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Biomedical subjects

J Herson

Publications and source records attributed to J Herson.

At least 19 recordsLinked to original sources

Comparative evaluation of urographic contrast media, inulin, and 99mTc-DTPA clearance methods for determination of glomerular filtration rate in clinical transplantation.

Plasma clearance of inulin (Cin), 99mTc-DTPA (CDTPA), and urographic contrast media (CCM) were determined simultaneously in 31 patients with varying levels of renal function evaluated in the setting of affiliated cardiac and renal transplantation programs. Cin and CDTPA were calculated from the ratio of simultaneously measured plasma concentration and urine excretion rate of these test agents (UxV/P). CCM was derived from x-ray fluorescence measurement of plasma iodine (PI) content following intravenous injection of 50 ml of nonionic, low-osmolar contrast media (180 mg I/ml). Urine collections were not required for CCM determinations. No adverse reactions attributable to CM occurred in any patient, and follow-up serum-creatinine values did not differ significantly from prestudy levels. CCM determined from the rate of decline in PI between 3 hr and 4 hr following administration of contrast media ("slope-intercept" technique) [Ccm-SI] correlated closely with corresponding levels of Cin (r = .86, P less than 0.0001). and CDTPA (r = 0.89, P less than 0.0001). Mean CCM-SI/Cin and CCM-SI/CDTPA ratios for the entire study cohort were 1.09 +/- 0.06 and 1.08 +/- 0.06, respectively. CCM-SI determinations also correlated well with CCM levels derived from a single measurement of PI ("single sample" technique) made at 3 hr following injection of contrast media (r = 0.94, P less than 0.0001). Both CCM-SI and CCM determined by the "single sample" method (CCM-3 degrees SS) tended to overestimate Cin and CDTPA, however, when the latter were less than 20 ml/min/1.73 m2 (mean CCM-SI/Cin and Ccm-3 degrees SS/Cin ratios 1.36 +/- 0.14 and 1.95 +/- 1.0, respectively. Reproducibility was evaluated by paired comparison of 3-hr vs. 4-hr "single sample" CCM determinations (r = 0.99, P less than 0.0001). In addition, analysis of the variation in iodine content between duplicate specimens obtained at each of these time intervals revealed a mean ratio of 1.0 +/- 0.01 (P = NS vs. identity). Contrast clearance determination utilizing the slope-intercept method is accurate, safe, pragmatic, and more precise than serum-creatinine and endogenous-creatinine clearance for measurement of renal function in clinical transplantation.

Contrast Media

Topical human fibroblast interferon for acute adenoviral conjunctivitis.

We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial investigating the use of topical human fibroblast interferon (HuIFN-beta) 7.5 x 10(5) IU/ml, one drop 5 times daily, in the treatment of acute epidemic conjunctivitis. Of 50 patients who were initially enrolled, tear-film cultures for adenovirus were positive from 26% for type 8, 12, or 19. Based upon a quantifiable conjunctivitis severity score of 37 patients evaluated after approximately 1 week of therapy, analysis of covariance showed a statistically significant greater improvement with topical HuIFN-beta compared with placebo for affected left eyes (P = 0.02) but not for right eyes (P = 0.5), an effect that could not be adequately explained. We suggest that a higher dosage of topical HuIFN-beta may prove useful in the control of more severely affected cases. This trial provides guidelines for future investigations of interferon in the treatment and prophylaxis of adenoviral keratoconjunctivitis.

Adenoviridae Infections

Projection from previous studies: a Bayesian and frequentist compromise.

We present methods that use the results of a previous study to predict the outcome of a specified comparative trial in which each subject's outcome is categorized dichotomously (e.g., response or no response). The methods can be generalized to other two-sample cases for which power can be calculated (e.g., exponential survival), and to one-sample cases such as demonstrating a minimal response rate or demonstrating superiority to a historic control. Bayesian methods are used on the results of the preliminary study to obtain a posterior distribution representing the state of knowledge of the parameters of interest. This distribution provides the probability that the experimental regimen is superior to the standard by any particular amount. The probability that a future study will demonstrate the superiority of the experimental treatment is obtained by using the posterior distribution to average the power of the test over the parameter space.

Bayes Theorem

Surgical management of irradiation-induced small bowel damage.

Seventy-seven patients, presenting with radiation small bowel injuries at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1962 and 1978, were analyzed retrospectively. The patients were divided into two categories: bowel bypass without resection, and resection of irradiated bowel. Each group was then analyzed for its short- and long-term complications. Ileocolectomy with end-to-end anastomosis was the surgical procedure of choice in those people undergoing resection. There was no difference in short-term complications noted between the two groups. The long-term complications of fistula formation and continued small bowel necrosis could be prevented by resection, as a primary procedure. The surgical details of ileocolectomy with end-to-end anastomosis are presented, along with an analysis of the complications encountered in both groups.

