Diagnosis, Therapy and Follow-up Care of Vulvar Cancer and its Precursors. Guideline of the DGGG and DKG (S2k-Level, AWMF Registry Number 015/059, November 2015.

Purpose: This is an official guideline, published and coordinated by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO, Study Group for Gynecologic Oncology) of the Deutsche Krebsgesellschaft (DKG, German Cancer Society) and the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics). The number of cases with vulvar cancer is on the rise, but because of the former rarity of this condition and the resulting lack of literature with a high level of evidence, in many areas knowledge of the optimal clinical management still lags behind what would be required. This updated guideline aims to disseminate the most recent recommendations, which are much clearer and more individualized, and is intended to create a basis for the assessment and improvement of quality care in hospitals. Methods: This S2k guideline was drafted by members of the AGO Committee on Vulvar and Vaginal Tumors; it was developed and formally completed in accordance with the structured consensus process of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Recommendations: 1. The incidence of disease must be taken into consideration. 2. The diagnostic pathway, which is determined by the initial findings, must be followed. 3. The clinical and therapeutic management of vulvar cancer must be done on an individual basis and depends on the stage of disease. 4. The indications for sentinel lymph node biopsy must be evaluated very carefully. 5. Follow-up and treatment for recurrence must be adapted to the individual case.

[Nomenclature of squamous cell precursor lesions of the lower female genital tract : Current aspects]. / Nomenklatur der plattenepithelialen Präkanzerosen des unteren weiblichen Genitales : Aktuelle Aspekte.

The majority of precancerous lesions of the lower female genital tract (intraepithelial neoplasia, IN) are caused by human papillomavirus (HPV) infections resulting in cellular atypia and in turn an altered tissue architecture. Depending on the pathogenesis, a distinction is made between vulvar intraepithelial neoplasia (VIN) classified as classical VIN associated with high-risk HPV infections (u-VIN) and differentiated VIN (d-VIN), which is associated with lichen sclerosus et atrophicus and p53 alterations. In the current World Health Organization (WHO) classification a novel grading system for squamous cell precancerous lesions of the lower female genital tract has been proposed, differentiating low grade squamous intraepithelial lesions (L-SIL) including condyloma and HPV-associated alterations plus VIN 1, vaginal intraepithelial neoplasia (VaIN 1) and cervical intraepithelial neoplasia (CIN 1) from high grade squamous intraepithelial lesions (H-SIL) with VIN 2 and 3, VaIN 2 and 3 as well as CIN 2 and 3. The use of p16 immunohistochemistry can assist the differentiation. The new binary classification, however, contradicts the German cytological nomenclature (Munich nomenclature III), which differentiated three grades of dysplasia in order to avoid overtreatment of patients with moderate IN. The individual nomenclatures are compared to each other. It is recommended to report the grade of precancerous lesions in addition to the SIL classification of the WHO.

[HPV-associated alterations of the vulva and vagina. Morphology and molecular pathology]. / HPV-assoziierte Veränderungen an Vulva und Vagina. Morphologie und Molekularpathologie.

Non-neoplastic HPV-induced alterations of the vulva and vagina are frequent. The traditional three-tier grading system of vulvar intraepithelial neoplasia (VIN) will be replaced by the definition of usual and simplex type of VIN. The usual type is characterized by a strong association to high-risk HPV infections, the occurrence at younger age and multifocality, mostly associated with non-keratinizing squamous cell carcinoma. The differentiated (or simplex) type is rare and shows an association to older age and p53 alterations and is typically diagnosed co-incidentally with keratinizing squamous cell carcinoma. Vaginal intraepithelial neoplasia (VAIN) is still graded into VAIN 1-3 where VAIN 1 and 2 are mostly associated with low-risk HPV infections and a high spontaneous regression rate whereas VAIN 3 represents a high-risk HPV-associated lesion with capable progression into (micro-)invasive carcinoma. The differential diagnosis between a non-neoplastic condylomatous lesion and VIN common type and VAIN may be aided by p16 immunohistochemistry. The HPV-associated invasive vulvo-vaginal cancers are verrucous carcinoma (low-risk HPV) and the high-risk HPV-induced (non-keratinizing) squamous cell carcinoma (NOS), the condylomatous (warty) carcinoma and the very rare vaginal squamo-transitional carcinoma.

