Ureteric kinking after colposuspension: a case report and review of the literature.
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Adult↗
Biomedical subjects
D A Sim
Publications and source records attributed to D A Sim.
Local-regional recurrence in breast cancer after mastectomy and adriamycin-based adjuvant chemotherapy: evaluation of the role of postoperative radiotherapy.
In an attempt to determine whether patients treated for breast cancer with radical or modified radical mastectomy and adjuvant chemotherapy benefit from postoperative radiotherapy, 400 women with Stages II-III breast cancer who received adjuvant chemotherapy based on the combination of Adriamycin and Cytoxan were analyzed retrospectively. Prognostic features which predicted a high risk of isolated local-regional relapse were identified. Thirty-eight percent of these patients were also treated with postoperative radiation in addition to adjuvant chemotherapy and were compared to those patients treated only with adjuvant chemotherapy. With a median follow-up of 60 months, 15% of the patients reviewed developed local-regional disease as the first site of relapse without concommitant systemic relapse. When examined univariately, stage of disease, tumor size, nodal status, and estrogen receptor status were strong prognostic variables. Age, cell type, location of tumor within the breast, menstrual status, radiation dose, and type of treatment were not significantly related to isolated local-regional relapse. However, patients who received postoperative radiation were significantly more advanced in their disease condition. When the factors were examined multivariately, the type of treatment along with stage of disease were found to be statistically significant prognostic indicators. About half of the patients were tested for estrogen receptor status. Multivariate analysis performed on this subset of patients showed that estrogen receptor status, type of treatment, and axillary nodal status were significant predictors of the risk of isolated local-regional relapse. This study suggests that patients treated with mastectomy and Adriamycin and Cytoxan-based adjuvant chemotherapy may benefit from postoperative radiation in reducing the risk of isolated local-regional recurrence.
Antineoplastic Combined Chemotherapy Protocols↗
Randomized trials in orthopaedics: why, how, and when?
There is increasing recognition that major new medical therapies should be rigorously evaluated before they are put into general clinical use. Randomized controlled trials provide the most unbiased assessment of the risks and benefits of such therapies. In this article, the most important aspects of the design and execution of a randomized clinical trial in orthopaedics are discussed. These include the reasons for and mechanisms of randomization, appropriate selection of patients and therapy, reasons for the blinding of therapy, types of measures of outcome that can be used, aspects of sample-size calculation and analysis of data, and ethics of randomized controlled trials.
Cementation↗
Unexpected toxicity associated with use of body surface area for dosing melphalan in the dog.
A multiinstitutional Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was administered at 7.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, less than 1500/mm3; and/or thrombocytopenia, less than 80,000/mm3), whereas only three of 13 dogs (23%) weighing greater than 14 kg developed severe myelosuppression (P = 0.016). We concluded that small dogs are at greater risk of developing bone marrow toxicity from i.v. melphalan than large dogs if body surface area is used to calculate the dose. Although both body surface area and weight were found to be significantly correlated with severity of toxicity, melphalan-induced toxicity in dogs can be more accurately estimated by body weight than by surface area, P = 0.008 versus P = 0.022, respectively. It may be necessary to prescribe antineoplastic agents that are eliminated by processes not primarily under metabolic influence or that produce side effects on tissue not correlated to basal metabolic rate on a parameter other than body surface area. In dogs, melphalan should be dosed on a weight basis, and treatment groups should be stratified by weight in randomized clinical studies, particularly when the weight range of treated subjects is great.
Animals↗
Influence of the duration of topical 13-cis-retinoic acid treatment on inhibition of mouse skin tumor promotion.
The effect of the time and duration of retinoid treatment on the inhibition of Stage II tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) was studied in CD-1 mice. All mice were initiated with 400 nmol of benzo(a)pyrene and received Stage I tumor promotion (3.2 nmol of TPA twice weekly for 2 wk). Animals were then randomized into groups which received 13-cis-retinoic acid during early, middle, or late Stage II promotion. 13-cis-Retinoic acid pretreatments starting on Day 1, Wk 8, or Wk 23 of Stage II promotion resulted in 47, 28, or 19% inhibition, respectively, of TPA-induced tumor formation. One-half of the mice receiving 13-cis-retinoic acid at Day 1 or Wk 8 were removed from the retinoid treatments at Wk 23, the time of cessation of TPA promotion. The inhibition of tumor formation remained constant during the 15-wk observation period after cessation of retinoid treatment, suggesting that retinoid inhibition of mouse skin tumor promotion is stable in the absence of further promotion and preceded the step of irreversible conversion of promoter dependence to promoter independence.
9,10-Dimethyl-1,2-benzanthracene↗
Cervical Chlamydia trachomatis infection in university women: relationship to history, contraception, ectopy, and cervicitis.
