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Biomedical subjects

K H Fife

Publications and source records attributed to K H Fife.

68 records · Page 4Linked to original sources
PubMed1983

Intravenous acyclovir for the treatment of primary genital herpes.

Thirty-one patients with first episodes of genital herpes were randomized in a double-blind fashion to intravenous treatment with saline placebo or acyclovir, 5 mg/kg body weight at 8-hour intervals, for 5 days. The median duration of viral shedding from genital lesions after the onset of therapy was significantly shorter for patients given acyclovir (2 days) than for those given placebo (13 days), p less than 0.001. Viral shedding from the pharynx, cervix, urethra, and urine were also shorter in acyclovir-treated patients. (p less than or equal to 0.01 for each comparison). Local and systemic symptoms were shortened by a mean of 5 days and healing of genital lesions by a mean of 12 days in acyclovir-treated patients. (p less than 0.01). Complications during treatment, such as extragenital lesions or urinary retention requiring catheterization, developed in four patients given placebo and in none given acyclovir. (p less than 0.05). Intravenous acyclovir substantially decreases the symptoms, duration of lesions, and complications of primary genital herpes.

Acyclovir↗
PubMed1982

Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients.

Herpes simplex virus (herpesvirus) was isolated from autopsy lung specimens of 20 patients with clinical, roentgenographic, and histologic evidence of pneumonia. Mucocutaneous herpesvirus infection preceded the onset of pneumonia in 17. Twelve patients had focal pneumonia, 10 of whom had concomitant herpetic tracheitis, esophagitis, or both. Eight patients had diffuse interstitial pneumonia, six of whom had dissemination of herpesvirus to the other organs. Of the eight lung isolates available for typing, seven were herpesvirus-1 and one, herpesvirus-2. A high prevalence of herpesvirus antibody in serum samples obtained before pneumonia and identical restriction endonuclease patterns between mucosal and lung isolates in individual patients indicated that, in most cases, herpesvirus pneumonia was due to endogenous reactivation of virus. Focal herpesvirus pneumonia appeared to result from contiguous spread of herpesvirus to lung parenchyma, whereas diffuse interstitial pneumonia appeared to be a manifestation of hematogenous dissemination of virus.

Adolescent↗
PubMed1980

Nucleotide sequence of the inverted terminal repetition in adeno-associated virus DNA.

The inverted terminal repetition in adeno-associated virus type 2 DNA has been sequenced. The terminal repetition contain 145 nucleotides of which the first 125 nucleotides can self-base pair to form a T-shaped hairpin structure. Both restriction endonuclease analysis with SmaI and BglI and direct sequence analysis of the SmaI fragments provide evidence for two sequences in the region of the terminal repetition between nucleotides 44 and 81. The two sequences represent an inversion of the first 125 nucleotides of the terminal repetition. Based on these data a model for adeno-associated virus DNA replication is presented which agrees in detail with a general model for eucaryotic DNA replication originally proposed by Cavalier-Smith (T. Cavalier-Smith, Nature [London] 18:672--684, 1976).

Base Sequence↗
PubMed1977

Evidence for two nucleotide sequence orientations within the terminal repetition of adeno-associated virus DNA.

Duplex adeno-associated virus (AAV) DNA, produced by annealing plus and minus virion single strands, has been digested with several bacterial restriction endonucleases. These studies reveal the existence of alternate secondary structures at the termini of duplex AAV DNA. Analysis of the sites of endo R-Hpa II cleavage, the products of complete endo R-Hpa II digestion, and the multiple terminal secondary structures leads to the conclusion that there are two possible nucleotide sequences at each end of AAV DNA. A model that attributes the terminal nucleotide sequence heterogeneity to two possible orientations of the first 120 nucleotides at each end of the DNA is proposed; in one case the sequence is 1 to 120; in the other case the sequence is inverted. An origin of the inversion is suggested based on previously described intermediates in AAV DNA replication.

Base Sequence↗
PubMed1976

Genome localization of adeno-associated virus RNA.

In previous work, linear duplex molecules of adeno-associated virus, type 2 (AAV2), DNA were cleaved with the restriction endonucleases R-EcoRI, R-HindII, and R-HindIII. The physical order of the specific fragments obtained was deduced and oriented with respect to the DNA strand polarity and the direction of transcription. Stable AAV RNA is transcribed only from 70% of the minus DNA strand. We report here RNA-DNA hybridization experiments using these restriction fragments to obtain a more accurate map of the portion of the AAV genome represented in stable RNA. The data obtained with several sets of restriction fragments annealed to either whole-cell RNA or poly(A)-containing RNA were internally consistent. The AAV RNA annealed with a continuous region of the AAV DNA, beginning at 0.18 map units (18%) from the left end of the molecule and ending at 0.88 map units. In addition, the restriction endonuclease BamHI was found to make one specific cleavage in AAV2 DNA at 0.22 map units, which is 0.04 map units (i.e., 160 nucleotides) to the right (""down stream'') of the point corresponding to the 5' end of the viral mRNA.