Prognostic significance of the detection of human papilloma virus L1 protein in smears of mild to moderate cervical intraepithelial lesions.

OBJECTIVE: To investigate whether it is possible to use detection of the human papillomavirus (HPV) L1 capsid protein to predict the course of mild or moderate cervical intraepithelial neoplasia (CIN). STUDY DESIGN: Pap smears from 279 women in whom CIN 1 and CIN 2 had been diagnosed by cytology and histology, who were known to have a high-risk HPV status and had a median follow-up of 25 months, were immunohistochemically stained for the HPV L1 protein. The staining results were correlated with the clinical course of the disease. RESULTS: HPV L1-positive patients showed regression in 49.1% of cases, stable disease in 41.5%, and progressive disease in 9.4%, whereas HPV L1-negative women had progression in 25.9% of cases (regression 33.3%, stable disease 40.7%; p=0.001). The effect was clearest in the group under 30 years of age. HPV L1-negative patients experienced progression significantly more often than women with a positive HPV L1 test (odds ratio 3.391). CONCLUSIONS: HPV L1-positivity was found to have prognostic significance in relation to disease progression in women with CIN 1 and CIN 2 and particularly in those less than 30 years of age.

Management and course of histologically verified cervical carcinoma in situ during pregnancy.

BACKGROUND: To study the rate of regression and progression into invasive disease of patients with histologically proven carcinoma in situ of the uterine cervix during pregnancy. METHODS: Prospective observation of all pregnant women with biopsy-proven carcinoma in situ of the uterine cervix, gained by colposcopic guided biopsy from 1996 to 2004 and correlation with the route of delivery and cytologic and histologic postpartum findings. RESULTS: Eighty-three patients with histologically verified carcinoma in situ during pregnancy were treated conservatively. Two patients were lost to follow-up, one patient had an abortion, and three are still pregnant. The study population of 77 patients were followed for a median of 140 days before delivery. Postpartum regression rate was 34.2%, two patients had a diagnosis of microinvasive cervical cancer on the postpartum cone biopsy, and persistent carcinoma in situ was found postpartum in 63.1% of patients. No difference was seen for the route of delivery. Both patients with microinvasive carcinoma were delivered by primary cesarean section and are disease-free after 24 and 38 months, respectively. CONCLUSIONS: We recommend conservative management for women with carcinoma in situ of the uterine cervix. We found no difference for the route of delivery regarding postpartum regression and recommend a postpartum evaluation after the puerperium. Colposcopic guided biopsy should rule out an invasive process during pregnancy. Cesarean section as the mode of delivery should be considered, if invasion is suspected.

Prognostic significance of serum antibodies to HPV-16 L1 virus-like particles in patients with invasive cervical cancer.

BACKGROUND: Persistent infection with high-risk human papilloma virus (HPV) is a prerequisite for the development of cervical cancer. The prognostic value of HPV-16 capsid antibodies in patients with invasive cervical cancer and its correlation with clinicopathological factors were investigated. PATIENTS AND METHODS: Serum samples from 150 patients with invasive cervical cancer and 40 healthy female control subjects were analyzed by ELISA for HPV-specific antibodies to HPV-16 L1 virus-like particles (VLPs). RESULTS: HPV-16 L1 antibodies were detectable in 65 out of 150 patients (43.3%) and in 12 out of 40 controls (30.0%). Seropositivity was correlated with prolonged, progression-free (p =0.012) and overall survival (p=0.043). Especially in the early FIGO-stages I and II antibodies to HPV-16 L1, VLPs predicted a better outcome. CONCLUSION: Antibodies to HPV-16 L1 capsid protein may be of prognostic value for patients with invasive cervical cancer and lack of HPV-16 L1 antibodies may indicate a group of patients with a poor prognosis.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Increased neuronal and glial expression of protein kinase C isoforms in neocortex of transgenic Tg2576 mice with amyloid pathology.

