Mitochondrial dysfunction increases pro-inflammatory cytokine production and impairs repair and corticosteroid responsiveness in lung epithelium.

COPD is characterized by chronic lung inflammation and irreversible lung tissue damage. Inhaled noxious gases, including cigarette smoke, are the major risk factor for COPD. Inhaled smoke first encounters the epithelial lining of the lungs, causing oxidative stress and mitochondrial dysfunction. We investigated whether a mitochondrial defect may contribute to increased lung epithelial pro-inflammatory responses, impaired epithelial repair and reduced corticosteroid sensitivity as observed in COPD. We used wild-type alveolar epithelial cells A549 and mitochondrial DNA-depleted A549 cells (A549 Rho-0) and studied pro-inflammatory responses using (multiplex) ELISA as well as epithelial barrier function and repair (real-time impedance measurements), in the presence and absence of the inhaled corticosteroid budesonide. We observed that A549 Rho-0 cells secrete higher levels of pro-inflammatory cytokines than wild-type A549 cells and display impaired repair upon wounding. Budesonide strongly suppressed the production of neutrophil attractant CXCL8, and promoted epithelial integrity in A549 wild-type cells, while A549 Rho-0 cells displayed reduced corticosteroid sensitivity compared to wild-type cells. The reduced corticosteroid responsiveness may be mediated by glycolytic reprogramming, specifically glycolysis-associated PI3K signaling, as PI3K inhibitor LY294002 restored the sensitivity of CXCL8 secretion to corticosteroids in A549 Rho-0 cells. In conclusion, mitochondrial defects may lead to increased lung epithelial pro-inflammatory responses, reduced epithelial repair and reduced corticosteroid responsiveness in lung epithelium, thus potentially contributing to the pathogenesis of COPD.

Should internal mammary chain (IMC) sentinel node biopsy be performed? Outcome in 90 consecutive non-biopsied patients with a positive IMC scintigraphy.

INTRODUCTION: Although the status of the regional lymph nodes is an important determinant of prognosis in breast cancer, harvesting sentinel nodes (SN) detected in the internal mammary chain (IMC) is still controversial. AIMS: To determine in how many patients a positive IMC-SN might change the systemic or locoregional adjuvant therapy, with a possible benefit in outcome. PATIENTS AND METHODS: During 6 1/2 years data of T1-2 breast cancer patients, having an SN procedure, were prospectively collected. Our policy was not to explore the IMC even if it was the only localization of an SN. RESULTS: In 86 of 571 patients lymphoscintigraphy showed an IMC-SN. In 64 of these, the axillary SN was negative and only 25 of these patients did not have an indication for adjuvant systemic treatment based on their tumor characteristics. In the literature, IMC metastases are found in 0-10% of axillary negative patients. Routine IMC-SN biopsies would have resulted in an indication for adjuvant systemic therapy in 2-3 of our patients. Four parasternal recurrences were found during a median follow-up of 51 months. CONCLUSIONS: Harvesting IMC-SNs is a procedure of which only a limited number of patients have therapeutical benefit. Even with a thorough selection of patients, the extra morbidity of the procedure should be weighed against the potential benefit for the patient.

Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression.

To determine the frequency of progressive MRI lesions shortly after radiotherapy for glioma with spontaneous improvement or stabilization, the authors studied a cohort of patients treated within two prospective phase III trials with radiotherapy only. In 9 out of 32 patients, the first post-radiotherapy MRI showed progressive enhancement. In 3 of these 9 the MRI improved or stabilized for 6 months without additional treatment. The authors conclude that patients with progressive lesions within 3 months after radiotherapy should not be eligible for phase II trials on recurrent glioma.

Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture.

We report a patient treated for small lymphocytic lymphoma/leukemia with cerebral venous and sinus thrombosis (CVST) after lumbar puncture with intrathecal administration of methotrexate (MTX). He also developed a cerebrospinal fluid flow block. This is the first report of an association between lumbar puncture and intrathecally administered MTX and the development of CVST. Intrathecal treatment in this patient was discontinued and he was successfully treated with high-dose low-molecular-weight heparin subcutaneously.

Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma.

UNLABELLED: Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma. METHOD: Gemcitabine 1250 mg m(-2) was administered on day 1 and day 8 and cisplatin 80 mg m(-2) was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1-31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5-7 months) with a median survival from registration of 9.6 months (95% CI 8-12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule.

Volume coronary angiography using targeted scans (VCATS): a new strategy in MR coronary angiography.

