Colorectal hemangioma: radiologic findings

The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma.     

Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-beta 1 mechanism

Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2+CD3/TCR-CD4-CD8- (triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2I+III-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL- 7, or CD2-MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3+CD8+CD4- cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8+ cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8+ cell-derived inhibition of TN cell growth. Analysis of CD8+ cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8+ cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output.     

Concomitant chemoradiation in patients with cervix cancer

Cervical cancer is the 2nd most common cancer among women, behind breast cancer. Concomitant chemoradiation has been assessed in more than 15 randomised clinical trials. A meta-analysis for overall survival showed a statistically significant difference in favour of chemoradiotherapy: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.14-1.26, p < 0.001, p hetero = 0.21). Disease-free survival was also statistically significantly higher in favour of chemoradiotherapy: RR = 1.26, 95%CI = 1.17-1.35, p < 0.001). The benefit was more pronounced in trials including a higher proportion of stage I and II patients. Concomitant chemoradiotherapy showed a significant benefit for both local control and distant metastasis. Gastrointestinal and haematological toxicities were significantly more frequent in the chemoradiotherapy group. Details of late toxicity were sparse and therefore it was not possible to conclude on an increase of late complication rate with concomitant chemoradiotherapy. The inclusion criteria were not the same in all the trials, resulting in populations with varying distributions in disease stages. In addition, the treatment schemas for both radiotherapy and chemotherapy used in these trials were different. These results were obtained with chemotherapy based on various molecules, including cisplatin, either alone or with other cytotoxic drugs, such as 5-fluorouracil. For a similar level of benefit, the combination of cisplatin, 5-fluorouracil and hydroxyurea was more toxic than cisplatin alone in one trial in which the two protocols were compared. Future randomised trials should also aim to establish optimal chemotherapy regimens for combination with radiotherapy.     

Comparison of molecular abnormalities in bronchial brushings and tumor touch preparations

BACKGROUND: Preneoplastic lung lesions and early-stage lung carcinomas are associated with molecular abnormalities. The authors performed a pilot study to evaluate the use of DNA fluorescence in situ hybridization (FISH) probes to ascertain whether these biomarkers can predict nonsmall cell lung carcinoma (NSCLC). METHODS: Fourteen bronchial brushings ipsilateral to the tumor (BB/Ts), tumor touch imprints, and touch imprints of the bronchus adjacent to the tumor obtained from 15 patients with early-stage NSCLC were analyzed. The LAVysion multicolor probe set consisting of probes to 5p15, 6, 7p12, and 8q2 and the in-house probes 3p22.1 and 10q22 was used. Using the LAVysion multicolor probe set, 25 epithelial cells were counted and considered positive if > 5 cells were abnormal. Using 3p22.1 and 10q22, > or = 100 nuclei per slide were scored. The results were tabulated as the percentage of cells with deletions compared with the centromeric probes 3 and 10. Greater than 2% of the deletions were positive for 3p22.1 and 10q22. Bronchial washings from patients without lung tumors were used as controls. RESULTS: The BB/Ts were negative for malignant cells by cytologic evaluation and the LAVysion probe set; however, the combined in-house probes for 3p22.1 and 10q22 tested on BB/Ts predicted cancer in 100% of cancer patients. FISH positivity in the lung cancers was 100% for 3p22.1 deletions, 79% for 10q22 deletions, and 57% for LAVysion probes. When compared with the bronchial epithelium, tumor cells showed a 3.7-fold excess of 3p22.1 deletions, a 2-fold excess of 10q22 deletions, and a 12.6-fold excess of abnormal cells. CONCLUSIONS: The current study indicated that detection of molecular abnormalities in bronchial epithelial cells via FISH was very useful in identifying patients at high risk for developing lung carcinoma. The molecular abnormalities identified in the BB/Ts were detected at elevated levels in the tumor specimens.     

Anatomy of pelvic and para-aortic nodal spread in patients with primary fallopian tube carcinoma

BACKGROUND: To describe characteristics of patients with nodal spread and the anatomy of pelvic and para-aortic node involvement in primary fallopian tube carcinoma. STUDY DESIGN: Between 1985 and 2003, 19 women with primary fallopian tube carcinoma underwent systematic bilateral pelvic and para-aortic lymphadenectomy up to the level of the left renal vein. Initial lymphadenectomy (without chemotherapy) was performed in 6 patients and in 13 patients lymphadenectomies were performed after chemotherapy at the time of second-look operation. RESULTS: Nine patients had nodal involvement: four in the pelvic area and eight in the para-aortic nodes. Two, one, and six patients had stages I, II, or III disease, respectively. When para-aortic nodes were involved, the left para-aortic chain above the level of the inferior mesenteric artery was the site most frequently involved (six patients). CONCLUSIONS: In patients with primary tubal carcinoma, the left para-aortic chain above the level of the inferior mesenteric artery is the most frequently involved. Lymphadenectomy should involve all pelvic and para-aortic chains up to the level of the left renal vein, even in patients with stage I disease.     

