Maxillary sinusitis in adults: an evaluation of placebo-controlled double-blind trials

BACKGROUND: In general practice, acute sinusitis is frequently diagnosed and treated with antibiotics. OBJECTIVE: This study aimed to determine the evidence for the effectiveness of antibiotic treatment in acute maxillary sinusitis in adults by assessing the methodological quality of placebo-controlled double-blind randomized trials. METHOD: An evaluation by four raters through a 35-item scoring-scale for internal and external validity of all placebo-controlled double-blind randomized trials on acute sinusitis found between January 1966 and July 1996. RESULTS: Eighty-five trials were excluded because they were not placebo-controlled, double-blind, randomized, or were carried out in patients with chronic sinusitis or in children. The three remaining trials were performed in different populations (one in general practice) between 1973 and 1978. Only one study claimed superiority of antibiotic treatment. Different inclusion criteria and major outcome measures were used by the authors. The reliability of major outcome events was reported poorly or not at all and in two studies outcome measures were clinically inappropriate. The studies scored 30-62% of the maximum attainable score for internal validity and 10-20% for external validity. CONCLUSION: The effectiveness of antibiotic treatment in acute maxillary sinusitis in a general practice population is not based sufficiently on evidence.      

Carrier-mediated transport in the hepatic distribution and elimination of drugs, with special reference to the category of organic cations

Carrier-mediated transport of drugs occurs in various tissues in the body and may largely affect the rate of distribution and elimination. Saturable translocation mechanisms allowing competitive interactions have been identified in the kidneys (tubular secretion), mucosal cells in the gut (intestinal absorption and secretion), choroid plexus (removal of drug from the cerebrospinal fluid), and liver (hepatobiliary excretion). Drugs with quaternary and tertiary amine groups represent the large category of organic cations that can be transported via such mechanisms. The hepatic and to a lesser extent the intestinal cation carrier systems preferentially recognize relatively large molecular weight amphipathic compounds. In the case of multivalent cationic drugs, efficient transport only occurs if large hydrophobic ring structures provide a sufficient lipophilicity-hydrophilicity balance within the drug molecule. At least two separate carrier systems for hepatic uptake of organic cations have been identified through kinetic and photoaffinity labeling studies. In addition absorptive endocytosis may play a role that along with proton-antiport systems and membrane potential driven transport may lead to intracellular sequestration in lysosomes and mitochondria. Concentration gradients of inorganic ions may represent the driving forces for hepatic uptake and biliary excretion of drugs. Recent studies that aim to the identification of potential membrane carrier proteins indicate multiple carriers for organic anions, cations, and uncharged compounds with molecular weights around 50,000 Da. They may represent a family of closely related proteins exhibiting overlapping substrate specificity or, alternatively, an aspecific transport system that mediates translocation of various forms of drugs coupled with inorganic ions. Consequently, extensive pharmacokinetic interactions can be anticipated at the level of uptake and secretion of drugs regardless of their charge.     

Acinar redistribution and heterogeneity in transport of the organic cation rhodamine B in rat liver

We studied a possible acinar heterogeneity in the transport of organic cations, using rhodamine B as model compound. Employing perfusions of isolated rat livers in the ante- and retrograde mode and quantitative fluorescence microscopy, Zones 1 and 3 were shown to be equally efficient in taking up rhodamine B. Ten minutes after injection in an antegrade perfusion, 95% of the dose was localized in the portal half of the acinus. Fifty minutes later, however, the amount of rhodamine B in Zone 1 had been reduced to 23%; 30 and 31% were in Zones 2 and 3, respectively, and the medium concentration was doubled. Thus, unchanged rhodamine B appeared to be transported downstream within the liver, either via the medium or directly from cell to cell, finally resulting in a relatively higher rhodamine B concentration in Zone 3. To obtain additional data, we designed a perfusion setup in which the zones could be studied separately. In both zones, the amount excreted into the medium was about 30 times the amount excreted into bile. Intracellular sequestration of rhodamine B and the rate constant for sinusoidal secretion were higher in Zone 3, while the sinusoidal uptake rates were equal; biliary excretion was higher in Zone 1. Acinar distribution changed with time because rhodamine B, primarily accumulated in Zone 1, was secreted into the sinusoids and taken up again by downstream cells. The finally higher rhodamine B concentration in Zone 3 was caused by a zonal heterogeneity in intracellular sequestration and sinusoidal secretion of rhodamine B.     

