Biomedical subjects

R Gonin

Publications and source records attributed to R Gonin.

At least 19 recordsLinked to original sources

PubMed2001

The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse.

BACKGROUND: Although concomitant alcoholism is widely believed to enhance liver disease progression in persons with hepatitis C virus (HCV) infection, this relationship has not been well quantified. OBJECTIVE: To quantify the relationship of transfusion-associated HCV infection and history of heavy alcohol abuse to development of cirrhosis. DESIGN: Retrospective cohort study. SETTING: Liver clinics in university and government hospitals. PATIENTS: Extended follow-up of 1030 patients in prospective investigations of transfusion-associated viral hepatitis conducted in the United States between 1968 and 1980. MEASUREMENTS: Development of cirrhosis and history of heavy alcohol abuse were determined from review of interviews with patients or their proxies, medical records, death certificates, and autopsy and biopsy reports. Logistic regression was used to estimate the risk for cirrhosis associated with transfusion-associated HCV infection and history of heavy alcohol abuse. RESULTS: The absolute risk for cirrhosis was 17% among patients with transfusion-associated HCV; 3.2% among patients with transfusion-associated non-A, non-B, non-C hepatitis; and 2.8% among controls. Patients with transfusion-associated HCV were more likely than controls to develop cirrhosis (odds ratio, 7.8 [95% CI, 4.0 to 15.1]). A history of heavy alcohol abuse was associated with a fourfold increased risk for cirrhosis. Hepatitis C virus infection plus a history of heavy alcohol abuse led to a substantial increase in risk for cirrhosis (odds ratio, 31.1 [CI, 11.4 to 84.5]) compared with controls without such a history. CONCLUSIONS: Heavy alcohol abuse greatly exacerbates the risk for cirrhosis among patients with HCV infection. This finding emphasizes the need to counsel such patients about their drinking habits.

Adult↗

PubMed2001

Use of the Dermatology Life Quality Index (DLQI) in a midwestern US urban clinic.

BACKGROUND: The Dermatology Life Quality Index (DLQI), a self-administered general dermatology quality of life instrument, was originally developed and published in a dermatology clinic at University Hospital of Wales. OBJECTIVE: Our goal was to test the feasibility of having patients answer the DLQI in a busy dermatology clinic and to find out to what extent results vary from those published in Wales. We also wanted to examine the validity of the index in terms of the correlation between DLQI scores and stage of illness (disease severity). METHODS: We administered the DLQI to 200 consecutive patients who were seen in a dermatology clinic at Indiana University Medical Center. Results were examined in light of results found by those who originated the DLQI. A pilot group of patients were given the DLQI and rated for severity of disease by means of the Dermatology Index of Disease Severity (DIDS). RESULTS: Overall, the DLQI is easy to administer and can be completed within 3 minutes. The scores in our study were compatible with those previously reported by the DLQI originators. There was a "ceiling" effect in that 11% of the patients indicated no quality of life impairment on the DLQI rating. This index shows stratification with severity of disease. CONCLUSION: The DLQI is an easy and efficient instrument for assessing quality of life in dermatology patients. Patients needed minimal assistance with the form. Our results were similar to those of the DLQI originators, and this further shows reliability and validity of the DLQI. In addition, this study further supports the use of DLQI as a quality of life instrument suitable for use in international studies.

Adolescent↗

PubMed2000

A new program to compute and evaluate continuously monitored stopping boundaries for clinical trials.

We present code for the calculation and evaluation of continuously monitored stopping boundaries for use in one-arm and two-arm clinical trials. These designs were first developed for one-arm trials by Thall, Simon and Estey (TSE) (P.F. Thall, R. Simon, E.H. Estey, Bayesian sequential monitoring designs for single-arm clinical trials with multiple outcomes, Stat. Med. 14 (1995) 357-379). Our code corrects some problems in the original TSE algorithms and extends these algorithms for use in a two-arm trial setting. It is written in S-Plus to improve interactivity for the statistically adept user, and employs external routines, dynamically loaded into S-Plus, to improve calculation efficiency. Efficient versions of our code require both a C compiler and the S-Plus program. Our code has been tested in UNIX and Microsoft Windows environments, and compiled code is available from our website. A numerical integration routine for the convolution of beta distributions is included.

Clinical Trials as Topic↗

PubMed2000

Optimal sampling times in bioequivalence tests.

