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Biomedical subjects

R Dodge

Publications and source records attributed to R Dodge.

At least 37 records · Page 2Linked to original sources
PubMed1994

Clinical outcome after neoadjuvant thermoradiotherapy in high grade soft tissue sarcomas.

In the treatment of soft tissue sarcomas, hyperthermia has been demonstrated to enhance tumor necrosis from radiation therapy. The current study reports the clinical course of patients treated with this neoadjuvant therapy regimen. Forty-four patients with deep, undisturbed, nonmetastatic, high grade soft tissue sarcomas completed a neoadjuvant treatment protocol with combined hyperthermia and radiation therapy followed by wide surgical resection. Negative surgical margins were obtained in 40 patients. There was one local recurrence, thus yielding a local control rate of 97.5%. All other failures were either through regional lymphatic spread or pulmonary metastasis. As a group, the patients at 36 months had a 72% overall and a 58% disease-free survival. The most common pathologic diagnosis was malignant fibrous histiocytoma (MFH), which demonstrated a 36-month survival of 52% vs. 82% for others (P = 0.02). Tumor size was not prognostically significant for disease free or overall survival (P = 0.13). Those patients with surgical margins < 1 cm had a significantly lower disease-free survival and overall survival in a multivariate analysis (P = 0.02 and P = 0.006, respectively). Overall survival did not correlate with either the number of hyperthermia treatments received or the amount of tumor necrosis. Although this neoadjuvant protocol results in excellent local control rates, overall survival rates are comparable to adjuvant therapy employing radiation alone.

Adult↗
PubMed1994

Findings before the diagnosis of asthma in young adults.

BACKGROUND: Asthma is a poorly understood disease. Risk factors are not established, and the natural history of the disease is unknown. OBJECTIVE: Using subjects of a community-based study, we have prospectively compared young adults destined to develop asthma with control subjects to determine differences between them before diagnosis. METHODS: Subjects were participants of the Tucson Epidemiologic Study of Airways Obstructive Disease. They were studied between the ages of 15 and 19 and subsequently every 1 to 2 years until they were at least 21 years old with questionnaire, spirometry, allergy skin testing, and serum IgE testing. RESULTS: Logistic regression showed that "wheeze" and "attacks of shortness of breath with wheeze" were independently predictive of asthma. Positive allergy skin test results occurred more frequently among subjects who later received a diagnosis of asthma, and initially these subjects had higher serum IgE levels than control subjects (geometric mean IgE = 173.8 IU/ml vs 52.5 IU/ml for control subjects; p < 0.005). Although initial spirometric testing did not distinguish between future asthmatic subjects and control subjects, repeat testing after diagnosis did show significant differences in flows at low lung volumes. CONCLUSIONS: These data suggest that symptoms and findings suggestive of asthma may be present for many years before diagnosis.

Adult↗
PubMed1994

The effect of the perflubron emulsion Oxygent on the calibration characteristics of polarographic oxygen electrodes.

The perfluorocarbon emulsion Oxygent improves normal tissue oxygenation. A clinical trial is planned to evaluate this effect in tumors. Polarographic oxygen electrodes were calibrated in solutions of saline +/- perflubron to assess whether Oxygent influenced probe behavior. Calibrations were linear under both conditions. There were no major differences in estimated oxygen tensions.

Calibration↗
PubMed1994

Differences in leucocyte-endothelium interactions between normal and adenocarcinoma bearing tissues in response to radiation.

Previously, we demonstrated that the interaction between leucocytes and endothelial cells in tumour tissues is greatly diminished compared with normal tissues under several induced inflammatory conditions. Radiation has been reported to cause release of inflammatory mediators and to promote neutrophil adhesions to cultured endothelial monolayers. In this study, we tested the hypothesis that radiation would cause increased leucocyte rolling and adhesion in both tumour and normal tissues. We examined these two parameters in response to 6 Gy of gamma-radiation in mammary adenocarcinomas implanted into rat skinfold window chambers as well as normal (i.e. non-tumour-bearing) preparations. Leucocyte rolling and adhesion were measured in terms of flux of rolling leucocytes (F(rolling)) and density of adhering leucocytes (D(adhering)) in microvessels. F(rolling) and D(adhering) were measured in two groups of preparations: irradiated and control. In normal preparations, F(rolling) and D(adhering) were both increased significantly by radiation. In contrast, in adenocarcinoma-bearing preparations, F(rolling) and D(adhering) were either unchanged (in the tumour centre) or reduced (in tumour periphery and the normal tissue surrounding the tumour) by radiation. Radiation did not cause changes in haemodynamics in these preparations, thus the observed changes in leucocyte rolling and adhesion could not be accounted for by haemodynamic factors. These results indicate that: (1) in normal preparations, radiation could cause inflammation as manifested by increased leucocyte rolling and adhesion; and (2) in tumour-bearing preparations, radiation caused changes in the vascular surface properties such that they became less adhesive to leucocytes. Such differences in radiation response may have important implications for radiation therapy and provide new insights into the unique features of tumours.

