Evaluation of clinico-radiological, bacteriological, serological, molecular and histological diagnosis of osteoarticular tuberculosis

Background:

The diagnosis of osteoarticular tuberculosis is clinico-radiological in endemic areas. However every patient does not have the classical picture. Osteoarticular tuberculosis is a paucibacillary disease hence bacteriological diagnosis is possible in 10-30% of the cases. The present study is undertaken to correlate clinico-radiological, bacteriological, serological, molecular and histological diagnosis.

Materials and Methods:

Fifty clinico-radiologically diagnosed patients of osteoarticular tuberculosis with involvement of dorsal spine (n = 35), knee (n = 8), shoulder (n = 1), elbow (n = 2) and lumbar spine lesion (n = 4), were analyzed. Tissue was obtained after decompression in 35 cases of dorsal spine and fine needle aspiration in the remaining 15 cases. Tissue obtained was subjected to AFB staining, AFB culture sensitivity, aerobic/anaerobic culture sensitivity histopathological examination and polymerase chain reaction (PCR) using 16srRNA as primer. Serology was performed by ELISA in 27 cases of dorsal spine at admission and one and three months postoperatively.

Results:

AFB staining (direct) and AFB culture sensitivity was positive in six (12%) cases. Aerobic/anaerobic culture sensitivity was negative in all cases. Histology was positive for TB in all the cases. The PCR was positive in 49 (98%) cases. All dorsal spine tuberculosis cases showed fall of IgM titer and rise of IgG titer at three months as compared to values at admission.

Conclusion:

Histopathology and PCR was diagnostic in all cases of osteoarticular tuberculosis. The serology alone is not diagnostic.     

New Insights into Breast Cancer Genetics and Impact on Patient Management

OPINION STATEMENT: The combined observation that 20-30% of all patients with breast cancer have a family history of the disease and the results from twin studies showing that 25% of breast cancer cases are heritable, indicate that this malignancy is one of the most commonly inherited cancers. Discovery of the BRCA1 and BRCA2 genes more than a decade ago has had a tremendous impact on patient care allowing for early detection and prevention of breast cancer. However, deleterious mutations within the BRCA1 and BRCA2 genes cause at most 3-8% of all breast cancer cases. New data indicate that genomic rearrangements within the same genes may occasionally identify additional carriers of nonfunctional BRCA1 and BRCA2 genes. Such genomic rearrangements are missed by conventional sequencing. The remainder of the unexplained familial risk is presumably due to other yet unidentified high penetrance genes, but polygenic mechanisms and high frequency low penetrance tumor susceptibility genes are likely to account for a greater proportion of familial breast cancers. In this regard, there is growing evidence that a common variant of the type I TGF-ss receptor, TGFBR1*6A, may account for approximately 5% of all breast cancer cases, a fraction similar to that attributable to BRCA1 and BRCA2. Such genes may also modify the penetrance of the BRCA1 and BRCA2 genes. In the next decade, screening for combinations of high and low penetrance genes will likely permit the identification of a large fraction of inherited breast cancer cases and will further reduce the burden of familial breast cancer.     

A genetic signature can predict prognosis and response to therapy in breast cancer: Oncotype DX

We now recognize that not all breast cancers are the same. Different characteristics in gene expression profiles result in differential clinical behavior. With the use of gene microarrays, different subtypes of breast cancer have been characterized. These subtypes include the basal, the ERBB2+, and the luminal A, B and C subtypes. The importance of these different subtypes lies in the fact that they differ in clinical outcome, with the basal and ERBB2+ subtypes having the worst prognosis and the luminal A group having the best prognosis. However, identification of these subtypes is still not clinically used. Other strategies for evaluating tumors in a clinical setting have been developed using smaller sets of genes. One such strategy is the 21-gene assay (Oncotype DX), which is currently in commercial use in the USA. One advantage of this test is the use of paraffin-embedded blocks instead of previous methods, which required fresh frozen tissue. Oncotype DX has been shown to predict 10-year distant recurrence in patients with estrogen receptor-positive, axillary lymph node-negative breast cancer. This genomic assay has also been shown to predict chemotherapy and endocrine therapy response. Large, prospective, randomized clinical trials are currently underway using this genomic test. Other similar tests are also finding their way in clinical practice. A 70-gene assay, which has been developed by a group in The Netherlands, is currently being used as a tool to assign treatment in women with early stage breast cancer. In the near future, clinical decisions will most likely be dictated by the genetic characteristics of the tumor, with the clinical characteristics becoming less important. Tailoring our treatment based on individual tumor characteristics will help us develop better therapeutic strategies and save many of our patients from receiving unnecessary toxic therapy.     