We investigated the influence of five- to sevenfold neuronal overexpression of the Swedish mutation of human APP695 (APPsw) in the transgenic mouse strain Tg2576 on neocortical protein kinase C (PKC) expression and subcellular distribution. Using specific antibodies to PKC alpha, PKC beta, PKC gamma, PKC epsilon and PKC zeta isoforms for Western blot analysis, we observed increased immunoreactivity for PKC alpha and PKC gamma isoforms in crude tissue homogenates from the neocortex of 16-month-old APPsw mice as compared with nontransgenic littermates, which was not present in 6 month-old Tg2576 mice. We also observed elevated levels of PKC alpha, PKC beta, PKC gamma and PKC zeta in membrane fractions and reduced concentrations of PKC alpha and PKC gamma in cytosolic fractions of aged Tg2576 mice, indicating that these PKC isoforms are in their activated state. In young, 6-month-old Tg2576 mice, however, the increase in membrane-bound PKC isoforms and concomitant decrease in cytosolic PKC isoforms was much less pronounced, demonstrating the age-dependent nature of alterations in PKC isoforms. Immunocytochemistry of brain sections supported these findings and revealed increased neuronal labelling for PKC alpha, PKC gamma and PKC lambda isoforms in neocortex of 16-month-old APPsw mice compared with nontransgenic littermates, with the increase being strongest for PKC gamma and PKC lambda isoforms. Additionally, PKC gamma and to a lesser extent PKC lambda isoforms were induced in reactive astrocytes in proximity to amyloid plaques. Our data indicate that neuronal overexpression of APPsw causes a dynamic change in neuronal expression and activation of multiple PKC isoforms known to be regulators of proteolytic amyloid precursor protein (APP) processing (PKC alpha) and of neuronal survival (PKC lambda and PKC zeta). The induction of the PKC gamma and PKC lambda isoforms in reactive astrocytes surrounding amyloid plaques might be required for astrocyte activation and astrocytic cytokine expression in response to amyloid plaque formation.

Induction of cytokines in glial cells surrounding cortical beta-amyloid plaques in transgenic Tg2576 mice with Alzheimer pathology.

beta-Amyloid plaque deposition observed in brains from Alzheimer patients, might function as immune stimulus for glial/macrophages activation, which is supported by observations of activated microglia expressing interleukin (IL)-1beta and elevated IL-6 immunoreactivity in close proximity to amyloid plaques. To elucidate the mechanisms involved in beta-amyloid-mediated inflammation, transgenic mice (Tg2576) expressing high levels of the Swedish double mutation of human amyloid precursor protein and progressively developing typical beta-amyloid plaques in cortical brain regions including gliosis and astrocytosis, were examined for the expression pattern of a number of cytokines. Using ribonuclease protection assay, interleukin (IL)-1alpha,-beta, IL-1 receptor antagonist, IL-6, IL-10, IL-12, IL-18, interferon-gamma, and macrophage migration inhibitory factor (MIF) mRNA were not induced in a number of cortical areas of Tg2576 mice regardless of the postnatal ages studied ranging between 2 and 13 months. Using immunocytochemistry for IL-1alpha,beta, IL-6, tumor necrosis factor (TNF)-alpha, and macrophage chemotactic protein (MCP)-1, only IL-1beta was found to be induced in reactive astrocytes surrounding beta-amyloid deposits detected in 14-month-old Tg2576 mice. Using non-radioactive in situ hybridization glial fibrillary acidic protein (GFAP) mRNA was detected to be expressed by reactive astrocytes in close proximity to beta-amyloid plaques. The local immune response detected around cortical beta-amyloid deposits in transgenic Tg2576 mouse brain is seemingly different to that observed in brains from Alzheimer patients but may represent an initial event of chronic neuroinflammation at later stages of the disease.

Insulin-sensitive GLUT4 glucose transporters are colocalized with GLUT3-expressing cells and demonstrate a chemically distinct neuron-specific localization in rat brain.

The insulin-sensitive glucose transporter (GLUT) 4, expressed primarily in peripheral tissue, has recently been detected also in the brain, demonstrating a region-specific distribution. To identify the chemical nature of neurons expressing GLUT4 and to disclose whether GLUT4-containing neurons also express the GLUT3 isoform, combined in situ hybridization for GLUT3 mRNA and double-labeling immunocytochemistry for GLUT4 and different cellular markers was performed in brain sections through rat basal forebrain, cerebral cortex, hippocampus, and cerebellum. In all brain regions examined, GLUT4 immunoreactivity was exclusively found in neurons, and GLUT4-immunoreactive cells were colocalized with neurons expressing GLUT3 mRNA. In rat basal forebrain, cholinergic and parvalbumin-containing gamma-aminobutyric acid-ergic cells demonstrated GLUT4 immunoreactivity, whereas calretinin-, calbindin-D-, and neuronal nitric oxide synthase-containing neurons did not express GLUT4 protein. Because brain GLUT4 transporters have been suggested to play a role in rapidly providing additional glucose to neurons under conditions of high-energy demand, the selective presence of GLUT4 in basal forebrain cholinergic cells may explain the specific vulnerability of these cells to a lack of glucose supply.

