PubMed Health⌕ Search

Biomedical subjects

J E Larson

Publications and source records attributed to J E Larson.

At least 19 recordsLinked to original sources
PubMed1991

Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group.

Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.

Adult↗
PubMed1991

Bypassing femoral cortical defects with cemented intramedullary stems.

The objective of this investigation was to examine the effect of cemented intramedullary stem bypass on bone torsional property in the presence of femoral cortical defect. We intended to test two hypotheses; first, intramedullary fixation without bypass will accentuate the stress concentration effect and second, there will be an optimal length of stem bypass beyond the defect. Cemented intramedullary stems were used to bypass 50% diaphyseal diameter unicortical defects in paired, fresh-frozen canine femora. One member of each pair served as an unaltered control and all specimens were tested to failure in torsion. Both single-tailed paired t-test and analysis of variance were used for data analysis. Bones subjected to the cortical defect and no bypass were substantially weakened, exhibiting only 44 +/- 8% of control side maximum torque (p less than 0.001). Positioning of the intramedullary stem with its tip at the center of the defect provided a small degree of strength improvement, achieving 60 +/- 7% of control side maximum torque. One and two diaphyseal diameter bypass, however, significantly (p less than 0.01) improved bone torsional strength, resulting in 80 +/- 6% and 84 +/- 13% of control side maximum torque, respectively. Three diameter bypass achieved only 68 +/- 8% of control side maximum torque. This significant (p less than 0.05) decline in strength when compared to two diameter bypass appears to indicate that the length of stem bypass beyond the cortical defect does have an optimum, probably due to the geometric characteristics of the canine femora.

Animals↗
PubMed1991

Analysis of prognostic factors and survival in patients with ovarian cancer treated with second-line hexamethylmelamine (altretamine).

Hexamethylmelamine (altretamine, HMM) 260 mg/m2/day p.o. for 14 days followed by a 14-day drug-free interval was administered to 52 outpatients with advanced ovarian cancer who had previously been treated with chemotherapy. Prior to HMM, 92% (48/52) of these patients had received cisplatin and cyclophosphamide with or without doxorubicin. Two more patients received other cisplatin-based regimens. At the completion of HMM therapy, 15% (8/52) displayed no evidence of disease (NED). Of these eight patients, five are still alive 32 to 82 months after altretamine therapy (median follow-up of 46 months). At 41 months, one patient died of intercurrent illness with no clinical evidence of recurrence; the other two patients died of their disease at 21 and 31 months following HMM therapy. The median survival of the total group was 11 months: nine months for patients who did not respond to altretamine and 46+ months for patients with NED after altretamine (p less than 0.05). Intermittent oral administration of single-agent altretamine was well tolerated: eight patients reported moderate gastrointestinal symptoms, and only one patient reported severe gastrointestinal symptoms. Moderate neurologic toxicity was reported by five patients. No WBC fell below 2000 mm3 and platelet counts fell below 100,000 mm3 in only three patients; no patient experienced severe hematologic toxicity. In this series of patients, the overall response (15%) was comparable to or better than those reported for more toxic chemotherapeutic regimens. On the basis of these data and those reported by other investigators, HMM warrants consideration as a reasonable option in the management of recurrent or persistent ovarian cancer.

Altretamine↗
PubMed1990

Hexamethylmelamine as a single second-line agent in ovarian cancer.

Fifty-two patients with advanced ovarian cancer were treated with single-agent hexamethylmelamine (HMM), 260 mg/m2 po per day for 14 days followed by 14 days off drug. All patients had been previously treated with chemotherapy. Of these patients, 92% (48/52) received cisplatin and cyclophosphamide +/- doxorubicin prior to hexamethylmelamine. Two additional patients received other cisplatin-based regimens. Fifteen percent (8/52) were found to have no evidence of disease (NED) at the completion of treatment with HMM. Five of these patients are alive at 12 to 65 months (median follow-up of 32 months); one patient died at 41 months of an intercurrent illness with no clinical evidence of recurrence; two patients died of recurrent tumor at 21 and 31 months. The median survival of the series of 52 patients is 11 months: 9 months for patients who did not respond versus 41 months for patients with NED post-HMM (P less than 0.05). The regimen was well tolerated: moderate gastrointestinal toxicity was reported by 8 patients; only one patient reported severe gastrointestinal toxicity. Moderate neurologic toxicity (primarily sensory) was reported by 5 patients, 3 patients experienced white counts less than 2000 or platelet counts less than 100,000, and no patient sustained severe hematologic toxicity. This moderate-dose intermittent regimen was associated with moderate toxicity and was well accepted by patients. The overall response is comparable to or higher than that reported for more toxic chemotherapy regimes. Based on these data and those recently reported by other authors, hexamethylmelamine should be considered in the treatment of recurrent ovarian cancer.

