causes of death. At the current state of scientific knowledge, however, an experimental antichlamydial treatment in coronary heart disease may only be justified in well controlled clinical trials.

In the last years several new data allow a controversial but convincing interpretation of the pathogenesis of atherosclerosis (arteriosclerosis). Atherosclerosis can be apparently the result of ultrachronic persistent infection by Chlamydia pneumoniae and not the result of different risk factors. The main arguments for the chlamydial genesis are: 1. Correlation of coronary heart disease and other atherosclerotic disease with antibodies against C. pneumoniae. 2. C. pneumoniae could be detected with different techniques (PCR, immunohistology, electromicroscopy, culture) in a high percentage in atheromas from different sites. 3. Three international studies with macrolides in coronary heart disease were successful. 4. The target cells of atherosclerosis (endothelia, macrophages, muscle cells) can be infected by C. pneumoniae in vitro. 5. Positive animal experiments. The Koch-Henle criteria for the proof of the etiology are largely fulfilled--even if there are doubts about the validity of these criteria in chronic local infections. A number of unexplainable aspect of atherosclerosis can be seen in a new light. The higher incidence of coronary heart disease in young males has a parallel in the remarkable androtropism of many bacterial diseases (pneumococcal pneumonia, tuberculosis). The reduction of incidence of atherosclerotic diseases since 1965 can be explained by the much higher intake of doxycyclin and macrolides. The low incidence of coronary heart disease in France--sometimes regarded as an effect of red wine--can be explained as a result of a much higher use of antichlamydial antibiotics. The increase of inflammatory parameters (C-reactive protein, fibrinogen, leucocytes) before acute coronary infarction are not risk factors but signs of an active chronic infection. The interpretation is possible, that atherogenic changes in lipids like increase of LDL and decrease of HDL are not risk factors but consequence of chronic arterial infection by chlamydia. The low incidence of atherosclerosis in the tropics--despite high frequency of chlamydial infection--is difficult to explain. Vascular infection can be related with the age of the patient at the primary infection. With low hygiene, intestinal primary infections in early childhood can be possible. Arterial infection would be thus a result of a primary infection in adolescence ("yet another poliomyelitis story"). There are good arguments for the thesis that C. pneumoniae is the primary cause of atherosclerosis and not a secondary invader. The consequence, nevertheless, is similar: Antibiotics get a key role. The macrolides roxithromycin, azithromycin, clarithromycin and the tetracyclin doxycyclin fulfill the criteria as potential antichlamydial agents. In general a longer treatment (6 to 8 to 12 weeks) seems advisable. It is necessary to start international studies with antibiotics in coronary infarction and other clinical manifestations of atherosclerosis. The relevant antibiotics licensed for chlamydial infections are cheap and safe. Despite of the urgent need for controlled studies, it seems already justified to treat high-risk patients with antibiotics. Meticulous protocols and long-term control of patients are necessary to evaluate the therapeutic effects. Preventive studies in patients without clinical manifestation of atherosclerosis are urgently needed. The risks of resistance or side effects are neglectable, but the organisation of such studies would be very difficult.

A prospective study was performed to analyse the relationship between urogenital infections caused by Chlamydia trachomatis and occlusions of the fallopian tubes with histologically confirmed chronic salpingitis and salpingitis isthmica nodosa. 110 infertile patients were tested for C. trachomatis infection. 23 patients with tubal occlusions and histologically confirmed chronic salpingitis (group 1) and eight patients with salpingitis isthmica nodosa (group 2) were compared to 13 patients with tubal occlusions after tuboligation (group 3), and to 66 patients with patent fallopian tubes as demonstrated by laparoscopy or hysterosalpingography (group 4). The prevalence of infections of the endocervix or urethra and the presence of Chlamydia in urine was low in all four groups. However, in groups 1 and 2, the median Chlamydia IgG and IgA serum antibody titres were significantly higher (p < or = 0.0002) than in groups 3 and 4. This result illustrates the association between urogenital infections with Chlamydia and tubal occlusions with histologically documented chronic salpingitis and salpingitis isthmica nodosa.

Under the hypothesis that a chronic infection of the cervical epithelium leads to a reduction in the immunological response, a study was carried out to compare the possible relationship between chlamydial infection and CIN. 187 patients were referred to hospital for histological confirmation because of a cytological smear result (PAP III and IV a). Smears were examined for chlamydia antigens using immunofluorescence. The presence of antichlamydial IgA and IgG was performed in serum using an indirect immunohistochemical method. These tests confirmed CIN in 163 patients. The infection rate with chlamydia was 52.9%, 15.9% of CIN patients showing an active chlamydial infection. Inclusion of topographical findings, together with differential evaluation of colposcopic results, with reference to the transformation zone, allow for a separation between inflammation and dysplasia. The confirmation of a positive chlamydial infection and colposcopic criteria may help to reduce the high percentage of false-positive findings in the problem-group of PAP III patients. It appears that reservations about smear controls after doxycyclin therapy--including treatment of sexual partners--is justified.

Chlamydia trachomatis cervical infection was observed in a 19-year-old woman with genital condylomata acuminata. To isolate C.trachomatis, cycloheximide-treated McCoy cells and a culture-independent monoclonal antibody were used. In addition, a single-antigen immunofluorescence test was made to determine the chlamydia antibody titer. Condylomata acuminata are induced by human papillomaviruses (HPV), predominantly types 6 and 11. This case shows that simultaneous genital infection of C.trachomatis and HPV requires special attention.

Uterine cervix biopsies from 20 women, in whom cell cultures were chlamydia-positive, were compared with 20 biopsies from chlamydia-negative women on the basis of inflammatory changes and proliferative epithelial reactions. There was a tendency towards severe chronic lymphocytic inflammations, especially those associated with the rare clinical picture of follicular cervicitis, and towards acute erosive forms and microabscesses to be found more frequently among the chlamydia-positive women. Hyperplasia of the reserve cells, which was probably connected with the more severe inflammatory reactions, with normotypical and dysplastic proliferations, was also seen more frequently in the chlamydia-positive group. The difficulty of distinguishing hyperplastic reserve cells from dysplastic squamous epithelia in cytological smears offers an explanation why such cases are relatively frequently overrated in cytological diagnosis. No chlamydia-typical changes of the cell nuclei or of the cytoplasm were found. It thus appears impossible to detect chlamydia in routine histological diagnosis.

Tracheal inoculation of bovine strains of Bedsonia was often followed by inflammatory processes in lung, trachea, nasal mucosa and also spleen, lymph nodes and brain. Lesions in the duct system and alveoli of the lung consisted of exudates containing neutrophilic granulocytes and proliferation of epithelial and mesenchymal cells. The initial changes were evidently located in the bronchioli. Elementary bodies were present in variable numbers. The formation of lesions seemed to be influenced by route of infection and concentration of the causal organisms in the inoculum.

The changes that occurred following nasal instillation of a bovine strain of Chlamydia psittaci were characterized by hypertrophy and proliferation of epithelial cells and exudates containing polymorphonuclear leukocytes, with acute bronchopneumonia and less intense inflammatory reactions in nasal and tracheal mucosa, spleen and pulmonary lymph nodes. The intestines, liver, kidney and brain were scarcely affected. There was little prospect of complete recovery from the clinically mild, or even subclinical, pneumonia within the period of observation since the causal agent was present continuously from the 12th hour to the 91st day after infection.