Endocervical Chlamydia trachomatis infection was found in 13 of 162 volunteer female university students (8%). Infection was correlated with younger age (p less than 0.05), less than or equal to 4 years of intercourse (p less than 0.05), a history of gonorrhea (p less than 0.01), and exposure to a partner with urethritis (p less than 0.01). Women who used intrauterine or barrier contraception had less infection (2%) than did women who used oral contraception (14.3%, p less than 0.05) or none at all (10.7%, p less than 0.05). Infection was strongly associated with a cervicitis score calculated from erythema, ectopy, discharge, and secretions that contained white blood cells (p less than 0.0001). By multivariate analysis, a proposed clinical approach was arrived at for testing for chlamydial organisms all women with cervicitis who were not using barrier contraception. The positive predictive value of this approach for chlamydial infection was 28%, and the negative predictive value 98.4%. Cervical ectopy was increased in women who used oral contraception (p less than 0.01), and infection was increased in women with ectopy, regardless of their contraceptive method (p less than 0.001). These results will aid in more rapid diagnosis of endocervical chlamydial infection and in the choice of contraception in young women and high-prevalence groups.
Adolescent↗
Analysis of prognostic variables in hyperthermia treatment of 161 patients.
From 1977-1982, 161 patients were treated using hyperthermia as an adjuvant in Phase I trials. Microwave applicators (MW), capacitively coupled plates (RF plates), interstitial localized current fields (LCF), and magnetic induction heating (MI) techniques were used together with radiation in 135 patients, with chemotherapy in 10 patients, and alone in 16 patients. Tumor volume response categories were no response (NR, less than 50% decrease); partial response (PR, 50% less than or equal to volume decrease less than 100%); and complete response (CR, complete disappearance). The CR rates and total response rates (CR + PR) were 38/160 (24%) and 90/160 (56%), respectively. There were highly significant differences among techniques in CR vs PR + NR (p = .001), and in CR + PR vs NR (p less than .0005). Response did not vary significantly with histologic category. Overall toxicity was 16%, and did not vary significantly with technique (p = .193). In the patient group treated with hyperthermia and radiation, multivariate analysis revealed that a set of three variables had prognostic importance for CR: technique (p = .011), radiation dose (p = .019), and tumor volume (p = .001, negatively correlated). A good correlation also existed between CR and the minimum tumor temperature averaged over all treatments, TMIN (p less than .0005). Temperature variables themselves were correlated with tumor volume. Minimum T correlated negatively with volume (p = .017) and TMAX correlated positively with volume (p = .026). In fewer than 50% of patients could minimum T greater than 40.7 degrees C be achieved. Our conclusions are: TMIN, tumor volume, radiation dose, and heating technique have prognostic value for initial response; variation in CR vs technique reflects variation in tumor volume treated and in minimum temperature achieved with these techniques; and acute toxicity of treatment is infrequent, but serious toxicity is possible with the interstitial technique.
Aged↗
Analysis of prognostic variables which influence early and long-term response of pet animal tumors to radiation alone and radiation plus heat.
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Adenocarcinoma↗
A review of the University of Arizona human clinical hyperthermia experience.
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Adenocarcinoma↗
The utility of thermal dose as a predictor of tumor and normal tissue responses to combined radiation and hyperthermia.
A total of 236 dogs and cats with a variety of cancers were randomized to receive radiation (XRT) or heat plus XRT. In those tumors which were heated, thermal gradients developed which varied in temperature minima and maxima. The influence of the thermal gradient characteristics on tumor and normal tissue responses was examined by correlation of response with the magnitude of gradient minima and maxima. Using multivariate analysis, the influence of other factors such as tumor histology, volume, site, heat treatment method, and number of heat fractions on tumor response was examined. Of all factors examined, tumor volume and non-site-specific average minimum equivalent min at 43 degrees emerged as consistent predictors of both complete response rate (p less than 0.001) and duration response (p less than 0.05). No significant enhancement of moist desquamation or late fibrosis was seen for heat + XRT versus XRT alone. The incidence of direct thermal injury to skin was positively correlated with maximum intratumoral equivalent min at 43 degrees. These results indicate that a therapeutic gain is achievable with heat + XRT, but successful application of the therapy is dependent on achieving high tumor thermal gradient minima and low maxima.
Animals↗
Importance of minimum tumor temperature in determining early and long-term responses of spontaneous canine and feline tumors to heat and radiation.