The aim of this study was to explore the clinical possibilities of a new strategy for magnetic resonance imaging of the coronary arteries. Thirteen patients were studied by volume coronary angiography using targeted scans (VCATS) to visualize the major coronary arteries in a series of breath-holds. The proximal coronary arteries were clearly seen in 92% and the mid segments in 50-70% of the patients. VCATS was able to visualize a total vessel length of the left main (LM) (mean: 9.4+/-3.4 mm), of the left anterior descending (LAD) 69+/-20 mm, of the right coronary artery (RCA) 90+/-33 mm and of the left circumflex (LCX) 41+/-18 mm. There was a reasonable correlation between the VCATS and conventional coronary angiography (CAG) for vessel diameter (r = 0.71), with a slight overestimation of 0.7 mm by VCATS. There were nine significant stenoses present of which six were correctly detected, three were missed and one false positive was present. VCATS is fast strategy for visualizing the major coronary artery branches and has the potential to detect significant stenoses in these branches.

MR coronary angiography with breath-hold targeted volumes: preliminary clinical results.

PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS: Thirty-eight patients referred for elective coronary angiography were included. The coronary arteries were localized during single-breath-hold, three-dimensional imaging of the entire heart. MR coronary angiography was then performed along the major coronary branches with a double-oblique, three-dimensional, gradient-echo sequence. Conventional coronary angiography was the reference-standard method. RESULTS: Adequate visualization was achieved with MR coronary angiography in 85%-91% of the proximal coronary arterial branches and in 38%-76% of the middle and distal branches. Overall, 187 (69%) of 272 segments were suitable for comparison between conventional and MR coronary angiography. The diagnostic accuracy of MR coronary angiography for the detection of hemodynamically significant stenoses was 92%; sensitivity, 68%; and specificity, 97%. The sensitivity in individual segments was 50%-77%, whereas the specificity was 94%-100%. CONCLUSION: Adequate visualization of the major coronary arterial branches was possible in the majority of patients. The observed accuracy of MR coronary angiography for detection of hemodynamically significant coronary arterial stenosis is promising, but it needs to be higher before this modality can be used reliably in a clinical setting.

Lymphedema and lymphocysts following lymphadenectomy may be prevented by omentoplasty: A pilot study.

OBJECTIVES: Pelvic lymph node dissection as part of the staging surgery for cervical carcinoma interrupts the afferent lymphatics, so the lymph drains retroperitoneally. New surgical techniques designed to leave the peritoneum open after the retroperitoneal dissection, in particular the application of a pedicled omentoplasty along the dissection route, have been advocated to prevent the formation of lymphocysts and lymphedema. We investigated the possible benefit of pedicled omentoplasty in preventing lymphocysts and lymphedema following pelvic lymph node dissection. METHODS: In this pilot study with historical controls we compared the formation of lymphocysts and lymphedema following two different surgical techniques for pelvic node dissection: group I (historical controls), in which the dorsal peritoneum was left open, and group II, in which the dorsal peritoneum was left open with application of a pedicled omentoplasty. In these two groups of gynecologic patients, we compared the lymph flow patterns and the occurrence of lymphedema following systemic pelvic lymphadenectomy. The two groups were of comparable clinical status and consisted of 12 (group I) and 10 (group II) patients. Lymphocysts, if any, were detected by CT scan, the lymph flow patterns were visualized by dynamic lymphscintography, and lymphedema was visualized by physical examination and magnetic resonance imaging of the groin and the upper leg. RESULTS: In both groups a distinct intraperitoneal absorption of the lymph fluid was observed. Pedicled omentoplasty seemed to facilitate the absorption or transport of lymph fluid, resulting in less lymphedema in the upper leg. CONCLUSION: It appeared that leaving the dorsal peritoneum open to give the lymph stream the opportunity to pour into the abdominal cavity is important in preventing lymphocysts and lymphedema. The dynamic lymphscintigraphy described in this paper showed that the intraabdominal lymph flow is absorbed by the peritoneum and even more quickly by the pedicled omentum.

Magnetic resonance imaging of the coronary arteries: imaging planes and resulting anatomy in two-dimensional imaging.

Magnetic-resonance imaging techniques use different imaging planes than does conventional coronary angiography to acquire longer segments of a coronary artery in a single tomographic slice. At first sight, these planes appear rather puzzling, because the coronary arteries are displayed in unfamiliar orientations. In this article we will review the existing methodology for obtaining the orientations for the proximal coronary arteries and describe the associated anatomical landmarks that can be seen. Additional orientations for the middle segment of the circumflex and distal right coronary artery are introduced. These orientations are used both in various acquisition techniques and for evaluation of three-dimensional data when using multiplanar reformatting.

