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S N Goodman

Publications and source records attributed to S N Goodman.

At least 19 recordsLinked to original sources
PubMed2000

Quantitative neurologic assessment of ataxia-telangiectasia.

BACKGROUND: Ataxia telangiectasia (A-T) is a rare disorder with many distinctive neurologic features. Although there is substantial individual variation in the rate of progression of these features, their relationship to one another or to age has not been characterized. METHODS: We formulated and tested multiple elements that assess different neurologic functions known to be affected by A-T. The overall index was applied to 52 patients with A-T, 2 to 29 years of age. RESULTS: Seven elements items proved to be informative, and three elements were added based on face validity. In a linear regression model of individuals under 19 years of age, controlled for correlation within sibships, age accounted for 87% of the variation in the A-T Index. CONCLUSION: Despite substantial individual variability of the phenotypic elements of A-T, scores on this multidimensional index have a very high correlation with age, indicating that there is a characteristic rate of progression of the disease, although functional domains in the brain are differentially affected. The pattern of scores suggests that a severe and a mild form of A-T may be distinguished by this quantitative measure. With further development this index may become useful as an outcome measure for treatment studies and prognosis.

Adolescent↗
PubMed2000

Novobiocin in combination with high-dose chemotherapy for the treatment of advanced breast cancer: a phase 2 study.

We conducted the first phase 2 and pharmacologic study to evaluate the combination of novobiocin (a coumeromycin antibiotic that has been shown to augment alkylating agent cytotoxicity in experimental models) and high-dose cyclophosphamide and thiotepa followed by autologous marrow support in women with chemosensitive advanced breast cancer. Its aims were (1) to determine progression-free survival (PFS) and overall survival (OS), (2) to evaluate the pharmacokinetics of cyclophosphamide and thiotepa, and (3) to measure the ability of novobiocin to reverse alkylator drug resistance in vitro. Forty-one women with chemotherapy-responsive advanced breast cancer received cyclophosphamide (4 g/m2) for peripheral blood stem cell mobilization (treatment 1) followed by high-dose cyclophosphamide (1.5 g/m2 per day for 4 days), thiotepa (200 mg/m2 per day for 4 days), and novobiocin (4 g/day orally for 7 days) (treatment 2) and autologous marrow support. The median PFS was 10 months (range, 0.2-70.6 months) and OS, 21.5 months (range, 0.2-70.6 months). There was no statistically significant relationship between PFS or OS and area-under-the-curve values of cyclophosphamide, thiotepa, or 4-hydroxycyclophosphamide. Patient plasma samples (n = 12) obtained during novobiocin therapy were able to reverse alkylator drug resistance in an in vitro colony-forming assay. Correlative laboratory studies in an in vitro model system demonstrated that patient plasma after novobiocin treatment resulted in the magnitude of resistance reversal that had been predicted by prior preclinical experiments. Clinically, however, this activity of novobiocin did not translate into a substantial increase in PFS or OS compared with historical controls treated with high-dose alkylator therapy alone.

Adult↗
PubMed2000

Prevention of thromboembolism in atrial fibrillation. A meta-analysis of trials of anticoagulants and antiplatelet drugs.

OBJECTIVE: Appropriate use of drugs to prevent thromboembolism in patients with atrial fibrillation (AF) involves comparing the patient's risk of stroke and risk of hemorrhage. This review summarizes the evidence regarding the efficacy of these medications. METHODS: We conducted a meta-analysis of randomized controlled trials of drugs used to prevent thromboembolism in adults with nonpostoperative AF. Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until May 1998. MAIN RESULTS: Eleven articles met criteria for inclusion in this review. Warfarin was more efficacious than placebo for primary stroke prevention (aggregate odds ratio [OR] of stroke = 0.30, 95% confidence interval [CI] 0.19, 0.48), with moderate evidence of more major bleeding (OR 1.90; 95% CI 0.89, 4.04). Aspirin was inconclusively more efficacious than placebo for stroke prevention (OR 0.56, 95% CI 0.19, 1.65), with inconclusive evidence regarding more major bleeds (OR 0.81, 95% CI 0.37, 1.77). For primary prevention, assuming a baseline risk of 45 strokes per 1,000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was evidence suggesting fewer strokes among patients on warfarin than among patients on aspirin (aggregate OR 0.64, 95% CI 0.43, 0.96), with only suggestive evidence for more major hemorrhage (OR 1.60, 95% CI 0.77,3.35). However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared with aspirin was low (5.5 per 1,000 person-years) compared with an older group (15 per 1,000 person-years). CONCLUSION: In general, the evidence strongly supports warfarin for patients with AF at average or greater risk of stroke. Aspirin may prove to be useful in subgroups with a low risk of stroke, although this is not definitively supported by the evidence.