Adult↗
PubMed1990

Rhabdomyosarcoma of the uterus in a postmenopausal patient.

Pure rhabdomyosarcomas of the female genital tract most commonly occur in infancy or childhood as sarcoma botryoides (embryonal rhabdomyosarcoma) and involve the vagina and cervix. Such tumors rarely occur in adults. A pure rhabdomyosarcoma of the uterus that arose in a postmenopausal patient is described. The pertinent literature is discussed.

Aged↗
PubMed1989

Tetracycline promoter mutations decrease non-B DNA structural transitions, negative linking differences and deletions in recombinant plasmids in Escherichia coli.

The ability to clone a variety of sequences with varying capabilities of adopting non-B structures (left-handed Z-DNA, cruciforms or triplexes) into three loci of pBR322 was investigated. In general, the inserts were stable (non-deleted) in the EcoRI site (an untranslated region) of pBR322. However, sequences most likely to adopt left-handed Z-DNA or triplexes in vivo suffered deletions when cloned into the BamHI site, which is located in the tetracycline resistance structural gene (tet). Conversely, when the promoter for the tet gene was altered by filling-in the unique HindIII or ClaI sites, the inserts in the BamHI site were not deleted. Concomitantly, the negative linking differences of the plasmids were reduced. Also, inserts with a high potential to adopt Z-DNA conformations were substantially deleted in the PvuII site of pBR322 (near the replication origin and the copy number control region), but were less deleted if the tet promoter was insertion-mutated. The deletion phenomena are due to the capacity of these sequences to adopt left-handed Z-DNA or triplexes in vivo since shorter inserts, less prone to form non-B DNA structures, or random sequences, did not exhibit this behavior. Sequences with the potential to adopt cruciforms were stable in all sites under all conditions. These results reveal a complex interrelationship between insert deletions (apparently the result of genetic recombination), negative supercoiling, and the formation of non-B DNA structures in living Escherichia coli cells.

Chromosome Deletion↗
PubMed1989

Bowel obstruction in patients with ovarian carcinoma: analysis of prognostic factors.

A retrospective study was performed in which patients with both bowel obstruction and ovarian carcinoma admitted to the gynecologic oncology service at the Milton S. Hershey Medical Center between July 1, 1980, and June 30, 1987, were examined. Thirty-three patients were identified who fulfilled the inclusion criteria for bowel obstruction that did not occur in the postoperative period. Historical, physical, nutritional, and laboratory variables thought to contribute to patient survival were evaluated by a retrospective chart review. Survival time was not significantly related to presence or absence of tumor at obstruction, type of intervention whether medical or surgical, patient age, or interval from initial diagnosis of ovarian cancer to obstruction. Survival time was found to be significantly related to the prognostic index initially proposed by H. B. Krebs and D. R. Goplerud [Obstet. Gynecol. 61, 327-330 (1983)], P = 0.002. This prognostic index incorporates a multifactorial assessment of patient status including age, nutritional status, tumor spread, ascites, and prior chemotherapy and radiotherapy and can be used to evaluate patients at the time of presentation with intestinal obstruction and to help select optimal treatment for palliation.

Adolescent↗
PubMed1989

Pelvic exenteration: a morbidity and mortality analysis of a seven-year experience.

