Health technology assessment.
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Biomedical subjects
Publications and source records attributed to A Long.
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In the human T-cell lymphoma line, HuT 78, proliferation and phorbol ester-induced growth arrest and differentiation were inhibited by the protein kinase C (PKC) inhibitor, staurosporine. By contrast, an alternative PKC inhibitor, H-7, inhibited proliferation but not phorbol ester-induced growth arrest. The cell line was found to contain both alpha and beta isoforms of PKC by Western blot techniques. A cell line, K-4, was cloned from HuT 78 in the presence of H-7 and this clone was found to be positive for PKC-alpha only. PKC-beta did not return on cultivation in the absence of H-7. Proliferation of K-4 was insensitive to inhibition with both H-7 and staurosporine. However, phorbol ester-induced growth arrest remained staurosporine sensitive. Phorbol-stimulated IL-2 secretion was minimal in the PKC-beta-deficient cell line. These data suggest that PKC-beta may be a regulatory enzyme for proliferation and stimulated interleukin-2 secretion in HuT 78 cells. Heterogeneity of responses to PKC activation may reflect the use of different isozymes in different intracellular pathways. The K-4 cell line should provide a useful tool in the dissection of involvement of PKC isozymes in cellular function.
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In order to study the effect of clofazimine, a powerful antimycobacterial and antiinflammatory agent, 49 patients with active Crohn's disease were randomized to either corticosteroids plus clofazimine 100 mg daily (N = 25) or to steroids and matching placebo (N = 24). A total of 28 patients (58%) went into disease remission (clofazimine 16, placebo 12; P = NS) with a fall in disease activity score from 10.5 +/- 4.4 to 3.3 +/- 3.5. Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study (clofazimine 12, placebo 6; P = NS). Side effects were minor and consisted of skin rash and increased pigmentation. Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn's disease but may have a role in either disease maintenance or combination chemotherapy.
Several novel compounds having both a 2-nitroimidazole nucleus and a fluorescent ring system in their molecular structure were prepared and evaluated as potential fluorescent probes for hypoxia. Bioreduction of nitroimidazoles, which is inhibited by oxygen, is known to lead to binding of bioreductive metabolites to cellular macromolecules and this provides a mechanism for binding the fluorescent moiety to hypoxic cells. These compounds can incorporate a wide range of fluorophors and can therefore be designed to suit the laser-line wavelengths available for excitation of fluorescence in the flow cytometer. Several nitroimidazoles with naphthalimide side chains were rapidly taken up into cells and became concentrated in the cells, thus reducing their concentration in the extracellular medium. This suggests a potential microscopic bioavailability problem with probes of this type when used in vivo as they would become progressively depleted in the extracellular fluid as they diffused from blood vessels, through layers of packed cells in tumors, to the hypoxic cells where they could undergo hypoxia-specific metabolism. Synthesis of nitroimidazoles with coumarin fluorophors led to several potentially useful probes for hypoxia; substituents on the coumarin fluorophor had a marked effect on the cellular fluorescence of these compounds.
Numerous methods have been proposed for the detection of hypoxic cells using nitroimidazoles labelled with both radioactive and stable isotopes where the isotopic label becomes bound as a result of reductive metabolism of the nitro group. A new probe for hypoxia, 7-(4'-(2-nitroimidazol-l-yl)-butyl)-theophylline, is described where an immunologically recognisable hapten (theophylline) is covalently linked to a 2-nitroimidazole. Bioreduction of the nitroimidazole leads to binding of bioreductive metabolites, and hence the theophylline side-chain, to intracellular molecules. Immunochemical procedures are then used to stain cells containing the bound theophylline using an FITC-conjugated anti-serum. Flow cytometric analysis of stained cells is facilitated by co-staining cellular DNA, which allows discrimination of single cells in the sample and rejection of cell clumps and debris. The alternative use of an immunoperoxidase-conjugated anti-serum has been used to demonstrate the localisation of hypoxic cells in frozen tumour sections.
Among deep venous thromboses of the calf, isolated gastrocnemic vein thrombosis is a rare condition. Its main characteristics could be extracted from 5 cases. Following a positional or mechanical triggering factor, the diagnosis is suggested by pain localized to the calf. Ultrasonography shows the intraluminal thrombus better than phlebography, since the gastrocnemic veins, which bypass the larger deep veins, can be opacified only after a garrot is placed above the knee. The thrombus may extend to the popliteal vein, with a risk of pulmonary embolism and post-phlebitis disease. Treatment consists of anticoagulants and elastic bandage.
Seventeen surgical biopsy specimens of the axillary or subclavian artery were obtained from patients who had inflammatory, nonatherosclerotic arterial lesions and were studied retrospectively. Initial roentgenologic clinical, and histologic findings were evaluated and compared with final diagnosis. Histological examination suggested Takayasu's disease in 11 patients whereas the roentgenologic and clinical signs led us to suspect Takayasu's disease in only eight instances. Takayasu's disease was confirmed in these eight cases later in the course of the disease. In six patients subclavian artery biopsy specimens showed lesions consistent with Horton's disease in contrast to roentgenologic and clinical signs which suggested Takayasu's disease. In five patients, the final diagnosis was Horton's disease and in one, the diagnosis remained unknown. Of 13 patients who had revascularization procedures, bypasses remained patent in patients followed from nine months to 16 years (mean: 68 months). Histopathologic criteria are more reliable than roentgenologic or clinical signs in the diagnosis of Takayasu's disease. The subclavian artery is frequently involved in Takayasu's disease and is a desirable site for retrieval of diagnostic specimen when a revascularization procedure is entertained.