Reproducibility and validity of a Yan-style portable citric acid cough challenge

Although many different methods of measuring cough reflex sensitivity have been published, few are simple enough to use outside of a hospital or laboratory environment. The aim of this study was to develop a simple, quick, and portable cough challenge, assess its reproducibility, and compare its results with those measured by an existing established hospital protocol. Twenty-five volunteers performed cough challenges based on an established hospital dosimeter protocol, and, on a separate occasion, by a protocol inhaling citric acid from DeVilbiss 40 hand-held nebulisers (citric acid concentrations of 10-3000 mM). Reproducibility of the hand-held cough challenge was assessed in 11 volunteers. Cough thresholds were consistently higher by the hand-held method than by the hospital dosimeter method. The geometric mean citric acid concentrations causing two coughs (threshold D2) were 3.14 and 2.77 log mM, respectively (p<0.001). The geometric mean (95% CI) difference between the tests was 0.51 log mM (0.18-0.83) of the average of the two values. Cough D2 thresholds attained by the two techniques did, however, show significant correlation (r=0.95, p<0.0001). The coefficient of repeatability for the hand-held method was 0.40 log mM. Administering citric acid from DeVilbiss 40 hand-held nebulisers offers a rapid, portable, and reproducible cough challenge in healthy volunteers. The results correlate well with an existing Mefar dosimeter challenge, but give two to three times greater cough thresholds.     

First case of a centropelvic recurrence after radical trachelectomy: literature review and implications for the preoperative selection of patients

BACKGROUND: To report the first case of a centropelvic recurrence in a patient who underwent a radical trachelectomy (RT) for a stage IB1 cervical carcinoma. CASE: A 32-year-old woman presented with a stage IB1 adenocarcinoma that was treated by radical trachelectomy. The tumor measured 21 x 20 mm. Minimal lymphatic space involvement was observed close to the tumor associated with 30 negative nodes and free margins. The upper free margin measured only 5 mm. Twenty-six months after the surgical procedure, the patient became pregnant. Clinical examination and pap smears were normal 2 months prior. During the first trimester, ultrasonography depicted a suspicious lesion in the bladder. Abdomino-pelvic magnetic resonance imaging (MRI) demonstrated a suspicious 20-mm tumor in the bladder associated with suspicious common iliac nodes. Cystoscopy and biopsies were carried out which confirmed recurrent disease. The patient received external radiation therapy combined with concomitant chemotherapy. CONCLUSIONS: More data are required to establish what is the safety distance between the tumor and the uterine transection. A distance of 5 mm or less is likely to be too limited for radical trachelectomy to be accepted as treatment for cervical cancer.     

Vasoconstrictive effects of endothelin-1, endothelin-3, and urotensin II in isolated perfused human lungs and isolated human pulmonary arteries

BACKGROUND: Urotensin II (UII) has been identified as a ligand for the orphan receptor GPR14 through which it elicits potent vasoconstriction in humans and non-human primates. The pulmonary vasculature is particularly sensitive; human UII (hUII) exhibits a potency 28 times that of endothelin (ET)-1 in isolated pulmonary arteries obtained from cynomolgus monkeys. However, hUII induced vasoconstriction in isolated human intralobar pulmonary arteries is variable, possibly as a result of location dependent differences in receptor density or because it is only uncovered by disease dependent endothelial dysfunction. METHODS: The vasoactivity of both hUII and gobi UII (gUII) in comparison with ET-1 and ET-3 was studied in isolated perfused lung preparations (n = 14) and isolated intralobar pulmonary arteries (n = 40, mean diameter 548 (27) microm) obtained from 17 men of mean (SE) age 67 (2) years and eight women of mean (SE) age 65 (3) years with a variety of vascular diseases. RESULTS: ET-1 (10 pM-100 nM) and ET-3 (10 pM-30 nM) elicited vasoconstriction in the lung preparations, inducing comparable increases in pulmonary arterial pressure of 24.8 (4.5) mm Hg and 14.5 (4.9) mm Hg, respectively, at 30 nM (p = 0.13). Similarly, ET-1 (10 pM-300 nM) and ET-3 (10 pM-100 nM) caused marked vasoconstriction in isolated pulmonary arteries, inducing maximal changes in tension of 4.36 (0.26) mN/mm and 1.54 (0.44) mN/mm, respectively, generating -logEC(50) values of 7.67 (0.04) M and 8.08 (0.07) M, respectively (both p<0.05). However, neither hUII nor gUII (both 10 pM-1 micro M) had any vasoactive effect in either preparation. CONCLUSION: UII does not induce vasoconstriction in isolated human pulmonary arterial or lung preparations and is therefore unlikely to be involved in the control of pulmonary vascular tone.     

Phenotypic expression of the targeted null-mutation in the dopamine transporter gene varies as a function of the genetic background

The dopamine transporter (DAT) plays a critical role in calibrating the duration and intensity of dopamine (DA) neurotransmission. Mice in which the DAT gene has been genetically deleted exhibit constitutively high levels of extrasynaptic DA and spontaneous hyperactivity. Numerous studies have characterized the adaptive molecular, physiological, and behavioural consequences of abnormal DA neurotransmission in these mice. In order to determine the genetic background contribution to these phenotypes, the DAT mutation was transferred on C57BL/6JOrl (B6) or DBA/2JOrl (D2) inbred backgrounds for more than ten generations of back-crossing to derive three B6-, D2-, and B6xD2(F(1))-DAT strains. We observed that the genetic background dramatically affects phenotypes previously reported on DAT knockout (KO) mice. Depending on the genetic background, it was possible to restore survival, growth rate and ability to lactate. Interactions with the genetic background were found to modulate both quantitative and qualitative patterns of novelty-driven spontaneous hyperactivity. The paradoxical calming effect of cocaine was observed for all DAT-KO mice. However, the genetic background influenced individual threshold responses to both locomotor and rewarding effects of cocaine. These findings reveal the extent of phenotypic variation associated with the DAT mutation. They also provide concrete arguments against the assumption that the normal function of a gene can be inferred directly from its mutant phenotype.