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.      

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.      

Relative and absolute bioavailability of cibenzoline capsules and tablets in healthy subjects

Eighteen healthy adult volunteers completed an open-label, four-way crossover study designed to determine the bioequivalency of 160-mg cibenzoline [2-(2,2-diphenylcyclopropyl)-4,5-dihydro-1H-imidazole] capsules and tablets, their relative bioavailability compared with an oral solution of the drug, as well as the absolute bioavailability of these dosage forms compared with an intravenous infusion of the drug. Blood samples obtained at specified times after drug administration were assayed for cibenzoline by HPLC, and pharmacokinetic parameters were estimated from the resulting plasma concentration-time profiles. Comparisons were made between the tablet and capsule to assess bioequivalency, between the solid dosage forms and a solution to assess relative bioavailability, and between the oral forms and an intravenous infusion to assess absolute bioavailability. The pharmacokinetic parameters for each oral dosage form were similar and ratios of mean parameters indicated that the solid dosage forms were bioequivalent and completely bioavailable relative to an oral solution. The ratios of the area under the plasma concentration-time profiles (AUC) for the capsule, tablet, and oral solution to that of the intravenous infusion were 0.85, 0.83, and 0.86, respectively, indicating that orally administered cibenzoline has an absolute bioavailability of approximately 85%.     

High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.     

Expression of actin isoforms and intermediate filament proteins in childhood orbital rhabdomyosarcomas

The diagnosis of orbital rhabdomyosarcoma (RMS) in childhood gives rise to several clinical and anatomo-pathological problems. Antibodies recognizing structural proteins and cytoskeletal components have been shown to increase the diagnostic accuracy of different neoplastic lesions. In this study we examined anatomo-clinically and, where possible, by means of immunohistochemistry and electron microscopy, a series of 14 cases of orbital RMS in childhood. In the 12 cases studied by immunohistochemistry, desmin was always present, although showing variable patterns, and alpha-sarcomeric actin was found in 10 cases. alpha-Smooth muscle actin was always absent. The other markers tested (myoglobin, polyclonal actin, vimentin and enolase) proved unreliable for several reasons. We conclude that antibodies against desmin and alpha-sarcomeric actin are useful for the diagnostic definition of RMS. In addition, immunohistochemical analysis supplies data regarding the degree of tumor differentiation and may be applied to monitor radio- and chemotherapy.     

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy

OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.     

Endothelin receptor expression in human decidua

The endothelins are signalling peptides that act via two receptors, ET(A) and ET(B). In the human endometrium, endothelin receptors have been demonstrated in glands and stroma and have been shown to vary during the course of the menstrual cycle. The present study was undertaken to determine whether or not expression of endothelin receptors changes during pregnancy or after administration of exogenous progestagens. The expression of the receptors was correlated with the appearance of basement membrane components during decidualization of the endometrial stroma. Decidual specimens (n = 15) were obtained during the first trimester of pregnancy and 10 at term. Sixteen pairs of endometrial biopsies were obtained from women with menorrhagia before and after exposure to exogenous progestagens. A total of 15 hysterectomy specimens were used as controls for the expression of stromal basement membrane proteins in the absence of decidualization. Autoradiography was carried out with selective ligands for ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of ligand binding was then compared with the distribution of laminin alpha2 light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and collagen IV were expressed in stromal decidual cells in the first trimester of pregnancy. ET(B) was also found on endometrial glandular epithelium. Quantitative macro-autoradiography and multiple regression analysis demonstrated a highly significant positive correlation (P < 0.001) between expression of ET(B) and laminin alpha2 light chain. In the third trimester qualitative examination suggested a reduction of ET(A) in the stroma. Progestagen-induced decidua exhibited a similar pattern to that found in first trimester decidua. This study has demonstrated up-regulation of ET(B) during the progesterone- dependent process of decidualization and suggests a paracrine or autocrine role for endothelins in the decidua.