Anticoagulants↗
PubMed2000

A prospective pharmacologic evaluation of age-related toxicity of adjuvant chemotherapy in women with breast cancer.

Despite increasing evidence of benefit from adjuvant chemotherapy, older women with breast cancer are commonly given less aggressive treatment than younger patients. Conflicting prior data regarding age-related toxicity prompted this prospective study. Forty-four women (aged 35-79 years) with early-stage breast cancer were treated with four cycles of adjuvant therapy with doxorubicin 60 mg/m2 i.v. and cyclophosphamide 600 mg/m2 i.v. every 21 days. They were monitored for myelosuppression, cardiotoxicity, and decrease in quality of life. Pharmacokinetics were analyzed using cycle 1 plasma samples. Bone marrow granulocyte and macrophage colony-forming units (CFU-GM) were assayed in vitro for dose response to 4-hydroperoxycyclophosphamide and doxorubicin before cycle 1. There was moderate evidence of age-related decrease in nadir absolute neutrophil count (ANC) when age was viewed as a continuous variable. On average there was a 10/microliter drop in cycle 1 nadir ANC for every year increase in age (p = 0.02). However, when age was viewed as a categorical variable (age < 65 vs. > or = 65 years), a similar proportion of women in each group reached an ANC < 100 (18% vs. 19%). Neither neutropenic complications, alteration in cardiac function, nor change in quality of life scores were significantly age related (p > 0.12). Pharmacokinetic analyses did not demonstrate age-related differences in the clearance of either doxorubicin or cyclophosphamide (p > 0.8). Pharmacodynamic analysis of individual patient bone marrow progenitor cell sensitivity did not reveal any correlation with age (p > 0.48). In women undergoing adjuvant therapy for breast cancer, no clinically significant age-related trends in toxicity were observed. These data suggest that older age alone should not exclude patients from receiving adjuvant therapy with doxorubicin and cyclophosphamide.

Adult↗
PubMed2000

The evidence regarding the drugs used for ventricular rate control.

OBJECTIVE: Our goal was to determine what drugs are most efficacious for controlling the ventricular rate in patients with atrial fibrillation. SEARCH STRATEGY: We conducted a systematic review of the literature published before May 1998, beginning with searches of The Cochrane Collaboration's CENTRAL database and MEDLINE. SELECTION CRITERIA: We included English-language articles describing randomized controlled trials of drugs used for heart rate control in adults with atrial fibrillation. DATA COLLECTION/ANALYSIS: Abstracts of trials were reviewed independently by 2 members of the study team. We reviewed English-language abstracts of non-English-language publications to assess qualitative consistency with our results. MAIN RESULTS: Forty-five articles evaluating 17 drugs met our criteria for review. In the 5 trials of verapamil and 5 of diltiazem, heart rate was reduced significantly (P <.05), both at rest and with exercise, compared with placebo, with equivalent or improved exercise tolerance in 6 of 7 comparisons. In 7 of 12 comparisons of a beta-blocker with placebo, the beta-blocker was efficacious for control of resting heart rate, with evidence that the effect is drug specific, as nadolol and atenolol proved to be most efficacious. All 9 comparisons demonstrated good heart rate control with beta-blockers during exercise, although exercise tolerance was compromised in 3 of 9 comparisons. In 7 of 8 trials, digoxin administered alone slowed the resting heart rate more than placebo, but it did not significantly slow the rate during exercise in 4 studies. The trials evaluating other drugs yielded insufficient evidence to support their use, but those drugs may yet be promising. CONCLUSIONS: The calcium-channel blockers verapamil or diltiazem, or select beta-blockers are efficacious for heart rate control at rest and during exercise for patients with atrial fibrillation without a clinically important decrease in exercise tolerance. Digoxin is useful when rate control during exercise is less a concern.

Adrenergic beta-Antagonists↗
PubMed1999

Toward evidence-based medical statistics. 1: The P value fallacy.

