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Biomedical subjects

B Bültmann

Publications and source records attributed to B Bültmann.

At least 19 recordsLinked to original sources

Sudden cardiac death in myotonic dystrophy type 2.

Medical records and follow-up data were reviewed in 297 genetically proven myotonic dystrophy type 2 (DM2) patients. Patients were selected by the criteria of cardiac sudden death before age 45. Sudden death occurred in four patients, three of whom were cardiological asymptomatic, and one with a history of heart failure. Cardiac histopathology showed dilated cardiomyopathy in all, and conduction system fibrosis in two patients. Pathogenetic CCUG ribonuclear inclusions were demonstrable in cardiomyocytes.

Adult↗

Fibromuscular dysplasia of the renal artery responsible for renovascular hypertension: a histological presentation based on a series of 102 patients.

BACKGROUND: Fibromuscular dysplasia (FMD) is a rare non-atherosclerotic and non-inflammatory disease in the arterial system. The purpose of the study was a retrospective analysis of FMD in the renal artery. PATIENTS AND METHODS: A total number of 102 patients (mean age: 36.9 years) who suffered from renovascular hypertension underwent a surgical therapy. The operative specimens of the renal arteries were analysed with the lightmicroscop using histological and immunohistochemical methods. RESULTS: 101 patients (99.02%) presented a medial FMD (extensive-medial subtype in 56 patients, 54.9%, subadventitial subtype in 29 patients, 28.4% and combined subtype in 16 patients, 15.7%). In 1 patient (0.98%) an adventitial FMD was found. We observed the following complications: true and dissecting aneurysms (75 patients, 74.5%), arterio-venous fistulae (2 patients, 1.96%) and chronic thrombosis (10 patients, 9.8%). CONCLUSIONS: With the progress in angioplasty, not all patients suffering from FMD undergo a primary surgical therapy and therefore this lesion is less seen in the daily work of the histopathologist.

Adult↗

Detection and typing of human papillomavirus by e6 nested multiplex PCR.

A nested multiplex PCR (NMPCR) assay that combines degenerate E6/E7 consensus primers and type-specific primers was evaluated for the detection and typing of human papillomavirus (HPV) genotypes 6/11, 16, 18, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 56, 58, 59, 66, and 68 using HPV DNA-containing plasmids and cervical scrapes (n = 1,525). The performance of the NMPCR assay relative to that of conventional PCR with MY09-MY11 and GP5+-GP6+ primers, and nested PCR with these two primer sets (MY/GP) was evaluated in 495 cervical scrapes with corresponding histologic and cytologic findings. HPV prevalence rates determined with the NMPCR assay were 34.7% (102 of 294) in the absence of cervical intraepithelial neoplasia (CIN 0), 94.2% (113 of 120) in the presence of mild or moderate dysplasia (CIN I/II), and 97.8% (44 of 45) in the presence of severe dysplasia (CIN III). The combination of all four HPV detection methods applied in the study was taken as "gold standard": in all three morphological subgroups the NMPCR assay had significantly (P < 0.0001) higher sensitivities than the MY09-MY11 and GP5+-GP6+ assays and sensitivities comparable or equal to those of the MY/GP assay. All 18 HPV genotypes investigated were detected among the clinical samples. The ratio of high- to low-risk HPV genotypes increased from 4:1 (80 of 103) in CIN 0 to 19:1 (149 of 157) in CIN I to III. Multiple infections were detected in 47.9% (124 of 259) of the patients. In conclusion, the novel NMPCR method is a sensitive and useful tool for HPV DNA detection, especially when exact HPV genotyping and the identification of multiple HPV infections are required.

DNA Primers↗

Urinary bladder biopsies in spinal cord injured patients.