Adenocarcinoma↗
PubMed1994

The relation of sleep complaints to respiratory symptoms in a general population.

Based on data obtained from the Tucson Epidemiologic Study of Chronic Lung Disease that included body weight, questionnaire responses, and spirometry, we found that among subjects with no respiratory symptoms, 28.0 percent reported insomnia (difficulty initiating or maintaining sleep) and 9.4 percent reported daytime sleepiness. Among subjects with respiratory symptoms, cough and/or wheeze, the rates of sleep complaints increased. With one symptom, 39.1 percent reported insomnia and 12.4 percent reported daytime sleepiness. With both symptoms, the rates were 52.8 percent and 22.8 percent, respectively. Overall, we found significant relationships between rates of respiratory symptoms and sleep complaints (trend chi 2 = 73.9, p < 0.001 for insomnia; trend chi 2 = 37.9, p < 0.001 for daytime sleepiness). In separate analyses, obesity, snoring, and a diagnosis of lung disease also influenced the rate of sleep complaints but, when we employed logistic regression, we found that obesity, respiratory symptoms, gender, and age were the only variables related to the risk of insomnia or daytime sleepiness.

Adult↗
PubMed1994

Determinants of percent predicted FEV1 in current asthmatic subjects.

We analyzed the determinants of the percent predicted FEV1 of a large group of diagnosed asthmatic subjects in the Tucson Study of Airway Obstructive Diseases. The 261 subjects were 6 to 88 years old, and 150 (57.5 percent) were female. Although 29.1 percent of the subjects were current smokers and 24.1 percent were ex-smokers, we found that pack-years of smoking was not related to lung function. In addition, age of onset of disease, duration of asthma, eosinophil count, serum IgE level, and allergy skin test reactivity status did not influence the %FEV1. We did find that both severity of wheezing and age of the subject related significantly to %FEV1, and an interaction term of these two variables replaced wheeze and age in the multiple regression equation. Current physician-diagnosed chronic bronchitis and the reported severity of exertional dyspnea also related to %FEV1.

Adult↗
PubMed1994

Pentostatin treatment for hairy cell leukemia patients who failed initial therapy with recombinant alpha-interferon: a report of CALGB study 8515.

Eighty-five hairy cell leukemia (HCL) patients who had failed initial therapy with recombinant alpha interferon were enrolled for pentostatin therapy. All had HCL confirmed by central pathology review and were eligible for evaluation. The median age was 55 years (range 31-83 years). Fifteen patients were between 31- and 40-years-old. There were 72 males (85%) and 13 females (15%). Fifty-four patients (64%) had prior splenectomy. All had been previously treated with interferon; nine had achieved a complete response (CR), 36 had a partial response (PR), 35 had stable disease (SD), and five patients had progressive disease. Patients with a CALGB performance status (PS) of 0-2 (78 patients) received 4 mg/m2 i.v. on days 1 and 15, repeated every 4 weeks. Patients with a performance status of 3 or 4 (seven patients) were started at 2 mg/m2 i.v. in the absence of grade 3 toxicity, the dose was escalated. Complete responses were seen in 36 patients (42.4%) and 35 patients had partial responses (41.2%) for an overall response rate of 83.6%. Median time to best response was 6.5 months. Eight patients had stable disease, and one patient had progressive disease. Three patients died early during the treatment phase and two were not evaluable due to treatment violations. Of seven patients with a CALGB performance status of 3 or 4, there were no CRs and only two PRs. Of 31 evaluable PS 0-2 patients who had previously achieved only stable disease on interferon, 13 had a CR on pentostatin and 12 had a PR. Based on PS 0-2 patients, the median follow-up is 44 months and 36 month remission duration and survival rates and 95% confidence intervals are 84% (CI 68-93%) and 91% (CI 81-96%). The 36 month survival rate was 29% (CI 10-58%) for PS 3-4 patients. Drug dosage was modified in 39 (51%) of 76 evaluable patients. Leukopenia and/or infection were the most frequent toxicities leading to a dose modification. Pentostatin is an effective agent and induces an excellent response in relapsed HCL patients previously treated with alpha-interferon (alpha-IFN).