Glucose metabolism in cholinoceptive cortical rat brain regions after basal forebrain cholinergic lesion.

To address the question whether the changes in cortical glucose metabolism observed in patients with Alzheimer's disease are interrelated with, or consequences of, basal forebrain cholinergic cell loss, an experimental approach was employed to produce cortical cholinergic dysfunction in rat brain by administration of the cholinergic immunotoxin 192IgG-saporin. [14C]D-glucose utilization in brain homogenates, D-glucose-displaceable [3H]cytochalasin B binding to glucose transporters (GLUT). Northern and Western analyses, as well as in vivo [14C]2-deoxyglucose autoradiography were used to quantify the regional glucose metabolism. Basal forebrain cholinergic lesion resulted in transient increases in glucose transporter binding in cortical regions displaying reduced acetylcholinesterase activity, already detectable seven days after lesion with peak values around 30 days post lesion. Western analysis revealed that the changes in total glucose transporter binding are mainly due to changes in the GLUT3 subtype only, while the levels of GLUT1 and GLUT3 mRNA (Northern analysis) were not affected by cholinergic lesion. Both immunocytochemistry and in situ hybridization demonstrated preferential localizations of GLUT1 on brain capillaries and GLUT3 on neurons, respectively. A lesion-induced transient decrease in [14C]D-glucose utilization seven days post lesion was detected in the lesion site, whereas cholinoceptive cortical regions were not affected. In vivo [14C]deoxyglucose uptake was transiently increased in cholinoceptive cortical regions and in the lesion site being highest between three to seven days after lesion. The cholinergic lesion-induced transient up-regulation of cortical glucose transporters and deoxyglucose uptake reflects an increased glucose demand in regions depleted by acetylcholine suggesting functional links between cortical cholinergic activity and glucose metabolism in cholinoceptive target regions.

Cardiomyoplasty - improvement of muscle fibre type transformation by an anabolic steroid (metenolone).

Dynamic cardiomyoplasty, a method to support ventricular function by the chronically stimulated latissimus dorsi muscle wrapped around the heart is accompanied by a loss of mass and force of the transplanted muscle. These effects and the fast-to-slow transformation of the muscle could be possibly influenced by the additional administration of anabolic steroids. In this study, the left latissimus dorsi muscles of 12 sheep were electrically conditioned (group A). In 12 other animals (group B), stimulation was combined with the administration of metenolone (100 mg/week). Biopsies were taken from the right and left muscles at the beginning and after 6 and 12 weeks of treatment, frozen and cross-sectioned. The muscle fibre type composition was studied enzymhistochemically (SDH-staining and Myosin-ATPase-reaction) and immunocytochemically (using antibodies against different myosin heavy chains, MHC). Furthermore, the expression of different MHC isoforms was investigated electrophoretically. The untreated latissimus dorsi muscle contains 20% type I fibres expressing slow MHC and 80% type II fibres expressing fast MHC. After 6 weeks, the respective fibre type composition was 42 and 58% (group A) and 80 and 20% (group B). After 12 weeks, the percentage of the type I fibres rose in group A to 59% and in group B to 98%. In accordance with these morphological results, the MHC pattern determined electrophoretically showed a corresponding shift from the fast to the slow isoform. Therefore, the administration of metenolone avoids severe muscle atrophy, and improves and accelerates fast to slow fibre type conversion necessary for successful cardiomyoplasty.

Effect of an anabolic steroid (Metenolon) on contractile performance of the chronically stimulated latissimus dorsi in sheep.