Basic principles of magnetic resonance imaging.

Magnetic resonance imaging (MRI) is a noninvasive imaging technique that is becoming more and more important in clinical cardiology. Physicians must understand the basic principles of MRI before reliable use in practice is possible. Therefore, we will give an introduction to basic MRI principles necessary to understand the difficulties of cardiac MRI. First the generation of a signal by the combination of a strong magnetic field, radiofrequency pulses, and temporary changes in the magnetic field is explained. Then, the processes of localization of different points in an image, resolution, and signal-to-noise ratio are highlighted. Finally, the influence of tissue characteristics such as T1 and T2 on the contrast of an image are discussed.

Magnetic resonance imaging of the coronary arteries: techniques and results.

Recently a new noninvasive imaging technique, magnetic resonance imaging (MRI) has been developed that has the potential to assess the coronary arteries. MRI of the coronary arteries is a challenging task because of the motion of the vessels during cardiac contraction and the motion of the heart with respiration. Several two-dimensional and three-dimensional acquisition techniques have been developed to overcome these problems. In this article we will describe different conventional MR techniques such as spin-echo and gradient-echo imaging. Also, we will describe new developments in MRI as ultrafast breathhold techniques using echo planar imaging or targeted volume scanning. Other new developments are respiratory gating techniques with or without respiratory motion correction. Finally, we will review the results of these techniques in the detection of coronary artery bypass graft patency, coronary artery stenosis, and the evaluation of coronary artery anomalies.

The diagnostic accuracy of magnetic resonance imaging and cerebrospinal fluid cytology in leptomeningeal metastasis.

Diagnostic decision making in the case of patients suspected of having leptomeningeal metastasis (LM) can be very difficult. The results of cerebrospinal fluid (CSF) cytology can be repeatedly negative, and the predictive value of gadolinium-enhanced magnetic resonance imaging (MRI) is not well known. We report the results of CSF cytology and Gd MRI in 61 patients with known cancer, suspected of having LM. We combined our data with those from a similar study and calculated the sensitivity and specificity of CSF and Gd MRI, in the absence of a "gold standard diagnosis." CSF cytology was positive for LM in 35 patients and MRI in 38. With CSF cytology sensitivity 75% and specificity 100%, with Gd MRI sensitivity was 76% but specificity only 77%. We conclude that Gd MRI provides strong support in the diagnosis of LM in patients with cancer who have negative results on CSF cytology.

Magnetic resonance imaging of the coronary arteries: clinical results from three dimensional evaluation of a respiratory gated technique.

BACKGROUND: Magnetic resonance coronary angiography is challenging because of the motion of the vessels during cardiac contraction and respiration. Additional challenges are the small calibre of the arteries and their complex three dimensional course. Respiratory gating, turboflash acquisition, and volume rendering techniques may meet the necessary requirements for appropriate visualisation. OBJECTIVE: To determine the diagnostic accuracy of respiratory gated magnetic resonance imaging (MRI) for the detection of significant coronary artery stenoses evaluated with three dimensional postprocessing software. METHODS: 32 patients referred for elective coronary angiography were studied with a retrospective respiratory gated three dimensional gradient echo MRI technique. Resolution was 1.9 x 1.25 x 2 mm. After manual segmentation three dimensional evaluation was performed with a volume rendering technique. RESULTS: Overall 74% (range 50% to 90%) of the proximal and mid coronary artery segments were visualised with an image quality suitable for further analysis. Sensitivity and specificity for the detection of significant stenoses were 50% and 91%, respectively. CONCLUSIONS: Volume rendering of respiratory gated MRI techniques allows adequate visualisation of the coronary arteries in patients with a regular breathing pattern. Significant lesions in the major coronary artery branches can be identified with a moderate sensitivity and a high specificity.

Negative sural nerve biopsy in neurolymphomatosis.

Patients with non-Hodgkin's lymphoma occasionally develop widespread invasion of peripheral nerves by tumor cells or neurolymphomatosis (NL). Clinically this usually results in asymmetrical, progressive, and painful polyneuropathy. Diagnosis rests on the identification of tumor cells in peripheral nerves. To avoid false-negative biopsy findings in patients with malignant lymphomatous infiltration of peripheral nerves it has been recommended to biopsy clinically involved nerves. We present two patients with histologically confirmed NL in whom sural the nerve biopsy finding was negative despite clinical and neurophysiological evidence of involvement of the sural nerve a. The clinical features of NL are reviewed. Some patients with neurolyphomatosis have only focal or proximal involvement of nerves, requiring the biopsy of an affected part of these nerves. Magnetic resonance imaging may be useful in identifying affected nerves.