Adult↗
PubMed1993

A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery.

OBJECTIVE: Our aim was to determine the relative efficacy and complications of low-dose heparin and intermittent pneumatic calf compression for the prevention of postoperative venous thrombosis in patients undergoing surgery for gynecologic malignancy. STUDY DESIGN: Randomized trial comparing 107 patients treated with low-dose heparin to 101 patients treated with intermittent pneumatic calf compression was performed. All patients were evaluated with iodine-125 fibrinogen scanning of the legs. Clinical and laboratory variables associated with bleeding complications were recorded prospectively. RESULTS: Venous thrombosis was diagnosed in seven patients receiving low-dose heparin and in four receiving intermittent pneumatic calf compression (p = 0.54). Low-dose heparin patients received more blood transfusions postoperatively (p = 0.02), had increased volume of retroperitoneal drainage (p = 0.02), and the activated partial thromboplastin time was more frequently prolonged (p = 0.001). CONCLUSIONS: Low-dose heparin and intermittent pneumatic calf compression provide similar reduction in reducing the incidence of postoperative venous thrombosis. However, low-dose heparin is more frequently associated with postoperative bleeding complications.

Aged↗
PubMed1993

Antecedent features of children in whom asthma develops during the second decade of life.

In this report we compare 36 subjects in whom asthma was first diagnosed between the ages of 10 and 20 with 297 control subjects. All subjects were studied at age 5 to 9. Among the subjects who acquired a new diagnosis of asthma (NDA), the diagnosis was usually preceded by lower respiratory tract symptoms (31 of the 36 subjects had respiratory symptoms or a diagnosis of rhinitis or chronic bronchitis before asthma developed). Among those tested, more of those with NDA had positive allergy skin test results (56.5%) before diagnosis than control subjects (29.6%; p < 0.05), and the subjects with NDA had higher levels of serum IgE than control subjects (mean log serum IgE = 2.27 in subjects with NDA, 1.76 in control subjects; p < 0.05). Pulmonary function tests revealed no significant differences in the groups before diagnosis. Using logistic regression, we determined that wheezing, cough, a diagnosis of chronic bronchitis, and a positive allergy skin test result were independent risk factors for asthma. When combinations of variables were used, subjects with wheezing and a positive allergy skin test result, cough and a positive test result, and also those with a prior diagnosis of chronic bronchitis alone were at highest risk of a subsequent diagnosis of asthma.

Adult↗
PubMed1993

Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy.

OBJECTIVE: The authors determined whether microscopically positive surgical margins are detrimental to the outcome of early stage breast cancer patients treated with conservation surgery and radiation therapy. SUMMARY BACKGROUND DATA: The optimal extent of breast surgery required for patients treated with conservation surgery and radiation therapy has not been established. To achieve breast preservation with good cosmesis, it is desirable to resect as little normal tissue as possible. However, it is critical that the resection does not leave behind a tumor burden that cannot be adequately managed by moderate doses of radiation. It is not known whether microscopically positive surgical margins are detrimental to patient outcome. METHODS: The records of 259 consecutive women (262 breasts) treated with local excision (complete removal of gross tumor with a margin) and axillary dissection followed by radiation therapy for clinical stage I and II infiltrating ductal breast cancer at Duke University Medical Center and the University of North Carolina between 1983 and 1988 were reviewed. Surgical margins were considered positive if tumor extended to the inked margins; otherwise the margins were considered negative. Margins that could not be determined, either because the original pathology report did not comment on margins, or because the original specimen had not been inked were called indeterminate. RESULTS: Of the 262 tumors, 32 (12%) had positive margins, 132 (50%) had negative margins, and the remaining 98 (38%) had indeterminate margins. There were 11 (4%) local failures; 3/32 (9%) from the positive margin group, 2/132 (1.5%) from the negative margin group, and 6/98 (6%) from the indeterminate group. The actuarial local failure rates at 5 years were 10%, 2%, and 10%, respectively, p = 0.014 positive vs. negative, p = 0.08 positive vs. indeterminate (log rank test). Margin status had no impact on survival or freedom from distant metastasis; 63 patients who originally had positive or indeterminate margins were re-excised. Two of 7 with positive margins after re-excision versus 1/56 rendered margin negative had a local recurrence. CONCLUSIONS: The authors recommend re-excision for patients with positive margins because of improved local control of those rendered margin negative and identification of those patients at high risk for local failure (those who remain positive after re-excision). Because margin status impacts on local control, tumor margins after conservation surgery should be accurately determined in all patients.