Twenty patients have undergone pelvic exenteration at the University Hospital of the Pennsylvania State University from 1979 to 1985. The majority of operations were performed for cancers of the cervix or vagina that recurred following radiotherapy. Operative mortality was 5.0%. Of those surviving the procedure, 16 patients (84%) were rehospitalized for complications that occurred more than 30 days after exenteration. The majority of these involved the gastrointestinal or urinary tracts. Fifty-eight percent of the complications requiring surgical intervention occurred more than 1 year after surgery while 74% of the complications managed conservatively occurred within 1 year of surgery. The 2-year survival for all patients was 70%; survival decreased to 58% at 5 years. The most important risk factor for reduced survival was the extension of tumor laterally into the surgical margins.

Adult↗
PubMed1989

Scalene lymph node biopsy in the preoperative evaluation of patients with recurrent cervical cancer.

From 1982 to 1987, 24 patients with recurrent carcinoma of the cervix underwent scalene lymph node biopsy prior to exploration for exenteration. Patients with palpable nodes were excluded from the study. There was no significant morbidity associated with the procedure. None of the 24 patients was found to have metastases to the scalene lymph nodes. From this study it would seem unjustifiable to perform this procedure on all patients undergoing evaluation for exenteration.

Biopsy↗
PubMed1989

Use of CA 125 to monitor patients with ovarian epithelial carcinomas.

The CA 125 radioimmunoassay has been increasingly used to monitor the course of patients with ovarian epithelial carcinomas. The purpose of this report is to describe our experience in the use of this assay and to better define its clinical utility. Fifty-one patients had serum CA 125 follow-up during primary chemotherapy. All 51 patients demonstrated either a normal CA 125 level at the completion of chemotherapy or a substantial fall in CA 125 values with treatment. In 48 of 51 patients, the drop in CA 125 levels was temporally related to the clinical regression or remission of tumor. Forty of these patients underwent second-look laparotomy; 23 patients (58%) had residual disease. A total of 45 patients had serum CA 125 determinations at the time of second-look laparotomy. Eight patients with microscopic disease and 11 of 18 patients with gross residual disease had a "negative" (less than 35 U/ml) CA 125 level. The predictive value of an elevated CA 125 level was 1.00. However, the predictive value of a negative value was only 0.50. Hence, a negative CA 125 level cannot be a substitute for a second-look laparotomy. Only 7 of 18 patients (39%) with gross residual disease at second-look surgery had an elevated CA 125 level. Patients with an elevated CA 125 and gross residual tumor at the second-look laparotomy uniformly demonstrated large, bulky disease. Furthermore, the survival of patients with gross residual disease at second-look laparotomy correlated with the preoperative CA 125 value. Serum CA 125 determinations also show promise in the follow-up of patients with a negative second-look laparotomy. The serum CA 125 level from patients with a "negative" second-look laparotomy can become elevated months before recurrent disease is appreciated.

Actuarial Analysis↗
PubMed1989

Pelvic fibromatosis: case report and review of literature.

The case report of a patient with pelvic fibromatosis is described. Excision of the tumor without sacrificing organs or major vessels was performed. Although not malignant, this tumor can be life-threatening due to its locally invasive properties. A variety of therapeutic options are discussed.

Adult↗
PubMed1989

Management of malignant, mixed mesodermal tumors of the uterus.

Forty-two patients with malignant, mixed mesodermal tumors of the uterus were identified by retrospective chart review. Only 2 patients were premenopausal at the time of diagnosis. Six of the patients had previously received pelvic radiotherapy. Surgical/pathologic findings were inconsistent with clinical staging in 17 of the patients. Patients with stage I tumors were found to have extrauterine extension of tumor in 39% of the cases. Overall, 2- and 5-year actuarial survival rates were 40 and 18%, respectively. The surgical extent of disease was a major prognostic factor in patient survival (P = 0.006). Patients with tumors showing no invasion or invasion limited to the inner two-thirds of the myometrium also demonstrated a significant survival advantage as compared to those with deeper myometrial invasion (P = 0.02). However, no statistically significant relationship was demonstrated between survival and patient age, the nature of the sarcomatous element (homologous or heterologous), or the presence of cervical involvement. Patients with recurrent or persistent disease did poorly; only 4 patients have survived more than 1 year after documentation of recurrent disease. Two patients had prolonged disease stabilization with radiotherapy and cisplatin. Another patient with pulmonary metastases had a 6-month, complete response to cisplatin.

