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Biomedical subjects

M R Wallace

Publications and source records attributed to M R Wallace.

At least 127 records · Page 7Linked to original sources
PubMed1993

Cats and toxoplasmosis risk in HIV-infected adults.

OBJECTIVE: To establish the prevalence and incidence of toxoplasmosis in an adult human immunodeficiency virus (HIV) population, and to determine if cat ownership contributes to the risk of toxoplasmosis. DESIGN: Retrospective record and laboratory review, coupled with a patient survey. SETTING: A tertiary-care military hospital HIV program. PATIENTS: A total of 723 HIV-infected adults, all former or current US military personnel. MAIN OUTCOME MEASURES: Prevalence and incidence of serologic evidence of toxoplasmosis infection. RESULTS: A total of 723 HIV-infected patients had serial Toxoplasma IgG antibody determinations. Seventy patients (9.7%) were positive on their initial screen; the seronegative patients were tested annually for 1 to 5 years (mean duration of follow-up, 2.1 years). Only 13 patients (2.0%) who were initially seronegative acquired antibodies to Toxoplasma gondii. None of the patients who seroconverted developed clinical disease. A pet history was available on 12 of 13 patients who seroconverted; only one (8.3%) had owned or lived in a household with a cat during the period of seroconversion. The calculated attributable risk of cat ownership/exposure for toxoplasmosis seroconversion in this population is -2.9 per 100 persons annually. CONCLUSION: Toxoplasma antibody seroconversion in an adult HIV-infected population is unusual and appears unrelated to cat ownership or exposure.

AIDS-Related Opportunistic Infections↗
PubMed1993

Genetic linkage analysis applied to unaffected women from families with breast cancer can discriminate high- from low-risk individuals.

Up to 20 per cent of cases of breast cancer diagnosed in women under the age of 45 years may be caused by an autosomal dominant gene. A present difficulty is differentiation of mutation carriers from non-mutation carriers in high-risk families. Genetic linkage analysis has been used to localize a susceptibility gene (BRCA1) on chromosome 17q12-21 between markers 42D6 and MFD188, a region 5-10 million base pairs in length. Odds in favour of linkage to this region were greater than 100,000:1 in 15 families with breast cancer. In eight families in which the probability of linkage was above 75 (range 79.2-99.9) per cent, 19 women were identified who were at high lifetime risk of breast cancer (range 80.6-87.2 per cent) and 37 whose risk was similar to that for the general population (range 9.8-16.4 per cent). Genetic risk prediction of this kind may enable high-risk screening clinic resources to be concentrated on those most likely to benefit.

Adult↗
PubMed1993

Treatment of varicella in the immunocompetent adult.

Varicella in the immunocompetent adult is an infrequent but potentially serious infection. Previous studies in immunocompetent hosts and normal adults have demonstrated the value of intravenous acyclovir in the treatment of varicella-zoster virus infections. Oral acyclovir has also shown efficacy in both normal adults with zoster (shingles) and immunocompetent children with varicella. A recently completed double-blind placebo-controlled study of oral acyclovir in immunocompetent adults with uncomplicated varicella also demonstrated efficacy. Therapy within the first day reduced the time to 100% crusting of skin lesions from 7.4 to 5.6 days, and reduced the duration of fever by one-half day. Symptoms were also diminished. These benefits were observed only when therapy was initiated within 24 hours of the appearance of the rash. Adults with complicated varicella (usually symptomatic varicella pneumonia) should receive intravenous acyclovir. Several new agents for varicella-zoster therapy are being evaluated; brovavir is a new agent currently being compared to placebo in the treatment of adult varicella.

Acyclovir↗
PubMed1993

Ciprofloxacin versus ceftriaxone in the treatment of multiresistant typhoid fever.

A randomized trial comparing ceftriaxone (3 g given parenterally per day for 7 days) to ciprofloxacin (500 mg given orally twice a day for 7 days) in the treatment of blood culture positive typhoid fever was conducted. Twenty patients were openly randomized to receive ciprofloxacin and 22 to receive ceftriaxone. The outcome was classified as clinical failure in 6 patients (27%) in the ceftriaxone group, but in none in the ciprofloxacin group (p = 0.01). The mean duration of fever was four days in the ciprofloxacin group and about five days in the ceftriaxone group (p = 0.04). In the six patients in the ceftriaxone group who experienced failure, therapy was switched to ciprofloxacin and the patients became afebrile and asymptomatic within 48 hours. Patients with resistant strains of Salmonella typhi and patients with sensitive strains responded equally well to ciprofloxacin therapy. Analysis of a subset of 12 of the multiresistant strains revealed that resistance was encoded for by a transferable 180 kilobase plasmid. Ciprofloxacin represents a useful treatment option in areas where multiresistant strains are likely to be encountered.

Bacteriophage Typing↗
PubMed1993

Characterization of a single base-pair deletion in neurofibromatosis type 1.