Adult↗
PubMed1992

Diminished leukocyte-endothelium interaction in tumor microvessels.

Leukocyte-endothelium interaction in vivo consists of the rolling of leukocytes along the vascular wall and, under certain conditions, their adherence to endothelial cells. In a rat tumor microcirculation model (mammary adenocarcinoma implanted in rat skinfold window chamber), we demonstrated that this interaction, measured as flux of rolling leukocytes and density of adhering leukocytes, was significantly reduced in tumor microvessels compared to normal microvessels, both under control conditions and during inflammation induced by N-formylmethionylleucylphenylalanine (1 microM), bacterial lipopolysaccharide (1 microgram/ml), or tumor necrosis factor alpha (500 units/ml). We also measured the blood flow shear rate in the tumor and normal microvessels and found that the difference in shear rate between the two types of microvessels could not account for the differences in leukocyte-endothelium interaction. The diminished leukocyte-endothelium interaction in tumors under various stimulated conditions suggests that a number of adhesion molecules may not be expressed properly on tumor endothelial cells.

Adenocarcinoma↗
PubMed1992

Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990.

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus.

Adenocarcinoma↗
PubMed1992

Basal cell carcinoma treated with Mohs surgery. A comparison of 54 younger patients with 1050 older patients.

The average age of patients with basal cell carcinoma (BCC) is over 60 years, and fewer than 5% of patients with this tumor are under 30 years of age. A comparison of younger (15 to 30 years) and older (56 to 70 years) patients with BCC was conducted to identify specific tumor or host features associated with BCC occurring early in life. According to data collected over an 11-year period, 54 of 2728 (2%) BCCs occurred "de novo" in younger patients. In contrast to the predominantly male older group, most of the younger patients were female. An increased use of tanning booths and hair-dyes was associated with the younger patients (P less than .001). More overall sunlight exposure and actinic keratoses were associated with the older patients (P less than .01). Defect and lesion sizes were smaller (P less than .01) in the younger group. Location, histology, and clinical morphology did not differ appreciably between the two groups. De novo BCCs in younger and older patients are similar, although some differences do exist.

Adult↗
PubMed1992

Improved palliation of cerebral metastases in epithelial ovarian cancer using a combined modality approach including radiation therapy, chemotherapy, and surgery.

PURPOSE: Recent reports suggest an increasing incidence of CNS metastases in patients with ovarian cancer. We reviewed our experience in the management of brain metastases from ovarian carcinoma and merged our results with those of several other series reported in the literature to determine prognostic factors and the role of chemotherapy, radiation therapy, and surgery. PATIENTS AND METHODS: From 1977 to 1990, 15 of 795 patients who were treated for epithelial ovarian cancer at Duke University developed brain metastases. Fourteen of the patients were treated for their brain metastases; this included radiation therapy (RT; four), surgery and RT (one), RT and systemic chemotherapy (six), and all three treatment modalities (three). A meta-analysis was performed that combined the data from the current series with those of several recent clinical series that reviewed patients with brain metastases from ovarian carcinoma (67 patients total) to elucidate the impact of treatment and extent of disease on survival. RESULTS: In the current series, median survival (MS) after the diagnosis of brain metastases was 9 months. For the combined series, MS was 5 months. Thirteen patients who were treated with whole-brain RT and systemic chemotherapy (MS, 7 months), 10 patients who were treated with RT and surgery (MS, 10 months), and nine patients who were treated with all three modalities (MS, 16.5 months) had significantly longer survival than 19 patients who were treated with RT alone (MS, 3 months) (P = .05, P = .01, and P < .001, respectively). In a multivariate analysis, the only variable that provided prognostic information was treatment, namely the addition of systemic chemotherapy or surgery to RT for the treatment of brain metastases. CONCLUSION: Multimodal treatment of patients with brain metastases from ovarian cancer can result in significant palliation.