Light chain deposition disease without detectable light chains in serum or urine. Report of a case and review of the literature.

A patient presenting with a nephrotic syndrome and chronic renal failure caused by light chain deposition disease (LCDD) without detectable light chains in serum and urine is presented. Only a few patients with LCDD but without detectable light chains in serum and urine have hitherto been reported. The diagnosis was made by light-microscopic and immunofluorescent examination of a percutaneous renal biopsy. The histological differential diagnosis of LCDD includes diabetic glomerulosclerosis, renal amyloidosis and membranoproliferative glomerulonephritis. For the histological diagnosis of LCDD, immunofluorescence using anti-kappa and anti-lambda antisera is essential. Although renal involvement is a constant feature in LCDD, other sites of deposition of light chains have been reported. The absence of detectable light chains in serum or urine is discussed.     

Laparoscopic cholecystectomy using abdominal wall retraction

Background: Disadvantages related to CO₂ pneumoperitoneum have led to development of the abdominal wall retractor (AWR), a device designed to facilitate laparoscopic surgery without conventional pneumoperitoneum (15 mmHg CO₂). We investigated the effects of the AWR on hemodynamics and gas exchange in humans. We also investigated whether the use of an AWR imposed extra technical difficulties for the surgeon. A pilot study revealed that cholecystectomy without low-pressure pneumoperitoneum was technically impossible. Methods: A prospective randomized controlled trial: Twenty patients undergoing laparoscopic cholecystectomy were randomly allocated into group 1: AWR with low-pressure pneumoperitoneum (5 mmHg), or group 2: conventional pneumoperitoneum (15 mmHg). Results: Surgery using the AWR lasted longer, 72 ± 16 min (mean ± SD) vs 50 ± 18 min compared with standard laparoscopic cholecystectomy. There were no differences between the groups with respect to hemodynamic parameters, although a small reduction of the cardiac output was observed using conventional pneumoperitoneum (from 3.9 ± 0.7 to 3.2 ± 1.1 l/min) and an increase during AWR (from 4.2 ± 0.9 to 5.2 ± 1.5 l/min). Peak inspiratory pressures were significantly higher during conventional pneumoperitoneum compared to AWR. A slight decrease in pH accompanied by an increase in CO₂ developed during pneumoperitoneum and during the use of the AWR. In both groups arterial PO₂ decreased. Conclusions: The results indicate that the view was impaired during use of the AWR and therefore its use was difficult and time-consuming. Possible advantages of this devices' effects on hemodynamics and ventilatory parameters could not be confirmed in this study.     

Convergence of occipital nerve and superior sagittal sinus input in the cervical spinal cord of the cat

Co-existence of facial and occipital pain may occur in occipital neuralgia, migraine and cluster headache; suggesting convergence of trigeminal and cervical afferents. Such convergence has been shown in humans and other animals, but the site and extent of this are uncertain. In anaesthetized adult cats, the superior sagittal sinus and occipital nerve were stimulated electrically, and extracellular recordings made in the dorsolateral area of the upper cervical cord using glass-coated tungsten electrodes. Of 49 units in 10 cats, 33 (67%) had input from the superior sagittal sinus and the occipital nerve. Thirteen (27%) had superior sagittal sinus input and 3 (6%) had occipital nerve input. Convergent receptive fields were identified mechanically in 7 units. These experiments in cats show convergent input from occipital nerve and superior sagittal sinus on dorsolateral area units in two-thirds of cases studied. This experimental site of trigeminocervical convergence may relate to referral of pain in occipital neuralgia and other headaches.     

Nonsteroidal anti-inflammatory drugs (NSAIDs) and the kidney

In patients with PG-dependent renal function, NSAID administration constantly reduces GFR and RBF in a dose-dependent fashion. In this situation, the risk of overt acute renal failure is high and should be taken into proper account. In contrast, the incidence of NSAID-related renal structural alterations appears to be very low, yet the absolute number of patients may be significant considering the wide use of such drugs. Concerning the antiproteinuric effect of NSAIDs, the unfavourable ratio risk/benefit does not seem to support their indication in proteinuric nephropathies. The development of PGHS-2 selective inhibitors is promising, and may open new therapeutical strategies in the treatment of the progression of renal disease.