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Biomedical subjects

W L Drew

Publications and source records attributed to W L Drew.

At least 19 recordsLinked to original sources
PubMed1992

Direct inactivation of herpes simplex virus type-2 by rat epidermal protein.

Proteins were extracted from corneocytes of skin of 2-day-old rats and fractionated by gel filtration and cation exchange column chromatography. The different protein fractions were tested for direct inactivation of herpes simplex virus infectivity as determined by reduction of plaque formation. The most effective protein fractions against herpes simplex virus were a neutral pH buffer soluble and mol. wts. ranging from 20 K to 30 K. Amino acid composition of the proteins were virtually identical to epidermal histidine-rich proteins. The activity was significantly (P less than 0.001) stronger against type-2 than type-1. The activity was most stable at pH 7.2 and the rate of inhibition increased in a time-dependent manner up to 4 h. The 50% effective dose was estimated as 1.1 micrograms protein/ml.

Amino Acids↗
PubMed1992

Cytomegalovirus infection in patients with AIDS.

Advances in the field of antiviral therapy are now occurring with increasing frequency and rapidity and often generate varying degrees of confusion among those of us whose practices are focused primarily on therapy with antibacterial agents. How to treat cytomegalovirus infections in patients infected with the human immunodeficiency virus constitutes one of the best examples of the quandaries engendered by these advances, and the topic is reviewed in this first AIDS Commentary update. Given the U.S. Food and Drug Administration's recent approval of foscarnet, this discussion is very timely; it is particularly relevant for clinicians to be made aware of current lines of thought regarding induction versus maintenance therapy, the benefits of efficacy versus adverse effects of drug-related toxicity, and the interactions between antiretroviral drugs and ganciclovir or foscarnet. Dr. W. Lawrence Drew's career in this area has been long-standing and productive, and he is one of the leading experts in the field. In this update he addresses these perplexing issues.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Nonpulmonary manifestations of cytomegalovirus infection in immunocompromised patients.

Nonpulmonary manifestations of cytomegalovirus (CMV) infection in immunocompromised patients include chorioretinitis, gastrointestinal infection, and central nervous system disease. Diagnosis of end organ disease, especially in the gastrointestinal tract, is best substantiated by histologic evidence of CMV inclusions. Positive cultures of CMV provide evidence for supporting infection but do not define actual end organ disease. Satisfactory treatment of the disease can be accomplished with ganciclovir or foscarnet, although these agents only suppress virus replication. In many instances, severe CMV-induced end organ disease in immunocompromised patients will progress despite treatment. In some instances, resistance to the antiviral agent is the basis for drug failure. Patients at high risk for CMV disease can be identified, and studies of prophylaxis are in progress.

Antibodies, Viral↗
PubMed1992

Therapeutic algorithm for treatment of cytomegalovirus retinitis in persons with AIDS. A roundtable summary.

Foscarnet and ganciclovir appear to be of similar effectiveness in halting active infection when given as induction therapy and in forestalling progression of disease when given as maintenance therapy in persons with AIDS who have cytomegalovirus (CMV) retinitis. The primary dose-limiting toxicity of foscarnet is nephrotoxicity, whereas that of ganciclovir is neutropenia. The availability of two effective agents with different toxicities permits selection of initial treatment for CMV retinitis based on individual patient characteristics and provides an alternative for therapy if drug intolerance or viral resistance develops. An approach to treatment of first-episode and recurrent CMV retinitis based on patient and drug characteristics is presented. Case reports detailing the use of foscarnet and ganciclovir and problems encountered in patient management are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Prevalence of resistance in patients receiving ganciclovir for serious cytomegalovirus infection.

Seventy-two AIDS patients treated with ganciclovir for cytomegalovirus (CMV) disease were prospectively monitored for the development of drug-resistant virus. No resistant strains were found in 31 patients before therapy or among seven culture-positive patients treated for less than or equal to 3 months. Of 13 culture-positive patients treated for greater than or equal to 3 months, 5 excreted virus resistant (ED50, greater than 12 microM, or ED90, greater than 30 microM) to ganciclovir. Thus, 38% of patients and receiving ganciclovir for greater than 3 months and excreting virus or, overall, 7.6% of the patients were excreting CMV resistant to the drug.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis in patients with AIDS.

Infections caused by cytomegalovirus (CMV) resistant in vitro to ganciclovir, defined as requiring greater than 6 mumols of ganciclovir for ED50 have developed in some AIDS patients with progressive CMV retinitis despite chronic ganciclovir therapy. Two such patients (CMV isolates ED50, 9.5-14.5 mumols) were treated with foscarnet, an antiviral pyrophosphate analogue to which both patients' isolates demonstrated in vitro susceptibility (ED50, less than or equal to 300 mumols). Each patient had documented retinitis progression, at 2- and 1- to 5-week intervals, respectively, despite high-dose intravenous ganciclovir therapy. Both patients responded to foscarnet therapy with cessation of viral shedding in urine and blood. After foscarnet therapy was started, retinitis stabilized in the two patients for 12 and 25 weeks, respectively, before progression recurred. Therefore, foscarnet may be effective in immunocompromised patients with rapidly progressive CMV retinitis whose CMV isolates have developed in vitro resistance to ganciclovir.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir.