In bioequivalence studies, drug formulations are compared in terms of bioavailability parameters such as the area under the concentration-time curve (AUC), the maximum concentration (Cmax), and the time to maximum concentration (t(max)). Accuracy in measuring these parameters directly affects the accuracy of bioequivalence tests. Because the number of blood draws per patient is limited, the blood collection times must be spaced so that concentration-time curve measurements can produce accurate bioavailability parameter estimates. This paper describes an optimization approach for calculating optimal time designs for one-compartment models, but is sufficiently general for other compartmental models. Simulation indicates that the optimal design improves the accuracy of AUC estimation.

Area Under Curve↗

PubMed2000

Phase II study of doxorubicin and paclitaxel as second-line chemotherapy of small-cell lung cancer: a Hoosier Oncology Group Trial.

Forty-six evaluable patients with recurrent small-cell lung cancer were entered on a phase II Hoosier Oncology Group (HOG) protocol evaluating bolus doxorubicin 40 mg/m2 followed by paclitaxel 175 mg/m2 over 3 hours. Courses were repeated every 3 weeks for a maximum of 6 courses. Therapy was well-tolerated with grade III neurotoxicity in 5 patients (11%), grade III/IV emesis in 5 (11%), and grade III mucositis in 2 patients. One patient had grade IV myalgias and one patient had grade III cardiotoxicity. The main toxicity was myelosuppression. Twenty-nine patients (63%) had grade IV and 8 (17%) grade III granulocytopenia. Nine patients (20%) were hospitalized for granulocytopenic fever. There was no treatment-related mortality. Nineteen of 46 patients (41%) had an objective response, including 3 complete remissions. Two of 14 patients with refractory disease (progression less than 3 months after initial therapy) responded, compared to 17 of 32 (52%) with sensitive disease (progression beyond 3 months of initial chemotherapy regimen).

Adult↗

PubMed1998

Effect of breathing on the detection of in vivo simulated pulmonary nodules by spiral CT.

OBJECTIVE: To determine the effect of breathing on the detection of small dense pulmonary nodules of threshold conspicuity by spiral computed tomography (SCT). MATERIALS AND METHODS: Forty pulmonary nodules of high density were created by endobronchial deployment of 2 and 4mm diameter beads in the peripheral airways of five anaesthetized dogs. SCT was performed during induced breath-hold and quiet breathing, using 5 mm collimation, pitch 2 and reconstruction of contiguous 5 mm slices. Scans were reviewed by six radiologists. Detection rates were measured as the number of nodules seen by at least one reader. The data was modelled using ordinal logistic regression for repeated measures, and the Wald Chi-square statistic used to test if there was a breath-hold vs. breathing effect on reader confidence level. RESULTS: There was no difference in detection rates for breath-hold vs. breathing SCT (28 vs. 25, respectively; P=0.48). This was also true when only the 2 mm nodules (n=24) were considered (12 vs. 11, respectively; P=0.77). Reader confidence level was significantly higher for breath-hold vs. breathing SCT (Wald Chi-square statistic with 6 degrees of freedom=19.0; P=0.0041). CONCLUSION: SCT can be performed during quiet breathing without a significant reduction the overall detection rate for small dense pulmonary nodules, though reader diagnostic confidence level is reduced.

Animals↗

PubMed1998

Rapid engraftment after allogeneic transplantation using CD34-enriched marrow cells.

Bone marrow cells expressing the surface antigen CD34 comprise approximately 1% of harvested marrow and are highly enriched for marrow progenitor cells, including the cells believed to be responsible for long-term engraftment following bone marrow transplantation (BMT). Selection of CD34-expressing cells was applied in allogeneic BMT (alloBMT) to decrease the number of T lymphocytes in the infused marrow in an attempt to prevent severe graft-versus-host disease (GVHD). We report 14 patients who underwent HLA-identical sibling-matched alloBMT with marrow-enriched for CD34 cells using the Isolex 300 SA device. Patients received total body irradiation, thiotepa, cyclophosphamide, antithymocyte globulin and methylprednisolone prior to marrow infusion. No post-transplantation immunosuppressive therapy was given except for a 5-week course of steroids. The purity of the infused marrow was 64.9+/-6.0% (mean +/- s.e.m.) CD34-positive cells and patients received a mean of 1.24+/-0.21 x 10(6) CD34 cells/kg. A mean of 9.4+/-1.7 x 10(4) CD3 T cells/kg were present in the CD34-enriched product, representing a 2.7+/-0.1 log depletion. There were no graft rejections and patients achieved a sustained absolute granulocyte count of >500 in a median of 10.5 days and a sustained platelet engraftment of >20000 untransfused in a median of 27 days. Patients were discharged a median of 21.5 days after marrow infusion. There were no instances of grade III or IV graft-versus-host disease (GVHD) and no unexpected adverse events during the transplant hospitalization. With a median follow-up of 12 months, the estimated 100 day survival is 86+/-9%. CD34 selection in alloBMT permits rapid engraftment without unanticipated toxicities.