STUDY DESIGN: A series of 94 urinary bladder biopsies in spinal cord injured (SCI) patients were histopathologically and statistically analysed. OBJECTIVES: The following hypotheses were examined: (1) The number of clinical bladder infections per year in each patient does not influence the histopathological type of inflammation of the urinary bladder; (2) The duration of the spinal cord lesion does not have a strong effect on the type of inflammation; (3) The different neurological levels (upper and lower motor neuron lesions) do not relate to a specific histopathology. SETTINGS: All patients received their treatment at the Swiss Paraplegic Centre in Nottwil, near Lucerne (Switzerland). METHODS: The samples were taken from the bladder fundus during endoscopic urologic operations. Histopathological standard procedures were carried out. Statistical analysis including Kruskal-Wallis and Chi-square tests were performed. RESULTS: Histopathological analysis showed abnormal alterations of the urinary bladder mucosa in 86 SCI-patients: (91.5%). 63 cases (67.0%) showed a chronic type and 23 cases (24.5%) showed a subacute type of inflammation. A normal urinary bladder was found in eight cases (8.5%). The three hypotheses were statistically not rejected. CONCLUSION: Results demonstrated no correlation between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa.

Adolescent↗

Human papillomavirus type 16-associated primary squamous cell carcinoma of the rectum.

Primary squamous cell carcinoma (SCC) of the colorectum is an extremely rare malignancy of unknown etiology and pathogenesis. We describe an 87-year-old man with primary SCC of the rectum. Routine histology demonstrated a squamous metaplasia-dysplasia sequence of the rectal mucosa with subsequent malignant transformation. Molecular biologic analysis using polymerase chain reaction (PCR) and in situ hybridization revealed the presence of human papillomavirus type 16 (HPV-16) DNA within metaplastic, dysplastic, and SCC lesions and in tumor-free rectal mucosa. Moreover, nested reverse-transcription PCR showed transcriptional activity of the viral E6/E7 oncogenes in tumor tissue and tumor-free rectal mucosa. By contrast, 4 typical adenocarcinomas of the rectum and their adjacent normal mucosa were found to be negative for HPV by nested PCR. In line with the well-established concept of HPV-associated anogenital carcinogenesis, our results strongly suggest an etiologic role of HPV-16 in the pathogenesis of the metaplasia-dysplasia-SCC sequence in the case described.

Adenocarcinoma↗

Lymph node micrometastases of cutaneous melanoma: increased sensitivity of molecular diagnosis in comparison to immunohistochemistry.

The presence of regional lymph node metastases is one of the most significant prognostic factors for predicting survival in patients with clinical stage I or II cutaneous melanoma. For accurate staging of the primary tumor a sensitive technique is required to detect occult nodal micrometastases. This prospective diagnostic study was designed to evaluate the incidence of nodal micrometastases using nested reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase in comparison to immunohistochemical examination. Furthermore, the incidence of melanoma micrometastases detected by RT-PCR was analysed in correlation to major prognostic factors. A total of 466 regional lymph nodes from 79 patients with primary cutaneous melanoma (tumor thickness > 0.75 mm) were investigated. In 49 lymph nodes from 31 patients immunohistochemistry demonstrated melanoma metastases. Using tyrosinase RT-PCR, nodal micrometastases were detected in 136 lymph nodes from 52 patients including all lymph nodes positive by immunohistochemical examination. Out of the 417 lymph nodes negative by immunohistochemistry, 87 nodes (21%) were identified to express tyrosinase by the RT-PCR technique. Among the 48 patients negative by immunohistochemical assessment, 21 (44%) had nodal micrometastases (n = 40) using RT-PCR. All 68 lymph nodes from 46 non-melanoma patients serving as negative controls for tyrosinase RT-PCR were negative. The detection of melanocytic nodal micrometastases by tyrosinase RT-PCR is a highly specific method with a sensitivity significantly higher than that achieved by immunohistochemistry (p < 0.0001). Patients with nodal micrometastases identified exclusively by RT-PCR had significantly higher tumor thickness as compared to patients with negative results by RT-PCR (p < 0.01).

Biomarkers, Tumor↗

Detection of human papillomavirus type 16 E6/E7 oncogene transcripts in dysplastic and nondysplastic cervical scrapes by nested RT-PCR.

