Determination of left atrial appendage morphology.
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Biomedical subjects
Publications and source records attributed to G Ernst.
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We wanted to find out if chest pain in cardiac syndrome X can be a manifestation of neuromuscular disorders. Five patients with cardiac syndrome X (3 women, 2 men), aged 34 to 70 years, consented with a clinical neurological examination, muscle enzyme testing, electroneurography of the right median and peroneal nerves and electromyography of the right brachial biceps and anterior tibial muscles. A neuromuscular disorder was found in 1 of the 5 investigated patients. The 60-year-old man presented with a monoparesis of the left leg and sensory dysfunction of the left upper and lower limb. He was diagnosed as having either posttraumatic myelopathy or radiculopathy. Since chest pain in cardiac syndrome X can be caused by neuromuscular disorders, a comprehensive neurological examination is recommended in patients with this disorder.
Comparative genomic hybridization (CGH) was used to study genomic imbalances in 77 squamous cell carcinomas of the head and neck (HNSCC) and in four cell lines derived from oral carcinomas. Particular attention was paid to all tumors characterized by a gain of two specific chromosomal segments, i.e. 3q26-qter and 5p14-p15. The 57 tumors containing both or one of the two imbalances were compared with 20 tumors lacking both with regard to genomic complexity, as well as to associated genomic, histopathologic and clinical peculiarities. 60% of the oral, and 66% of the non-oral cancers exhibited a gain of 3q26-qter, while a gain of 5p14-p15 was found in 66% of the oral, but only in 48% of the non-oral tumors. 48% of all tumors were characterized by both gains together, 26% exhibited only one of the two alterations. It could be shown that presence of both, gain of 3q26-qter and 5p14-p15, was clearly associated with a significantly higher complexity of genomic changes which was not only expressed as a high frequency of DNA copy number alterations (CNAs) but was also connected with a considerable number of additional amplifications of various chromosomal segments and a high conformity of the patterns of genomic imbalances in these tumors. Clear differences of the extent and of the patterns of genomic imbalance could be observed between oral and non-oral tumors. With respect to histopathological parameters, no clear association could be found for specific imbalances to the grade of differentiation, nor the invasiveness or metastatic status of the tumors. However, a higher number of patients with tumors characterized by gain of 3q26-qter plus 5p14-p15 died within a short period (i.e. less than 15 months) after excision of the tumor compared to the group without these imbalances. The implications of these findings are discussed from the oncogenetic and clinical aspects and in comparison with other reports.
Complex mechanisms have evolved in mammalian cells for regulating cellular lifespan. Normal cells demonstrate a strictly limited growth potential and senescence after a defined number of cell divisions. In contrast, tumor cells often exhibit an apparently unlimited proliferation potential and are termed immortalized. It has been proposed that the progressive shortening of the tips of the eukaryotic chromosomes--the telomeres--is an important component of senescence and is involved in the control of cell cycle. The enzyme telomerase adds TTAGGG repeats onto mammalian telomeres, preventing their shortening. Telomerase is normally inactive in most somatic cells, but detectable in tumor cells. The activation of telomerase in malignant cancers seems to be an important step in tumorigenesis in order to gain the ability of indefinite proliferation and to become immortal. This review describes the present knowledge of telomeres and telomerase and their role in cellular senescence and human aging. It summarizes aspects of telomerase in cancer and its function as a diagnostic and prognostic tumor marker.
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We review the present knowledge of telomeres and telomerase with special attention to their role in cell proliferation, cellular senescence, and human aging. We summarize the functional aspects of telomerase in cancer, as well as its role as a useful diagnostic and prognostic tumor marker, and discuss possible approaches to telomerase inhibition as a target for cancer therapy.