In 12 sheep the left latissimus dorsi muscles (LD) were conditioned by chronic electrostimulation with a pulse generator (Itrel, Medtronic). Six animals (group B) received a weekly intramuscular injection of an anabolic steroid (Metenolon). After 14 weeks the contraction parameters of the left LDs (group A and B) and right LDs (control group) were investigated. The increase in weight of the conditioned LDs was 11.07% (+/- 1.06%) in group A and 79.97% (+/- 40.8; P < 0.05) in group B. The force capacity under stimulation patterns which were just tetanic was 1.15 kp in group A and 4.13 kp in group B (P < 0.05); under supramaximal stimulation patterns it was 4.23 kp (A) and 6.0 kp (B) (P = ns). The force time relation (dF/dt) was 6.7 kp/s for the left LDs in group A versus 16.4 kp/s for the right LDs (P < 0.01); in group B it was 5.13 kp/s for the left LDs versus 15.8 kp/s for the control muscles (P < 0.05). The maximal force (Fmax) per 100 g muscle weight did not differ significantly (A: 2.42 kp/100 g; B: 2.52 kp/100 g). In conclusion, the LD muscles which were subjected to both anabolic therapy and electrical stimulation showed a significant increase in their force capacity due to an enormous increase in mass. Fibre type transformation was complete only in group B. No fibre deterioration was observable in either group. No anabolic side effects were detected in the animals. With the use of anabolic steroids, therefore, a clearer direct increase in contractility on the left ventricle should be expected ("squeezing" theory), as well as a contribution to reduction in wall tension and myocardial oxygen consumption, respectively, according to Laplace's Law (via the considerable increase in thickness).

[The effect of a Bordetella live vaccine on the occurrence and manifestation of atrophic rhinitis suum and the aerogenous infection burden in field strains of the agent]. / Untersuchungen zum Einfluss eines Bordetellen-Lebendimpfstoffes auf das Auftreten und die Ausprägung der Rhinitis atrophicans suum sowie den aerogenen Infektionsdruck durch Feldstämme des Erregers.

A field study was carried out in a large scale unit for swine breeding and fattening with the object to influence the high morbidity rate of Atrophic Rhinitis and pneumonia with the help of a Bordetella live vaccine. The results show that it is possible to decrease the infectious pressure by B. bronchiseptica and to reduce the pathomorphological signs of Atrophic Rhinitis in consequence of the application of the live vaccine. The pathologic-anatomical investigations of nasal turbinates in immunized slaughtered fattening pigs show a significant lower morbidity concerning Atrophic Rhinitis and a higher percentage of pigs without changes at conchae nasales and septum nasi. We find also a lower contamination of the air with B. bronchiseptica field strains during vaccine application. The results also explain that a high infectious pressure by B. bronchiseptica and the possibility of communication between unvaccinated and vaccinated groups of pigs counteract a better efficiency of the vaccine. The decrease of the morbidity rate of Atrophic Rhinitis appears so much more important because toxicogenic Pasteurella multocida strains were isolated from nasal swabs of vaccinated pigs during the investigations. But these strains influenced the Atrophic Rhinitis frequency only accidentally. All results as a whole point out that in pig houses with a high animal density one has to pay more attention to virulent B. bronchiseptica strains than it was been done till now.

[The tenacity of Bordetella bronchiseptica in the air]. / Tenazitätsuntersuchungen von Bordetella bronchiseptica im luftgetragenen zustand.

The survival time of Bordetella bronchiseptica (phase I and III) has been determined at a temperature of 21 degrees C and 27 degrees C and at a relative humidity of 32%, 58% and 76% in a rotating aerosol chamber. The highest survival time (118.8 min half-life time) has been found at 21 degrees C and 76% relative humidity in B. bronchiseptica (phase I). An increasing temperature (from 21 degrees C to 27 degrees C) causes a lower survival time. The phase I strains react more sensitive to this changing of environment than phase III strains. An increase of relative humidity leads to a higher survival time concerning phase I strains. In contrast phase III strains of B. bronchiseptica react with an increasing survival time. On the basis of the detected half-life time one must suppose an aerogenous distribution of the germ in all stages of animals, especially in intensive husbandry.

[Characterization of strains of Bordetella bronchiseptica isolated from animal housing air and of the airborne infection pressure proceeding from them]. / Charakterisierung aus der Stalluft isolierter Stämme von Bordetella bronchiseptica und der von ihnen ausgehende aerogene Infektionsdruck.

