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V Knight

Publications and source records attributed to V Knight.

At least 55 records · Page 3Linked to original sources

Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice.

Ribavirin, amantadine, and the two drugs in combination given in small-particle aerosol were highly effective in the treatment of influenza A infection in mice. Treatment was started 72, 96, and 120 h after inoculation and was given continuously for 4 days. With increasing delay in start of treatment, there was a pronounced reduction in effectiveness of ribavirin but not in that of amantadine. The combination treatment reflected the loss of ribavirin activity. Leukocyte infiltration and virus titers in the lungs were inversely related to the effectiveness of treatment. Influenza B infection treated 72 h after inoculation responded only to ribavirin, as indicated by the criteria described for influenza A. Intraperitoneal administration of drug begun 72 h after inoculation in regimens equivalent to aerosol afforded less protection than aerosol treatment.

Aerosols

Inhibition of lymphocyte proliferative responses by ribavirin.

When added to cultures of human peripheral blood lymphocytes, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibited antigen- and mitogen-induced proliferative responses as determined by [3H]thymidine incorporation. Dose-dependent suppressive effects were obtained when concentrations of 5 to 60 microgram of ribavirin per ml were added at culture initiation or up to 96 h thereafter. Ribavirin inhibited [3H]uridine and [3H]leucine incorporation by concanavalin A-activated and normal lymphocytes although not as severely as deoxyribonucleic acid synthesis. The capacity of ribavirin to interfere with lymphoproliferative responses was entirely reversed by guanosine and, to a lesser extent, by adenosine and xanthosine. These studies demonstrate that ribavirin is a reversible inhibitor of lymphocyte nucleic acid synthesis and suggest that the drug may be immunosuppressive when administered in vivo.

Cells, Cultured

Gas-chromatographic determination of amantadine in human urine.

We describe a gas--liquid-chromatographic method for determining the concentration of amantadine hydrochloride in urine with beta-phenylethylamine as internal standard. The urine sample is made alkaline and extracted with 0.5 mL of chloroform. After centrifugation the aqueous layer is aspirated, and an aliquot of the organic layer is injected directly into the gas chromatograph. Concentration and instrument response are linearly related between 2 and 125 mg/L. The limit of detection was 0.5 mg/L. Mean analytical recovery was calculated to be 97%.

Amantadine

Amantadine aerosol in humans.

Seven well volunteers and three patients with a naturally occurring influenza A/USSR/77 (H1N1)-like infection were given amantadine by small-particle aerosol with a Collison generator modified for this purpose. Inhalation periods for the volunteers were increased on consecutive weekends from 15 min to 1 h, 4 h, 9 h, and 2 consecutive days of 6 h each. The particle size was 1.2-micrometer mass median diameter, and the concentration of inhaled aerosol ranged from 47 to 75 microgram/liter. Estimates of retained doses in 9 h were 74 to 149 mg. About two-thirds of the dose was recovered in the urine. Pulmonary function studies did not vary significantly from base-line values and were within a normal range for five of seven volunteers. Two volunteers with a moderate reduction in mid-maximal flow before exposure had a total of three episodes of coughing and wheezing associated with moderate reductions in mid-maximal flow values. These episodes cleared spontaneously or improved promptly after isoproterenol therapy. The patients with influenza tolerated the treatment well and recovered promptly.

Adult

Inhibition of in vitro proliferative responses of human lymphocytes by rimantadine hydrochloride.

Rimantadine hydrochloride (alpha-methyl-1-adamantanemethylamine hydrochloride) inhibits the in vitro proliferative response of human peripheral blood lymphocytes to mitogenic and antigenic stimulation. Addition of drug (25 micrograms/ml) at the initiation of 5-day cultures suppressed the responses to phytohemagglutinin, pokeweed mitogen, and concanavalin A by 25, 65, and 90%, respectively. Similarly, responses to streptokinase-streptodornase, tetanus toxoid, and A2/Aichi influenza vaccine were significantly inhibited at concentrations as low as 10 micrograms of rimantadine per ml. Viability studies on 5-day cultures using trypan blue exclusion showed no significant difference between drug-treated and untreated controls. Furthermore, addition of drug on day 3 of 8-day cultures, at a time when the majority of cells had undergone blastogenesis, greatly suppressed the responses to these mitogens. These studies suggest that, in addition to its antiviral action, rimantadine interferes with the generation of cellular immune responses.

Adamantane

Inhibition of influenza virus uncoating by rimantadine hydrochloride.

In freeze-thaw lysates of MDCK cells infected with 32P-labeled influenza virus A/WSN in the presence of added RNase, acid-precipitable radioactivity diminished to about 50% of initial values within 90 min after a 1-h virus adsorption period. A similar preparation containing rimantadine at a concentration of 50 micrograms/ml exhibited only a 10% reduction in acid-precipitable radioactivity. These findings suggest that rimantadine interferes with uncoating of influenza virus in infected cells.

Adamantane

The core course in medical microbiology at Baylor College of Medicine.

During the past five years at Baylor College of Medicine student performance in microbiology, as measured by scores on the examination of the National Board of Medical Examiners, has improved from less (mean of 78 percent) than the national average of 80+ percent to considerably greater than the national average (mean of 85 percent). Only about one-half the time usually given to microbiology is allotted to the course at Baylor (107 hours). Principal features of the course are annually revised lecture handouts, medically oriented laboratory sessions with a manual written especially for the course, and clinical demonstrations of infectious disease. The pattern of performance in the microbiology course did not occur in two other basic science courses at Baylor. The improvement in performance appeared to be related to the course format, increased teaching proficiency, and the allocation of hours to the various subdisciplines.

Allergy and Immunology

Clinical trials of bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines in the elderly.

