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Biomedical subjects

D L Tyrrell

Publications and source records attributed to D L Tyrrell.

At least 73 records · Page 4Linked to original sources
PubMed1987

Rhinofacial zygomycosis caused by Conidiobolus coronatus: a case report including in vitro sensitivity to antimycotic agents.

A case of zygomycosis caused by Conidiobolus coronatus, occurring in a 31-year-old priest from the Ivory Coast, is reported. Lesions eventually resolved after 2 1/2 years, during which the patient was variously treated with intravenous amphotericin B and miconazole as well as surgical resection. It is difficult to be certain which, if any, of these treatments contributed to resolution of lesions. A report of in vitro sensitivity data to a variety of antifungal agents is included.

Adult↗
PubMed1987

A proposed mechanism for the selective inhibition of human cytomegalovirus replication by 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-fluorouracil.

The biological activities of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-fluorouracil (2'F-ara-FU), 1-(3'-deoxy-3'-fluoro-beta-D-arabinofuranosyl)-5-fluorouracil (3'F-ara-FU) and 1-beta-D-arabinofuranosylthymine (ara-T) were compared in human cytomegalovirus (HCMV)-infected and noninfected human fibroblasts. 2'F-ara-FU inhibited HCMV plaque formation (ED50, 16 microM for AD 169 strain) at lower concentrations than 3'F-ara-FU (ED50, 100 microM for AD 169). These nucleoside analogues are expected to be phosphorylated to their 5'-phosphate forms by cellular thymidine kinase in HCMV-infected cells. The thymidine kinase activities in the virus-infected and noninfected cells were compared. Cellular thymidine kinase was increased in the virus-infected cells and showed better phosphorylation of 2'F-ara-FU than did 3'F-ara-FU. HCMV DNA polymerase was purified using affinity column chromatography, and the inhibitory effect of the 5'-triphosphate derivatives of 2'F-ara-FU (2'F-ara-FUTP) and 3'F-ara-FU (3'F-ara-FUTP) against viral and host DNA polymerase alpha was examined. No significant difference in the effectiveness of inhibition was observed between viral DNA polymerase and host polymerase alpha. However, viral polymerase incorporated 2'F-ara-FUTP into newly synthesized DNA, whereas polymerase alpha did not utilize 2'F-ara-FUTP as a substrate. Thus, viral polymerase differs from host polymerase alpha in its recognition and utilization of 2'F-ara-FUTP. This difference may be important to the design of selective antiviral agents for HCMV.

Antiviral Agents↗
PubMed1986

Colonic biopsy in verotoxin-induced hemorrhagic colitis and thrombotic thrombocytopenic purpura (TTP).

Sporadic cases and occasional outbreaks of hemorrhagic colitis recently have been associated with the rare Escherichia coli serotype O157:H7, which is now recognized as an important identifiable cause of bloody diarrhea in patients in whom more common gut pathogens cannot be detected. The authors report such a case in a 49-year-old woman who developed thrombotic thrombocytopenic purpura (TTP) and hemorrhagic transverse and descending colitis with a lesion having many of the features of pseudomembranous colitis. While pseudomembrane formation has been described in the hemolytic uremic syndrome (HUS), these features have not, to the authors' knowledge, been described in a patient with hemorrhagic colitis and TTP secondary to a verotoxin-producing serotype of E. coli.

Bacterial Toxins↗
PubMed1986

Pharmacokinetics and metabolism of E-5-(2-[131I]iodovinyl)-2'-deoxyuridine in dogs.

E-5-(2-Iodovinyl)-2'-deoxyuridine (IVdU) is a potent inhibitor of herpes simplex virus type 1 replication in vitro. The selective antiviral activity of IVdU is due to preferential phosphorylation by the herpes simplex virus type 1-encoded thymidine kinase. This selective sequesteration provided the rationale for the development of radioiodinated IVdU as a potential radiopharmaceutical compound for use in noninvasive diagnosis of herpes simplex virus encephalitis. We studied the pharmacokinetics and the in vivo metabolism of [131I]IVdU in dogs. The radioactive components in plasma were characterized and quantitated by radio high-pressure liquid chromatography. During incubation with dog blood, [131I]IVdU was metabolized to the corresponding base (E)-5-(2-iodovinyl)uracil. 131I-labeled (E)-5-(2-iodovinyl)uracil accounted for 73% of the total radioactivity present in plasma after 2 h of incubation, suggesting that phosphorolysis of the nucleoside is the major degradation pathway of IVdU in blood. The in vivo studies showed that there was an initial rapid clearance of the tracer from blood, followed by a second very slow clearance phase. Evaluation of the renal excretion of the radiotracer showed that only 8% of the injected dose was excreted by kidneys over an 8-h period. IVdU was rapidly metabolized to three radioactive compounds. Two of these metabolites, the base (E)-5-(2-iodovinyl)uracil and iodide, were characterized. The radioactivity associated with these metabolites was responsible for the slow clearance phase. Our results suggest that the development of [131I]IVdU as a radiopharmaceutical compound will require measures to prevent its rapid degradation in vivo.