Infections with high-risk human papillomaviruses (e.g., HPV-16) play an important role in the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (IC). Continued expression of the viral E6 and E7 genes is believed to be a key factor for oncogenic transformation of infected cells. Two spliced transcripts of the E6/E7 oncogenes, termed E6*I and E6*II, can be detected by reverse transcriptase polymerase chain reaction (RT-PCR). To increase the sensitivity of detecting E6/E7 transcripts in cervical scrapes we took advantage of a nested RT-PCR (nRT-PCR) protocol. In a series of 30 HPV-16-positive patients with histologic diagnoses ranging from nondysplastic epithelium to IC, the application of nRT-PCR significantly improved the detection of E6/E7 transcripts compared to conventional RT-PCR. The prevalence of E6/E7 spliced transcripts correlated with lesion severity and the nRT-PCR protocol allowed detection of these transcripts even in nondysplastic epithelium and CIN I lesions. Therefore, in epidemiologic follow-up studies, detection of E6/E7 transcripts by nRT-PCR should prove to be a useful diagnostic tool for risk evaluations regarding the development of CIN and its progression to cervical cancer, especially in high-risk HPV-type-infected patients with CIN 0 and CIN I.

Blotting, Southern↗

Extensive pectoral muscle necrosis after defibrillation: nonthermal skeletal muscle damage caused by electroporation.

A 37-year-old Italian male developed a myocardial infarct with subsequent ventricular fibrillation. He was defibrillated seven times with up to 360 Joules. Thirteen days later the patient died of recurrent myocardial infarct due to thrombotic occlusion of the left circumflex coronary artery. At autopsy, necrosis of the right pectoralis muscle was observed. Electroporation is the pathogenetic mechanism of skeletal muscle damage due to multiple defibrillations with high energy levels.

Adult↗

Detection of human papillomavirus 16 transcriptional activity in cervical intraepithelial neoplasia grade III lesions and cervical carcinomas by nested reverse transcription-polymerase chain reaction and in situ hybridization.

Continued expression of the oncogenes E6 and E7 of human papilloma virus "high risk" type 16 (HPV16) initiates neoplastic transformation and maintenance of the malignant phenotype in cervical carcinoma cells. The transcriptional activity of the HPV16 E6/E7 oncogenes was investigated in HPV16-containing cervical cell lines, cervical carcinomas, and cervical intraepithelial neoplasia grade III lesions using the techniques of reverse transcription-polymerase chain reaction (RT-PCR), Southern blotting, and in situ hybridization. To facilitate detection of the full-length HPV16 E6/E7 oncogene transcript and its characteristic splice products E6*I and E6*II in cervical tissues, a nested RT-PCR (nRT-PCR) assay was designed. Specific detection of HPV E6/E7 oncogene transcripts in clinical specimens was found to be improved by nRT-PCR, being as sensitive as the combination of conventional RT-PCR and subsequent Southern blot hybridization. Regarding the progression of premalignant lesions to cervical cancer, detection of the HPV transcriptional activity by nRT-PCR may provide additional information for risk evaluations. Moreover, improvements in the amplification of HPV oncogene transcripts may also be advantageous for monitoring the activity of HPV before and after transcript-targeted gene therapy of cervical cancer.

Carcinoma↗

[Clostridium sordellii sepsis with intravascular haemolysis].

HISTORY AND CLINICAL FINDINGS: A 37-year-old chronic alcoholic had increasingly frequent haematemesis and recently had developed upper abdominal pain. His general condition had clearly deteriorated and he was finally admitted as an emergency. There were no previous illnesses other than alcoholism. He had a fever of 39.0 degrees C on admission, his sclerae were icteric and his abdomen was hard and resistant to palpation. He was slightly drowsy. INVESTIGATIONS: Laboratory tests indicated haemolysis with a haemoglobin of 10 g/dl, lactate dehydrogenase concentration of 330 U/l, urobilinogenuria and a raised white blood cell count of 11,500/microliter. Sonography revealed liver cirrhosis and ascites. TREATMENT AND COURSE: Because of the haematemesis a gastroscopy was performed, during which the patient went into acute shock from which he died. At autopsy the cause of the bleeding was found to be an ulcer at the oesophagocardiac junction. The gastrointestinal tract was filled with blood. He also had alcoholic liver cirrhosis with portal hypertension, as well as splenomegaly as sign of a septicaemia. Histologically masses of rod-shaped bacteria were found, especially in the heart, but also in liver, kidneys and peritoneum, which bacteriologically were identified as Clostridium sordellii. CONCLUSION: In patients with impaired immunological resistance Clostridium sordellii may cause an acute and quickly fatal septicaemia with intravascular haemolysis.