The gene which is responsible for neurofibromatosis type 1 (NF1) is located on chromosome 17 (17q11.2). The NF1 gene is approximately 350 kilobases (kb) long and exhibits an extremely high mutation rate; therefore, most patients are expected to have unique mutations. To date, relatively few mutations have been well characterized. We report here a de novo single base pair (bp) deletion in one NF1 allele in a patient diagnosed with NF1 and leukemia. We further characterized this mutation at the RNA level by allele-specific oligonucleotide (ASO) hybridization which demonstrated that the mutant allele is transcribed.

Adolescent↗
PubMed1993

Endothelium-derived nitric oxide modulates renal hemodynamics in the developing piglet.

The developing mammal exhibits lower renal blood flow (RBF) and higher renal vascular resistance (RVR) than its adult counterpart. The maturational pattern of renal hemodynamics involves the synchronous increase in RBF and decrease in RVR with age. In spite of considerable investigation, the mechanisms involved in the regulation of renal hemodynamics in the developing animal remain largely unexplained. Specifically, the role of the vasodilator endothelium-derived nitric oxide (EDNO) in the regulation of developing renal hemodynamics is not known. These experiments examined the intrarenal effect on the renal hemodynamics of the developing piglet and adult pig of the EDNO competitive inhibitor N-nitro-L-arginine methylester (L-NAME) at three doses (50, 5, and 3 micrograms/kg/min). During basal conditions, the developing piglet exhibited lower RBF and higher RVR than the adult pig. All doses of intrarenal L-NAME produced significant decreases in RBF and increases in RVR in both groups. The 3-micrograms/kg/min L-NAME dose did not change mean arterial pressure. The developing piglet exhibited significantly greater changes at all doses. After the 50-micrograms/kg/min infusion, piglet RBF decreased 45% and adult pig RBF decrease 29%; piglet RVR increased 128% and adult pig RVR increased 51%. After a 5-micrograms/kg/min infusion, RBF decreased 28% in the piglet and 14% in the adult pig; RVR increased 75% in the piglet compared with 27% in the adult pig. After 3 micrograms/kg/min L-NAME, piglet RBF decreased 29% and adult RBF decreased 9%; RVR increased 47% in the piglet versus 13% in the adult pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Linkage of a major breast cancer gene to chromosome 17q12-21: results from 15 Edinburgh families.

DNA from members of 15 pedigrees each containing between three and eight cases of breast cancer have been collected from southeastern Scotland. Polymorphic markers on chromosome 17q were screened to locate a putative breast cancer gene by using DNA from relevant individuals within these families. Pairwise LOD scores were calculated for markers D17S74, NM23, D17S588, and D17S579. The maximal summated LOD for the 15 families was 5.44 at theta = .034, when D17S588 (42D6) was used. In these breast cancer families, a subset which did not give evidence for linkage to this region could be identified.

Adult↗
PubMed1993

Cell-mediated immunity to HIV-1 in Walter Reed stages 1-6 individuals: correlation with virus burden.

Cell-mediated immunity (CMI) to human immunodeficiency virus-1 (HIV-1) was assessed in a blinded fashion for a patient group (n = 79) representing Walter Reed (WR) stages 1-6. At the same time, viral load was quantitatively measured by two different methods, specifically, virus isolation and HIV viral DNA copy number as measured by the polymerase chain reaction (PCR). After unblinding it was determined that the ability to generate a lymphoproliferative response to an inactivated gp120-depleted HIV (HIV-ag) and tetanus toxoid diminished with advancing WR staging, with complete anergy to HIV-ag and tetanus at stage 6. As a group, individuals whose peripheral blood mononuclear cells (PBMC) proliferated to HIV-ag were either virus isolation negative or produced low levels of virus as measured by p24 antigen (< 250 pg p24) on day 7. Similarly, HIV DNA copy number in the HIV-ag responders was low (< 200 copies/4 x 10(5) PBMC). In contrast, antigen proliferation to tetanus toxoid did not correlate with virus load. Thus, clinical progression as defined by the WR staging system appears to coincide with a loss of CMI to HIV. More importantly, the low viral load measured in HIV-ag responders suggests a link between viral burden and CMI to HIV which might be exploited in the design of immunotherapies for HIV-infected individuals.

Cell Division↗
PubMed1992

Treatment of adult varicella with oral acyclovir. A randomized, placebo-controlled trial.

