Biomedical subjects
Publications and source records attributed to D P Calfee.
Delusions of parasitosis, though uncommon, are an important cause of distress for affected patients and frequently of frustration for their physicians. They occur primarily in middle-aged or older women, who have the delusional belief that they are infested with parasites. Although the vast majority of cases involve dermatologic manifestations, some patients may have delusions of intestinal infection, as illustrated by this case.
The epidemiology of brain abscess has changed with the increasing incidence of this infection in immunocompromised patients, particularly solid organ and bone marrow transplant recipients, and the decreasing incidence of brain abscess related to sinusitis and otitis. A number of new neuroimaging modalities, including single photon emission computed tomography, positron emission tomography, perfusion magnetic resonance imaging, and magnetic resonance spectroscopy, provide an initial noninvasive approach to diagnosis. The recommendations for the management of intracranial mass lesions in human immunodeficiency virus-infected individuals has changed as the incidence of toxoplasmic encephalitis has decreased with the use of trimethoprim-sulfamethoxazole prophylaxis. The epidemiology, pathogenesis, microbiology, clinical presentation, diagnosis, treatment and prognosis of brain abscess in the beginning of the 21 st century are provided in this review.
The local immune response to influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1). The study was part of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 2x/day for 5 days), a highly selective inhibitor of influenza A and B virus neuraminidases, on the clinical symptoms of influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-alpha, interferon-gamma, IL-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha and -1beta increased in response to influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of influenza.
Zanamivir is a potent inhibitor of influenza A and B virus neuraminidases and is active topically in experimental and natural human influenza. We conducted this double-blinded, placebo-controlled study to evaluate the safety and efficacy of intravenously administered zanamivir. Susceptible volunteers were randomized to receive either saline or zanamivir (600 mg) intravenously twice daily for 5 days beginning 4 h prior to intranasal inoculation with approximately 10(5) 50% tissue culture infectious doses (TCID50) of influenza A/Texas/36/91 (H1N1) virus. Reductions in the frequency of viral shedding (0% versus 100% in placebo, P < 0.005) and seroconversion (14% versus 100% in placebo, P < 0.005) and decreases in viral titer areas under the curve (0 versus 11.6 [median] log10 TCID50. day/ml in placebo, P < 0.005) were observed in the zanamivir group, as were reductions in fever (14% versus 88% in placebo, P < 0.05), upper respiratory tract illness (0% versus 100% in placebo, P < 0.005), total symptom scores (1 versus 44 [median] in placebo, P < 0.005), and nasal-discharge weight (3.9 g versus 17.5 g [median] in placebo, P < 0.005). Zanamivir was detectable in nasal lavage samples collected on days 2 and 4 (unadjusted median concentrations, 10.5 and 12.0 ng/ml of nasal wash, respectively). This study demonstrates that intravenously administered zanamivir is distributed to the respiratory mucosa and is protective against infection and illness following experimental human influenza A virus inoculation.
Epidemic influenza continues to be associated with significant morbidity in the general population, and mortality in the elderly and other high risk patients. Although the case fatality rate averages less than 0.01%, tens of thousands of deaths occur each year. Control through immunisation programmes has not been possible due to incomplete protective efficacy and antigenic variations that occur frequently. Currently available anti-influenza medications (amantadine and rimantadine) have had limited success due to underutilisation, lack of activity against influenza B, the rapid development of viral resistance to the drugs, and adverse effects. A new class of antiviral agents designed to inhibit influenza neuraminidase, an important surface glycoprotein, is currently under active development for use in the prophylaxis and treatment of influenza A and B infections. Two of these compounds, zanamivir (GG167) and GS4104 (the ethyl ester prodrug of GS4071) have reached clinical trials. Most studies of zanamivir have involved topical administration by inhalation of dry powder aerosols and/or intranasal doses of aqueous solutions. These routes rapidly provide high local concentrations at the sites of delivery. GS4104 is administered orally, which allows for greater ease of administration, and probably more uniform distribution of the parent compound GS4071 in the respiratory tract. Both have shown potent inhibitory activity against influenza in animal models and experimental human influenza with excellent tolerability profiles. Zanamivir treatment has been shown to reduce the severity and duration of naturally occurring, uncomplicated influenza illness in adults. Clinical resistance to these drugs has not been recognised as a significant problem to date, although strains resistant to each agent have been produced in the laboratory. This class of agents shows considerable promise as a novel approach to prophylaxis and treatment of influenza infections. Ongoing studies should provide the data needed to allow the addition of 1 or more of the neuraminidase inhibitors to the clinician's anti-influenza armamentarium.