Abscess

A method to detect excess risk of disease in structured data: cancer in relatives of retinoblastoma patients.

It is often of interest to know whether there is increased occurrence of a trait in a pedigree or other structured set of epidemiological data. In answering such questions most current methods use aggregate measures, such as relative risk, that may not relate the outcome for each individual to that individual's risk. In this paper we present a simple method, and its computational algorithm, to overcome this limitation. This new method also permits one to identify high-risk families or subsets of a collection of data, which is not always possible using other approaches. In a study of cancer risk among relatives of retinoblastoma patients, by applying this new method it was found that 11 of 33 families each obtained through a unilateral retinoblastoma patient are at statistically high risk of cancer at all sites combined, while there are 15 of 47 such families obtained through a bilaterally affected proband. These results are unlikely to have occurred by chance, indicating an overall excess risk in the ancestors of these retinoblastoma cases. The proposed test procedure does not specify the cause of elevated risk; however, a method is proposed that provides some indication regarding possible causal mechanisms under some circumstances.

Biometry

Carcinoma of the cervical stump.

This review is a retrospective analysis of 263 patients with carcinoma of the cervical stump treated at The University of Texas M. D. Anderson Hospital and Tumor Institute between 1963 and 1975. Symptomatology, stage distribution, and histology of carcinoma of the cervical stump showed no significant differences from cervical carcinoma of the intact uterus. Depending on the tumor stage, tumor volume, and distorted anatomy, treatment consisted of various combinations of intracavitary radium and transvaginal and external radiation. The 5-year survival was 100% in stage 0, 91% in stage I, 77% in stage II, 46% in stage III, and 37% in stage IV. The results achieved are similar to those in cervical cancer of the intact uterus. The complication rate was 30% and there were 9 (3.7%) deaths related to radiation complications.

Adenocarcinoma

Cancer mortality in relatives of retinoblastoma patients.

The risk of other cancers in relatives of retinoblastoma (RTB) patients was determined by a survey of the mortality experience of siblings, parents, parental siblings, and grandparents of all U.S. or Canadian RTB patients referred to The University of Texas M.D. Anderson Hospital and Tumor Institute between 1944 and 1980. Expected mortality was ascertained by the application of age-, sex-, race-, and calendar year-specific U.S. mortality rates to the observed person-years. Among 607 relatives of 33 unilateral-sporadic RTB probands, no excess in cancer deaths was observed (observed/expected = 18/22). Among 733 relatives of 47 bilateral-familial RTB probands, a slight excess in cancer deaths was observed (41/31). A significant excess in cancer deaths was occurred in relatives under age 55 years (18/9) and in fathers (7/1) of the bilateral RTB probands. To determine whether the cancer excess was related to some unique allele associated with second tumors in RTB survivors, the cancer mortality of 203 relatives of the 14 RTB patients with second tumors was examined, and no excess was observed (11/11). To determine whether the excess might be attributable to an unexpressed RTB gene or precursor, the mortality experience was examined in 6 kindreds in which parents, unaffected by RTB, had more than 1 child with RTB. Among these 72 relatives a significant excess in cancer deaths was observed (8/2). The findings demonstrate a modest overall cancer excess in relatives of hereditary RTB patients and suggest it may be attributable to an unexpressed RTB gene or precursor in a small number of kindreds. Mechanisms for an apparent "precursor" might involve a delayed mutation, genetic mosaicism, or a submicroscopic balanced chromosomal translocation.

Adolescent

Role of "third-look" laparotomy in the guidance of ovarian cancer treatment.

Twenty-seven patients with Stage III epithelial ovarian carcinoma received a "third-look" celiotomy. Each patient received a minimum of an additional 12 courses of chemotherapy after persistent tumor had been documented at a "second-look" procedure. Twelve of the twenty-seven patients have died. No tumor-associated deaths occurred in patients with grade 1 neoplasms. Of the patients with microscopic disease at the second-look procedure who came to third-look laparotomy, none had died secondary to tumor growth. The survival time of patients with microscopic disease at third-look is greater than that of patients with macroscopic disease (P = 0.0009). In patients who had effective tumor reductive surgery performed at second-look, the third-look findings were highly predictive as to survival. Long-term chemotherapy had a significant incidence of related mortality. Four of the twenty-seven patients died as a direct result of the chemotherapeutic toxicity. The patients receiving melphalan for at least 24 courses appeared to be at greatest risk, with 23% dying from either aplastic bone marrow changes or leukemia. The morbidity associated with third-look laparotomy was not excessive. Many factors need careful review prior to planning a third-look laparotomy. This retrospective study demonstrates that patients with either a grade 1 neoplasm or only microscopic disease at the second-look procedure do well regardless of the third-look findings.