Adult↗
PubMed1992

Radical hysterectomy in obese women.

OBJECTIVE: To determine whether there is a significant difference in treatment outcome and acute and chronic complications in obese compared with non-obese women having radical hysterectomy for early-stage cervical cancer. METHODS: From 1970-1985, 320 women underwent a class III radical hysterectomy and pelvic lymphadenectomy for stage IB-IIA invasive cervical cancer at Duke University Medical Center. Forty-three of these women weighed at least 80 kg and had a body weight greater than 25% above their ideal predicted weight. These women were compared to 277 patients with normal weight for height. RESULTS: The median age, incidence of diabetes mellitus and hypertension, number of nodes removed at lymphadenectomy, disease-free survival, length of hospital stay, and serious surgical or medical complications were the same in the two groups. However, obese patients had a significantly higher estimated blood loss, greater incidence of transfusion, and longer operative times. CONCLUSIONS: Survival is not compromised and the incidence of serious complications is not increased in obese patients treated with radical hysterectomy, but the operative technique is more difficult, the procedure lasts longer, and the surgery is associated with greater blood loss.

Adult↗
PubMed1992

Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber.

Fischer 344 rats with R3230 Ac mammary carcinomas implanted in dorsal flap window chambers served as a model to obtain measurements of perivascular and stromal oxygen tension in normal and tumor tissues using Whalen recessed-tip microelectrodes (3- to 6-microns tip). Perivascular measurements were made adjacent to vessels with continuous blood flow. Thus the measurements and models provided are reflective of conditions leading to chronic hypoxia. Perivascular oxygen tensions averaged 72 +/- 13 mmHg in normal tissue vessels adjacent to tumor, 26 +/- 5 mmHg in tumor periphery, and 12 +/- 3 mmHg in tumor central vessels. There was a significant trend toward lower perivascular oxygen tensions in the tumor center (Kruskal-Wallis test, P = 0.002). A similar tendency was seen with a limited number of stromal measurements. Krogh cylinder models, which incorporate these data for perivascular oxygen tension, along with morphometric data obtained from the same tumor model suggest that hypoxic regions will exist between tumor vessels in the tumor center unless O2 consumption rates are well below 0.6 ml/100 g/min. The low perivascular measurements observed near the tumor center combined with the theoretical considerations suggest, for this model at least, that tissue oxygenation may best be improved by increasing red cell velocity and input pO2 and reducing oxygen consumption. The low perivascular oxygen tensions observed near the center also suggest that conditions conducive to increased red cell rigidity exist, that drugs which can decrease red cell rigidity could improve tumor blood flow and oxygenation, and that the endothelium of those vessels may be susceptible to hypoxia-reoxygenation injury.

Animals↗
PubMed1992

Adjuvant therapy with intraperitoneal chromic phosphate (32P) in women with early ovarian carcinoma after comprehensive surgical staging.

From 1974-1990, 23 women with stage I and five with stage II epithelial ovarian carcinoma received intraperitoneal chromic phosphate (32P) as the only form of adjuvant therapy after complete debulking and comprehensive surgical staging laparotomy. Surgery consisted of total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, peritoneal washings for cytology, multiple biopsies of pelvic and abdominal peritoneum, and selective pelvic and para-aortic lymphadenectomy. Intraperitoneal 32P therapy was administered a median of 7 days after laparotomy. Significant toxicity was minimal; none of these patients required surgery for bowel obstruction. Overall 5-year survival was 90 and 100%, but disease-free survival was only 65% (95% confidence interval [CI] 36-86%) and 60% (95% CI 12-81%) for patients with stage I and II disease, respectively. Two patients developed intraperitoneal and six systemic relapses; all patients received cisplatin regimens after relapse. Univariate analysis of age, stage, histology, Ovarian Cancer Study/Gynecologic Oncology Group risk status, lesion size, and presence or absence of capsular adhesions revealed that only an age of 50 or more years had an adverse effect on disease-free survival (P less than .03). This study suggests that determination of early-stage disease and host-tumor biology may be the most important factors in determining the survival of women with early ovarian cancer defined by comprehensive surgical staging. Intraperitoneal 32P does not appear to be effective adjuvant therapy in these women.

Adult↗