Octreotide seems to have a beneficial effect on variceal bleeding, and long-term administration for the prevention of rebleeding is currently being evaluated. Experimental studies have suggested a ...beneficial effect of chronic octreotide treatment on renal function, while clinical studies have shown variable effects. Twenty-five cirrhotic patients with portal hypertension were randomized in a double-blind design to placebo or a single subcutaneous dose of a long-acting formulation of octreotide (octreotide-LAR) (20 mg). Renal function tests were performed before dosing and repeated after 30 days. The patients were in sodium steady state at the time of study. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by a constant infusion clearance technique. Renal sodium handling was determined by lithium and sodium clearance measurements. Therapeutic serum levels of octreotide along with a reduction of insulin-like growth factor I (IGF-I) (P < .01) and an increase of IGF binding protein 1 (P < .05) were demonstrated. No effect of octreotide was observed on GFR, ERPF, or filtration fraction (GFR/ERPF). Changes in clearance and extraction fraction of sodium and lithium during octreotide treatment were not significantly different from those of placebo. In addition, no changes in free water clearance, urinary flow rate, or 24-hour Na excretion were demonstrated. A significant increase of mean arterial pressure (+5 mm Hg; P < .01) was observed after treatment with octreotide-LAR. It is concluded that in spite of increased arterial pressure, octreotide-LAR has no significant effect on renal hemodynamics and tubular function in clinically stable cirrhotic patients with portal hypertension. (HEPATOLOGY 2001;34:471-477.)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Ongoing negotiations on the general practitioner contract raise the question of remunerating general practitioners for increased workload resulting from the shift from secondary to primary care. A ...review of the literature shows that there is little evidence on whether a shift of services from secondary to primary care is responsible for general practitioners' increased workload, and scope for making generalisations is limited. The implication is that general practitioners have little more than anecdotal evidence to support their claims of greatly increased workloads, and there is insufficient evidence to make informed decisions about remunerating general practitioners for the extra work resulting from the changes. Lack of evidence does not, however, mean that there is no problem with workload. It will be increasingly important to identify mechanisms for ensuring that resources follow workload.
Abstract Ongoing negotiations on the general practitioner contract raise the question of remunerating general practitioners for increased workload resulting from the shift from secondary to primary ...care. A review of the literature shows that there is little evidence on whether a shift of services from secondary to primary care is responsible for general practitioners' increased workload, and scope for making generalisations is limited. The implication is that general practitioners have little more than anecdotal evidence to support their claims of greatly increased workloads, and there is insufficient evidence to make informed decisions about remunerating general practitioners for the extra work resulting from the changes. Lack of evidence does not, however, mean that there is no problem with workload. It will be increasingly important to identify mechanisms for ensuring that resources follow workload.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Rapid aetiological diagnosis of bacterial meningitis is crucial for the early targeting of antimicrobial and adjuvant therapy. Broad-range polymerase chain reaction (PCR) targeting the 16S rRNA gene ...allows aetiological diagnosis of bacterial meningitis when applied to cerebrospinal fluid (CSF). We assessed the additional diagnostic effect of applying a novel broad-range real time PCR and subsequent DNA sequencing to culture, microscopy, and broad-range conventional PCR on CSF in patients with suspected bacterial meningitis. Broad-range conventional PCR and broad-range real time PCR with subsequent DNA sequencing were applied to 206 CSF specimens collected consecutively from 203 patients aged 6 d to 86 y. Patients' charts were reviewed for clinical information. 17 pathogens were identified by PCR and DNA sequencing or culture. Three specimens were negative by culture but positive by broad-range real time PCR. Three specimens were positive by culture but negative by broad-range real time PCR. Compared with culture, the sensitivity of broad-range real time PCR was 86%, and the specificitiy 98%. Conventional PCR resulted in a sensitivity of 64% and specificity of 98%. Broad-range real time PCR was generally comparable to culture of CSF and may be a useful supplement, particularly when antimicrobial therapy has been administered. Broad-range real time PCR was more sensitive than broad-range conventional PCR and microscopy.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
5-Azido-2,5-dideoxy-beta-D-erythro-pentofuranosyl nucleosides 10 and their corresponding alpha-anomers 11 have been synthesized by condensation of methyl ...3-O-acetyl-5-azido-2,5-dideoxy-beta-D-erythro-pentofuranoside (7) with silylated nucleobases followed by deprotection with methanolic ammonia. Reaction of silylated thymine (19) with methyl 2,3-di-O-benzoyl-5-deoxy-5-fluoro-D-arabino-pentofuranoside (15) and methyl 5-azido-2,3-di-O-benzoyl-5-deoxy-alpha-D-arabino-pentofuranoside (17 alpha) afforded a mixture of the alpha-nucleosides 20 and the acyclo nucleosides 5-fluoro- and 5-azido-2,3-O-dibenzoyl-5-deoxy-1-O-methyl-1-(thymin-1-yl)-D -arabinitol (22). Compounds 20 and 22 were deprotected with methanolic ammonia to give the acyclic nucleosides 21 and 23, respectively. The new nucleosides were inactive against HSV-1 and HIV-1.
D-dimer, a fibrin degradation product containing the gamma-gamma crosslink of fibrin, can now be assayed by the use of highly specific monoclonal antibodies. Such assays are not influenced by ...fibrinogenolysis and measurements can be performed on citrated plasma. The diagnostic values of four such assays--two based on ELISA technique and two on latex agglutination--were evaluated in 108 out of 118 consecutive patients admitted with suspected deep venous thrombosis of the leg. With cut-off limits defined by a pilot study and with venography as reference, a negative D-dimer test was confirmed in 45 of 46 patients (98%; 95% confidence limits: 88-99.9%) after ELISA-M, in 43 of 44 (98%; 88-99.9%) after ELISA-S, in 54 of 67 (81%; 69-89%) after Latex-M and in 40 of 44 (91%; 78-97%) after Latex-S. A positive D-dimer test was confirmed in 61% (48-73%), 59% (46-71%), 63% (47-78%), and 55% (42-67%) respectively. These data suggest the use of one of the ELISA assays for screening. A negative D-dimer test excludes deep venous thrombosis, whereas a positive D-dimer should be followed by venography. By this procedure a 40% reduction of venographic examinations can be expected.