An important problem exists in the interpretation of modern medical research data: Biological understanding and previous research play little formal role in the interpretation of quantitative results. This phenomenon is manifest in the discussion sections of research articles and ultimately can affect the reliability of conclusions. The standard statistical approach has created this situation by promoting the illusion that conclusions can be produced with certain "error rates," without consideration of information from outside the experiment. This statistical approach, the key components of which are P values and hypothesis tests, is widely perceived as a mathematically coherent approach to inference. There is little appreciation in the medical community that the methodology is an amalgam of incompatible elements, whose utility for scientific inference has been the subject of intense debate among statisticians for almost 70 years. This article introduces some of the key elements of that debate and traces the appeal and adverse impact of this methodology to the P value fallacy, the mistaken idea that a single number can capture both the long-run outcomes of an experiment and the evidential meaning of a single result. This argument is made as a prelude to the suggestion that another measure of evidence should be used--the Bayes factor, which properly separates issues of long-run behavior from evidential strength and allows the integration of background knowledge with statistical findings.

Bayes Theorem↗
PubMed1999

Toward evidence-based medical statistics. 2: The Bayes factor.

Bayesian inference is usually presented as a method for determining how scientific belief should be modified by data. Although Bayesian methodology has been one of the most active areas of statistical development in the past 20 years, medical researchers have been reluctant to embrace what they perceive as a subjective approach to data analysis. It is little understood that Bayesian methods have a data-based core, which can be used as a calculus of evidence. This core is the Bayes factor, which in its simplest form is also called a likelihood ratio. The minimum Bayes factor is objective and can be used in lieu of the P value as a measure of the evidential strength. Unlike P values, Bayes factors have a sound theoretical foundation and an interpretation that allows their use in both inference and decision making. Bayes factors show that P values greatly overstate the evidence against the null hypothesis. Most important, Bayes factors require the addition of background knowledge to be transformed into inferences--probabilities that a given conclusion is right or wrong. They make the distinction clear between experimental evidence and inferential conclusions while providing a framework in which to combine prior with current evidence.

Bayes Theorem↗
PubMed1999

Genetic epidemiology of mutated K-ras proto-oncogene, altered suppressor genes, and microsatellite instability in colorectal adenomas.

BACKGROUND: The genetic epidemiology of colorectal adenomas has not been studied prospectively in colonoscopy patients without cancer. AIMS: To study genetic alterations in colorectal adenomas and correlate these with patient demographics and adenoma characteristics. METHODS: Mutations and allelic deletions in 201 adenomas from 60 patients were compared with demographic features, adenoma characteristics, and family history. RESULTS: The most common alteration was K-ras proto-oncogene mutation, present in 35% of adenomas and 65% of patients. Patients 65 years of age and older had a decreased probability of K-ras mutations (26% versus 45%). Overexpression of p53 gene product was present in only 6% of adenomas but was more frequent in villous or tubulovillous adenomas (19% versus 3%). Allelic loss of chromosome 18q was present in only 2% of adenomas and was significantly less frequent than p53 overexpression. DNA replication errors (RER) were present in 7% of adenomas and 15% of patients, including multiple adenomas in four patients (two with hereditary non-polyposis colorectal cancer syndrome). Only 36% of RER positive adenomas had alteration of BAT-26 alleles, none had alteration of BAT-25, and only one (8%) had mutation in the transforming growth factor beta type II receptor gene. RER positive adenomas were more likely to have a K-ras mutation. In patients with multiple adenomas, there was concordance of p53 overexpression and RER but not of K-ras mutations. CONCLUSIONS: Genetic progression in colorectal adenomas is heterogeneous, involving factors related to patient age and the presence of RER for the occurrence of ras mutations, but different intraindividual characteristics for the occurrence of p53 alterations and RER.

Adenoma↗
PubMed1999

Rectal epithelial apoptosis in familial adenomatous polyposis patients treated with sulindac.