Adult↗
PubMed1988

In vivo existence of left-handed DNA.

A genetic-biochemical assay has been developed to investigate the in vivo existence and consequences of unusual DNA structures. Left-handed DNA was shown to exist in living Escherichia coli. The EcoRI methyltransferase gene (temperature-sensitive) was cloned to serve as a probe for perturbed GAATTC sites in vivo. This plasmid was cotransformed with different plasmids containing inserts that had varying capacities to form left-handed helices or cruciforms with a target EcoRI site in the center or at the ends of the inserts. Inhibition of methylation in vivo was found for the stable inserts with the longest left-handed helices. In vitro methylation with the purified M.EcoRI enzyme agreed with the in vivo results.

Bacterial Proteins↗
PubMed1988

Cytosine methylation as an effector of right-handed to left-handed DNA structural transitions.

Cytosine methylation has energetic and structural influences on left-handed Z-DNA formation in supercoiled plasmids. The restriction and modification enzymes from Haemophilus haemolyticus (HhaI and M.HhaI) provide a system to locate and analyze small segments of Z-DNA in large supercoiled plasmids. An approach is outlined that uses M.HhaI as an in vivo conformational probe for the detection of unusual DNA structures in a living cell. Also, characteristic features of the M.HhaI gene and protein are discussed.

5-Methylcytosine↗
PubMed1988

Multiple DNA secondary structures in perfect inverted repeat inserts in plasmids. Right-handed B-DNA, cruciforms, and left-handed Z-DNA.

The capabilities of five recombinant plasmids, containing relatively long (approximately 60-100 base pairs) perfect inverted repeat (IR) inserts, to support supercoil stabilized non-B-DNA structures were studied in vitro. The IRs were also alternating purine-pyrimidine sequences, thus, each could form either left-handed Z-DNA or cruciforms. Single-strand specific endonucleases, restriction endonucleases and methylases, and OsO4 modifications were used to characterize the DNA structures. Two-dimensional gel electrophoretic studies indicated that three of the five IRs formed both cruciforms and Z-DNA. (C-G) containing inserts preferred to form Z-DNA, whereas (T-G) sequences favored cruciforms. In vivo supercoil relaxation experiments demonstrated the existence of cruciforms in Escherichia coli. The physiological significance of these structures is discussed.

Base Sequence↗
PubMed1988

Methylation of cytosine in the 5-position alters the structural and energetic properties of the supercoil-induced Z-helix and of B-Z junctions.

The structural and energetic consequences of cytosine methylation in the 5-position on the supercoil-dependent B-Z equilibrium in alternating dC-dG sequences cloned into recombinant plasmids were investigated. The helical parameters determined with the band shift method for right-handed [10.7 base pairs (bp)/turn] and left-handed (12.8 bp/turn) 5MedC-dG inserts were different from the helical repeat values for unmethylated dC-dG inserts (10.5 bp/turn in the right-handed and 11.5 bp/turn in the left-handed form). We analyzed the thermodynamic parameters delta GBZ (free energy difference per base pair between right-handed and left-handed helix structure), delta Gjx (free energy for formation of one B-Z junction), and b (helix unwinding at a junction region) for varying lengths of dC-dG inserts by two-dimensional gel electrophoresis and application of a statistical mechanics model. A comparison of plasmids fully methylated in vitro with HhaI methylase and their unmethylated counterparts revealed that delta Gjx is not significantly changed by cytosine methylation. However, this base modification results in an approximate 3-fold decrease of delta GBZ and an approximate 2-fold decrease of the unwinding b at B-Z junction regions. Analysis of a pair of related plasmids, each containing two dC-dG blocks, revealed qualitatively different transition behaviors. When the two dC-dG blocks were separated by 95 bp of a mixed sequence, they underwent independent B to Z transitions with separate nucleation events and junction formations. When the two blocks were separated by only a 4 bp GATC sequence, only one nucleation event was necessary, and the Z-helix spread across the nonalternating GATC region.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Topoisomerases, Type I↗