Formulating questions and locating primary studies for inclusion in systematic reviews

Much time and effort are spent on designing primary research studies. Similar care must be given to planning systematic reviews. The review should be based on an important, well-focused question that is relevant to patient care. By formulating the question properly, the criteria that primary studies must meet to be included in the review become clear. These criteria, which comprise the types of persons involved, exposure, control group, outcomes, and study designs of interest, can then be refined so that they are clinically relevant, sensible, and workable. Inclusion criteria that are too narrow will limit the amount of data in the review, thereby increasing the risk for chance results and making the review less useful for the reader. Reviews should include studies whose designs offer the least biased answer to the question being asked. To maximize available data and reduce the risk for bias, as many relevant studies as possible need to be identified, regardless of publication status or language. Multiple overlapping search strategies should therefore be used and must be carefully planned. Strategies include searching the many electronic databases available (after careful consideration of which terms to enter), manually searching journals and conference proceedings, searching bibliographies of articles, searching existing registers of studies, and contacting companies or researchers. The time taken to formulate the question adequately and develop appropriate searches will increase the chance of producing a high-quality, meaningful review.     

Biochemical alterations of the tunica albuginea in impotence

PURPOSE: The objectives of this study were to quantify the immunohistochemical stainings of collagen types I, III and IV, and investigate the value of glycohistochemical staining with 3 lectin types specific to a particular glycan structure, Arachis hypogaea, Triticum vulgare and concanavalin A, as a method of defining possible changes in the collagen structure of the tunica albuginea in potent and impotent patients. MATERIALS AND METHODS: The study involved 4 normal men, 4 with pure venous leakage and 4 with pure arterial disease. Collagen types I, III and IV, and lectins Arachis hypogaea, Triticum vulgare and concanavalin A were studied using a cell image processor. The labeling index relates to the percentage of staining and mean optical density relates to the staining intensity. RESULTS: Mean labeling index values for the 3 types of collagen and lectins were similar (p > 0.05). Mean optical density value relating to collagen type I was significantly higher in the arteriogenic group than in the other groups (p < 0.05), while mean optical density value of collagen type IV was significantly higher in the venogenic group than in the 2 other groups (p < 0.05). Mean optical density values relating to the 3 lectin types were similar in the 3 clinical groups (p > 0.05). CONCLUSIONS: An alteration in the distribution and structure of the various collagen types and lectins in the tunica albuginea of impotent patients has been shown that may interfere with normal function and lead to impotence.     

Multiple peaks in high-performance liquid chromatography of proteins. beta-Lactoglobulins eluted in a hydrophobic interaction chromatography system

The hypothesis of Geisler (Brain Res. 212 (1981) 198-201), in which the different spontaneous-rate classes of primary auditory neurons were accounted for by the different sizes of uniquantal EPSPs relative to the gap between resting membrane and threshold potentials, was represented with an expanded model which included relative refractory effects. The spike rates generated by the expanded model, when plotted vs. estimated sound level, are qualitatively similar to those of experimentally obtained rate-level curves. The hypothesis is also consistent with recent ultrastructural data which suggest that average quantal-release rates for any particular primary auditory neuron are inversely related to its spontaneous rate. The model's recovery processes following spike generation (hazard functions) are also similar to those observed experimentally.     

Lectin-like characteristics of recombinant human interleukin-1beta recognizing glycans of the glycosylphosphatidylinositol anchor

We found that 35S-labeled recombinant human interleukin-1beta (rhIL-1beta) binds phosphatidylinositol-specific phospholipase C-treated human placental alkaline phosphatase, phosphatidylinositol-specific phospholipase C-treated trypanosome surface variant glycoproteins, and urinary uromodulin immobilized on plates or immobilized on CNBr-activated Sepharose 4B. The interaction between rhIL-1beta and these glycoproteins was lectin-like, since it was inhibited in the presence of specific saccharides, i.e. mannose 6-phosphate or synthetic Ac-NH.CH2.CH2. PO4--->6Manalpha1-->(+/-2Manalpha1-->+/-6Manalpha1-->) propyl at about 1 microM. On the other hand, a wide variety of compounds including biantennary sugar chains derived from these glycoproteins as well as ethanolamine phosphate, inositol phosphate, mannose 6-sulfate, mannose 1-phosphate, glucose 6-phosphate, and mannitol 6-phosphate did not show any inhibitory effect at concentrations up to 1 mM. These results indicate that rhIL-1beta interacts with these glycoproteins via the mannose 6-phosphate diester of glycans on the glycosylphosphatidylinositol (GPI) anchor. Furthermore, when monolayers of polarized Madin-Darby canine kidney cells on polycarbonate filter membranes were incubated with 35S-rhIL-1beta in either the apical or basolateral chamber, 35S-interleukin-1beta was found to bind specifically to the apical membranes with a Ka value of 4.6 x 10(7) M-1, and the specific interaction was inhibited by 1 microM mannose 6-phosphate. Since the mannose 6-phosphate diester moiety exists only in the GPI glycans on plasma membranes, it was evident that interleukin-1beta can directly interact with the mannose 6-phosphate diester component of the intact glycan of GPI anchors on plasma membranes.     