Adolescent↗

PubMed1998

Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies: a phase I trial.

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m2/24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen for metastatic disease. Gallium was administered at a fixed dose of 300 mg/m2/day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m2 was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 microg/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m2 and 225 mg/m2 with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase II dosage is gallium nitrate at 300 mg/m2/day over 120 hours, with paclitaxel at 110 mg/m2 over 24 hours without G-CSF or 225 mg/m2 over 24 hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of this modified regimen for outpatient administration are in progress.

Adult↗

PubMed1998

Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience.

PURPOSE: In a previously reported randomized Southeastern Cancer Study Group (SECSG) trial, three cycles of chemotherapy were found to be equivalent to four cycles in patients with favorable-prognosis germ-cell cancer. We have conducted a follow-up analysis of patients treated at Indiana University (Indianapolis, IN) to compare long-term survival between the two groups and to examine factors associated with survival. PATIENTS AND METHODS: Sixty-nine patients with minimal-stage and 49 patients with moderate-stage disseminated germ-cell tumors were randomized to either three or four courses of bleomycin, etoposide, and cisplatin (BEP) administered every 3 weeks. Median follow-up time is 10.1 years (range, 7 months to 12.6 years). Ninety-two percent of patients have an actual follow-up time of > 5 years, and 97.5% of patients have an actual follow-up time of > 3 years. RESULTS: Survival analysis shows no significant difference between the two treatment groups in terms of overall (P = .80) or disease-free (P = .93) survival. Several clinical variables were examined by univariate analysis; only serum human chorionic gonadotropin (HCG) had an impact on survival. There were two disease-related deaths in 104 patients with HCG < or = 1,000 mIU/mL and five disease-related deaths in 14 patients with HCG greater than 1,000 mIU/mL (P < .001). Ninety-eight percent (95% CI, 95.2 to 100) of patients with favorable prognosis germ-cell tumor with an initial HCG of < or = 1,000 mIU/mL are alive without evidence of disease at 5+ years. CONCLUSION: With long-term follow-up, there is no statistically significant difference in survival between three or four cycles of BEP chemotherapy in patients with favorable prognosis germ-cell carcinoma. Serum HCG elevation of greater than 1,000 mIU/mL is a significant predictor of poor outcome in patients with otherwise good-risk disease.

Adolescent↗

PubMed1998

Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor.

PURPOSE: This study was designed to assess the effectiveness of vinblastine, ifosfamide, and cisplatin (VeIP) as second-line therapy in patients with recurrent germ cell tumors with previous treatment with cisplatin plus etoposide, usually in combination with bleomycin. PATIENTS AND METHODS: From July 1984 through December 1989, 135 patients with progressive, disseminated germ cell tumors after cisplatin-etoposide-based combination therapy induction chemotherapy were treated with VeIP. Patients who progressed within 3 weeks of previous cisplatin therapy were not eligible. Progression was documented by biopsy or increasing serum markers. No exclusion was made on the basis of metastatic site or performance status. The dosages were vinblastine 0.11 mg/kg/d (days 1 and 2), ifosfamide 1.2 gm/m2/d (days 1 through 5), and cisplatin 20 mg/m2/d (days 1 through 5), with courses repeated every 21 days for four cycles. RESULTS: Sixty-seven (49.6%) patients achieved a disease-free status after chemotherapy with or without surgical resection of residual carcinoma or teratoma. Overall, 42 (32%) patients are alive and 32 (23.7%) are continuously free of disease. None of the 32 patients with nonseminomatous extragonadal tumors are disease-free compared with 30 of 100 patients with gonadal primaries. Two of three extragonadal seminomas are continuously disease-free. CONCLUSION: VeIP is capable of producing durable complete remissions in patients with disseminated germ cell cancer who relapse after cisplatin-etoposide-based induction therapy. Long-term disease-free survival is not seen in those patients with extragonadal nonseminomatous germ cell tumors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Maximum intensity projection images in the detection of simulated pulmonary nodules by spiral CT.