Antineoplastic Agents

A prospective randomized clinical trial of melphalan and cis-platinum versus hexamethylmelamine, adriamycin, and cyclophosphamide in advanced ovarian cancer.

From May 1978 until November 1980, 169 previously untreated patients with advanced epithelial ovarian cancer were entered into a prospective randomized clinical trial comparing the combination of hexamethylmelamine, Adriamycin, and cyclophosphamide (HAC) to a combination of melphalan and cis-platinum. Eleven patients were excluded from analysis and another 5 patients were excluded from response analysis. Of 153 patients evaluable for response, there were 47, or 30.7%, complete responders (all determined surgically), 6 partial responders, and 100 nonresponders. The response rate for the HAC group was 31% and for the melphalan-platinum group was 37.8%. The overall response rate was 34.6%. Residual tumor diameter (less than or greater than 2 cm) exerted a statistically significant effect on response--47.8 vs 24.4%. Of the 47 complete responders, 7, or 14.9%, have relapsed, with the median duration of remission of 44+ months. Of the 158 patients evaluable for survival, 90 patients have died, with a median survival time of 27.9 months (HAC = 26.4 months, melphalan-platinum = 29.6 months). Age, FIGO stage, histologic grade, and residual disease all exerted a significant effect on survival time. Second-line therapy in the treatment failures was of no benefit. Hematologic toxicity was greater in the melphalan-platinum group. Gastrointestinal toxicity was severe in both groups. Other toxicities were minor and infrequent.

Adult

Endodermal sinus tumor of the ovary: the M. D. Anderson experience.

Forty-one patients with pure endodermal sinus tumor of the ovary who were treated at the M. D. Anderson Hospital from 1944 to 1981 are retrospectively reviewed. The median age of these patients was 19 years. The most common presenting symptom was abdominal pain, occurring in 33 patients (80%). No bilateral ovarian involvement was noted at initial surgery. With the exception of 1 patient treated by surgery alone, only patients treated with postoperative combination chemotherapy survived. Twenty-one of the 41 patients are alive and well. Sixteen of 22 patients treated with vincristine, actinomycin-D, and cyclophosphamide have survived. The roles of second-look laparotomy and alpha-fetoprotein monitoring are discussed. Optimal treatment seems to consist of surgery followed by aggressive combination chemotherapy.

Adolescent

Practical side of multistage clinical trials for screening new agents.

Coordinating center operations are recommended for carrying out multistage phase II clinical trials in oncology. The relevant statistical issues in designing phase II trials are summarized. The predictive probability approach to multistage design is briefly described, along with an interactive computer program that facilitates design selection. A multistage trial monitoring form is described, along with data manager-biostatistician responsibilities for monitoring the trial for possible early termination. Procedures are recommended for dealing with patients who cannot be evaluated by response, for minimizing or eliminating selection bias introduced by clinician knowledge of interim results, and for minimizing clinician tendency to report responding patients sooner than those not responding.

Clinical Trials as Topic

Bleomycin and mitomycin-C (BLM-M) in recurrent squamous uterine cervical carcinoma.

Bleomycin and mitomycin-C (BLM-M) induction therapy was administered to 23 patients with recurrent squamous carcinoma of the uterine cervix. Six patients (26%) responded. Although these results are much lower than originally reported with BLM-M, there is statistical evidence that patients with disease outside the previous radiation therapy field have improved or more easily determined responses. There was no difference in survival between responders and nonresponders for patients who survived at least six weeks. Therapy was found to be relatively nontoxic with no deaths related to therapy.

Adult

A randomization list generator for biomedical experiments.

The paper describes RANLST, an interactive program to produce random sequences for randomizing patients or animals to treatments in biomedical experiments. The program allows the user to specify strata, seed value for the random generator, equal or unequal treatment allocation, and unrestricted or restricted randomization. An illustrative example is included.

Animals

Squamous cell carcinoma of the pyriform sinus.

This is a review of 418 patients with cancer of the pyriform sinus who had complete treatment at University of Texas M. D. Anderson Hospital, treated over a 28-year time span. Treatment modalities used included radiation therapy, surgery, and planned combined treatment, primarily in the form of surgery and postoperative radiation therapy. Superficial lesions, with no impairment of laryngeal motility, are suitable for irradiation therapy planned for cure. (The policies of treatment have changed throughout the years). Analysis is made comparing the results of the larger groups of patients treated by surgery only, or surgery followed by postoperative radiation therapy. There is a significant lower incidence of failure above the clavicle in the combined treatment group, and a better 5-year survival. Rate of recurrences and the specific sites of failure above the clavicles are discussed, as well as the means of preventing such. The causes of death between 2 and 5 years are presented.

Aged