OBJECTIVE: To assess the efficacy of oral acyclovir in treating adults with varicella and to describe the natural history of adult varicella. DESIGN: Double-blind, placebo-controlled randomized trial. SETTING: A naval hospital. PATIENTS: One hundred forty-eight of 206 consecutive adult active duty Navy and Marine Corps personnel who were hospitalized for isolation and inpatient therapy of varicella and who could be treated within 72 hours of rash onset completed the study. The diagnosis of varicella was confirmed by acute and convalescent serology in 143 of 144 patients with available paired sera. INTERVENTION: Patients were randomly assigned to receive either acyclovir, 800 mg orally five times per day for 7 days, or an identical placebo. Separate randomization codes were used for patients presenting within 24 hours of rash onset and for those presenting 25 to 72 hours after rash onset. MEASUREMENTS: Daily lesion counts, symptom scores, temperature measurements, and laboratory tests were used to monitor the course of the illness. RESULTS: Early treatment (initiated within 24 hours of rash onset) reduced the total time to (100%) crusting from 7.4 to 5.6 days (P = 0.001) and reduced the maximum number of lesions by 46% (P = 0.04). Duration of fever and severity of symptoms were also reduced by early therapy. Late therapy (25 to 72 hours after rash onset) had no effect on the course of illness. Only four patients had pneumonia, and no encephalitis or mortality was noted. CONCLUSIONS: Early therapy with oral acyclovir decreases the time to cutaneous healing of adult varicella, decreases the duration of fever, and lessens symptoms. Initiation of therapy after the first day of illness is of no value in uncomplicated cases of adult varicella. The low frequency of serious complications of varicella (pneumonia, encephalitis, or death) precluded any evaluation of the possible effect of acyclovir on these outcomes.

Acyclovir↗
PubMed1992

NF1-related locus on chromosome 15.

A neurofibromatosis type I (NF1)-related locus has been identified on chromosome 15. It contains a partial copy of the NF1 GAP-related domain, which is known to interact with the ras protooncogenes. However, the chromosome 15 sequence contains multiple deletions resulting in frameshift mutations and stop codons in several highly conserved sequence blocks. The locus on chromosome 15 therefore represents an NF1 pseudogene. This nonprocessed NF1 pseudogene may produce additional fragments in Southern blotting, pulsed-field gel, and PCR experiments with some NF1 cDNA probes or oligonucleotides. In addition, certain regions of the NF1 gene also cross-hybridize with a locus on chromosome 14. These loci must be considered in mutation analysis of patients with NF1 since aberrant findings may not always reflect changes in the NF1 gene.

Base Sequence↗
PubMed1992

A yeast artificial chromosome contig encompassing the type 1 neurofibromatosis gene.

The yeast artificial chromosome (YAC) system (Burke et al., 1987, Science 236: 806-812) allows the direct cloning of large regions of the genome. A YAC contig map of approximately 700 kb encompassing the region surrounding the type 1 neurofibromatosis (NF1) locus on 17q11.2 has been constructed. A single YAC containing the entire NF1 locus has been constructed by homologous recombination in yeast. In the process of contig construction a novel method of YAC end rescue has been developed by YAC circularization in yeast and plasmid rescue in bacteria. YACs containing homology to the NF1 region but mapping to another chromosome have also been discovered. Sequences of portions of the homologous locus indicate that this other locus is a nonprocessed pseudogene.

Base Sequence↗
PubMed1992

A comparison of procedures for analysing microsatellite (CA)-repeat polymorphisms.

Dinucleotide repeat sequences ('microsatellites') have been used as polymorphic genetic markers following amplification in the polymerase chain reaction (PCR). We have compared several methods of analysing the PCR products. The most reliable and unambiguous results were obtained when the PCR products were probed with a specific dinucleotide repeat oligonucleotide, so that only the microsatellite-containing products were detectable.

Breast Neoplasms↗
PubMed1992

Quantitation of HIV viral burden by PCR in HIV seropositive Navy personnel representing Walter Reed stages 1 to 6.

To quantitate the amount of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMC) of 78 infected individuals, we have developed a polymerase chain reaction (PCR) assay that is both quantitative and sensitive. Quantitation was based on incorporation of a 32P end-labelled primer (SK39) in the PCR reaction and on comparison after electrophoresis with known amounts of HIV DNA. A linear relationship was obtained between the natural logarithms of the radioactive counts detected and the number of HIV-1 DNA copies (10-1000 copies) from the standard DNA. HIV copy numbers from patient samples were then extrapolated from the standard curves. This sensitive and reproducible method was compared with virus isolation which is a semiquantitative evaluation of viral burden. HIV DNA levels correlated with virus isolation, i.e., high viral burden (100-1000 HIV copies) were found in most samples from which virus was isolated after only 7 days in culture; low viral burden (less than 100 HIV copies) was observed in samples from which virus was isolated after 14 to 21 days in culture. These estimates of viral burden were then compared with the clinical stage of the individuals.

DNA, Viral↗
PubMed1992

Detection of varicella-zoster virus DNA in the oropharynx and blood of patients with varicella.

The polymerase chain reaction (PCR) was used to detect varicella-zoster virus (VZV) DNA in respiratory epithelial cells and in peripheral blood leukocytes from adults with varicella. VZV DNA was detected in oropharyngeal epithelium in 62% of patients early in the course of varicella; the amount of VZV DNA declined with time and was detectable in only 22% of patients for greater than 6 days. VZV DNA was also detected in peripheral blood leukocytes in 74% of patients early in disease and was detected in both polymorphonuclear and mononuclear leukocytes. PCR demonstrated the presence of VZV DNA in the oropharynx and blood of most patients during varicella, in contrast to the ability to detect VZV in these tissues by viral culture.

Adult↗