The relationship between clinical severity, as judged by a clinical scoring method, and the degree of radiological change on a chest X-ray, was assessed in 153 children with acute bronchiolitis. There was no statistical correlation between clinical severity and the degree of radiological change. The majority of radiographs were requested on the assumption that it was a useful routine investigation. We suggest that the request for a chest X-ray in acute bronchiolitis should be made only when the need for intensive care is being considered, where there has been an unexpected deterioration in the child's condition or the child has an underlying cardiac or pulmonary disorder.
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Our experience with 91 operated cases in 84 patients (47 men, 37 women) relates essentially to arterial diseases resulting from overloading and diabetic arteriopathy. Diagnosis of critical ischemia is easy in clinical conditions, but it is advisable to rely on universally recognized hemodynamic standards to define this condition. Ankle pressure should be less than 400 mmHg and the Doppler trace flat or barely perceptible. Patients in our series had a mean ankle pressure of 32.4 mmHg. Local examination can determine the extent of gangrene, whereas general examination detects numerous, often associated defects diabetes, coronary artery disease, rhythm disorders, arterial hypertension, etc. As far as possible, these defects are to be corrected before surgery. X-ray examination (M. Kasbarian) is frequently done in conjunction with conventional aorto-arteriography and digital angiography. The later technique allows arteries to be visualized which are not seen with the conventional technique. The x-ray examination will indicate whether revascularization is feasible, although it cannot show whether it will be efficient. In our series, opacification of the plantar arches was predictive neither of success nor failure. But do tests exist which can predict the success of a revascularization attempt? It would be necessary to be able to estimate ankle pressure after the operation, and several methods have tried to do this. TcPO2 would seem to be a good examination. The possibilities of nuclear magnetic resonance are being studied, and the results thus far are promising. Preoperative explorations are carried out in a different situation. Arteriography performed in the operating room is a simple act which can reveal a usable downstream bed not indicated in preoperative X-rays, although it provides no hemodynamic data. Measurement of peripheral resistances would appear to be a very good predictive examination. Flow measurements by infusion or electronic flowmeter also seem to be predictive for bypass results. Unfortunately, these measurements are at present not widely performed and the critical threshold is assessed differently. Given the difficulty of correctly estimating the value of these numerous methods, many surgeons, ourselves included, have chosen to revascularize patients whenever the upstream bed as evaluated by X-ray indicates the presence of at least one viable artery.
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A new design for a rat restraining device is described. Features of the device include facilities to allow the accommodation of rats of a very wide weight range and to maximize its convenience in use in a variety of procedures including the collection of blood, feces, and urine. The restrainer is designed to minimize stress in the rat in the course of pharmacokinetic or pharmacological studies. The device is particularly useful for studies involving chronically cannulated animals.
A histological diagnosis of Horton's disease was made in 4 patients with lesions of the axillary-subclavian arteries by biopsy of these vessels. Unilateral biopsy of the temporal artery, performed initially in 2 of these patients, during surgery in one and immediately after surgery in another, had been negative in 3 cases and insufficient for a diagnosis in 1 case. For temporal biopsy to be valuable, the arterial fragment resected must be long enough and serial histological sections must be performed to avoid false-negative results. It is only when these conditions are fulfilled that negative results may be considered. Horton's disease of the axillary-subclavian arteries is relatively frequent, and histological studies of these vessels have already been used to assert the diagnosis in case of negative or non-performed temporal biopsy, whether or not the arteriographic findings were suggestive of the disease. The indications for subclavian biopsy remain to be determined. It can be carried out for diagnostic purposes in case of clinically atypical suspected Horton's disease revealed by axillary-subclavian lesions and negative temporal biopsy, particularly when revascularization proves necessary.
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A prospective study was undertaken to examine the immunohistochemical expression of tumor antigen Cal9-9 in 56 colorectal cancers and 95 colonic adenomas, divided into 65 primary polyps and 30 polyps synchronous with colorectal cancer. Seventy five per cent of tumours were positive for Cal9-9. Antigen was expressed more frequently in advanced Duke's C and D and poorly differentiated colorectal cancer. Overall 51% of adenomas were positive for Cal9-9. Antigen expression correlated significantly with increasing size (p less than 0.001), synchronicity with colorectal cancer (p less than 0.001), severe dysplasia (p less than 0.001) and villous typing (p less than 0.003). Discriminate analysis using the first three variables correctly classified 79% of positive and 89% of negative Cal9-9 results. The similar frequency of antigen expression seen in colorectal cancers and their synchronous adenoma suggests a field change in the tumour bearing colon. Adenomas positive for Cal9-9 may have a greater malignant potential for carcinomatous change.