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Biomedical subjects

L G Davis

Publications and source records attributed to L G Davis.

At least 19 recordsLinked to original sources

Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir.

OBJECTIVE: To assess the effect of the antiviral drug acyclovir on the frequency of subclinical shedding of herpes simplex virus (HSV) in the genital tract. DESIGN: A double-blind, placebo-controlled, crossover clinical trial. SETTING: A university-based virology research clinic. PATIENTS: 34 women with herpes simplex virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years' duration. INTERVENTION: Participants were randomly assigned to receive either acyclovir, 400 mg twice daily for 70 days, followed by a 14-day washout period, and then placebo for 70 days, or the study medications in the reverse order. MEASUREMENTS: Women collected daily genital swabs of the vulvar, cervicovaginal, and perianal areas for HSV culture, maintained a diary of genital lesions, and were examined at the time of recurrences. RESULTS: In an intent-to-treat analysis of the initial treatment period, 15 of the 17 women who received placebo and 3 of the 17 women who received acyclovir had at least 1 day of subclinical shedding (P < 0.001). Among the participants who received placebo, subclinical shedding occurred on 64 of 928 (6.9%) days compared with 3 of 1057 (0.3%) days among the participants who received acyclovir (P < 0.001). The relative risk for subclinical shedding was 0.09 (95% CI, 0.03 to 0.35) for the women who received acyclovir compared with the women who received placebo. In a paired analysis of 26 women who completed both arms of the study, acyclovir therapy was associated with a decrease in the frequency of subclinical shedding; subclinical shedding occurred on 83 of 1439 (5.8%) days with placebo, and on 6 of 1611 (0.37%) days with acyclovir (P < 0.001)--a 94% reduction. The frequency of subclinical shedding was reduced at all anatomic sites and in all patients. CONCLUSIONS: Daily therapy with oral acyclovir suppresses subclinical shedding of HSV-2 in the genital tract, suggesting that studies to evaluate the use of acyclovir in preventing HSV-2 transmission are warranted.

Acyclovir

The effect of irrigation with chlorhexidine or saline on plaque vitality.

24 adult patients suffering from Adult periodontitis were assigned to 4 groups: the 1st rinsed for 1 min with 0.2% chlorhexidine gluconate (CHX); the 2nd group were irrigated for 15 s with 0.2% CHX in a pulsed oral irrigator; the 3rd group rinsed for 1 min with saline and the 4th group were irrigated for 15 s with saline. Plaque vitality was measured after the 4 experimental procedures, using the method described by Netuschil et al. and scored using the method described by Rundegren et al. The results showed that a single rinse or irrigation with 0.2% CHX solution decreased the % of viable micro-organisms, but the vitality of the bacteria remained unchanged in saline groups. Statistical analysis indicated that irrigation with CHX was more effective at reducing plaque vitality than rinsing with CHX.

Adult

Bacillary angiomatosis in patients with AIDS: multiorgan imaging findings.

PURPOSE: To describe the varied clinical manifestations and imaging findings encountered in bacillary angiomatosis, an infectious complication of the acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Clinical, imaging, and histopathologic findings in nine men (aged 26-50 years) with AIDS and bacillary angiomatosis were described. This condition often manifests as vascular skin lesions that resemble those of Kaposi sarcoma, fever, and anemia and is due to infection with Bartonella (Rochalimaea) henselae. RESULTS: Common imaging findings included lung nodules, mediastinal adenopathy, peripheral adenopathy, pleural effusions, ascites, abdominal adenopathy, soft-tissue masses, and low-attenuation lesions in the liver and/or spleen. Most notably, nodes and soft-tissue lesions were dramatically enhanced with injection of contrast material, which is presumably because the lesions are composed to a large extent of well-formed capillaries. CONCLUSION: Bacillary angiomatosis, a treatable infection, should be considered in patients with AIDS, particularly when Kaposi sarcoma is suspected clinically.

Acquired Immunodeficiency Syndrome

The effect of porcelain laminate veneers on gingival health and bacterial plaque characteristics.

The aim of this study was to evaluate the response of microbial plaque and gingival inflammation to the placement of porcelain laminate veneers on anterior teeth. 9 patients, 7 female and 2 male (mean age of 30 years), with a total of 35 veneers were examined. The volume of gingival crevicular fluid (GCF), level of neutral proteolytic enzyme activity, gingival index (GI), plaque index (PlI) and plaque bacteria vitality were measured at baseline and after the placement of veneers. The volume of GCF increased after the placement of veneers (p = 0.03). No statistically significant differences were found in proteolytic enzyme activity or GI (p > 0.05). There were statistically significant reductions in PlI (p = 0.000) and plaque bacteria vitality (p = 0.018). Further research is required to assess the long-term influence of porcelain laminate veneers on gingival health and microbial plaque characteristics.