This study was undertaken to investigate the use of maximum intensity projection (MIP) images in the detection of pulmonary nodules by spiral CT (SCT). 40 pulmonary nodules of high density were created by endobronchial deployment of 2 and 4 mm beads in the peripheral airways of five anesthetized dogs. Standard SCT was performed with 5 mm collimation, pitch 2 and reconstruction of contiguous slices. MIP images were generated from overlapped slabs of seven consecutive 3 mm slices, reconstructed at 2 mm intervals and acquired at pitch 2. Scans were reviewed by six radiologists. The data were modelled using ordinal logistic regression for repeated measures, and the Wald chi 2 statistic used to test if there was a difference in nodule detection and reader confidence level between the two techniques. MIP imaging increased the odds of nodule detection by 2.18 (p = 0.0002). Reader confidence level for nodule detection was significantly higher with MIP images (p < 0.00001). MIP images improve the detection rate for small high density pulmonary nodules and increase reader confidence level, when compared with standard SCT.

Animals↗

PubMed1998

Prospective randomized trial of 5-fluorouracil versus 5-fluorouracil plus levamisole in the treatment of metastatic colorectal cancer: a Hoosier Oncology Group trial.

The purpose of this study was to compare the objective response rate, duration of remission, and survival of 5-fluorouracil (5-FU) versus those of 5-FU plus levamisole in metastatic colorectal cancer using the same dose and schedule of these agents as in the North Central Cancer Treatment Group and intergroup studies of adjuvant therapy. Patients with no prior history of chemotherapy for metastatic disease were entered on this Hoosier Oncology Group randomized Phase III trial. Patients were stratified by Karnofsky performance status and presence or absence of liver metastases. They were randomized to receive 450 mg/m2 5-FU i.v. for 5 days followed by 15 mg/kg i.v. weekly (arm 1) or the same dose of 5-FU plus levamisole 50 mg p.o. every 8 h for 3 days every 2 weeks (arm 2). The duration of treatment for both arms was 26 weeks. From April 1990 to March 1995, 199 patients were entered. One hundred eighty-two patients, 91 in each arm, were fully evaluable. The response rates were 12% on arm 1 and 13% on arm 2. The median duration of response was 18 weeks on both arms. The median survival was 48 weeks on arm 1 and 41 weeks on arm 2 (P = 0.20). This study failed to show any improvement in survival, response, or duration of remission with the addition of levamisole to 5-FU in the treatment of metastatic colorectal cancer.

Adult↗

PubMed1997

Pain and treatment of pain in minority patients with cancer. The Eastern Cooperative Oncology Group Minority Outpatient Pain Study.

BACKGROUND: Clinics that primarily see members of ethnic minority groups have been found to provide inadequate treatment of cancer-related pain. The extent of undertreatment of pain in these patients and the factors that contribute to undertreatment are not known. OBJECTIVES: To evaluate the severity of cancer-related pain and the adequacy of prescribed analgesics in minority outpatients with cancer. DESIGN: Prospective clinical study. SETTING: Eastern Cooperative Oncology Group. PATIENTS: 281 minority outpatients with recurrent or metastatic cancer. MEASUREMENTS: Patients and physicians independently rated severity of pain, pain-related functional impairment, and pain relief obtained by taking analgesic drugs. Analgesic adequacy was determined on the basis of accepted guidelines. RESULTS: 77% of patients reported disease-related pain or took analgesics; 41% of patients reporting pain had severe pain. Sixty-five percent of minority patients did not receive guideline-recommended analgesic prescriptions compared with 50% of non-minority patients (P < 0.001). Hispanic patients in particular reported less pain relief and had less adequate analgesia. CONCLUSIONS: The awareness that minority patients do not receive adequate pain control and that better assessment of pain is needed may improve control of cancer-related pain in this patient population.

Adult↗

PubMed1997

Continuously monitored stopping boundary methodologies: the issues of sensitivity, association and trial suspension.

Thall et al. consider a continuous monitoring strategy for multiple discrete outcomes to determine whether a trial should terminate early. We evaluate important issues raised in the application of a continuous monitoring strategy for multiple outcomes. Specifically, we evaluate: (i) the sensitivity of such a methodology to small perturbations in the stopping boundaries; (ii) the need to employ accrual buffers when a trial approaches a stopping boundary-a large buffer implying that temporary suspension is unwarranted; and (iii) the role of association among the multiple outcomes of interest. Simulation studies demonstrate that the methodology is sensitive to small perturbations in the stopping boundaries, that the size of an accrual buffer can vary widely over the course of a trial, and that the extent of association among multiple outcomes plays a large role in determining the stopping properties of a trial. We illustrate these issues using the HLA non-identical donor bone marrow transplant trial, with two discrete outcomes.

