Comparison of cefdinir and penicillin for the treatment of streptococcal pharyngitis. Cefdinir Pharyngitis Study Group

Cefdinir, an oral cephalosporin active against Streptococcus pyogenes (group A beta-hemolytic streptococci [GABHS]), is also resistant to degradation by most oropharyngeal beta-lactamases. This multicenter, randomized, controlled, double-masked study assessed the tolerability and efficacy of 2 dosing regimens of cefdinir in the treatment of pharyngitis due to GABHS. Adults and adolescents with pharyngitis due to GABHS received cefdinir 600 mg QD, cefdinir 300 mg BID, or penicillin V 250 mg QID each for 10 days. A throat culture and clinical assessment were obtained 4 to 9 days after completion of therapy. Of 919 patients enrolled, 644 (70.1%) were microbiologically assessable. The eradication rates 4 to 9 days after completion of therapy were 91.4% in the cefdinir QD group, 91.7% in the cefdinir BID group, and 83.4% in the penicillin group (P = 0.02 for cefdinir QD vs penicillin, P = 0.01 for cefdinir BID vs penicillin, P = 0.95 for cefdinir QD vs cefdinir BID). Clinical cure rates were also superior with cefdinir QD (94.8%, P = 0.02) and cefdinir BID (96.3%, P < 0.01) compared with penicillin (88.9%). Diarrhea was more common in the cefdinir groups (P < 0.001). Seventeen cefdinir patients and 4 penicillin patients discontinued therapy because of adverse reaction (P = 0.13). Ten days of treatment for streptococcal pharyngitis with cefdinir QD or BID is superior to treatment with penicillin V for the eradication of GABHS from the pharynx, although it is associated with a higher rate of adverse reactions.     

Comparison of a 5 day regimen of cefdinir with a 10 day regimen of cefprozil for treatment of acute exacerbations of chronic bronchitis

Patients with acute exacerbations of chronic bronchitis were treated with cefdinir 300 mg bd for 5 days or cefprozil 500 mg bd for 10 days in a prospective, randomized, double-blind, multicentre study. Of the 548 patients enrolled, 281 (51%) were evaluable. The clinical cure rates at the test-of-cure visit were 80% (114/142) and 72% (100/139) for the evaluable patients treated with cefdinir and cefprozil, respectively. Respiratory tract pathogens were isolated from 409 (75%) of 548 admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. The microbiological eradication rates at the test-of-cure visit were 81% (157 of 193 pathogens) and 84% (166 of 198 pathogens) for the evaluable patients treated with cefdinir and cefprozil, respectively. Adverse event rates while on treatment were equivalent between the two treatment groups. The incidence of diarrhoea during therapy was higher for patients treated with cefdinir (17%) than for patients treated with cefprozil (6%) (P < 0.01), but most cases were mild and did not lead to discontinuation of treatment. These results indicate that a 5 day regimen of cefdinir is as effective and safe in the treatment of patients with acute exacerbations of chronic bronchitis as a 10 day regimen of cefprozil.     

Meigs syndrome revisited

The association of a benign ovarian tumor with ascites and hydrothorax that resolve after tumor resection is known as Meigs syndrome, and its importance was first emphasized by Meigs and Cass in 1937. The importance of Meigs syndrome is that the presence of ascites and pleural effusion does not necessarily indicate that a pelvic mass is malignant. The benign tumors in Meigs syndrome are usually fibromas or fibrothecomas and constitute 4% of all ovarian neoplasms. The authors present a case of Meigs syndrome with an ovarian fibroma. They focus on the evaluation of pleural fluid in the setting of an ovarian mass and then briefly discuss the imaging of ovarian fibromas and fibrothecomas.     

NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release

The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.     