Gradient echo MRI for measurement of the pulmonary autograft diameter after transplantation to the aortic root: validation and comparison with ultrasound.

The purpose of this study was to s the value of MRI for measurement of pulmonary autograft diameters after transplantation to the aortic root in adults. Thirty-eight adults underwent this operation. MRI and transesophageal echocardiography (TEE) were performed in 30 and 27 patients, respectively, after a mean follow-up period of 2.8 years. For internal validation of MRI, measurements at the diastolic short and long axes of the sinus level were used. Pulmonary autograft diameters were measured and compared with MRI and TEE at five different levels: the subannular region (1), annulus (2), sinus (3), sinotubular junction (4), and the distal part of the autograft (5). The correlation coefficient (r2) between long- and short-axis measurements for corresponding sinuses was .97. Diameters obtained with MRI were 1 to 3 mm larger than those obtained with TEE (P < .05), except for the annulus at systole (P > .3). Cine gradient echo MRI is an appropriate technique to evaluate pulmonary autograft diameters during follow-up. Concordance with TEE was good, apart from a systematic difference of approximately 2 mm.

A comparison of adult pulmonary autograft diameter measurements with echocardiography and magnetic resonance imaging.

UNLABELLED: In 38 consecutive patients the pulmonary autograft was used in aortic root replacement. Investigations were performed with transthoracic echocardiography, transoesophageal echocardiography and magnetic resonance imaging in 31, 27 and 27 patients respectively. The mean age at operation was 28.7 years (range 19.0-52.0) and the follow-up period was 2.8 years (range 0.8-6.7). The pulmonary autograft diameter was measured at the subannular region (1), at the annulus at the hinge points of the valve leaflets (2), at the sinus (3), at the sino-tubular junction (4) and at the distal part of the autograft (5). With transoesophageal echocardiography the mean systolic measurements at levels 1 to 5 were 32, 31, 42, 35 and 34 mm, respectively. The corresponding diastolic measurements were smaller: 25, 28, 42, 35 and 34 mm respectively. There was no significant difference between transthoracic echocardiography and transoesophageal echocardiography measurements of the proximal autograft (levels 1-3). Diameters obtained with magnetic resonance imaging were 1 to 3 mm larger than those obtained with transthoracic echocardiography and transoesophageal echocardiography (P < 0.05), except the annulus at systole (P > 0.3). CONCLUSIONS: The mean pulmonary autograft diameters measured using transthoracic echocardiography, transoesophageal echocardiography and magnetic resonance imaging were larger than native aortic and pulmonary diameters of a normal population in the same age group. Diameters of the distal 2 levels could not be imaged reliably with transthoracic echocardiography. Magnetic resonance imaging diameter measurements were, in general, larger than with echocardiography.

99mTc-SPECT in the diagnosis of skull base metastasis.

OBJECTIVE: To evaluate the role of bone SPECT in diagnosing metastasis to the skull base in cancer patients. BACKGROUND: Skull base metastasis often causes characteristic clinical syndromes. Antitumor treatment ameliorates or stabilizes symptoms in most patients. Diagnosis may be difficult when neuroimaging studies are negative (as occurs in about one-quarter of patients). Case reports have suggested a role for bone SPECT in these patients. METHODS: We reviewed the charts of all patients (1993-1996) at our institution who had skull base SPECT and at least one neuroimaging study (CT or MRI) for clinically suspected metastasis to the base of the skull. Bone SPECT, CT, and MRI were blindly re-evaluated. RESULTS: We studied 56 patients, of whom 36 had skull base metastasis. Twenty patients had other causes of the clinical syndrome, including leptomeningeal and posterior fossa metastasis, or benign causes. In 29 of 36 patients (81%) with skull base metastasis, CT or MRI clearly demonstrated the lesion. Bone SPECT identified a hot spot in the appropriate region of the skull base in 28 of 36 patients (78%). All seven patients with negative CT or MRI had positive SPECT and four of these had a response to anti-tumor treatment. CONCLUSIONS: SPECT of the skull base can demonstrate lesions not identifiable by CT or MRI. In cancer patients suspected of having skull base metastasis, we recommend SPECT of the skull base when CT or MRI studies are negative.

Neurolymphomatosis of the median nerve.

A patient with a non-Hodgkin's lymphoma had a painful axonal neuropathy of the median nerve due to lymphomatous infiltration. The median nerve lesion was the only site of tumor recurrence for 5 months and could be diagnosed with MRI. The median neuropathy responded to chemotherapy.