Telomeres, the extreme ends of chromosomes, play an important role in chromosome structure and function. The shortening of telomeres is one of the supposed mechanisms of cellular aging and death. Because of end replication problems the length of telomeres decreases with every cell cycle. This may lead to chromosome instability and additional genetic alterations possibly responsible of significant tumor development. In many cancer cells the length of telomeres depends on a balance between the loss of telomeric repeats, at each replication cycle, and the telomere lengthening, by the enzyme telomerase, which is repressed in most normal somatic cells. Many tumor cells demonstrate shortened telomeres in comparison to the corresponding normal tissue. In some types of human cancers the reduction of telomeric repeats was correlated with increasing disease severity. We analyzed Southern blots of HINF1-digested DNA of a large number of renal cell carcinomas (RCC) including different tumor areas, secondary tumors and metastases (76 cases with 142 tumor samples) for changes in the length of telomeric repeats using the oligonucleotide probe (TTAGGG)3 and found telomere shortening in 54%, suggesting that a reduction of the telomeric repeat length is not a general characteristic in RCC. Intratumor heterogeneity was demonstrated in seven cases. But also two RCC, with elongated telomeres in the tumor tissue, were observed. Shortened telomeres do not seem to be associated with advanced stages of tumor development or specific histopathological subtypes of RCC.
BACKGROUND: When examining the left atrial appendage by transesophageal echocardiography, differences in size and shape of the left atrial appendage are to be observed. The study was carried out with the aim of investigating the morphology of the left atrial appendage and to find associations with pathologic cardiac findings. METHODS AND RESULTS: In 220 cases (106 female, 114 male, mean age 72 +/- 13 years) a cast of the left atrial appendage was made after the post mortem examination by using synthetic resin. In 198 cases an ECG was available (sinus rhythm n = 143, atrial fibrillation n = 55). The casts were described in respect to course and ramifications of the principal axis. The casts were measured concerning orifice diameters, outline, and volume. Most frequently (42%) the course of the principal axis was angulated below 100 degrees. More than five ramifications of the principal axis were found in 56% of the casts. The volume ranged from 770-19,270 mm3 (mean 5,220 +/- 3,041). When comparing the clinical and autopsy-data of the patients with the morphology of the casts, associations could be found between the volume of the casts and atrial fibrillation (7,060 mm3 as compared to 4,645 mm3 in sinus rhythm, P < 0.01), left ventricular hypertrophy (5,740 mm3 as compared to 4,639 mm3 without hypertrophy, P < 0.01), myocardial scars (5,923 mm3 as compared to 4,891 mm3 without scars, P < 0.05), closed foramen ovale (5,515 mm3 as compared to 4,037 mm3 with patent foramen ovale, P < 0.01), and left atrial appendage thrombi (8,566 mm3 as compared to 5,027 mm3 without thrombi, P < 0.01). CONCLUSION: Left atrial appendages are formations greatly varying in volume and shape. This variability should be considered when interpreting images of the left atrial appendage, and in particular when diagnosing thrombi.
To date, it has remained unclear whether orbit-infiltrating T cells in patients with Graves' ophthalmopathy (GO) represent a primary immune response in which a limited number of T cell clones driving the disease are activated against specific antigens, or whether they participate in a non-specific inflammatory process. To characterize these T cells at the molecular level, we examined the T cell antigen receptor (TcR) V gene repertoire in situ in retroorbital tissue specimens obtained from patients with early and late stages of clinically severe GO and from patients with non-GO orbital conditions. Ribonucleic acid extracted from orbital tissue and peripheral blood lymphocytes (PBL) was reverse transcribed and amplified using the polymerase chain reaction and 22 V alpha and 24 V beta gene-specific oligonucleotide primers. The resulting TcR V alpha and V beta transcripts were verified by Southern hybridization analysis using TcR C region-specific, digoxigenin-labeled oligonucleotide probes. Compared with matched PBL, the retroorbital TcR V alpha and V beta gene repertoire expressed was heterogeneous, but revealed marked restriction of V gene usage in samples derived from retroorbital connective tissue and extraocular muscle of all eight patients with severe GO of short duration studied. In contrast, greater diversity of the TcR V beta gene repertoire and loss of TcR V alpha gene restriction was noted in four patients with late GO undergoing reconstructive eye muscle surgery. Unrestricted TcR V gene usage was demonstrated in orbital tissue and PBL samples obtained from control subjects. These results suggest that retroorbital TcR V gene usage is variable but markedly restricted during the earlier stages of GO. With increasing disease duration, greater diversity of the TcR V gene repertoire appears to develop, and oligoclonality of the T cell response may be lost. Selection of patients with early stages of GO will be important when further dissecting TcR usage and antigen specificity of orbit-infiltrating T lymphocytes in GO.
