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Biomedical subjects

R B Roberts

Publications and source records attributed to R B Roberts.

At least 19 recordsLinked to original sources
PubMed1994

Cost-effectiveness of infective endocarditis prophylaxis for mitral valve prolapse with or without a mitral regurgitant murmur.

To assess the cost-effectiveness of prevention of infective endocarditis (IE) and to calculate cost-effectiveness of currently recommended regimens in patients with mitral valve prolapse (MVP), data on risk of death, complications, and health-care use, and cumulative incremental health-care costs due to the occurrence of IE were combined with data on the prevalence and manifestations of MVP, estimated years of life lost, and efficacy of antibiotic prophylaxis. Effectiveness and costs of standard endocarditis prophylaxis regimens were calculated per IE case prevented and years of life saved. Under the most likely scenario, oral amoxicillin prophylaxis for all MVP patients would prevent 32 cases of IE per million dental procedures at approximate costs of $119,000 per prevented case and $21,000 per year of life saved. Limiting prophylaxis to patients with mitral murmurs would prevent 80 cases of IE per million procedures at costs of about $19,000 per prevented case and $3,000 per year of life saved. Erythromycin prophylaxis was slightly less expensive than amoxicillin per benefit because of lower cost and lack of drug anaphylaxis, whereas intravenous ampicillin was 7 to 30 times more costly. Sensitivity analyses suggested that erythromycin prophylaxis might be cost-saving under some scenarios, whereas intravenous ampicillin use might cause net loss of life. Thus, prevention with oral antibiotics of the cumulative morbidity and incremental health care costs due to IE in MVP patients is reasonably cost-effective for MVP patients with mitral murmurs.

Adult↗
PubMed1994

Severe measles pneumonitis in adults: evaluation of clinical characteristics and therapy with intravenous ribavirin.

Between February and April 1991, six adults were admitted to the New York Hospital because of measles pneumonitis. The diagnosis was confirmed by serology and/or viral culture. Uncommon clinical features among patients with this diagnosis included thrombocytopenia, hepatitis, myositis, and hypocalcemia. All patients were markedly hypoxic (initial alveolar--arterial oxygen gradients while the patients were breathing room air, 40-61 mm Hg); four required support with mechanical ventilation. All patients received therapy with intravenous ribavirin (20-35 mg/[kg.d]) for 1 week. The respiratory status of five patients (one of whom was positive for human immunodeficiency virus [HIV]) who were treated early (days 2-5 of illness) promptly improved; all abnormal parameters eventually returned to baseline. Treatment of the sixth patient, who was presumed to be HIV-infected, was initiated on hospital day 22; this patient died of progressive oxygenation failure on day 38. We conclude that life-threatening measles pneumonitis in adults may be more common that previously appreciated, regardless of the patient's immune status. Therapy with intravenous ribavirin was well tolerated by our patients and was associated with reversal of respiratory compromise.

Adult↗
PubMed1990

A phase 1 study of ribavirin in human immunodeficiency virus-infected patients.

An open phase 1 study comparing two daily doses of oral ribavirin (1200 and 1600 mg) for 12 weeks was conducted at a single site. Eight human immunodeficiency virus (HIV)-infected adult men with lymphadenopathy or early AIDS-related complex (ARC) symptoms were enrolled in each treatment group. No anti-HIV effect was observed as evaluated by coculture of patients' peripheral blood mononuclear cells or by the level of serum p24 antigenemia. Neither enhancement of two functional lymphocyte markers (specific antigen-induced blastogenesis or interferon-gamma production) nor reduction in serum beta 2-microglobulins was noted. Mild clinical adverse reactions and anemia were observed in both treatment groups. Significant reductions in total lymphocytes, T lymphocytes (CD2 cells), and T lymphocyte subsets (CD4 and CD8 cells) were most notable in the 1600-mg group. Reduction in the lymphocyte populations was most likely due to a direct ribavirin lymphotoxic effect. These observations indicate that ribavirin had no demonstrable beneficial effect on virologic or immunologic HIV surrogate markers at daily doses associated with adverse reactions.