Bayes Theorem↗

PubMed1997

Detection of pulmonary metastases with pathological correlation: effect of breathing on the accuracy of spiral CT.

BACKGROUND: CT of the chest for suspected pulmonary metastases in adults is generally performed using a breath-hold technique. The results may not be applicable to young children in whom breath-holding may be impossible. OBJECTIVE: Determine the effect of breathing on the accuracy of pulmonary metastasis detection by spiral CT (SCT). MATERIALS AND METHODS: Prior to euthanasia four anesthetized dogs with metastatic osteosarcoma underwent SCT with a collimation of 5 mm and a pitch of 2, during both induced breath-hold and normal quiet breathing. Images were reconstructed as contiguous 5-mm slices. Macroscopically evident metastases were noted at postmortem. Hard-copy SCT images were reviewed by ten radiologists, each of whom circled all suspected metastases. SCT images were compared with postmortem results to determine true and false positives. RESULTS: The pathologist identified 132 macroscopically evident pulmonary metastases. For metastasis detection, there was no significant difference between breath-hold SCT and breathing SCT. CONCLUSION: In our animal model, SCT can be performed during normal resting breathing without significant loss of accuracy in the detection of pulmonary metastases.

Animals↗

PubMed1997

Prevalence of acne keloidalis nuchae in football players.

BACKGROUND: Acne mechanica (AM) is common in football players. Severe cases of nuchal AM may precede acne keloidalis nuchae (AKN). Factors that may be associated with the progression of nuchal AM to AKN are unknown. The prevalence of AKN in football players has not been reported. OBJECTIVE: We investigated the frequency of nuchal AM and AKN within a susceptible population and attempted to identify factors that may be associated with AKN. METHODS: Four hundred fifty-three high school, collegiate, and professional football players were examined for the presence of nuchal AM or AKN. Those with positive findings completed a questionnaire regarding their disease. RESULTS: Nuchal AM was more prevalent in high school players (15.5%) than older players (1.2%). AKN was more frequent in players beyond the high school level and was found exclusively in blacks. AKN was not associated with a positive family history of AKN nor a positive personal or family history of keloid formation. CONCLUSION: AKN occurs almost exclusively in blacks. The level of football play may be associated with the development of AKN. Positive family history of AKN and positive family or personal history of keloids is not associated with AKN development.

Acne Keloid↗

PubMed1997

Outcomes research: an overview.

During the past few years there has been significant interest in studying methods that document outcomes of medical care. Outcomes management should result in higher quality health care at lower cost. However, what does outcomes research mean and how does it apply to dermatology and specifically to the individual dermatologist? This article reviews the evolution of medical outcomes research and presents the status of the current instruments, indices, and methods.

Dermatology↗

PubMed1997

Salvage chemotherapy with vinblastine, ifosfamide, and cisplatin in recurrent seminoma.

PURPOSE: Salvage therapy for disseminated germ cell tumors of all histologic subtypes with vinblastine, ifosfamide, and cisplatin (VeIP) will cure approximately 25% of patients. The purpose of this study was to evaluate the activity of VeIP in patients with recurrent seminoma. PATIENTS AND METHODS: We conducted a retrospective review of 24 patients with recurrent seminoma who were treated at Indiana University with VeIP as second-line chemotherapy. All patients had received cisplatin-containing regimens as primary chemotherapy and seven had also received prior pelvic radiotherapy. All patients received four courses of VeIP. RESULTS: The minimum follow-up duration was 2 years (range, 2 to 9.1), with a median follow-up time of 7 years. Twenty of 24 patients (83%) achieved a complete remission (CR) following VeIP alone. One additional patient was rendered disease-free (NED) with the resection of residual carcinoma. Eight patients have relapsed. Four of six patients with extragonadal primary tumors and two of four who failed to achieve CR with initial chemotherapy are continuously NED with VeIP. Overall, 13 of 24 (54%) are long-term survivors with VeIP salvage chemotherapy. CONCLUSION: VeIP has significant curative potential in patients with recurrent seminoma and appears to produce a higher CR rate and more long-term survivors than is achieved in patients with nonseminomatous disease.

Adult↗