Adult

A double-blind, placebo-controlled cytogenetic study of oral acyclovir in patients with recurrent genital herpes.

The antiherpes drug acyclovir breaks chromosomes in vitro at millimolar concentrations and at highly toxic doses in rodents but does not induce single-gene mutations. Recurrent genital herpes patients were examined to determine if such chromosomal damage occurs in peripheral lymphocytes during acute or chronic acyclovir therapy. Patients were randomly assigned to receive acyclovir suppressively and for recurrences, placebo suppressively and acyclovir for recurrences, or placebo suppressively and for recurrences (n greater than or equal to 20 for each group; all treatment double-blind). Normal volunteers and acyclovir-treated cultures served as additional controls. Cytogenetic analyses were done at enrollment (pretreatment), on day 5 of acute acyclovir or placebo treatment for the first postenrollment recurrence (postacute), and at the end of a year on study (postchronic). Cells in metaphase, 150 for each patient, were examined at each time point for structural and numerical chromosomal abnormalities. No cytogenetic effects of chronic or acute oral acyclovir treatment were found relative to lifestyle controls, pretreatment controls, or placebo treatment.

Acyclovir

Anatomical localization of calmodulin mRNA in the rat brain with cloned cDNA and synthetic oligonucleotide probes.

Calmodulin is a small, acidic calcium-binding protein that regulates a number of calcium-dependent enzyme activities and is thought to be involved in neurotransmission. To begin to explore further the regulation of this important protein in the brain, we have cloned a rat calmodulin cDNA and designed an oligonucleotide probe based on this sequence. Both the cDNA and oligonucleotide probes revealed a markedly heterogeneous distribution of hybridization signal for calmodulin mRNA in the rat brain. The greatest apparent abundance of mRNA for calmodulin was seen in the hippocampus and cerebral cortex, whereas many brain regions showed relatively low hybridization signal, including the striatum and portions of the hypothalamus and brainstem.

Animals

A double-blind, placebo-controlled study of oral acyclovir in postherpetic neuralgia.

Twenty-one patients with postherpetic neuralgia of two- to 84-months duration participated in a double-blind, placebo-controlled study of oral acyclovir. Pain perception was assessed with the Melzack Pain Questionnaire at baseline and at two-to six-week intervals during the ensuing six months. Clinically significant pain reduction occurred in eight patients: four received acyclovir, and four received a placebo. Several treatment strategies have been advocated for relief of postherpetic neuralgia. Results of the present study demonstrate the need for a double-blind, placebo-controlled paradigm to substantiate the efficacy of new clinical approaches. The same caveat applies to the more common syndromes encountered in psychiatric practice.

Acyclovir

Characterization of a cDNA encoding rat sterol carrier protein2.

Sterol carrier protein2 (SCP2) is a 13.2-kD protein that is thought to be involved in the intracellular transport of cholesterol. Using synthetic oligonucleotides based on the protein sequence of SCP2, a clone (SP43) was isolated from a rat liver cDNA library. The DNA sequence revealed that the cDNA could encode a polypeptide of 273 amino acids (28.9 kD) or 143 amino acids (15.3 kD) in which the carboxy-terminal 123 amino acids are identical to the SCP2 protein. RNA blot hybridization revealed that a variety of rat tissues contain a homologous RNA of a size similar to SP43 (approximately 1.5 kb). Levels of SCP2 mRNA increased in parallel with cytochrome P450scc mRNA in the immature gonadotropin-primed rat ovary. The isolation of a cDNA clone encoding SCP2 will facilitate studies on its role in cholesterol metabolism.

Amino Acid Sequence

Proteolytic processing of beta-amyloid precursor by calpain I.

The beta-amyloid peptide is a core component of the neuritic plaques that accumulate in Alzheimer's disease. Since the beta-peptide resides within a family of precursor proteins (APPs), proteolytic processing of APP is required for beta-amyloid deposition into plaques. Here, we have examined the role played by the calcium-dependent cysteine protease calpain I in APP processing. Immunoblotting with a specific APP antiserum was used to assess the in vitro degradation of rat brain APP, which appears as a triplet of polypeptides of Mr 110-130 kDa. Both soluble and membrane-bound APP were extraordinarily sensitive to activated calpain I. APP contains at least 3 distinct calpain I cleavage sites. The most protease-sensitive site was located within the highly acidic structural motif called the PEST domain, a second site was upstream of the putative N-linked glycosylation sites, and a third generated a 16 kDa carboxy-terminal fragment that contains the beta-peptide. Based on light microscopic immunohistochemistry, APP and calpain I were extensively colocalized within large numbers of neurons distributed throughout the rat brain, with especially high levels of each in neocortical layer 5, subiculum, globus pallidus, entopeduncular nucleus, anterodorsal and reticular thalamic nuclei, motor trigeminal nucleus, deep cerebellar nuclei, and Purkinje cells. Both antigens were most prevalent within neuronal perikarya. Intraventricular kainate infusion, which is known to cause rapid activation of hippocampal calpain I, produced a 32% decline in APP levels after 24 hr, suggestive of in vivo degradation of APP by calpain I. Following kainate-induced neuronal loss, both APP and calpain I immunoreactivities appeared in the surrounding reactive astroglia. These results indicate that calpain I may be involved in the normal and, perhaps, pathological processing of APP, and that this processing could occur in either neurons or reactive astrocytes. Calcium influx and calpain I activation may provide a mechanism by which excitatory neurotransmission regulates APP metabolism.