AIDS-Related Complex↗
PubMed1990

A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 and 800 mg) and a placebo was performed at four medical centers geographically distributed throughout the USA. One hundred and sixty-four HIV-infected adult men with lymphadenopathy were enrolled over a 2-month period and received active treatment for 24 weeks followed by a 4-week interval during which they did not receive the study drug. A marked interlaboratory variation in HIV isolation from peripheral blood mononuclear cells was observed, underscoring the critical role of quality assurance in similar multicenter trials. Nevertheless, the combined data indicate that ribavirin did not significantly suppress HIV activity (on measurement of reverse transcriptase activity) after week 6 or reduce serum p24 antigenemia.

AIDS-Related Complex↗
PubMed1990

A multicenter clinical trial of oral ribavirin in HIV-infected patients with lymphadenopathy. The Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin and placebo was conducted at four medical centers. One hundred sixty-four adult men with lymphadenopathy were enrolled over a 2-month period and randomized to receive ribavirin 800 mg (53 subjects), ribavirin 600 mg (55 subjects), or placebo (56 subjects). Active treatment was administered for 24 weeks followed by a 4-week washout period. Nine subjects receiving placebo, four receiving ribavirin 600 mg, and none in the 800 mg group developed AIDS during the 24 weeks of active treatment. One patient randomized to the 800 mg group had Kaposi's sarcoma at study entry and was included in the intent-to-treat analysis. An overall significant difference in progression to AIDS was observed among the three treatment groups (p = 0.028) with patients randomized to receive 800 mg having a significantly longer time to AIDS than placebo patients (p = 0.012; relative risk, 9.0; 95% confidence interval, 1.1 to 70.8). There was no significant difference between the 600 mg and placebo groups (p = 0.15; relative risk, 2.3; 95% confidence interval, 0.7 to 7.6). Baseline CD4 cell count and hematocrit made independent contributions and formed a multivariate prognostic set for these progression data. The significant treatment superiority of 800 mg compared to placebo remained after adjustment for these factors (p = 0.019). After deletion of patients with major protocol violations at entry, the difference between the 800 mg and placebo treatment remained significant (p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Progression to AIDS in patients with lymphadenopathy or AIDS-related complex: reappraisal of risk and predictive factors.

PURPOSE: In 1985, we reported that acquired immunodeficiency syndrome (AIDS) developed in 14 of 81 (17%) men with generalized lymphadenopathy followed prospectively for an average of 13 months. The presence of oral thrush or constitutional symptoms, or both, or severely impaired T4+ cell responses to specific antigen (interferon-gamma production) accurately identified patients at immediate risk for AIDS. The purpose of the current report is to describe the progress of these 81 patients during the three and a half years since enrollment and to include new data on initial serum levels of beta 2 microglobulin and human immunodeficiency virus (HIV) p24 antigen. PATIENTS AND METHODS: The mean age of the 81 patients was 35.4 years; 79 were homosexuals and two were drug abusers. Immunologic testing was performed once at the time of enrollment in all patients. Seventy-seven of the 81 patients were seropositive for HIV antibody. Frozen samples of serum, also obtained at initial study, were assayed in 1988 for beta 2 microglobulin and HIV p24 antigen. The clinical status of patients was determined six, 14, and 36 months after enrollment was closed (June 1984) by either interview and examination or telephone contact with private physicians. RESULTS: After three and a half years of follow-up, 42 patients have developed AIDS, including (1) 77% who had had thrush or symptoms, or both, (2) 80% to 88% of those who originally demonstrated marked immunologic abnormalities (skin test anergy, less than 200 T4+ cells/mm3, T4/T8 cell ratio of less than 0.5, severely impaired interferon-gamma production [less than 25 U/mL], or elevated serum beta 2 microglobulin level [greater than 3.0 mg/L], and (3) 95% of patients with HIV p24 antigenemia. However, AIDS also developed in 51% of patients who had had more apparently benign initial manifestations (lymphadenopathy alone, herpes zoster), in 41% to 54% despite normal initial results for either T4+ cell number, interferon-gamma secretion, beta 2 microglobulin, or skin testing, and in 44% of those whose sera did not contain HIV antigen. CONCLUSION: These updated results demonstrate the remarkably poor prognosis of patients with generalized lymphadenopathy or AIDS-related complex irrespective of initial clinical, immunologic, and serologic findings, and suggest that essentially all such persons may be candidates for antiviral therapy.

