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Biomedical subjects

M Myers

Publications and source records attributed to M Myers.

At least 55 records · Page 3Linked to original sources
PubMed1998

Suppression of plasma viral load below 20 copies/ml is required to achieve a long-term response to therapy.

BACKGROUND: Current guidelines state that the goal of antiretroviral therapy for HIV-infected individuals is to suppress plasma viral load (pVL) to below 400 copies/ml. METHODS: Predictors of achieving and maintaining pVL suppression were examined in a randomized trial of combinations of zidovudine, nevirapine and didanosine in patients with CD4+ T cell counts of between 200 and 600 x 10(6) cells/l who were naive to antiretroviral therapy and AIDS-free at enrolment. RESULTS: One hundred and four patients had pVL > 500 copies/ml at baseline and a pVL nadir below 500 copies/ml. Of these, 77 patients experienced an increase in pVL above 500 copies/ml. The median number of days of pVL suppression to below 500 copies/ml was 285 (42) for patients with pVL nadir < or = (>) 20 copies/ml (P = 00.0001). The relative risk of an increase in pVL above 500 copies/ml associated with a pVL nadir below 20 copies/ml was 0.11 (P = 0.0001). The relative risks of an increase in pVL above 5000 copies/ml associated with a pVL nadir below 20 copies/ml or between 20 and 400 copies/ml were 0.05 [95% confidence interval (CI), 0.02-0.12] and 0.37 (95% CI, 0.23-0.61) respectively, compared with individuals with a pVL nadir > 400 copies/ml. Individuals with a pVL nadir < or = 20 copies/ml were at a significantly lower risk of virologic failure than individuals with a pVL nadir of between 21 and 400 copies/ml (P = 0.0001). CONCLUSIONS: Our results demonstrate that suppression of pVL below 20 copies/ml is necessary to achieve a long-term antiretroviral response. Our data support the need for a revision of current therapeutic guidelines for the management of HIV infection.

Anti-HIV Agents↗
PubMed1998

Induction-maintenance antiretroviral therapy: proof of concept.

OBJECTIVE: To investigate the concept of aggressive initial combination therapy followed by reduction to a less demanding maintenance regimen with respect to its potential for sustaining viral suppression. DESIGN: Durable viral suppression to < 20 HIV RNA copies/ml plasma was achieved with zidovudine-nevirapine-didanosine (ZDV-NVP-ddl) therapy. Potential for sustained antiviral response was explored for patients who began with ZDV-NVP-ddl and subsequently interrupted ddl. METHODS: Antiretroviral-naive patients were treated with ZDV-NVP, ZDV-ddl, or ZDV-NVP-ddl. Viral load was measured with the Amplicor assay (limit of quantification 400 copies/ml) and by the Ultra Direct assay (limit of quantification 20 copies/ml) when the Amplicor result was < 500 copies/ml. Treatment adherence for each drug was recorded, including all dose adjustments. RESULTS: Five patients who had begun treatment with ZDV-NVP-ddl discontinued ddl for at least 6 weeks after achieving viral load levels below detection. All were documented to have sustained their viral load at < 20 copies/ml during the ddl interruption. Two patients permanently discontinued ddl, both with sustained viral load below detection for more than 1 year while treated with ZDV NVP. In contrast, no patient initially receiving ZDV-NVP was able to maintain viral load below detection for sustained periods; none had viral load below detection after week 12 of treatment. CONCLUSIONS: After induction with ZDV-NVP-ddl, patients were able to sustain viral suppression with a regimen (ZDV NVP) that was only transiently effective as initial therapy. There was no evidence of virologic escape, even with the most sensitive measure of plasma viral load.

Anti-HIV Agents↗
PubMed1998

A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

CONTEXT: Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. OBJECTIVE: To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. DESIGN: Double-blind, controlled, randomized trial. SETTING: University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). PATIENTS: Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). INTERVENTION: Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA. RESULTS: Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08). CONCLUSIONS: Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.

Adult↗
PubMed1998

Complete cDNA sequence of the Ki-ras proto-oncogene in the liver of wild English sole (Pleuronectes vetulus) and mutation analysis of hepatic neoplasms and other toxicopathic liver lesions.

A complete copy of Ki-ras b cDNA from English sole (Pleuronectes vetulus), a benthic marine flatfish, was cloned and sequenced. The percent identity between the predicted amino acid sequence of English sole and human Ki-ras b was 97%, whereas the percent identity between the English sole gene and rainbow trout or Rivulus Ki-ras b was 98%. Areas of amino-acid sequence conservation included codons 12, 13, and 61, the positions in which mutations are observed in ras cellular oncogenes in other species. The 5' untranslated region (UTR), consisting of 217 nt, was not highly GC rich but contained four ATG start codons upstream of the major open reading frame. The 3' UTR, containing 26 nt, was AU rich. Analysis of Ki-ras mutations was performed on a variety of necrotic, preneoplastic, and neoplastic lesions in livers from 13 English sole collected from contaminated waterways in Puget Sound, WA. Despite reports of Ki-ras mutations in hepatic tumors from other fish, no mutations in codons 12, 13, or 61 were found in hepatic lesions from English sole by direct DNA sequencing of polymerase chain reaction-amplified genomic DNA. Although mutations could exist at levels below the detection limits of this analysis, the results suggest that Ki-ras has a role in liver carcinogenesis that varies according to the fish species or carcinogen. Furthermore, future studies of the etiology of chemically induced cancer in feral English sole should consider mutations in other cancer-related genes, such a5p53, Ha-ras, and N-ras.