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Following the original description of HCV in 1989 a tremendous amount of sequence data is now available. Based on the 8 complete nucleotide sequences published so far at least 4 genotypes can be distinguished. Partial sequences of additional HCV isolates indicate the existence of further genotypes. A serological typing is not yet possible. For detection of virus, reverse transcription and amplification of the 5' non coding region is most commonly performed. This region of the genome is highly conserved among all isolates. In this study we used regions of the E1 and E2 gene in order to classify HCV isolates. The nucleotide sequences of regions in E1 and E2 gene of different European isolates from Germany, Croatia, Hungary, and Rumania were determined and compared to recently published RNA sequences of American and Japanese HCV isolates. The cDNA, obtained by reverse transcription of viral RNA extracted from sera was amplified by nested PCR, cloned and sequenced. Within 564 nucleotides (nt) of E1 we found 87-90% homology (and 89-92% homology at aa level) compared to sequences of Japanese origin and 73-74% homology (77-81% at aa level) compared to the prototype HCV sequence (ptHCV-I). In all characterized isolates the sequence of E2 (643 nucleotides) showed a homology of about 83% at the nucleotide level as compared to genotype II sequences, and a homology of about 70% to genotype I. Our results confirm the existence of two hypervariable regions in the E2 gene of genotype II sequences. Our results also indicate together with other reports from European HCV isolates that genotype II is predominant in Europe.
A total of 19 patients (aged 17-66 years) with priapism received primarily conservative treatment in the form of aspiration of blood from the cavernous bodies and subsequent intracavernous (i.c.) administration of the alpha-adrenergic drug metaraminol. In 15 patients the priapism was due to i.c. injection of vasoactive agents; 1 patient each it had developed after hemodialysis, during oral prazosin medication, and in conjunction with Fabry's disease; and in 1 patient the etiopathogenesis was unknown. Treatment of priapism with metaraminol was successful in the first 15 patients and in 2 patients with priapism due to hemodialysis and oral prazosin medication. Therapy failed in long-lasting priapism associated with Fabry's disease and in priapism of unknown etiopathogenesis. Penile detumescence took place in the first 15 patients 3 min to 2.5 h after the injection of 2-4 mg metaraminol. Hemodialysis- and prazosin-linked priapism was treated with 5 and 2 mg metaraminol, respectively; in these patients erection subsided within 15 and 4 min after onset of therapy. In a further 2 patients in whom therapy had failed Al-Ghorab shunts were constructed, with the subsequent postoperative complication of erectile impotence. Injection of metaraminol must be carried out under strict supervision of the patient's circulatory system: doses of 4 mg metaraminol or more led to an increase in blood pressure and heart rate. In 15 patients with priapism induced by i.c. application of vasoactive agents, the analysis of blood gas parameters demonstrated a severe hypercapnia (70.3 +/- 10.0 mm Hg) and acidosis (pH 7.08 +/- 0.08) 5-10 h after the onset of erection, but severe hypoxia (37.0 +/- 16.6 mm Hg) was not found until erection had lasted for more than 10 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Priapism occurred as a result of leukostasis due to an extreme rise in leukocyte count (503,000/microliter, 96% lymphocytes) in a 46-year-old man with chronic lymphatic leukaemia. In addition to surgical treatment, anticoagulant administration and cytostatic treatment several courses of lymphapheresis were performed using a cell separator. This latter procedure quickly reduced the number of lymphocytes and improved the patient's operability.
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In 24 (4.8%) of 503 patients with renal tumors, the growth was located in solitary or residual kidneys, and the overall renal function was diminished. This was the indication used for tumor enucleation or partial nephrectomy. Of the patients with renal cell carcinoma, 75% were free of tumor after a mean follow-up of 27 months (8-65). There were 18 patients with stage 1 (T1, T2, N0, M0) and 2 with stage 2 tumors. Three patients had a angiomyolipoma and one underwent nephrectomy because of a late postoperative complication. This outcome compares favorably with the results of radical nephrectomy in cases with normal kidney function. In conclusion, enucleation or partial nephrectomy is justified in patients with impaired renal function and may be considered in patients with T1, G1 tumors in normal functioning kidneys.