BACKGROUND: Sulindac regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP), although the mechanism of polyp regression is unclear. AIMS: To determine whether differences occur in alteration of rectal epithelial apoptotic index and expression of apoptosis related proteins in FAP patients treated with sulindac compared with placebo. PATIENTS: Twenty one FAP patients; 12 had not undergone colectomy. METHODS: Patients with FAP were treated with sulindac 150 mg orally twice a day for three months (n=10) or placebo (n=11). Colorectal polyp number was determined and biopsies of the normal rectal mucosa were performed before and after three months of treatment. Response to treatment and alteration of the apoptotic ratio (index in base of crypt divided by index in surface epithelium) were evaluated. Bcl-2, bax, p21/WAF-1, and p53 proteins were assessed semiquantitatively by immunohistochemistry. RESULTS: Significant decreases in polyp number and in the apoptotic ratio were seen in patients treated with sulindac compared with controls. The mean percentage change in polyp number from baseline was -46% in the sulindac group and +13% in the placebo group (p=0.005). Mean percentage change in the apoptotic ratio was -8% and +25% in the sulindac and placebo treated patients, respectively (p=0.004). No differences in expression or compartmentalisation of apoptosis related proteins were noted between treatment groups. CONCLUSIONS: Sulindac regression of colorectal adenomas is accompanied by alteration of the rectal epithelial apoptotic ratio with relative increase in apoptosis in surface cells compared with the deeper crypt. The utility of the apoptotic ratio as an intermediate biomarker for colorectal tumorigenesis deserves further study.

Adenomatous Polyposis Coli↗
PubMed1998

Perceived value of providing peer reviewers with abstracts and preprints of related published and unpublished papers.

CONTEXT: Many journals provide peer reviewers with written instructions regarding review criteria, such as the originality of results, but little research has been done to investigate ways to improve or facilitate the peer review task. OBJECTIVE: To assess the value that peer reviewers place on receipt of supplemental materials (eg, abstracts of related papers and preprints of related unpublished manuscripts). DESIGN: Questionnaire survey sent to all 733 peer reviewers recruited by the Journal of the National Cancer Institute to review 356 manuscripts consecutively sent out for review from February 24, 1997, through January 16, 1998. The inclusion of supplemental materials with manuscript review packages was optional. MAIN OUTCOME MEASURE: The peer reviewers' assessment of the actual or potential usefulness of supplemental materials on the performance of peer review. RESULTS: A total of 481 (66%) of 733 questionnaires were returned. Of the 471 respondents' questionnaires that could be used, 217 (46%) indicated that they received abstracts, and 44 (10%) of 458 respondents indicated that they received preprints. Higher proportions of peer reviewers who received supplemental materials than those who had not received them felt that they were (or would be) useful to them when reviewing the manuscript (63% [95% confidence interval (CI), 57%-69%] vs 45% [95% CI, 38%-52%]; P<.001) and to the peer review process in general (80% [95% CI, 75%-85%] vs 64% [95% CI, 58%-70%]; P<.001). CONCLUSION: The majority of respondents indicated that supplemental materials helped (or would have helped) them evaluate manuscripts and valued them more highly when they actually received them.

Abstracting and Indexing↗
PubMed1998

Statistical reviewing policies of medical journals: caveat lector?

OBJECTIVE: To describe the current policies regarding statistical review of clinical research in biomedical journals. DESIGN: Cross-sectional survey. PARTICIPANTS: Editors of biomedical journals that publish original clinical research. MEASUREMENTS: General policies on statistical review, types of persons used for statistical reviewing, compensation of statistical reviewers, percentage of articles subject to such review, percentage of time statistical review makes an important difference, journal circulation, and selectivity. MAIN RESULTS: Of 171 journals, 114 (67%) responded to the survey. About one third of journals had policies that guaranteed statistical review for all accepted manuscripts. In approximately half of the journals, articles were sent for statistical review at the discretion of the editor. There was some evidence that statistical review policies differed between journals of different circulation size. In journals in the top quartile of circulation (> 25,000) the probability of definitely having a statistical review before an acceptance decision was 52%, but it was only 27% in journals in the lower three quartiles (p = .09). The probability of a statistical consultant on staff ranged from 31% in the bottom quarter, to 58% in the middle two, to 82% in the highest quarter (p < .001). Editors judged that statistical review resulted in an important change in a manuscript about half of the time. CONCLUSIONS: Except in the largest circulation medical journals, the probability of formal methodologic review of original clinical research is fairly low. As readers and researchers depend on the journals to assess the validity of the statistical methods and logic used in published reports, this is potentially a serious problem. This situation may exist because the cost of such statistical review can be considerable, and because finding appropriate reviewers can be difficult. It may also exist partly because editors or publishers may not regard such review as important. The professions of medical publishing, statistics, epidemiology, and other quantitative disciplines should work together to address this problem.

Cross-Sectional Studies↗
PubMed1998

CD34 augmentation improves allogeneic T cell-depleted bone marrow engraftment.