Alzheimer Disease

Horizontal transmission of hepatitis B virus.

Meta-analysis of seroprevalence surveys shows that horizontal transmission of hepatitis B virus (ie, that occurring without apparent parenteral, sexual, or perinatal exposure) is common in areas endemic for the virus. It occurs especially in pre-adolescent children. In developed countries, where endemicity of hepatitis B virus is low, horizontal transmission (probably via saliva or open wounds) may occur in households with a persistent carrier, but it is less efficient a means of infection than is sexual or perinatal transmission. Horizontal transmission also seems possible in pre-school day-care centres in developed countries, despite the small numbers of carriers in such places.

Adolescent

Nonradioactive detection of vasopressin mRNA with in situ hybridization histochemistry.

In situ hybridization histochemistry has been used successfully by many laboratories to detect mRNAs within single cells in the CNS. The detection of these hybrids in CNS tissue sections has been accomplished mainly with radioactive probes. However, radiolabeled probes have intrinsic limitations, including the long exposure time required for high resolution autoradiography and the inability to detect multiple RNA species within the same neuron. Here we report a new method to detect mRNA in situ using a synthetic DNA probe conjugated to alkaline phosphatase (AP). The probe was synthesized to be complementary to the glycoprotein coding region of vasopressin mRNA. Under normal hybridization conditions high resolution detection of vasopressin mRNA within individual neurons was routinely obtained within 8 h. The distribution of hybridization signal obtained with the AP-conjugated probe was identical to that observed with the same probe radiolabeled with [35S]dATP. Hybridization-positive neurons were found in all regions of the CNS that have been previously reported to synthesize vasopressin, including magnocellular neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus. Small diameter neurons were also observed in the suprachiasmatic nucleus, the accessory PVN, the bed nucleus of the stria terminalis, and a cell group along the ventral surface of the optic tract. These results suggest that nonradioactive detection of neuropeptide mRNA in situ can be easily accomplished within 24 h. Furthermore, the improved resolution with AP-conjugated oligonucleotide probes should enhance efforts to study the regulation of gene expression in the nervous system.

Alkaline Phosphatase

Expression of beta-amyloid precursor protein in reactive astrocytes following neuronal damage.

Although the beta-amyloid peptide is an established core component of neuritic plaques that accumulate in Alzheimer's disease, the mechanisms responsible for its deposition are not well understood. We now report that lesions of rat hippocampal neurons cause a time-dependent, long-lasting elevation of immunoreactivity for the beta-amyloid precursor protein (APP) in neighboring astrocytes, a cell type not normally containing the protein. The increase represents astroglial expression of the protein rather than a scavenging of APP released by damaged neurons. Immunoelectron microscopy confirmed that APP-containing cells are reactive astroglia, both surrounding capillaries and within the neuropil. These results demonstrate that neuronal damage stimulates APP expression in adult brain and suggest that reactive astrocytes may be a source of the beta-amyloid that forms neuropathological plaques in Alzheimer's disease.

Amyloid

Factors that influence the elderly to use traditional or nontraditional nutrition information sources.

This study analyzed sociodemographic variables, access to medical care, health status-related variables, and nutrition status-related variables to determine their ability to predict an orientation toward traditional or nontraditional nutrition information sources among aged subjects in Eugene, OR. Data were collected from 165 randomly selected subjects by trained interviewers using face-to-face interviews. Nutritionist orientation was measured by a Traditional/Nontraditional Index (TNT Index) developed for the study. Nutrition knowledge and misinformation, supplement use, and sources of nutrition information were also investigated. Predictors of nontraditional nutritionist orientation were acceptance of nutrition misinformation and male sex (adjusted R2 = .09). For women, predictors of a similar orientation were acceptance of nutrition misinformation, low knowledge of general nutrition information, and low functional health status (adjusted R2 = .19). Mean nutrition knowledge scores were high, with a mean of 4.7 (standard deviation [SD] = 0.8) on a scale ranging from 4 (high) to 8 (low). However, many of the subjects did not list dairy foods (28%) and grains (27%) as necessary in the diet. In addition, belief in certain nutrition myths was widespread. More than 58% were taking one or more supplements (mean = 1.4 supplements per day, SD = 1.98). Physicians were mentioned as most likely sources of nutrition information, with dietitians and health food store personnel mentioned second, indicating the importance of marketing efforts for registered dietitians.

Aged

Acyclovir prevents reactivation of herpes simplex labialis in skiers.

To determine the effectiveness of an antiviral to prevent herpes labialis during a brief, high-risk circumstance, 147 persons with a history of sun-induced recurrences were treated prophylactically with oral acyclovir or matching placebo and were observed during their ski holidays. Five (7%) of 75 acyclovir-treated subjects developed lesions compared with 19 (26%) of 72 persons in the placebo group.

Acyclovir

Prolonged continuous versus intermittent oral acyclovir treatment in normal adults with frequently recurring genital herpes simplex virus infection.

In Year 1 of this two-year trial, patients with six or more genital herpes recurrences in the past year received suppressive treatment with either acyclovir, 400 mg, or placebo, orally twice daily for one year, and physician-documented recurrences were treated with open-labeled acyclovir, 200 mg, orally five times per day for five days (acute treatment). In Year 2, patients received open-labeled acyclovir treatment either with daily suppressive therapy or intermittent acute therapy. Among 683 patients who completed two years of treatment, 348 received continuous suppressive treatment for two years, 276 received acute treatment in Year 1 and suppressive treatment in Year 2, 24 received suppressive treatment in Year 1 and acute treatment in Year 2, and 35 received acute treatment for two years. Patient groups receiving intermittent acute acyclovir treatment experienced means of 7.0 to 12.6 recurrences/year during treatment as compared with 1.4 to 1.9 recurrences/year among groups receiving continuous suppressive treatment. No patients who received acute treatment remained recurrence-free for two years as compared with 29 percent of patients receiving continuous acyclovir suppression for two years. There was no evidence of cumulative toxicity detected by clinical, hematologic, or blood chemistry evaluations performed monthly in Year 1 and quarterly in Year 2. Suppressive oral acyclovir therapy remained effective and well-tolerated in this two-year trial.

Acyclovir

Double-blind, placebo-controlled trial comparing long-term suppressive with short-term oral acyclovir therapy for management of recurrent genital herpes.

A total of 156 patients with frequently recurring genital herpes were enrolled in a randomized, double-blind, one-year trial comparing long-term suppressive and intermittent oral acyclovir therapy with placebo in the management of recurrent genital herpes. Subjects received either suppressive treatment with acyclovir, 400 mg twice daily for one year, and 200 mg five times per day for five days, for short-term treatment of recurrences; intermittent treatment with placebo, twice daily for one year, and oral acyclovir, 200 mg five times per day for five days, for short-term treatment of recurrences; or treatment with placebo, twice daily for one year, and five times per day for five days for short-term treatment of recurrences. Median time to first recurrence was 250 days for the suppressive group, 28 days for the intermittent group, and 23 days for the placebo group (p = 0.001). The median number of days per month with active disease was 0.32 for the suppressive group, 4.18 for the intermittent group, and 4.72 for the placebo group (p less than 0.001), with a median recurrence rate per 30-day treatment period of 0.08 recurrences/patient in the suppressive group, 0.70 in the intermittent group, and 0.74 in the placebo group (p less than 0.001). Median duration of recurrence was 5.0 days in the suppressive group compared with 6.0 days in the combined intermittent acyclovir plus placebo group (p = 0.001), and was reduced from 7.0 to 6.0 days when intermittent acyclovir treatment was compared with placebo treatment (p = 0.05). Daily administration of oral acyclovir for one year is superior to intermittent or placebo treatment in the management of patients with frequently recurring genital herpes.

Acyclovir

Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial.

Normal adults with six or more episodes of genital herpes in the previous year were enrolled in a one-year, multicenter, double-blind trial comparing placebo with 400 mg of acyclovir administered orally twice daily. Patients with episodes during the study were offered 200 mg of acyclovir administered orally five times daily for five days; this allowed comparison of suppressive and episodic treatment. After one year, 227 (44%) of 519 patients receiving suppressive treatment and seven (2%) of 431 receiving placebo (episodic) treatment remained free of recurrences, and the mean numbers of recurrences per year were 1.8 and 11.4, respectively. Among 67 patients who had received suppressive therapy for one year, the mean duration of lesions in the first episode following the discontinuation of treatment was 9.3 days compared with 7.3 days among 45 patients who had received episodic therapy for one year. Treatment was well tolerated, and no changes were noted in the in vitro susceptibility to acyclovir of herpes simplex virus cultured during or after the one-year trial. Continuous or episodic oral acyclovir therapy for one year remained safe and effective.

Acyclovir