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Biomedical subjects

J E Larson

Publications and source records attributed to J E Larson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Clinical relevance of presenting symptoms in the preoperative evaluation of pelvic masses.

BACKGROUND: There are few studies which have analyzed patients' presenting symptoms to evaluate whether a particular symptom is clinically significant. This study is aimed at determining whether any particular presenting symptom is important in the preoperative evaluation of a pelvic mass. MATERIALS AND METHODS: 130 charts of patients presenting with a pelvic mass were reviewed. A standard data collection technique was used to determine rate of occurrence as well as clinical statistical relevance of specific symptoms. RESULTS: 25 malignancies, 16 of gynecologic origin, were found. Of the variables studied, women older than 50 showed a 14 fold increase in RR (OR 23.3. 95 percent CI 5-104.8) and those with abdominal distention showed an OR 7.9 (95 percent CI 2-21.5). CONCLUSIONS: Abdominal distention showed statistical significance and may be useful in the preoperative assessment of a pelvic mass.

Abdominal Pain↗
PubMed1995

An intramolecular triplex in the human gamma-globin 5'-flanking region is altered by point mutations associated with hereditary persistence of fetal hemoglobin.

The properties of an intramolecular triplex formed in vitro at the 5'-flanking region of the human gamma-globin genes were studied by chemical and physical probes. Chemical modifications performed with osmium tetroxide, chloroacetaldehyde, and diethyl pyrocarbonate revealed the presence of non-paired nucleotides on the "coding strand" at positions -209 through -217. These reactivities were induced by negative supercoiling, low pH, and magnesium ions. Downstream point mutations associated with hereditary persistence of fetal hemoglobin (HPFH) altered the extent of the modifications and some of the patterns. Specifically, C-202-->G and C-202-->T significantly decreased the reactivities, whereas the patterns were increased and altered in the T-198-->C. C-196-->T and C-195-->G caused local decreases in reactivity. Modifications at the upstream flanking duplex were modulated by the composition of the vector sequence. In summary, our data indicates the formation of an intramolecular triplex between nucleotides -209 to -217 of the "non-coding strand" and the downstream sequence containing the HPFH mutations. All of the HPFH point mutations altered the structure. More than one sequence alignment is possible for each of the triplexes. In addition, a consequence of some of the point mutations may be to facilitate slippage of the third strand relative to the Watson-Crick duplex.

Acetaldehyde↗
PubMed1995

In utero gene transfer into the pulmonary epithelium.

In early gestation the internal surface of the lung is structurally simple and an ideal target for somatic gene transfer. The transfer of genes into the growing lung would be particularly useful in the prenatal correction of cystic fibrosis, which has devastating pulmonary complications. In addition, in utero gene therapy has the potential to immunotolerize the individual, and thereby to avoid the immune reactions now seen with the current generation of adenoviral vectors. We injected a replication-defective adenoviral vector containing the lacZ reporter gene (Ad5.CMVlacZ) into the amniotic fluid of rat pups on the 16th day of gestation. At 16 days of gestation, rat lungs are equivalent in maturity to those of a 22-week human fetus as their airways are lined with undifferentiated multipotential stem cells. The pups showed high-level reporter gene expression in their airways a week following birth (13 days following infection). The expression was maintained during a time when the lung volume increased approximately 20-fold, alveolarization occurred, and the epithelial cells differentiated. These data establish gene targeting of undifferentiated fetal cells as an effective means of gene therapy.

Adenoviridae↗
PubMed1993

Developmental control of collagen gene expression in the rat lung: confirmation of early observations of lung growth.

The short gestation period of the rat allows one to see rapid morphologic and biochemical changes in the lung. It has been shown that the rat lung undergoes a period of distension over the first several days of life followed by a rapid alveolar growth. Total lung collagen also increases during this time period. We have examined the changes in types I and III procollagen transcripts during the perinatal period and have compared them to the above observations. Total RNA was extracted from the lungs of offspring of time-pregnant Sprague-Dawley rats after large airways were removed. Northern hybridization was performed to determine the quality of steady-state RNA and rule out cross-hybridization while densitometric tracings of slot-blot hybridizations allowed comparative estimates of the target sequence of RNA. Immediately following birth, the steady-state mRNA procollagen levels increased and a shift to a predominant type I production occurred. These changes preceded the rapid increase of collagen content and alveolarization known to occur at three days of age. These data provide further evidence that collagen production is controlled at the level of transcription and in temporal and tissue-specific manners.

Animals↗
PubMed1993

Fabellar impingement in total knee arthroplasty. A case report.

Fabellar impingement can cause postoperative pain, swelling, and catching, and can significantly compromise the results of total knee arthroplasty. The appearance of a large fabella on preoperative radiographs should raise suspicion about possible impingement. Impingement against the femoral or tibial component of the prosthesis should be assessed by inspection and palpation during trial reduction. The fabella can be removed via the anterior approach prior to component fixation, although it tends to be firmly embedded in the lateral head of the gastrocnemius tendon and requires careful dissection. A separate posterolateral approach will most likely be needed to accomplish complete fabellar excision after the components are secured.

Aged↗
PubMed1993

Reoperation after condylar revision total knee arthroplasty.

Reasons for reoperation after knee revision surgery are implant loosening, sepsis, extensor mechanism problems, fractures of bone or prosthetic components, wear debris, and limited range of motion. The purpose of this study was to review the complications requiring reoperation in a large number of condylar revision total knee arthroplasties to determine the incidence and outcome after treatment. Six hundred fifty-five condylar revision total knee arthroplasties performed during a ten-year period were retrospectively reviewed. Forty-six knees without a history of arthroplasty infection required a total of 60 reoperations after the revision surgery. A reoperation was performed for extensor mechanism or patellar problems in 19 knees (41%), component loosening in ten knees (22%), deep infection in nine knees (20%), wound problems in nine knees (20%), tibiofemoral instability in eight knees (17%), limited range of motion in four knees (8%), and particulate debris synovitis in one knee (2%). All patients were observed for an average of 7.5 years. Twenty-four knees (52%) were considered clinical failures because of pain, limited motion, instability, and sepsis. Awareness of these failure modes may help to prevent complications by strict attention at the time of revision surgery to protection of the patellar tendon attachment and collateral ligaments, balancing of the extensor mechanism, preservation of the patellar blood supply, proper component position and sizing, restoration of the mechanical axis, and use of more constrained implant designs.

Adult↗
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↗