T cell depletion (TCD) performed by elutriation has decreased the incidence of acute and chronic graft-versus-host disease (GvHD) following bone marrow transplantation (BMT). However, as with all forms of TCD, patients may experience graft failure (10%), delayed engraftment, and mixed chimerism. Because 66%-75% of the CD34+ cells coseparate with the small lymphocytes, which are removed by elutriation, we designed a phase I trial in HLA-identical siblings to determine if the readdition of these previously lost small CD34+ cells would improve elutriation's engraftment kinetics. CD34+ cells were isolated from the small cell fraction of 10 consecutive donor grafts and infused into the recipients along with the TCD graft. The positively selected product had a mean T cell content of 1.2 x 10(5)/kg and was 80% CD34+, doubling the CD34+ content of the graft. All patients engrafted promptly with a median time to 500 neutrophils/mm3, untransfused 50,000 platelets/mm3, and discharge from the hospital of 19 (range 10-25), 24 (14-52), and 24 (18-29) days, respectively. Acute GvHD occurred in 2 patients, and no patient had chronic GvHD. Augmenting stem cell dose may be an efficient and safe alternative for overcoming TCD-associated delayed engraftment and graft failure, rather than increasing immunosuppression.

Adult↗
PubMed1998

CD44 expression in the stromal matrix of colorectal cancer: association with prognosis.

CD44, a cell hyaluronate receptor, is implicated in the metastatic behavior of some cancer cells. This study analyzed CD44 expression in topographic tissue sites of colorectal cancers to determine its association with patient survival and clinicopathological characteristics. Immunohistochemical localization of the core CD44 and the v6 splice variant domains was examined by use of paraffin-fixed sections from 133 stage II or III colorectal cancers that previously had been evaluated for other diagnostic markers. Expression in malignant epithelium, stromal matrix, and stromal cells was compared to patient survival by univariate, multivariate, and bootstrap (reproducibility) analysis. Core CD44 staining was present in the malignant epithelium of 85% of tumors, the stromal matrix of 90%, and the stromal cells of 98%. The v6 splice variant domain was present in the epithelium of 77% of tumors but was less frequent in the stromal matrix (12%; P < 0.001) and stromal cells (17%; P < 0.001). Absence of core CD44 immunoreactivity in the stromal matrix was associated with increased death rate (hazard ratio, 2.4; 95% confidence interval, 1.2-4.8; P = 0.02), making this one of the most significant adverse prognostic variables, along with an age of 60 years or older, poor differentiation of the cancer, extramural venous invasion, chromosome 18q allelic loss, and nonwhite race. This study shows that core CD44 and v6 splice variant antigens are differentially expressed in the epithelium and stroma of colorectal cancers. A model that includes core CD44 immunoreactivity in stromal matrix along with other prognostic factors may improve identification of high-risk and low-risk patients.

Adult↗
PubMed1997

Tumor-suppressive pathways in pancreatic carcinoma.

During tumorigenesis, positive selection is exerted upon those tumor cells that alter rate-limiting regulatory pathways. A corollary of this principle is that mutation of one gene abrogates the need for alteration of another gene in the same pathway and also that the coexistence in a single tumor of mutations in different genes implies their involvement in distinct tumor-suppressive pathways. We studied 42 pancreatic adenocarcinomas for genetic alterations in the K-ras oncogene and the p16, p53, and DPC4 tumor suppressor genes. All of them had the K-ras gene mutated. Thirty-eight % of the tumors had four altered genes, another 38% had three altered genes, 15% had two altered genes, and 8% of the tumors had one altered gene. Interestingly, we noted a high concordance of DPC4 and p16 inactivations (P = 0.007), suggesting that the genetic inactivation of p16 increases the selective advantage of subsequent mutation in DPC4. No statistically significant association was identified between the alteration of these cancer genes and pathological or clinical parameters. This type of multigenic analysis in human tumors may serve to substantiate experimental tumor models and thus increase our understanding of the truly physiologically relevant tumor-suppressive pathways that are abrogated during human tumorigenesis.

Adenocarcinoma↗
PubMed1996

p53 mutation and locoregional treatment failure in head and neck squamous cell carcinoma.