AIDS-Related Complex↗
PubMed1988

T lymphocyte responses to mycobacterial antigen in AIDS patients with disseminated Mycobacterium avium-Mycobacterium intracellulare infection.

Patients with acquired immunodeficiency syndrome (AIDS) who have Mycobacterium avium-Mycobacterium intracellulare (MAI) infection typically have widely disseminated disease, often fail to respond to multi-drug chemotherapeutic regimens, and show little or no inflammatory tissue response. To determine if this clinicopathologic state correlates with in vitro lymphocyte responses to specific antigen, peripheral blood mononuclear cells from 18 patients with AIDS who had MAI bacillemia were stimulated with either particulate (heat-killed bacille Calmette Guérin [BCG]) or soluble (M intracellulare) mycobacterial antigens. In comparison to reactive cells from healthy control subjects testing positive with purified protein derivative of tuberculin (PPD) or from MAI-colonized (non-AIDS) control subjects, cells from 16 (89 percent) patients with AIDS essentially failed to show any antigen-induced proliferative activity or secretion of gamma-interferon; however, in two patients, antigen-stimulated proliferation of gamma-interferon production was modest but within the range of responses of normal healthy control subjects. Thus, although an occasional patient with AIDS can develop disseminated MAI infection despite the presence of antigen-reactive cells in vitro, most MAI-infected patients with AIDS display a striking defect in responsiveness to both particulate and soluble mycobacterial antigens. Since treatment with gamma-interferon activates the mononuclear phagocyte in vivo, these results suggest a rationale for a trial of gamma-interferon therapy in patients with AIDS who have disseminated MAI infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

T4+ cell production of interferon gamma and the clinical spectrum of patients at risk for and with acquired immunodeficiency syndrome.

To fully characterize the relationship between the clinical manifestations of human immunodeficiency virus infection and T4+ cell defects, we determined T4+ cell number and interferon gamma (IFN-gamma) production in 238 patients. For asymptomatic homosexuals, patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and patients with fully established AIDS, clinical status correlated linearly with both T4+ cell number and T4+ cell-derived (antigen-stimulated) IFN-gamma secretion. For asymptomatic homosexuals, abnormalities in T4+ cell number and IFN-gamma generation were similar irrespective of human immunodeficiency virus seropositivity. For patients with ARC, those with lymphadenopathy (LA) alone or LA plus zoster or thrombocytopenia displayed T4+ cell defects similar to those observed in asymptomatic homosexuals. Patients with ARC with LA plus constitutional symptoms and/or oral thrush, however, had fewer T4+ cells, were strikingly more deficient in IFN-gamma production, and closely resembled those with AIDS. Among patients with AIDS, certain individuals with Kaposi's sarcoma (KS) alone were sufficiently less cytopenic and less immunodeficient than patients with opportunistic infections (Ols) to suggest that the immune impairment that predisposes to KS may differ. At the time patients with KS developed Ols, however, T4+ cell number and IFN-gamma-generating capacity had declined to the remarkably low levels observed in virtually all patients with Ols alone.

AIDS-Related Complex↗
PubMed1987

In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes.