This placebo-controlled evaluation in elderly persons of inactivated influenza virus vaccines containing 200 or 400 chicke cell-agglutinating units of both A/New Jersey/76 and A/Victoria/75 antigens revealed mild systemic reactions in 7.8% and moderate reactions in 4.9% of vaccinees. These reactions were more common after administration of whole-virus than subvirion vaccines, more frequent in females than males, and more frequent in persons with low initial titers of antibody to A/New Jersey antigen. Local inflammation occurred in 18.7% of vaccinees (predominantly females) and frequently was seen with systemic reactions, but did not correlate with antibody response. Titers of antibody to A/New Jersey antigen were initially high and 99% of vaccinees had titers of greater than 1:20 after vaccination. Titers of antibody to A/Victoria antigen were initially low, and 56% of vaccinees had titers of greater than 1:20 after vaccination. Fourfold or greater increases in titer occurred in about 50% of vaccinees for each virus, most often concomitantly. Antibody responses to subvirion and whole-virus vaccines were similar, and increased responses with higher doses coincided with increased reactogenicity. Later revaccinations because of low titers of A/Victoria antibody produced negligible antibody responses.

Adult

Influenza.

The most universally employed measurement of the impact of epidemics and pandemics is the excess of mortality due to influenza and pneumonia. Other criteria are absenteeism from school and work, and all three will show positive indications when epidemics are of substantial size. During the 1974-1975 influenza season in Houston, school and industrial absenteeism and the increase in influenza and pneumonia deaths, despite a newly devised statistical procedure, did not signal an epidemic. However, a system of community surveillance of febrile respiratory illness with cultures for influenza virus during late January and early February 1975 gave unmistakable evidence of an influenza epidemic, with more than 600 virus isolations and an estimated occurrence of 50,000 cases of the disease. It is believed that this type of study can explore facets of the epidemiology of the disease not hitherto adequately examined. From this surveillance, which will continue through the summer months, it is hoped to gain further knowledge of the occurrence of antigenic drift and shift, and of the details of the early origin and progress of epidemics. Current speculation is that there will be another world pandemic before 1980 caused by a derivative of A strains presently circulating; in 1985-1991, a pandemic is predicted to be caused by a virus antigenically related to the swine agent of 1918. The purity of vaccines has been increased in recent years through ultracentrifugation and high-efficiency filtration, so that dosages can be increased while severity of reactions is reduced. The current level of dosage of vaccine for adults is 1200 chick cell agglutinating units, almost double what it was a dozen years ago. Recently, vaccines have been prepared more rapidly by the use of viral recombinants that incorporate the surface antigens of newly emerged epidemic strains into the core of older strains that grow well in embryonated eggs. This practical device greatly reduces the lead time in the preparation of new vaccines. The main problem in immunization against influenza is the need to reimmunize every 1-3 years. This creates an enormous requirement for vaccine and therefore a problem of selection of recipients. Currently, it is recommended that aged persons and those with cardiovascular, pulmonary and other chronic illnesses should receive the vaccine. Pregnant women are not more susceptible than others to the disease, and they should receive vaccine only if they have some other indications for immunization. Schoolchildren probably are important in transmission of the disease, but at present there is no special recommendation to immunize them. Young children occasionally have severe febrile convulsions when immunized against influenza, and those with this history probably should not be immunized. Amantadine is useful as a prophylactic agent in A(H3N2) influenza infections, and several reports suggest therapeutic benefits as well. Its benefits probably have not been fully utilized...

Amantadine

Diagnosis of herpes simplex virus infection by immunofluorescence.

The utility of the indirect immunofluorescent antibody (IFA) technique for diagnosis of herpes simplex virus (HSV) infection was examined by testing specimens for this agent from 31 patients with encephalitis or meningitis, 17 with conjunctivitis, 19 with genital disease, and 1 with genital disease and meningitis. Brain biopsy tissue from four patients with encephalitis was positive by IFA and virus culture for HSV. Leukocytes in cerebrospinal fluid from these four patients and one with HSV meningitis were also positive by IFA, but virus isolation attempts on the fluid were all negative. Conjunctival scrapings from two patients with conjunctivitis were positive for HSV by both IFA and virus culture. Eleven of 12 culture-positive lesions of herpes progenitalis were positive by IFA, and 1 dark field-positive syphilitic chancre was also positive for HSV by both IFA and culture. Evidence for specificity of the results was provided by internal controls in each test and negative results from patients with other diagnoses. Thus, the IFA technique constituted a rapid, sensitive, and specific diagnostic method for the diagnosis of HSV infections.

Brain

Antigenicity of licensed whole virion and subvirion influenza vaccines in "high risk" persons.

The frequency and magnitude of serum antibody response to type A and B influenza virus induced by whole virion and subvirion vaccines were essentially comparable. Immunization was followed in vaccinated individuals by an antihemagglutinin antibody response to the common antigenic determinant shared by the type A H3N2 viruses. Relatively few individuals developed antibody to the type-specific determinant.

Adult

Hepatic carbamyl phosphate synthetase and ornithine transcarbamylase in mouse influenze A and influenze B infection.

In mice infected with mouse-adapted influenza A/PR/8/34, hepatic carbamyl phosphate synthetase (CPS) activity was reduced to 88%, and ornithine transcarbamylase (OTC) was reduced to 83% of control values. In mice infected with mouse-adapted B/Lee/40, CPS activity was 98% was 94% of control values. These limited reductions in enzyme activity were attributed to a nonspecific debilitating effect of acute influenzal pneumonia. These findings suggest that the pronounced reduction of CPS and OTC activities reported in Reye's syndrome in man are not a general manifestation of the severity of influenza infection.

Adult