Animals↗
PubMed1984

Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection.

One hundred nineteen patients with primary and 31 patients with nonprimary first-episode genital herpes were treated for ten days with 200 mg of acyclovir capsules or placebo capsules orally five times daily. Among acyclovir recipients with primary genital herpes, the median duration of viral shedding (two days), time to crusting of all lesions (seven days), time to healing of all lesions (12 days), and duration of local pain (five days) and constitutional symptoms (three days) were shorter than among placebo recipients (9, 10, 16, 7, and 6 days, respectively). Among patients with nonprimary first-episode genital herpes, oral acyclovir shortened the median duration of viral shedding but had no significant effect on the duration of lesions or symptoms. The time to first recurrence and frequency of recurrences were similar in acyclovir- and placebo-treated patients. Oral acyclovir treatment of primary first-episode genital herpes shortens the duration of viral shedding and symptoms and accelerates healing, but it does not appear to influence subsequent genital recurrences.

Acyclovir↗
PubMed1984

Comparative cervical microflora shifts after cefoxitin or cefazolin prophylaxis against infection following cesarean section.

The aerobic and anaerobic cervical microflora was determined before operation and on day 4 after operation in groups of women undergoing a clinical trial of prophylaxis with three doses of cefoxitin, cefazolin, or placebo for infectious complications of nonelective cesarean section. Floral shifts occurred post partum, with return of Escherichia coli and Bacteroides fragilis and a decrease in Candida colonization. No significant differences in flora existed preoperatively among patients receiving cefoxitin, cefazolin, or placebo, but by day 4, both antibiotic groups had greater enterococcal colonization. This difference was more marked with cefoxitin than with cefazolin. No difference in E. coli or B. fragilis colonization was noted by day 4 in placebo and antibiotic groups. Resistance developing in isolates in the antibiotic groups was mainly a result of enterococcal colonization. Results of this study indicate that a three-dose cephalosporin prophylactic regimen resulted in a significant selection of resistant enterococcal colonization but there was no increase in nosocomial infection in the antibiotic groups compared to the placebo group. There did not appear to be significant differences in either species selection or antibiotic resistance of aerobic or anerobic microflora between the cefoxitin and cefazolin groups.

Bacteria, Aerobic↗
PubMed1984

Synthesis of 131I, 125I and 82Br labelled (E)-5-(2-halovinyl)-2'-deoxyuridines.

Radiohalogenated (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU, 4) and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU, 5) were synthesized by reaction of (E)-5-(2-carboxyvinyl)-2'-deoxyuridine (1) with radiolabelled iodide or bromide in the presence of chloramine-T. A "no-carrier-added" synthesis of [131I]IVDU was completed within 30 min providing a radiochemical yield of 65%. Alternatively, radioactive iodine was incorporated into IVDU using a halogen isotope exchange reaction catalyzed by cuprous ion. [82Br]BVDU was also prepared by direct neutron activation of unlabelled BVDU.

Antiviral Agents↗
PubMed1984

The molecular length of measles virus RNA and the structural organization of measles nucleocapsids.

Full-length measles virus RNA molecules isolated from purified virions or nucleocapsids and examined by electron microscopy were 5.12(+/- 0.12) micron in length, corresponding to a molecular weight of 5.2 (+/- 0.1) X 10(6). Purified virions examined by negative staining in the electron microscope exhibited a pleomorphic range of particle sizes varying in diameter between 300 nm and 1000 nm. Purified nucleocapsids had dimensions of 21 nm (diameter) X 1254(+/- 7) nm (length) and a central core of diameter about 5 nm. Full-length nucleocapsids were composed of 204 (+/- 3) protein discs. The pitch of the nucleocapsid helix was calculated to be 6.1 nm and the helix angle, alpha, to be 8 degrees 16'. Approximate volume calculations indicate that each enveloped virus particle contains multiple nucleocapsids.

Animals↗
PubMed1984

Quantitative uptake studies of 131I-labeled (E)-5-(2-iodovinyl)-2'-deoxyuridine in herpes simplex virus-infected cells in vitro.

We have synthesized a 131I-radiolabeled antiviral compound (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVdU) and shown that this agent was selectively trapped within rabbit kidney cells, infected in vitro by thymidine kinase-positive (TK+) herpes simplex virus (HSV). The uptake of 131I-labeled IVdU was specific, as it was not concentrated within either HSV (TK-) or mock-infected cells. In certain conditions, over 40% of the radiolabel was selectively trapped within HSV (TK+)-infected cells. This was a 20- to 30-fold increase over the uptake of 131I-labeled IVdU by HSV (TK-) or mock-infected cells. The uptake of 131I-labeled IVdU varied directly with (i) the dose of the virus used to infect the rabbit kidney cells; (ii) the concentration of radiolabeled IVdU added to the system; and (iii) the time of exposure of IVdU to infected cells. The ability of this agent to be trapped within HSV (TK+)-infected cells merits further evaluation in animal models as it has potential as a noninvasive, herpes-specific diagnostic test, in particular for HSV encephalitis.

Animals↗
PubMed1983

Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section.