Cytomegalovirus strains with reduced in vitro susceptibilities to ganciclovir have been recovered from patients who failed long-term ganciclovir therapy. The ganciclovir-resistant clinical isolates in this study were unable to induce ganciclovir phosphorylation in virus-infected cells. The viral DNA polymerase function appeared unaltered in one genetically pure ganciclovir-resistant strain, compared with that of its wild-type ganciclovir-sensitive counterpart. All nine of the ganciclovir-resistant strains were susceptible to foscarnet. Moreover, these strains were sensitive to inhibition both by vidarabine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), antiviral agents that are activated by cellular enzymes, and by (S)-1(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), which is a monophosphate nucleoside analog. The in vitro resistance to ganciclovir of the ganciclovir-resistant clinical isolates studied was attributed to the inability of the cells infected with these isolates to phosphorylate ganciclovir; the virally encoded DNA polymerase did not appear to play a role in this ganciclovir resistance.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Clinical use of ganciclovir for cytomegalovirus infection and the development of drug resistance.

Cytomegalovirus (CMV) infection is extremely common in patients with advanced human immunodeficiency virus infection, in whom it can produce a variety of clinical syndromes. Ganciclovir is a guanosine analogue that selectively inhibits CMV DNA polymerase when intracellularly phosphorylated to its active form. In patients with CMV retinitis, induction therapy with ganciclovir results in high rates of clinical and virologic response; maintenance therapy is required to forestall progression of disease. Clinically relevant resistance of CMV to ganciclovir has recently been reported. Decreased phosphorylation of ganciclovir to its active form has been observed in cells infected with resistant strains, suggesting that CMV may encode a ganciclovir-phosphorylating enzyme whose function is deleted by mutation, conferring resistance. Further study is needed to establish the mechanism of resistance and to define the prevalence of resistance in the clinical setting.

Cytomegalovirus↗
PubMed1990

Comparison of bactericidal activity of five antibiotics against Staphylococcus aureus.

Ten volunteers were given each of five antibiotics, sequentially, until steady state was reached. Peak and trough sera were then drawn, and bactericidal titers were determined to two different isolates of Staphylococcus aureus, both sensitive in vitro to all antibiotics tested. The antibiotics were cephalexin, trimethoprim/sulfamethoxazole (TMP/SMZ), clindamycin, dicloxacillin, and ciprofloxacin. Mean peak serum bactericidal titers (SBT) were significantly higher for cephalexin than for dicloxacillin, ciprofloxacin, and TMP/SMZ (P less than .05). The difference between cephalexin and clindamycin did not achieve statistical significance. Dicloxacillin, clindamycin, and ciprofloxacin were not statistically different from each other. Mean SBT for TMP/SMZ was less than 1:2, significantly less than that achieved by the other antibiotics. Only clindamycin achieved a trough SBT greater than 1:2. This was statistically significant compared with each of the other antibiotics.

Adult↗
PubMed1990

Comparison of conventional and shell vial cultures for detecting cytomegalovirus infection.

We tested 606 specimens for cytomegalovirus infection. Fifty-two specimens were positive by conventional culture versus forty-three by pre-cytopathic effect detection. Twenty-nine specimens were positive by both methods. Because of toxicity, specimens should be set up on both conventional and shell vial culture systems to achieve maximum sensitivity.

Cytomegalovirus Infections↗
PubMed1989

Multisite evaluation of a monoclonal antibody reagent (Syva) for rapid diagnosis of cytomegalovirus in the shell vial assay.

A pre-cytopathic effect (CPE) monoclonal antibody reagent (Syva Co., Palo Alto, Calif.) was evaluated in four laboratories for the rapid detection of cytomegalovirus (CMV) in shell vial cell cultures at 16 to 24 h and 40 to 48 h postinoculation. Results were compared with those obtained by inoculation of the specimen into conventional tube cell cultures that were examined for the presence of typical CMV CPE and subsequently tested by reaction with the monoclonal antibody reagent in an indirect immunofluorescence test. Of 937 specimens, CMV was positive in 184 (20%). CMV was detected twice as frequently in shell vials only (n = 29) as in conventional tube cell cultures (n = 14). Pre-CPE shell vial assay was 91% sensitive (range, 84 to 98%) and 96% specific (range, 93 to 98%) compared with the detection of CPE in conventional tube cell cultures. Overall, 137 of 166 (83%) and 143 of 166 (86%) of the CMV strains were detected at 16 to 24 h and 40 to 48 h postinoculation, respectively. The Syva reagent produced sensitive and specific results for the rapid detection of CMV infection in shell vial cell cultures and reliably confirmed the presence of the virus as detected by CPE in conventional tube cell cultures.

Antibodies, Monoclonal↗
PubMed1989

Susceptibility testing of herpes viruses.

The plaque reduction or CPE assay has been the mainstay of virus sensitivity testing for both research and clinical work. These procedures have undergone a significant amount of methologic change in recent years. Almost completely lacking are results that clearly define the best parameters for correlating virus sensitivity to clinical outcome. Those few results that are available do not appear to show a direct correlation between virus sensitivity and clinical response.

Culture Media↗
PubMed1988

Herpesvirus infections (cytomegalovirus, herpes simplex virus, varicella-zoster virus). How to use ganciclovir (DHPG) and acyclovir.

Herpes viruses (HSV, CMV, VZ) are very frequent in AIDS patients and often exist in a chronic or progressive form. Clinically evident CMV retinitis occurs in approximately 10 per cent of AIDS patients but can be effectively treated with a new nucleoside analogue DHPG (Gancyclovir). Perianal ulcers, proctitis, and other clinical syndromes caused by HSV can be effectively treated with acyclovir (ACV) and HSV recurrences can be prevented by daily administration of ACV. Zoster in a young adult may be the first indication of immunodeficiency due to HIV. Because VZV is less susceptible to ACV than HSV, intravenous ACV or high-dose oral therapy is required to achieve inhibitory blood levels.

Acquired Immunodeficiency Syndrome↗