Cell-mediated immunity in pigeon breeders' lung: the effect of removal from antigen exposure

Eighteen precipitin-positive pigeon breeders, thirteen symptomatic (SPB), with extrinsic allergic alveolitis (EAA), and five asymptomatic (APB), without lung disease, underwent bronchoalveolar lavage (BAL). Cytospins were prepared on which differential cell counts were performed. Immunocytological methods, using monoclonal antibodies, were performed to identify lymphocyte and macrophage subsets. Marked abnormalities in cell populations were observed in both groups but with no suggestion of differences between the groups. All subjects had a lymphocytosis in BAL (SPB 45%; APB 29%). These lymphocytes were almost exclusively T-cells. The cluster designation CD4/CD8 ratio was decreased (SPB 0.86; APB 1.13) and a significantly higher proportion of these cells than normal expressed UCHL1 (an antigen associated with the common leucocyte antigen complex) indicating immune commitment. In the macrophage population increased proportions of cells expressing antigens associated with interdigitating cells (RFD1+) and mature macrophages (RFD7+) were also abnormal. When six SPB patients were relavaged after isolation from pigeons for three weeks, there was a significant reduction in the lymphocytosis and in the proportion of UCHL1+ lymphocytes. This was accompanied by reductions in the percentage of macrophages expressing RFD1 and UCHL1. We suggest that EAA in pigeon breeders is associated with a cell-mediated immune response which is down-regulated by isolating patients from exposure to pigeon derived antigens.     

Changes in the Expression of Pituitary Adenylate Cyclase-Activating Polypeptide in the Human Placenta during Pregnancy and Its Effects on the Survival of JAR Choriocarcinoma Cells

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with survival-promoting actions, has been observed in endocrine organs and is thought to play a role in reproductive functions, including pregnancy. PACAP occurs in two forms, 27 and 38 amino acid residues, with PACAP38 being the predominant form in human tissues. In the present study, we determined the concentrations of PACAP38 and PACAP27 in first-trimester and full-term human placentas using radioimmunoassay. We found high levels of PACAP38 and lower levels of PACAP27 in different parts of the full-term human placenta. PACAP38 content increased in the placenta during pregnancy, both on the maternal side and on the fetal side. The effects of PACAP on the survival of JAR human choriocarcinoma cells were investigated using flow cytometry and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cell viability assay in cells exposed to the widely used chemotherapeutic agent methotrexate (MTX). It was found that PACAP neither influenced the survival of JAR cytotrophoblast cells nor affected cellular response to the death-inducing effect of the chemotherapeutic agent MTX. The present observations further support the significance of PACAP in the human placenta. The observation that PACAP did not influence the effects of MTX may have future clinical importance, showing that PACAP does not decrease the effects of certain chemotherapeutic agents.     

Experimental infections with West Nile virus

PURPOSE OF REVIEW: West Nile virus emerged recently in North America as a serious human and animal pathogen. This review summarizes the use of experimental infections with West Nile virus in diverse vertebrate species that have been used to answer fundamental questions about the host response, pathogenesis of West Nile virus infection and virus evolution. RECENT FINDINGS: West Nile virus has an extremely broad vertebrate host range. Infection of common species of birds has defined those with high vs. low potential to serve as amplifying hosts for the virus. In general, mammals (primates, horses, companion animals) are dead-end hosts for West Nile virus, although some circumstances (i.e. immunosuppression) may allow individuals to become capable of transmitting the virus to mosquitoes. Some mammals (rodents, rabbits, squirrels) and reptiles (alligators) have been found to develop a viremia of sufficient magnitude to predict at least low competence for infecting feeding mosquitoes. Finally, experimental infection of rodents, horses and primates with West Nile virus has been integral to developing and evaluating the efficacy of West Nile virus vaccines. SUMMARY: Experimental infection with West Nile virus has assisted in delineating those hosts important and not important to the transmission cycle, in understanding how the virus induces disease in susceptible hosts, and in validating the efficacy of vaccines used for control of disease.     

Effects of plasma transfusion on hepcidin production in human congenital hypotransferrinemia

Hepcidin is the key regulator of systemic iron homeostasis. We describe the modulation of hepcidin production induced by plasma transfusions in a patient with congenital hypotransferrinemia that offers a unique model in which to study the mechanism of hepcidin regulation by iron and erythropoiesis. Urinary hepcidin increased from zero at baseline, when hemoglobin and serum transferrin was low, to a maximum of 98 ng/mg creatinine on day 60, and subsequently decreased. Time-course of urinary hepcidin and serum transferrin concentration suggests that hepcidin production is regulated by the combination of marrow iron requirements and iron supply by transferrin.