Amino Acid Sequence↗
PubMed1997

Sonographic appearances of inverted Meckel diverticulum with intussusception.

This study illustrates the sonographic findings of inverted Meckel diverticulum acting as a lead point of an intussusception in five patients. In four patients, the inverted diverticulum was seen as a segment of blind-ending, thick-walled bowel projecting for a variable distance from the apex of the intussusceptum. The larger diverticula had a characteristic bulbous shape. The central serosal surface of the inverted diverticulum was filled with fluid in one patient, with fluid and fat in another, and with echogenic fat only in the other two. The presence of fat was confirmed by CT in one patient. The features illustrated in these four patients appear to be specific. In the fifth patient, the sonogram revealed a nonspecific echogenic mass at the apex of the intussusceptum. Recognition of these features on sonography may obviate the need for further investigation.

Child↗
PubMed1997

The appearance of inverted Meckel diverticulum with intussusception on air enema.

This paper presents the appearances of inverted Meckel diverticulum with an irreducible intussusception on air enema in four children. The inverted Meckel diverticulum appeared as a bulbous (3) or triangular (1) filling defect in the air column projecting off the distal end of the soft tissue mass of the irreducible intussusceptum. The bulbous defect appears to be highly suggestive, and may be specific, for inverted Meckel diverticulum. Earlier recognition of the presence of the Meckel diverticulum as the lead point of the intussusception could have changed the management in two of the children.

Air↗
PubMed1997

Diet and infant behavior.

We studied 142 preterm infants (mean gestation 31 weeks, mean birthweight 1364 g) fed prospectively varied protein and energy intakes. Infants were grouped as either slow or rapid growers based on rate of weight gain. Rapid growers had increased heart rates (166 vs 160 beats/min), respiratory rates (55.7 vs 53.9 bpm), energy expenditure (64.8 vs 61.6 kcal kg(-1) day(-1)), urinary C-peptide levels (1.59 vs 0.79 ng ml(-1)) and time in active sleep (78.0 vs 75.2%), and decreased spectral edge frequency in the electroencephalogram (2.96 vs 4.45 Hz) compared to slow growers. We conclude that preterm infants growing at varying rates manifest physiological and behavioral differences, and that these patterns may reflect altered autonomic balance.

Diet↗
PubMed1997

Effect of 10 percent carbamide peroxide on color of provisional restoration materials.

To improve esthetic results, nightguard vital bleaching of teeth using 10 percent carbamide peroxide, or CP, may be indicated when an anterior tooth is restored with a provisional crown. This study evaluated the effect of NGVB solutions containing 10 percent CP on the color stability of provisional restoration materials. Disks were fabricated from six representative provisional restoration materials and were tested in five different 10 percent CP bleaching agents. An orange discoloration occurred with provisional materials that contained methacrylate when they were exposed to 10 percent CP bleaching solutions.

Carbamide Peroxide↗
PubMed1997

Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring.

OBJECTIVE: To evaluate patterns of compliance with once versus twice daily administration of antihypertensive therapy (primary-outcome measure) and relevance of partial compliance for blood pressure control (secondary outcome measure). DESIGN: Multicentre, nonblinded, parallel group randomized design. SETTING: Nonacademic primary care practices across Canada. STUDY POPULATION: Patients with mild essential hypertension (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight patients were randomized to active treatment; 14 patients discontinued the study because of side effects. INTERVENTIONS: After a four-week placebo run-in period, patients were randomized to amlodipine 5 mg once-a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Doses were increased to 10 mg and 180 mg to achieve sitting diastolic blood pressure of 90 mmHg or less. OUTCOME MEASURE: During 20 weeks on active treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed doses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure control as determined by office blood pressure measurement. RESULTS: The percentage prescribed doses taken (by either pill count of MEMS) showed a high degree of compliance, similar for the two treatments. However, other parameters of compliance were significantly better with once versus twice daily therapy. Partial compliance (less than 80% by pill count) led to less blood pressure control with the short acting diltiazem, but did not affect blood pressure control for the long acting amlodipine. Side effects profiles did not differ between the two treatments. CONCLUSIONS: Within the constraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill-taking, but patterns of pill-taking are more erratic with twice versus once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure control can be offset by choosing agents with a duration of action well beyond the dosing interval.

Adolescent↗
PubMed1996

Influence of gender, race, and education on patient preferences and receipt of cardiac catheterizations among coronary care unit patients.