DNA Restriction Enzymes↗
PubMed1975

Study of the fine structure of adeno-associated virus DNA with bacterial restriction endonucleases.

A physical map of the adeno-associated virus type 2 genome has been constructed on the basis of the five fragments produced by the restriction endonucleases HindII + III from Hemophilus influenzae. There are three endo R-HindII cleavage sites and one endo R-HindIII site. Evidence has been obtained to support the existence of two nucleotide sequence permutations in adeno-associated virus DNA, the start points of which have been estimated to be separated by 1% of the genome. The three cleavage fragments produced by endo R-Eco RI have been ordered and oriented with respect to the endo R-HindII + III cleavage map.

Base Sequence↗
PubMedDate not supplied

Risk of recurrence after treatment of first-episode genital herpes with intravenous acyclovir.

To determine whether intravenous acyclovir treatment for a first episode of genital herpes could prevent or reduce subsequent recurrences, we combined and analyzed the results of two independently conducted, randomized, double-blind, placebo-controlled studies. Sixty-one patients were enrolled in the two trials; 30 received the drug, and 31 received placebo. At entry the demographic, epidemiologic, and clinical features of acyclovir- and placebo-treated patients from the two centers showed no significant differences. The median time to the first recurrence and the frequency of recurrences showed no significant differences when acyclovir and placebo recipients infected with either herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) were compared. However, irrespective of treatment, the median time to the first recurrence was significantly longer (293 days vs. 69 days; P less than .02) and the frequency of recurrence significantly less (0.11 recurrences per month vs. 0.43 recurrences per month; P less than .01) among patients with HSV-1 infection as compared with those who had HSV-2. It is concluded that in patients with first-attack genital herpes, the type of HSV is the most important determinant of subsequent recurrences and that intravenous acyclovir has little effect on subsequent recurrences.

Acyclovir↗
PubMedDate not supplied

Lack of evidence for intertypic recombinants in the pathogenesis of recurrent genital infections with herpes simplex virus type 1.

Clinical observations indicate that herpes simplex virus type 1 (HSV-1) is significantly less likely than herpes simplex virus type 2 (HSV-2) to establish latency in (or reactivate from) sacral ganglionic tissue. In an effort to identify viral functions associated with latency, we analyzed HSV-1 isolates from three patients with established recurrent genital herpes and sought evidence of DNA sequences and proteins similar to those found in HSV-2. By restriction endonuclease cleavage patterns and by DNA hybridization analysis using either whole HSV-2 DNA or several cloned segments of HSV-2 DNA as probes, we found that the three HSV-1 isolates from patients with recurrent genital herpes showed no unusual homology to HSV-2 as compared with other HSV-1 isolates. Similarly, the proteins of these isolates could not be distinguished from those of other HSV-1 isolates and were distinct from those of HSV-2. At this level of resolution, there was no evidence to suggest that these recurrent genital HSV-1 isolates were intertypic recombinants, nor did they show any other unusual similarity to HSV-2.

DNA Restriction Enzymes↗
PubMedDate not supplied

Cytomorphologic correlates of human papillomavirus infection in the "normal" cervicovaginal smear.

OBJECTIVE: To determine if cytologic abnormalities less striking than those usually considered diagnostic could predict the presence of human papillomavirus (HPV). STUDY DESIGN: Cervical scrapings were obtained from 403 women and examined by conventional Papanicolaou staining and for the presence of low- and high-risk human HPV DNA. The cytologic smears from 63 HPV DNA-positive and 63 matched HPV DNA-negative patients whose smears were initially read as normal or inflammatory were reviewed by a single cytotechnologist and a cytopathologist, who were blind to the HPV result. RESULTS: The cytologic diagnosis was upgraded to atypical squamous cells of undetermined significance (ASCUS) in nine cases and to low grade squamous intraepithelial lesion in one. All 10 upgraded cases were from the HPV DNA-positive group. A review diagnosis of ASCUS was significantly associated with both HPV in general and the presence of high-risk HPV DNA. Partial koilocytosis and multinucleation were associated with the detection of high-risk HPV DNA, while only partial koilocytosis was associated with the presence of low-risk HPV DNA. CONCLUSION: Because infection with high-risk HPV types is associated with cervical neoplasia, partial koilocytosis and multinucleation should be viewed with greater concern and possibly added to the ASCUS definition.

Adolescent↗