BACKGROUND: The p53 gene (also known as TP53) may be the most common genetic target involved in the malignant transformation of human cells. Direct sequence analysis has demonstrated that alteration of this gene occurs in approximately 45% of head and neck squamous cell carcinomas. The consequences of p53 mutations in these cancers with respect to tumor behavior and patient survival have not been rigorously determined. PURPOSE: We evaluated the implications of p53 mutations in relation to the control of locoregional disease and overall survival following radiation therapy. METHODS: Data from 110 consecutive patients with invasive disease who were treated with primary radiation therapy (given with curative intent) or with adjuvant radiation therapy (following complete surgical extirpation of gross disease) were included in the analysis. A 1.8-kilobase fragment of the p53 gene encompassing exons 5-9 was amplified from the DNA of stored (frozen) tumor specimens; the amplified DNA was cloned and sequenced by use of standard techniques. Overall survival and locoregional disease-free survival after the completion of radiation therapy were estimated by the Kaplan-Meier method; survival comparisons were made by use of the logrank test or proportional hazards regression models. Reported P values are two-sided. RESULTS: Fortyeight (44%) of the 110 tumors had cells bearing p53 mutations. The risk of locoregional recurrence following either primary or adjuvant radiation therapy was significantly greater (i.e., the time to recurrence was shorter) for patients whose tumors contained mutant p53 genes (univariate model hazard ratio [HR] for p53 mutation versus wild-type = 2.2; 95% confidence interval [CI] = 1.2-4.1; P = .02). The presence of regional lymph node metastases (presence versus absence, HR = 2.0; 95% CI = 1.0-4.2; P = .05) and treatment type (primary radiation therapy versus surgery plus adjuvant radiation therapy, HR = 2.3; 95% CI = 1.2-4.3; P = .01) were also associated with greater risks of locoregional failure. The presence of p53 mutations and lymph node metastases and treatment with primary, as opposed to adjuvant, radiation therapy remained significant risk factors in multivariate regression analysis. No relationship was demonstrated between p53 status and overall survival (mutant versus wild-type, HR = 1.1; 95% CI = 0.6-2.1; P = .66); however, a relationship was shown for tumor stage and overall survival (stages III and IV [more advanced] versus stages I and II [less advanced], HR = 3.3; 95% CI = 1.0-10.8; P = .05). Mutation of the p53 gene was not associated with patient age, sex, tumor stage, primary tumor site, regional lymph node status, degree of tumor cell differentiation, or treatment method. CONCLUSIONS: Mutation of the p53 gene is associated with an increased risk of locoregional failure in patients with invasive head and neck squamous cell carcinoma who are treated with radiation therapy.

Carcinoma, Squamous Cell↗
PubMed1996

Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy.

PURPOSE: To compare the efficacy and safety of inpatient oral antibiotic treatment (oral) versus standard parenteral antibiotic treatment (intravenous) for right-sided staphylococcal endocarditis in injection drug users. PATIENTS AND METHODS: In a prospective, randomized, non-blinded trial, febrile injection drug users were assigned to begin oral or intravenous (IV) treatment on admission, before blood culture results were available. Oral therapy consisted of ciprofloxacin and rifampin. Parenteral therapy was oxacillin or vancomycin, plus gentamicin for the first 5 days. Antibiotic dosing was adjusted for renal dysfunction. Administration of other antibacterial drugs was not permitted during the treatment or follow-up periods. Bacteremic subjects having right-sided staphylococcal endocarditis received 28 days of inpatient therapy with the assigned antibiotics. Test-of-cure blood cultures were obtained during inpatient observation 6 and 7 days after the completion of antibiotic therapy, and again at outpatient follow-up 1 month later. Criteria for treatment failure and for drug toxicity were prospectively defined. RESULTS: Of 573 injection drug users who were hospitalized because of a febrile illness and suspected right-sided staphylococcal endocarditis, 93 subjects (16.2%) had two or more sets of blood cultures positive for staphylococci; 85 of these bacteremic subjects (14.8%) satisfied diagnostic criteria for at least possible right-sided staphylococcal endocarditis (no other source of bacteremia was apparent) and entered the trial. Forty-four (oral, 19; IV, 25) of these 85 subjects completed inpatient treatment and evaluation including test-of-cure blood cultures. There were four treatment failures (oral, 1 [5.2%]; IV, 3 [12.0%]; not significant, Fisher's exact test). Drug toxicity was significantly more common in the parenterally treated group (oral, 3%; IV, 62%; P < 0.0001), consisting largely of oxacillin-associated increases in liver enzymes. CONCLUSIONS: For selected patients with right-sided staphylococcal endocarditis, oral ciprofloxacin plus rifampin is effective and is associated with less drug toxicity than is intravenous therapy.

Administration, Oral↗