Targeting angiogenesis in metastatic breast cancer

Angiogenesis has become an important target in the treatment of several solid tumors, including breast cancer. As monotherapy, antiangiogenic agents have demonstrated limited activity in metastatic breast cancer (MBC); therefore, they have generally been developed for use in combination with chemotherapies. Thus far, the experience with antiangiogenic agents for MBC has been mixed. The results from one study assessing addition of the monoclonal antibody bevacizumab to paclitaxel led to approval of bevacizumab for MBC. However, the modest improvement of progression-free survival rates in subsequent MBC studies has led to reappraisal of bevacizumab. Phase III studies have not produced evidence supporting use of the multikinase inhibitor sunitinib alone or in combination with MBC chemotherapy. Experience with sorafenib in a phase IIb program indicates potential when used in select combinations, particularly with capecitabine; however, phase III confirmatory data are needed. Although antiangiogenic therapies combined with chemotherapy have increased progression-free survival rates for patients with MBC, increases in overall survival times have not been observed. Some studies have tried to combine antiangiogenic agents such as bevacizumab and sunitinib or sorafenib, but that approach has been limited because of toxicity concerns. Sequential use of antiangiogenic agents with differing mechanisms of action may be an effective approach. Despite setbacks, angiogenesis will likely remain an important target of treatment for selected patients with MBC.     

Clinical features of juvenile Adamantiades-Beh?et's disease in Greece.

Adamantiades-Beh?et's disease (A-BD) is a chronic relapsing vasculitis of unknown etiology. This disease is relatively rare in children and only recently have series of patients been reported. The objective of this study was to describe the clinical features of the disease in juvenile patients, and to compare them with adult cases and with those juveniles reported in the literature.     

Association of MICA gene and HLA-B*5101 with Beh?et's disease in Greece.

PURPOSE: Beh?et's disease (BD) is known to be associated with HLA-B51 in many different ethnic groups. Recently MICA, a member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), was identified near the HLA-B gene, and a triplet repeat microsatellite polymorphism was found in the transmembrane (TM) region. Because a strong association with BD of one particular MICA-TM allele, A6, was shown in a Japanese population, the present study was conducted to investigate microsatellite polymorphism in Greek patients with BD to know whether this association is generally observed in BD occurring in other populations. METHODS: Thirty-eight Greek patients with BD and 40 ethnically matched control subjects were examined for MICA microsatellite polymorphism using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Similar to the Japanese patients with BD, the phenotype frequency of the MICA-TM A6 allele was significantly increased in the Greek patients with BD (50.0% in control subjects versus 86.8% in BD cases), with an odds ratio (OR) of 6.60 (P = 0.0012). The MICA-A6 allele was found in a high frequency both in males and females (weighted OR = 6.68; P = 0.0017). No association was found between the A6 allele and several disease features. A strong association exists between the MICA-TM A6 allele and the B*5101 allele in both the control subjects and patients with BD (weighted OR = 44.39; P = 0.0000023). CONCLUSIONS: This study revealed in Greek patients a strong association of BD with a particular MICA-TM allele, MICA-A6, providing insight into the molecular mechanism underlying the development of BD.     

Aufgaben der Ärztekammer und Kammerbeitrag

Abstrakt 1. überschreitet eine ?rztekammer durch bestimmte Ma?nahmen den ihr zustehenden Aufgabenbereich, so müssen die Mitglieder dagegen Unterlassungsklage erheben. 2. Zu den Aufgaben einer ?rztekammer geh?rt auch die Einrichtung und der Betrieb einer Akademie für ?rztliche Fort- und Weiterbildung und einer Schule zur Aus- und Fortbildung von Arzthelferinnen/medizinischen Fachangestellten. Die ?rztekammer darf die hieraus resultierenden Kosten bei der Bemessung des Kammerbeitrags berücksichtigen. (Leits?tze der Bearbeiterin)     

TGFBR1*6A and cancer risk: a meta-analysis of seven case-control studies.

PURPOSE: TGFBR1*6A is a hypomorphic polymorphic allele of the type I transforming growth factor beta receptor (TGFBR1). TGFBR1*6A is a candidate tumor susceptibility allele that has been associated with an increased incidence of various types of cancer. This study was undertaken to analyze all published case-control studies on TGFBR1*6A and cancer and determine whether TGFBR1*6A is associated with cancer. PATIENTS AND METHODS: All published case-control studies assessing the germline frequency of TGFBR1*6A were included. Studies assessing TGFBR1*6A in tumors were excluded. The results of seven studies comprising 2,438 cases and 1,846 controls were pooled and analyzed. RESULTS: Overall, TGFBR1*6A carriers have a 26% increased risk of cancer (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.07 to 1.49). Cancer risk for TGFBR1*6A homozygotes (OR, 2.53; 95% CI, 1.39 to 4.61) is twice that of TGFBR1*6A heterozygotes (OR, 1.26; 95% CI, 1.04 to 1.51). Analysis of various types of tumors shows that TGFBR1*6A carriers are at increased risk of developing breast cancer (OR, 1.48; 95% CI, 1.11 to 1.96), hematological malignancies (OR, 1.70; 95% CI, 1.13 to 2.54), and ovarian cancer (OR, 1.53; 95% CI, 1.07 to 2.17). Carriers of TGFBR1*6A who are from the United States are at increased risk of colorectal cancer (OR, 1.38; 95% CI, 1.02 to 1.86). However, Southern European TGFBR1*6A carriers have no increased colorectal cancer risk. There is no association between TGFBR1*6A and bladder cancer. CONCLUSION: TGFBR1*6A is emerging as a highfrequency, low-penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies.