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Biomedical subjects

M Remington

Publications and source records attributed to M Remington.

At least 19 recordsLinked to original sources

Ultraviolet-light-inactivated Cas-Br-M murine leukemia virus induces a protective CD8+ cytotoxic T lymphocyte response in newborn mice.

Newborn NFS/N mice are susceptible to the neurological disease induced by infection with Cas-Br-M murine leukemia virus (Cas), and do not develop a protective cytotoxic T cell (CTL)-mediated response to Cas infection. Here we demonstrate that whole UV light-inactivated Cas (UV-Cas), inoculated in newborn NFS/N mice, induced a strong, Cas-specific CTL response detectable 2 weeks postinoculation and persisting in vivo for > or = 36 weeks. The magnitude of the UV-Cas-induced splenic CTL response, mediated by CD8+ T cells, inversely correlated with the level of proviral cas env sequences detectable in the spleen of the UV-Cas-inoculated mice, as revealed by PCR amplification of tissue DNA. The transfer of UV-Cas-primed splenocytes, with Cas-specific CTL activity, protected 100% of recipient newborn mice from the development of neurological disease induced by infection with live Cas, for more than 28 weeks, and reduced the level of viral replication in the recipients.

Animals↗

Protein-specific cervical antibody responses to primary genital herpes simplex virus type 2 infections.

Antibodies to herpes simplex virus (HSV) have been demonstrated in cervicovaginal secretions but have not been analyzed for their viral protein targets, prevalence, isotype, or kinetics of development. A method was devised to collect cervical secretions from women with primary genital HSV-2. By Western blot, cervical IgG and IgA responses to HSV-2 proteins VP5, gB, and gD were detected in most patients within 2 weeks of onset and to gC/gE within 3 weeks. Cervical IgM and IgG responses to gG, VP16, and ICP35 developed later and were more variable. Cervical IgM to most proteins appeared within 6-10 days. Cervical IgA and IgG persisted for weeks, but cervical IgM waned. Western blot profiles of serum IgG and cervical IgG to individual HSV-2 proteins were similar; those of serum IgA and cervical IgA differed. These findings suggest a universal, complex immune response to HSV-2 infection in the female genital tract.

Adult↗

A randomized, double-blind, comparative trial comparing high- and standard-dose oral acyclovir for first-episode genital herpes infections.

Orally administered acyclovir ameliorates the clinical course and decreases the duration of viral shedding in patients with first-episode genital herpes infections. We investigated in a randomized, double-blind, comparative trial whether a higher (4 g) than standard (1 g) daily dose of oral acyclovir results in greater clinical benefit and influences the time to first recurrence. A total of 139 patients with first-episode genital herpes were randomized to receive orally 4 or 1 g of acyclovir daily. A total of 52 subjects were excluded from the efficacy analysis because most had recurrent disease. Of 87 eligible subjects, 28 (32%) had primary herpes simplex virus type 1 (HSV-1) infections, 48 (55%) had primary HSV-2 infections, and 11 (13%) had nonprimary HSV-2 infections. We did not find any statistically significant differences in the duration of symptoms or viral shedding between the two dose groups, nor did the median time to first recurrence differ between the two groups. Initiation of therapy with either dose within the first 3 days of the appearance of symptoms shortened the duration of the first episode. Adverse gastrointestinal effects developed in 8% of subjects receiving the higher dose, whereas no adverse reactions were observed among those receiving the standard dose (P = 0.10). We conclude that, in comparison with standard therapy, higher-dose oral acyclovir does not result in additional clinical benefit or modify the time to first recurrence. The present study may have implications for the development and efficacy of congeners of acyclovir which provide higher levels in blood than the standard dose of acyclovir.

Acyclovir↗

Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture.

The sensitivity of a rapid enzyme immunoassay test (HerpChek Direct Herpes Simplex Virus Antigen Test [DuPont Medical Products, Wilmington, Del.]) for the detection of herpes simplex virus (HSV) antigens in patient specimens was compared with HSV culture. HerpChek positivity for HSV occurred with 179 (65%) of 275 lesion specimens, whereas culture for HSV was positive for 145 (53%) lesions (P = 0.002). HerpChek was twice as sensitive as culture for the detection of HSV in late-stage lesions and was equivalent to culture for the detection of HSV in early lesions. We conclude that HerpChek provides greater sensitivity than culture for HSV detection in late-stage genital lesions.

Adolescent↗

Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction.

To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes, and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus 3 of 17 days by viral isolation (P less than .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure of HSV infection than routine viral culture and that PCR detects the presence of HSV at times when culture is negative.

Adult↗

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↗

Transmission of genital herpes in couples with one symptomatic and one asymptomatic partner: a prospective study.

To determine the risk of transmission of genital herpes simplex virus (HSV) infection, we prospectively studied, for a median of six months, 38 couples who had been together for a median of 10 mo. In each couple, one partner had a history of symptomatic genital herpes and one did not. At entry, of the 38 asymptomatic, exposed partners, 21 were seronegative, and results of western blot analysis showed that seven had antibody to HSV type 1 (HSV-1), four to HSV type 2 (HSV-2), and six to both HSV-1 and HSV-2. One of the 28 exposed partners without antibody to HSV-2 at enrollment asymptomatically acquired HSV-2 infection, but four of 10 with antibody to HSV-2 at enrollment developed culture-proven HSV-2 infection during follow-up. Restriction endonuclease analysis of DNA from paired isolates revealed identical strains in three couples and different strains in one. In this group of asymptomatic sex partners of persons with genital herpes, asymptomatic and unrecognized acquisition of HSV-2 infection was common, but more than half of the exposed partners remained free of HSV-2 infection after a median of 16 mo of sexual contact.

Adult↗

Detection of herpes simplex virus DNA from genital lesions by in situ hybridization.

Lesion specimens from 118 episodes of recurrent genital herpes were used to compare herpes simplex virus (HSV) isolation with a direct specimen test for in situ DNA hybridization utilizing a biotinylated probe. The frequency of detection of HSV was similar with both tests; HSV was isolated from 81% of vesicular lesions, 76% of pustules, and 67% of ulcers, while HSV DNA was detected in 77, 76, and 55% of lesions in these stages, respectively. Utilizing both methods, HSV was identified in 91, 94, and 79%, respectively. The sensitivity and specificity of the DNA probe in comparison to standard viral isolation in tissue culture were 92 and 63%, respectively. Seven DNA-positive, viral isolation-negative specimens were obtained from patients who had positive culture confirmation at some time subsequent or prior to enrollment, suggesting that these were true positive results. The sensitivity of the DNA probe was dependent on cellular content of the specimen, and 36 (28%) of the 127 submitted specimens had fewer than 20 nonsuperficial cells. The DNA probe was rapid and convenient; its major disadvantage was the lack of type-specific information. The performance of the probe in lower-prevalence populations and in asymptomatic shedding of HSV remains to be evaluated.

Cells, Cultured↗

Diagnosis of herpes simplex virus by direct immunofluorescence and viral isolation from samples of external genital lesions in a high-prevalence population.

One hundred thirty specimens from 108 consecutive patients with a history of recurrent genital ulcerations were used in a study comparing herpes simplex virus (HSV) isolation with a direct fluorescent-antibody (DFA) technique using mouse monoclonal antibodies. HSV was isolated from 70% of vesicular lesions, 67% of pustular lesions, 32% of ulcerative lesions, and 17% of crusted lesions, whereas the DFA technique detected HSV antigen in 87, 67, 30, and 10% of lesions in similar stages, respectively. When both methods were used, HSV was identified in 97, 79, 45, and 17% of vesicles, pustules, ulcers, and crusted lesions, respectively. The overall sensitivity and specificity of the DFA technique in comparison with virus isolation (VI) were 74 and 85%, respectively. Of the 17 patients from whom DFA-positive, VI-negative samples were obtained, HSV was subsequently isolated from a genital lesion in 14, suggesting that they were not DFA false-positives. Similarly, of the 46 patients whose initial lesion samples were DFA and VI negative, 37 (80%) had HSV identified from subsequent genital lesions during follow-up. Thus, a single sample for VI or DFA testing from a recurrent genital lesion had a sensitivity of only 53 and 51%, respectively. Combining the DFA technique and VI increased the sensitivity of laboratory diagnosis of a single recurrent episode of genital HSV; however, repetitive laboratory testing was often required to confirm the diagnosis of recurrent genital HSV infection.

Antibodies, Monoclonal↗

The outcome of neurotic disorders after out-patient and day hospital care.

New psychiatric out-patients with depressive, phobic, and anxiety neurosis were randomly allocated to out-patient care or to one of two types of day hospital treatment, one specialising in psychotherapy and the other offering all forms of day care. Of 106 patients who entered the study, 78 had assessments of psychiatric symptomatology and social adjustment both before treatment and after 4, 8 and 24 months. There was no significant difference in outcome between depressive, phobic, and anxiety neurosis, and no overall difference in response to treatment between the three types of care. Suicidal symptoms were significantly less common in out-patients. In many respects, neurotic disorder can be regarded as a single syndrome.

Ambulatory Care↗

A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection.

Patients with frequently recurring genital herpes were enrolled in a double-blind placebo-controlled trial comparing 200-mg acyclovir capsules, given five or two times daily, with placebo. Of 47 placebo recipients, 44 (94 per cent) had recurrences during the 120-day treatment period, compared with 13 (29 per cent) of 45 patients treated with acyclovir five times daily and 18 of 51 (35 per cent) treated with acyclovir twice daily (P less than 0.001 for each regimen compared with placebo). The median time to the first clinical recurrence was 18 days in placebo recipients, compared with over 120 days in both acyclovir-treated groups (P less than 0.001 for both groups compared with placebo). The mean monthly recurrence rate during the medication period was 0.86 in placebo recipients, compared with 0.13 in patients treated with acyclovir five times daily and 0.14 in patients treated with acyclovir twice daily (P less than 0.001 for both groups compared with placebo). While receiving therapy, 86 of 96 acyclovir-treated patients had over a 50 per cent reduction in their pretreatment recurrence rate. Breakthrough recurrences in acyclovir recipients were of shorter duration and associated with a lower frequency of viral shedding than recurrences in placebo recipients. After medication was discontinued, the subsequent recurrence rate returned to pretreatment frequencies. Daily oral acyclovir was well tolerated. We conclude that oral acyclovir given for four months markedly reduces but does not completely prevent recurrences of genital herpes and does not influence the long-term natural history of the disease.

Acyclovir↗

Intestinal transit of solid and liquid components of a meal in health.

The aim of this study was to test the hypothesis that, under physiologic conditions, the human small bowel discriminates between the solid and aqueous components of chyme, that is, that in a fashion analogous to the stomach, the intestine would allow the liquid fraction to progress at a faster rate than solid particles. To evaluate this hypothesis, we took advantage of a gamma-emitting solid marker, 131I-fiber, previously developed in our laboratory, that is recognized by the stomach as a solid and that is emptied at a slower rate than liquid markers. Thus, 131I-fiber enters the intestine during feeding at a slower rate than a liquid marker, being eventually excreted in the feces physically and chemically unchanged. We also developed a mathematical method to calculate the intestinal transit spectrum based on scintigraphic data obtained from 6 healthy individuals who ingested 131I-fiber and technetium 99m (99mTc)-diethylenetriaminepentaacetic acid (DTPA)-water with a meal. The results disprove the hypothesis by showing that whereas 131I-fiber, as expected, leaves the stomach at a much slower rate than 99mTc-DTPA-water, both markers progress along the small bowel separately but at similar speeds. Our method for measuring intestinal transit provides a more comprehensive quantification of chyme transit in the human small bowel than earlier methods and should prove a useful technique for further noninvasive studies of transit after feeding.

Adult↗

Abnormalities in gastrointestinal motor activity in patients with short bowels: effect of a synthetic opiate.

We have investigated the fasting and postprandial patterns of gastrointestinal pressure activity in a group of patients with extensive (greater than 100 cm) resections of the distal small bowel. Each short bowel patient was studied on 2 consecutive days with random single blind administration of either loperamide (6 mg at 5 h and at 30 min before the meal) or placebo, and 20 healthy controls were studied on single days (13 basal fasting, 7 placebo). During fasting, the duration of the interdigestive motor complex was significantly shorter in patients with short bowel syndrome (71.1 +/- 15.6 min vs. 109 +/- 7.8 min for controls, p less than 0.03); hence, the frequency of complexes was increased. The duration of phase 2 was strikingly shorter in patients (18.7 +/- 7.0 min vs. 52.9 +/- 8.5 min for controls, p less than 0.03). Gastric emptying and postprandial motor activity were identical in patients and controls. During fasting, loperamide prolonged phase 3 (7.6 +/- 2.2 min vs. 4.3 +/- 1.1 min for placebo, p less than 0.03). Postprandially, loperamide shortened the time from meal ingestion to the first phase 3 by 50% (p less than 0.003), and increased motility index and frequency of contraction in the gut (p less than 0.01). Thus, gut motor activity in the short bowel syndrome is characterized by more frequent interdigestive motor complexes, marked reduction in phase 2 activity, and a normal feeding pattern. Loperamide therapy increases feeding activity while at the same time shortening its duration.

Adult↗

Inhibition of postprandial pancreatic and biliary secretion by loperamide in patients with short bowel syndrome.

Patients with the short bowel syndrome are usually afflicted by chronic diarrhoea and treated with opiate drugs, yet little documentation of the effects of such drugs on digestive function is available. In the present study we found that acute oral administration of loperamide resulted in 50% inhibition of postprandial trypsin and bilirubin output in patients with short bowel syndrome. These changes are consistent with an opiate effect.

Adult↗

Controlled comparison of day-hospital and outpatient treatment for neurotic disorders.

106 patients with anxiety, phobic, and depressive neuroses referred to the outpatient clinics of 6 psychiatrists were randomly assigned to outpatient care or two forms of psychiatric day care. Ratings of symptoms and social adjustment were recorded before treatment and after 4 and 8 months in 89 patients. There were no important differences in the outcome of day care and outpatient treatment although patients were more satisfied with the outpatient service. Because outpatient care is more economical of time and personnel it should be preferred to psychiatric day care for many neurotic disorders.

Ambulatory Care↗

Comparative reliability of categorical and analogue rating scales in the assessment of psychiatric symptomatology.

The reliability of 26 items from the ninth edition of the Present State Examination (PSE) was assessed using both the conventional categorical scales and separately constructed analogue scales. Reliability was also calculated when the analogue responses were rescaled down to 2, 3 and 4 categories. The levels of inter-rater agreement obtained were comparable to those achieved in previous studies of PSE reliability, although as expected the levels of agreement on audiotapes were greater than those for independent interviews performed on the same day. These levels were not significantly affected by any of the changes in scale format, but there were apparent differences in reliability depending on the statistics used. In selecting or constructing a psychiatric rating scale, the question of reliability should not influence the choice of a categorical or continuous scale, or the number of scored points in the scale.

Psychiatric Status Rating Scales↗

Reliability of a schedule for rating personality disorders.

The inter-situational, inter-rater and temporal reliability of a schedule for rating personality disorders is described. In an initial study with a simplified form of the schedule in patients from different wards of a psychiatric hospital inter-situational reliability between raters was higher for patients with personality disorders than with no personality disorder. Using the full schedule, inter-rater reliability, using audiotaped and separate interviews, and temporal reliability at interviews conducted a mean of 12.5 months apart all reached a satisfactory level, suggesting that the schedule may be a useful instrument for measuring deviant personality traits. The interview may be used with a subject or an informant but agreement between ratings made with informants and psychiatric patients during illness was low, and the schedule is not recommended for use with patients alone during acute episodes of illness.

Humans↗