To determine the potential immunotherapeutic role of interferon-gamma (IFN-gamma) as a mononuclear phagocyte-activating agent, we examined the effector cell function of peripheral blood monocytes from healthy donors and acquired immunodeficiency syndrome (AIDS) patients after either in vitro and/or in vivo treatment with recombinant (r) IFN-gamma. When assayed immediately after a 24-hr in vitro pulse with 300 U/ml, normal and AIDS monocytes behaved similarly with little augmentation of their intrinsically high levels of H2O2 release and activity against Toxoplasma gondii; in contrast, activity toward the more resistant intracellular pathogen, Leishmania donovani, was appreciably enhanced by rIFN-gamma. In addition, upon testing 4 to 6 days after in vitro pulsing, both normal and AIDS monocytes showed clear evidence of persistent activation in all three assays. The capacity of IFN-gamma to similarly activate monocytes in vivo was confirmed in all ten treated AIDS patients by examining cells before and after 24-hr infusions of 0.03 and 0.5 mg of rIFN-gamma/square meter (M2) of body surface area. For postinfusion monocytes tested after 1 day in culture, H2O2 release and antitoxoplasma activity were essentially unchanged, but antileishmanial effects were augmented. After 5 to 7 days in culture, monocytes from treated patients showed 3.2- to 5.9-fold increases in H2O2-releasing capacity and increases of 49 to 68% and 35 to 61% in intracellular activity against T. gondii and L. donovani, respectively. These results indicate that the human monocyte can be induced by rIFN-gamma to express signs of both immediate and persistent activation and suggest that, as a direct activator of mononuclear phagocytes, rIFN-gamma may also have potential as an immunotherapeutic agent for patients with intracellular infections.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Ribavirin pharmacodynamics in high-risk patients for acquired immunodeficiency syndrome.

Ribavirin was administered orally in escalating doses for 2 or 4 weeks to 15 symptom-free, human immunodeficiency virus seropositive homosexual men with generalized lymphadenopathy. Reverse transcriptase activity was inhibited during therapy when steady-state plasma concentrations were greater than 6 mumol/L. These concentrations were achieved with 1200 or 2400 mg/day for 2 weeks or a loading dose of 2400 mg/day for 3 days followed by 600 mg/day for 4 weeks. Drug accumulation occurred at all doses. The elimination half-life appeared to be approximately 2 weeks. Reversible adverse reactions, principally resulting in central nervous system symptoms and anemia, correlated with dose and duration of therapy. Immunologic enhancement of T-lymphocyte-mediated mitogen-induced responses was observed in the majority of patients who had reduction in reverse transcriptase activity. However, specific T4+ lymphocyte-mediated antigen-induced responses increased to within the normal range in only three patients. Significant enhancement appeared to correlate with the severity of baseline antigen-induced functional impairment. These data indicate that oral ribavirin can be given for at least 1 month with acceptable toxicity at doses that appear to inhibit human immunodeficiency virus replication.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome.

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.

AIDS-Related Complex↗
PubMed1987

Regression of renal hypertrophy and elevated renal Na+,K+-ATPase activity after insulin treatment in streptozotocin-diabetic rats.

The effect of insulin treatment on the renal hypertrophy and elevated renal Na+,K+-ATPase activity in rats with streptozotocin (STZ)-induced diabetes was examined. Rats with STZ-diabetes of 6- to 8-week duration had significantly lower body weights, higher plasma and urinary glucose concentrations, greater urinary volumes, increased kidney weights, and increased kidney/body weights and protein/kidney weight ratios compared to those in saline-citrate-injected controls. Specific Na+,K+-ATPase activity per mg protein in both cortical and outer medullary kidney homogenates was significantly elevated in diabetic vs. control animals, as was total renal Na+,K+-ATPase activity. One week of insulin treatment returned elevated plasma glucose, urinary volume, the protein/kidney weight ratio, and cortical and outer medullary Na+,K+-ATPase activity per mg protein to control values. Kidney weights and kidney/body weight ratios of diabetic animals remained elevated, as did absolute total renal Na+,K+-ATPase activity. After 3 weeks of insulin treatment, kidney weight and total renal Na+,K+-ATPase activity in diabetic animals returned to control values, but body weights remained lower than those in the controls, resulting in continued elevation of kidney/body weight ratios in the diabetic animals. The concurrent regression of both renal hypertrophy and elevated Na+,K+-ATPase activity to normal levels after insulin treatment of STZ-diabetic animals implicates renal growth rather than a direct effect of insulin as the primary factor controlling elevation and regression of Na+,K+-ATPase activity in the diabetic kidney. This finding demonstrates that the effect of renal hypertrophy can outweigh the intrinsic effects of insulin on an important renal transport system and that this effect may be as important as lack of hormone in determining the renal physiological responses in the disease. It is suggested that the increased renal tubular Na+,K+-ATPase activity is a key component of the renal hypertrophy and hyperfunction seen in diabetes.