Synaptic-like microvesicles of neuroendocrine cells originate from a novel compartment that is continuous with the plasma membrane and devoid of transferrin receptor

We have characterized the compartment from which synaptic-like microvesicles (SLMVs), the neuroendocrine counterpart of neuronal synaptic vesicles, originate. For this purpose we have exploited the previous observation that newly synthesized synaptophysin, a membrane marker of synaptic vesicles and SLMVs, is delivered to the latter organelles via the plasma membrane and an internal compartment. Specifically, synaptophysin was labeled by cell surface biotinylation of unstimulated PC12 cells at 18 degrees C, a condition which blocked the appearance of biotinylated synaptophysin in SLMVs and in which there appeared to be no significant exocytosis of SLMVs. The majority of synaptophysin labeled at 18 degrees C with the membrane-impermeant, cleavable sulfo-NHS-SS-biotin was still accessible to extracellularly added MesNa, a 150-D membrane-impermeant thiol-reducing agent, but not to the 68,000-D protein avidin. The SLMVs generated upon reversal of the temperature to 37 degrees C originated exclusively from the membranes containing the MesNa-accessible rather than the MesNa-protected population of synaptophysin molecules. Biogenesis of SLMVs from MesNa-accessible membranes was also observed after a short (2 min) biotinylation of synaptophysin at 37 degrees C followed by chase. In contrast to synaptophysin, transferrin receptor biotinylated at 18 degrees or 37 degrees C became rapidly inaccessible to MesNa. Immunofluorescence and immunogold electron microscopy of PC12 cells revealed, in addition to the previously described perinuclear endosome in which synaptophysin and transferrin receptor are colocalized, a sub-plasmalemmal tubulocisternal membrane system distinct from caveolin-positive caveolae that contained synaptophysin but little, if any, transferrin receptor. The latter synaptophysin was selectively visualized upon digitonin permeabilization and quantitatively extracted, despite paraformaldehyde fixation, by Triton X-100. Synaptophysin biotinylated at 18 degrees C was present in these subplasmalemmal membranes. We conclude that SLMVs originate from a novel compartment that is connected to the plasma membrane via a narrow membrane continuity and lacks transferrin receptor.     

Synthesis and characterization of molybdenum disulphide formed from ammonium tetrathiomolybdate

An investigation has been carried out into the possibility of in situ formation of MoS2 within porous anodic films on aluminium, to improve subsequent tribological behaviour, by re-anodizing in thiomolybdate electrolyte. Acidification of thiomolybdate was employed to simulate the conditions for formation of the sulphide at the anodic film/electrolyte interface, followed by appropriate vacuum heat treatments to study possible temperature effects on the sulphide due to either friction or Joule heating during anodizing. The products of both acidification and heat treatment, characterized by X-ray powder diffraction and scanning electron microscopy, were compared with those formed by direct thermal decomposition of ammonium tetrathiomolybdate crystals. The precipitate formed by acidification was mainly amorphous molybdenum trisulphide (MoS3), which on heat treatment at 450 and 850°C yielded 3R-MoS2. 3R-MoS2 also formed by the thermal decomposition of thiomolybdate crystals. Thermogravimetric and differential thermal analyses showed that the decomposition of MoS3 to MoS2 occurred in the range 220–370°C and revealed the sequence of reaction steps. The findings suggest that mainly amorphous MoS3 is formed as a consequence of changes in the pH of the film/electrolyte interface during re-anodizing but the product is relatively easily transformed to crystalline MoS2 on moderate heating which may occur during wear processes.     

The transjugular stent implantation for the treatment of malignant portal and hepatic vein obstruction in cancer patients

BACKGROUND: The increase in portal vascular resistance is a significant complication of metastatic disease to the liver or locally advanced cancer, e.g., biliary cancer. PATIENTS AND METHODS: This paper describes the successful palliative treatment of two cancer patients with portal hypertension presenting with the symptoms of tense ascites, mesenteric congestion, and severe variceal bleeding. By creating a stenttract between a hepatic vein and a main branch of the portal vein and/or by placing an extendable stent into the portal vein, the transjugular intrahepatic portosystemic stent-shunt (TIPS) technique was used to decompress the portovascular system. RESULTS: The TIPS-technique offers a new, safe and effective palliation for malignant portal hypertension. In both patients, the symptoms of the portal hypertension disappeared after the procedure. This was accompanied by a significant improvement of the patients performance status allowing an early ambulation. CONCLUSION: Our findings demonstrate the feasibility and effectiveness of the TIPS procedure as a minimal invasive treatment for portal vein decompression in selected tumor patients.