A randomized double-blind placebo-controlled comparison of prophylactic cefoxitin, an antibiotic with good activity against anaerobic bacteria, with cefazolin, an agent effective predominantly against aerobes, was undertaken in 354 women who underwent nonelective cesarean section (124 receiving cefoxitin, 119 cefazolin, and 111 placebo). Among the placebo group, 24.3% developed genital tract-related infection, in comparison to 5.6% of the cefoxitin patients and 6.7% of the cefazolin patients (P less than 0.001). Standard febrile morbidity, fever index, and duration of postoperative hospital stay were also significantly less in the antibiotic prophylactic groups. For patients with febrile morbidity, the mean fever index was less in the cefoxitin group (24.8 degree-hours) than that in the cefazolin group (42.7 degree-hours), and this difference approached statistical significance (P less than 0.1, greater than 0.05). Postoperative hospital stay longer than 1 week for infectious morbidity occurred in 26% of cefoxitin patients, a significantly lower incidence compared to the 66% rate for patients who received cefazolin, and the 57% incidence for patients in the placebo group (P less than 0.05).

Adult↗
PubMed1983

Effects of prolonged cultivation in the presence of acyclovir on recovery of latent herpes simplex virus from human trigeminal ganglia.

The continuous presence of acyclovir prevented the in vitro reactivation of latent herpes simplex virus from cultures of human trigeminal ganglia derived from 23 randomly selected cadavers. When acyclovir was withdrawn after 30 days, herpes simplex virus was recovered from 3 of 18 cases. Herpes simplex virus was recovered in 9 of 20 (45%) control cases.

Acyclovir↗
PubMed1983

Interferon production by lymphocytes from multiple sclerosis and non-MS patients.

Peripheral blood lymphocytes from MS patients and non-MS patients were induced to produce interferon by incubation with canine distemper, mumps, Sendai, herpes simplex I, and two strains of measles viruses. Lymphocytes from MS patients produced as much pH 2 stable interferon as did those from non-MS patients in response to induction with any of these viruses. In addition, there were no significant differences in amounts of interferon produced by lymphocytes from MS patients in three different clinical stages of the disease.

Adult↗
PubMed1982

Evidence for an interaction between the membrane protein of a paramyxovirus and actin.

Evidence for an interaction of the membrane (M) protein of Newcastle disease and Sendai viruses with cellular actin was obtained by three different techniques. M protein linked to Sepharose 4B was found to bind actin, but not myoglobin or bovine serum albumin, and to selectively remove actin from a mixture of these three proteins. Sedimentation of a mixture of M protein and F-actin through a sucrose gradient resulted in sedimentation of M protein with actin. Control proteins, bovine serum albumin and cytochrome c, did not sediment with actin. In circular dichroism studies, M protein added to actin in a 1:1 complex resulted in a significant increase in negative ellipticity at 220 nm, which corresponds to an increase in alpha-helix and a decrease in beta-structure and random coil. This is indicative of an interaction between M protein and actin. It is possible that the frequent identification of cellular actin in a number of enveloped viruses may be attributed to the interaction of actin and M protein or its equivalent.

Actins↗
PubMed1981

Meningitis complicating transsphenoidal hypophysectomy.

The case records of 98 patients who underwent a transsphenoidal hypophysectomy between 1969 and 1979 were examined to establish the frequency of postoperative cerebrospinal rhinorrhea and meningitis. There were seven cases of rhinorrhea and six of meningitis following the procedure. Five of the six patients with meningitis had diabetes mellitus and three of the seven with rhinorrhea had meningitis; thus, both diabetes and rhinorrhea were established as significant risk factors (P less than 0.001) in the development of meningitis after this operation. There were two proven cases of meningitis due to anaerobic organisms and a further two suspected cases. The prophylactic use of antibiotics did not prevent the development of meningitis in this series of patients.

Adult↗
PubMed1981

Effect of liver disease on pharmacokinetics and toxicity of 9-beta-D-arabinofuranosyladenine-5-phosphate.

Plasma levels of 9-beta-D-arabinofuranosyladenine-5'-phosphate (ara-AMP) and its metabolites 9-beta-D-arabinofuranosyladenine (ara-A and 9-beta-D-arabinofuranosylhypoxanthine (ara-Hx) were determined by high-performance liquid chromatography in four patients with chronic active hepatitis positive for hepatitis B surface antigen and eight patients with severe herpesvirus infections and normal liver function. Ara-AMP was given intravenously over a 30-min period in doses ranging from 10 to 30 mg of ara-A equivalent/kg per day. The metabolism of ara-AMP did not differ significantly between the two patient groups. Ara-AMP was quickly converted to ara-A, which was rapidly deaminated to ara-Hx. The mean half-lives of ara-AMP, ara-A, and ara-Hx were 0.14 hr, 0.17 hr, and 3.5 hr, respectively. Thus, ara-AMP is rapidly metabolized and does not act as a depot form of ara-A. Patients with chronic active hepatitis demonstrated increased bone marrow sensitivity to ara-AMP and a musculoskeletal pain syndrome not observed in patients treated for herpesvirus infections.

Adult↗