Animals↗
PubMed1986

Relation between the presence of echocardiographic vegetations and the complication rate in infective endocarditis.

M-mode and two-dimensional echocardiograms of 77 patients with infective endocarditis were examined to determine if presence and/or size of vegetations on echocardiogram were predictive of morbidity and mortality. Patients with (n = 43) or without (n = 34) vegetations on echocardiogram did not differ significantly in the proportions developing congestive heart failure (23 of 43 or 53% vs 12 of 34 or 35%) or emboli (11 of 43 or 24% vs 6 of 34 or 18%), whereas a slightly lower proportion of those with vegetations required surgery (5 of 43 or 12% vs 7 of 34 or 21%) or died (3 of 43 or 7% vs 4 of 34 or 12%). No significant relationship was found between vegetation size and the frequency of complications, the need for surgery, or death. In contrast, patients whose echocardiograms demonstrated premature mitral valve closure or chordal or cusp rupture had a significantly higher incidence of heart failure (10 of 13 or 77% vs 22 of 60 or 37%, p less than 0.003) and surgery (3 of 13 or 23% vs 7 of 60 or 12%, p less than 0.05). We conclude that: the presence of vegetation on the initial echocardiogram is not predictive of the clinical course in infective endocarditis; vegetation size does not predict complications, need for surgery, or death; but valve cusp or chordal rupture and/or premature mitral valve closure are associated with congestive heart failure and the need for surgery.

Adolescent↗
PubMed1986

Complications of mitral valve prolapse. Disproportionate occurrence in men and older patients.

To determine factors influencing the strength of association between mitral valve prolapse and mitral regurgitation, ruptured chordae tendineae, and infective endocarditis, the prevalence of mitral prolapse in patients with disease was compared with both clinical and population control groups. The prevalence of mitral valve prolapse was 4 percent among population and clinical control groups (eight of 196 and 84 of 2,146, respectively) and was significantly higher (p less than 0.001) in patients with endocarditis (11 of 67, 16 percent), mitral regurgitation (17 of 31, 55 percent, and ruptured chordae (27 of 43, 63 percent). Odds ratios for complications in persons with mitral valve prolapse ranged from 4.6 for endocarditis to 41.4 for ruptured chordae in overall analyses, and from 6.8 for endocarditis to 53.0 for ruptured chordae based on age- and sex-matched case-control triplets (p less than 0.001 for each). All complications occurred disproportionately in men with mitral valve prolapse, in whom odds ratios ranged from 2.5 to 7.4 compared with an additional control group of unselected subjects with mitral valve prolapse. Compared with this control group, patients with mitral valve prolapse and endocarditis were slightly more likely to have a previously known heart murmur (odds ratio 3.2, difference not significant) but significantly more likely to have murmurs at the time of evaluation (odds ratio 8.5, p less than 0.01). Patients with mitral valve prolapse and mitral regurgitation and ruptured chordae tendineae were also significantly older than the unselected subjects with mitral valve prolapse (48 +/- 14 and 55 +/- 16 versus 38 +/- 14 years, p less than 0.005 for both). The concentration of risk of endocarditis in men with mitral valve prolapse and patients with antecedent murmur suggests that antibiotic prophylaxis is warranted in these groups but not in women without a murmur of mitral regurgitation.

Adolescent↗