Adult↗

[Association of bone marrow mastocytosis with extremely immature extramedullary mast cell sarcoma].

The case of a 63-year-old man with a widespread retroperitoneal tumor and two tumor nodules in the left testis is described. Histopathological and cytopathological examination of tissue from the retroperitoneal tumor led to a diagnosis of lymphoreticular neoplasia. The patient died in acute cardiac failure, five weeks after initial presentation. Autopsy revealed another tumor nodule in the right atrium. Macroscopically, the bone marrow appeared normal. The tumor cells were reactive for CD45, vimentin and chloroacetate esterase, but were uncreative with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens and antibodies against tryptase and c-kit (CD117), characteristic markers for mast cells. However, the bone marrow exhibited the typical picture of mastocytosis. A diagnosis of bone marrow mastocytosis with an associated secondary extramedullary mast cell sarcoma was established. The cause of death was heart failure due to arrhythmia caused by an exophytic atrioseptal tumor nodule.

Biomarkers, Tumor↗

[High malignant B-cell non-Hodgkin lymphoma of the heart: intravital diagnosis by transesophageal echocardiography controlled biopsy].

We report about a 66-year old patient with Non-Q-wave infarction in coronary artery two-vessel disease. During an echo- and transesophageal multiplane echocardiography preoperatively before a coronary artery bypass surgery a right atrium septal tumor of unknown form was discovered. The computerized axial tomography (CAT) and nuclear magnetic resonance (NMR) scans did not demonstrate extracardiac pathologic findings. A transesophageal echocardiography-guided biopsy of the right atrial septum over the vena femoralis and the right atrium enabled intra vitam a very early diagnosis of high malignant B-cell Non-Hodgkin-lymphoma without the need for thoracotomy. The diagnosis was confirmed histopathologically and immunohistochemically and early treatment with cytostatic therapy could begin. To our knowledge the transesophageal echocardiography-guided biopsy has never been described in the worldwide literature.

Aged↗

Ectopic prostatic tissue in the spleen.

Ectopic prostatic tissue was found in the spleen in a 49-year-old white man who died of wide-spread malignant mesothelioma. The prostatic origin of the tissue was affirmed by positive immunohistochemical staining for prostatic specific antigen and prostatic acid phosphatase.

Choristoma↗

Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets.

In order to identify organ and cellular targets of persistent enterovirus infection in vivo, immunocompetent mice (SWR/J, H-2q) were inoculated intraperitoneally with coxsackievirus B3 (CVB3). By use of in situ hybridization for the detection of enteroviral RNA, we show that CVB3 is capable of inducing a multiorgan disease. During acute infection, viral RNA was visualized at high levels in the heart muscle, pancreas, spleen, and lymph nodes and at comparably low levels in the central nervous system, thymus, lung, and liver. At later stages of the disease, the presence of enteroviral RNA was found to be restricted to the myocardium, spleen, and lymph nodes. To characterize infected lymphoid cells during the course of the disease, enteroviral RNA and cell-specific surface antigens were visualized simultaneously in situ in spleen tissue sections. In acute infection, the majority of infected spleen cells, which are located primarily at the periphery of lymph follicles, were found to express the CD45R/B220+ phenotype of pre-B and B cells. Whereas viral RNA was also detected in certain CD4+ helper T cells and Mac-1+ macrophages, no enteroviral genomes were identified in CD8+ cytotoxic/suppressor T cells. Later in disease, the localization of enteroviral RNA revealed a persistent type of infection of B cells within the germinal centers of secondary follicles. In addition, detection of the replicative viral minus-strand RNA intermediate provided evidence for virus replication in lymphoid cells of the spleen during the course of the disease. These data indicate that immune cells are important targets of CVB3 infection, providing a noncardiac reservoir for viral RNA during acute and persistent myocardial enterovirus infection.

Acute Disease↗