Strains of B. bronchiseptica were isolated from the air in farrowing and weaned piglet houses within the framework of follow-up investigations in an intensive pig breeding and fattening farm with 2600 productive sows. The strains were tested for their biological properties. The results show that virulent B. bronchiseptica-strains have been present as an aerosol in the air of both husbandry systems which refers to the infectious pressure of the animal house air. The number of isolated strains of B. bronchiseptica increases during both rearing phases of piglets. The toxin-forming ability of the strains from weaned piglet houses is higher in comparison with such from farrowing houses. This is a proof for the increasing infectious pressure during the rearing period. One has to take the transmission of virulent strains from animal houses with older pigs to such with younger one into account in case of a common air space. This could result in a lower impact of disinfection during the servicing period. The morbidity rate of atrophic rhinitis could be reduced by 60% in consequence of the application of a B. bronchiseptica-live vaccine. P. multocida couldn't be found neither on nasal mucous membrane nor in animal house air over the whole investigation period. All results as a whole point out that within the framework of the elaboration of a strategy for atrophic rhinitis control in pig houses with a high animal density one has to pay more attention to virulent B. bronchiseptica-strains in addition to toxinogenous strains of P. multocida.

[The pathology and pathogenesis of experimental Mycoplasma hyorhinis infection of piglets with and without thermomotor stress. 2. Electron microscopic study results]. / Untersuchungen zur Pathologie und Pathogenese der experimentellen Mycoplasma hyorhinis-Infektion der Ferkel ohne und mit thermomotorischer Belastung. 2. Mitteilung: Elektronenmikroskopische Untersuchungsergebnisse.

Electron microscopic investigations on the respiratory tract of piglets with and without Mycoplasma hyorhinis infection (10th day of life) partly combined with swim stress (15 degrees C water temperature) (n = 20/20) yielded the following results: colonization of Mycoplasma hyorhinis in the ciliary zone of trachea and bronchi in 15 out of 40 piglets (37.5%); the evidence rate of Mycoplasma hyorhinis in pneumonic lungs (8 out of 12 = 66.7%) was significantly higher than in nonpneumonic lungs (7 out of 28 = 25.0%) and highest in experimentally infected piglets with swim stress (9 out of 16 = 56.2%). Ultrastructural lesions: loss of cilia; bleb-formation; hydropic degeneration and desquamation of ciliary cells; the occurrence of cilia-free and immature epithelial cells; alveolar collapse; microatelectasis; oedematous swelling of pneumocyte I; accumulation of surfactant in the alveoli; hyperplasia of pneumocyte II; exudation of mononuclear macrophages and neutrophils with numerous digestion vacuoles; several lymphocytes and plasma cells, only a little lymphohistiocytic interstitial and peribronchial infiltration. Phagocytized mycoplasmas were found within the resorption vacuoles of neutrophils in the tracheobronchial area, for this once in alveoli, not (more) against in alveolar macrophages. The results were discussed with regard to etiology and pathogenicity of enzootic pneumonia in pigs.

[The pathology and pathogenesis of experimental Mycoplasma hyorhinis infection of piglets with and without thermomotoric stress. 1. Pathologico-anatomic, histologic and immunomorphologic study results]. / Untersuchungen zur Pathologie und Pathogenese der experimentellen Mycoplasma hyorhinis-Infektion von Ferkeln ohne und mit thermomotorischer Belastung. 1. Mitteilung: Pathologisch-anatomische, -histologische und immunmorphologische Untersuchungsergebnisse.

The effect of an experimental Mycoplasma (M.) hyorhinis infection (3 times intranasal instillation of 3-5 ml bouillon with 10(7) Colony forming units [CFU]/ml) in combination with a standard thermomotoric stress (swim-test) was studied in piglets using pathomorphological, immunomorphological and microbiological methods. The 92 piglets were divided into the following 5 groups: swimmers with infection (S-I; n = 19); swimmers without infection (S; n = 19); control piglets with infection (K-I; n = 21); controls without infection, but direct (K1; n = 16) or indirect contact (K2; n = 17) with experimentally infected animals. The experimental or spontaneous infection (direct or aerogenous infection) with M. hyorhinis caused in 30.4% of the piglets an acute or subacute, catarrhal-purulent bronchopneumonia with an interstitial component. Incidence and intensity of pneumonia were significantly higher in the groups with thermomotoric stress (independent from the mode of infection) than in the non-stressed groups. The M. hyorhinis pneumonia was characterized by a limited expansion and a trend to restitution. The causal agent (M. hyorhinis) was demonstrated with immunomorphological methods (immunofluorescence and PAP) in the ciliary zone of the nasal, tracheal and especially on the bronchial mucosa, and occasionally in the bronchioles and alveoli.