The extent to which a preference for less aggressive care explains the lower rate of invasive cardiac services for women and African-Americans is unknown. A prospective observational study of 272 patients admitted to the coronary care unit was conducted at a tertiary referral teaching hospital and a community teaching hospital. In stepwise multivariate analysis, having less than a college education, poor cardiac function, not having undergone a previous cardiac catheterization, being a patient in a nonreferral community hospital, and current smoking were positively associated with a patient's stating that he or she would disagree with a physician's recommendation for a cardiac catheterization. The step-wise multivariate model with cardiac catheterization as the dependent variable indicated that being a patient in a referral medical center, patient willingness to accept a physician's recommendation for a cardiac catheterization, severe heart disease, and having attended high school were predictive. Women did not differ from men in their preference for or receipt of cardiac catheterization. Patients in the coronary care unit with lower levels of education were less likely to undergo cardiac catheterization. This association was only partly explained by less educated patients' being less willing to accept a physician's recommendation to undergo cardiac catheterization.

Aged↗
PubMed1996

Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators.

OBJECTIVE: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. DESIGN: A 48-week, randomized, double-blind, placebo-controlled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units. PATIENTS: 398 adults who had HIV-1 infection, had 350 or fewer CD4+ T lymphocytes/mm3, and had had more than 6 months of previous nucleoside therapy. INTERVENTION: 1) Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing > or = 60 kg). MEASUREMENTS: CD4+ T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA HIV-1 infectivity titer in peripheral blood mononuclear cells; serum p24 antigen levels; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites. RESULTS: After 48 weeks of study treatment the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% Cl, 7% to 29%; P = 0.001), a 0.32 log10 lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (Cl, 0.05 to 0.59 log10 infectious units per million cells; P = 0.023), and a 0.25 log10 lower mean plasma HIV-1 RNA level (Cl, 0.03 to 0.48 log10 RNA copies/mL; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2%; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [Cl, 0.75 to 2.06]; P > 0.2), although the study had only moderate power to detect a major difference. CONCLUSIONS: Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens.

Adult↗
PubMed1995

Radiolabeled antibody combined with external radiotherapy for the treatment of head and neck cancer: reconstruction of a theoretical phantom of the larynx for radiation dose calculation to local tissues.

We propose to use radiolabeled antibodies in combination with external beam radiotherapy to improve locoregional control of head and neck cancer. In this case radiation toxicity to mucosa may become a dose-limiting factor and a calculation of the possible compensatory decrease to the external beam radiotherapy would be needed. For this purpose, the following theoretical phantom of a representative organ of this anatomic region, the larynx, was reconstructed and local dosimetric data were derived for a selection of beta-emitting isotopes. The phantom was reconstructed as cylindrical concentric tubes using the established values of an outer diameter of 38 mm and a height of 44 mm. Published mean adult larynx weight (28 g) and cartilage weight (14.7 g) were used. Mean mucosa weight from 5 mucosa samples of our patients was calculated to be 2.0 +/- 0.4 (SD) g. The remaining weight was apportioned to a fat/muscle compartment (11.3 g). The specific gravity of cartilage (1.10 g/cm3), mucosa (1.04 g/cm3), and fat/muscle (1.04 g/cm3) were used to cross-check the volume/mass disparity of the theoretical tubular tissue shells. The established maximum glottic diameter of 24 mm was used to calculate the central air column volume. Mean laryngeal tumor volume from 8 representative laryngeal tumors was 4.4 +/- 3.1 cm3. Tissue compartment thickness was 660 microns for mucosa, 3100 microns for muscle/fat, and 3320 microns for cartilage. These values allowed the calculation of dose absorbed fractions for a number of theoretical radioimmunoconjugates by extending the established calculation of absorbed fractions for spheres of known diameter to absorbed fractions of tissue planes (annuli) of known thickness. We calculated a Deq for the respective tissues in the larynx for 131I-, 186Re-, 188Re-, 67Cu-, 90Y-, and 153Sm-labeled HMFG1. Compensatory decrease to the external radiotherapy dose is 1.1 Gy for each injection of the radioimmunoconjugate we propose to use (131I-HMFG1). This would be best implemented through the modification of the external radiotherapy fractions falling within 2 effective half-lives of this radioconjugate in the mucosa.

Aged↗
PubMed1995

Phase I/II evaluation of nevirapine alone and in combination with zidovudine for infection with human immunodeficiency virus.

In these Phase I/II open-label clinical trials, 62 persons with human immunodeficiency virus type 1 (HIV-1) infection and CD4+ cell counts < 400/mm3 received nevirapine at doses of 12.5, 50, and 200 mg/day, alone or in combination with zidovudine, 200 mg q8h. Nevirapine was well tolerated in the doses tested. Mean steady-state trough levels were 0.23, 1.1, and 1.9 micrograms/ml for the 12.5, 50, and 200 mg/day doses, respectively. Early suppression of p24 antigen levels and increase in CD4+ cell count were reversed following rapid emergence of virus less susceptible to nevirapine. Resistant strains were isolated from all participants by 8 weeks. Nevertheless, reduction of p24 antigen levels to < 50% of baseline values persisted for 12 weeks or more in four of seven persons who received 200 mg nevirapine/day in combination with zidovudine: these individuals had been antigenemic on long-term zidovudine therapy. This study demonstrates a direct relationship between drug resistance and effects on surrogate markers in HIV-1 infection.

Adult↗