A total of 130 dogs and cats with squamous cell carcinomas, melanomas, fibrosarcomas, mammary adenocarcinomas, or mast cell sarcomas were randomized to receive radiation (XRT) or heat plus XRT. Time-temperature data for each monitored tumor location were converted to degree-minutes or equivalent min at 43 degrees (Eq43). Response rates and durations of response were compared for subgroups of histology, volume, site, and heat treatment method. Thermal gradients existed in all heated tumors. The influence of these gradients on tumor response was examined by correlation of response with degree-minutes and Eq43 minima, maxima, averages, and ranges. A pattern emerged from these analyses linking dose minima, maxima, and ranges with prognostic subgroups as classified by volume, site, or treatment method. The data indicated that the coolest part of the tumor governed the biological response to combined heat + XRT. Tumors which received a minimum of 35 Eq43 had significantly longer durations of response than did those receiving XRT alone or less than 3 Eq43 (p less than or equal to 0.006 and 0.014, respectively; log-rank test). Furthermore, broad temperature ranges were associated with power-limiting "hot spots" and invariably led to underheating in other areas of tumor. Multivariate analysis found minimum Eq43 on the first treatment to be the best predictor of long-term response (p less than 0.05). Other biological covariates of site, volume, and histology contributed strength to the model, which was independent of Eq43 (p less than 0.05).
Animals↗
Regional hyperthermia by magnetic induction in a beagle dog model: analysis of thermal dosimetry.
We have investigated magnetic induction heating techniques for achieving normal tissue hyperthermia in a beagle dog model to clarify the physics and physiology of "regional heating," to develop an animal model of regional heating in humans, and to develop a method of rapid regional heating in dogs for a normal visceral tissue toxicity study. Heating was done with a concentric coil or a coaxial pair of coils applied to the abdominal region, and with or without surface cooling blankets in each case. Thermometers were placed at multiple visceral and subcutaneous sites including an intraarterial thermocouple at the aortic arch level. With either electrode arrangement and no surface cooling, whole-body hyperthermia ( WBH ) at 42 degrees C was produced within 30 to 55 min with 250 W applied power; the 42 degrees C state could be maintained with 40 to 60 W of power. Thermal gradients in these cases reflected nonuniform power deposition superimposed upon arterial temperature elevation. With surface cooling blankets added, systemic heating was significantly reduced, and temperature gradients again reflected the nonuniform power deposition. Regional heating in a dog produces WBH unless sufficient surface cooling is used to provide a heat dissipation rate balancing the heat absorption rate; this latter case best models the use of inductive techniques in humans. The coaxial pair of coils, without surface cooling, produced rapid WBH and the visceral temperature maximum and minimum were within Tesoph + 0.21 degrees C and Tesoph - 0.07 degrees C, respectively (95% confidence index; Tesoph = esophageal temperature). This is an appropriate technique for the proposed toxicity study.
Animals↗
Cervical Chlamydia trachomatis and mycoplasmal infections in pregnancy. Epidemiology and outcomes.
In a prospective study of chlamydial and mycoplasmal infections in pregnancy, Chlamydia trachomatis occurred in 8.0%, Mycoplasma hominis in 23.5%, and Ureaplasma urealyticum in 72.3% of 1,365 enrollees. By multivariate analysis, C trachomatis was correlated with lower socioeconomic status, age 23 years or younger, and 12 years or less of schooling. Ureaplasma urealyticum was correlated with age 23 years or younger and lower socioeconomic status. Mycoplasma hominis was correlated with more than one recent sexual partner, first intercourse at age 17 years or younger, and higher socioeconomic status. These cervical infections did not predict low birth weight, abortion, stillbirth, prematurity, or premature rupture of membranes. Only M hominis predicted endometritis/fever after vaginal delivery (relative risk, 7.3). IgM-seropositive C trachomatis-infected women had more low-birth-weight infants and more premature rupture of membranes than either IgM-negative C trachomatis-infected women or C trachomatis culture-negative women. Thus, only certain subgroups of infected women may experience adverse pregnancy outcomes.
Adult↗
Dose-rate dependence of heat radiosensitization.
The dose rate dependence of heat radiosensitization was studied using rat astrocytoma cells in culture and a clinically relevant protocol of heat dose and heat radiation sequence. Cells were treated with a minimally toxic heat dose of 43 degrees C for 30 minutes, after which they were irradiated with varying doses of radiation at dose rates ranging from 0.567 to 300 cGy/min. This heat dose substantially reduced the extrapolation number (n), but had little effect on Do of the radiation survival curve at dose rates of 50 cGy/min or greater. At dose rates less than 10 cGy/min, 43 degrees C for 30 min had little effect on n and only for the lowest dose rate studied (0.567 cGy/min) was there a significant reduction in Do (60%). The thermal enhancement ratio did not vary inversely with radiation dose rate over the dose rate range studied but, instead, was maximal at the two dose rate extremes (0.567 and 300 cGy/min). These data demonstrate that a clinically relevant heat dose enhances very low dose rate, as well as high dose rate, ionizing radiation, but suggest that little benefit is to be gained from using dose rates intermediate between conventional radiotherapeutic high dose rates or dose rates representative of interstitial implants.
Animals↗
Correlation between initial and long-term responses of spontaneous pet animal tumors to heat and radiation or radiation alone.
Most early-phase testing of new therapeutic modalities involves analysis of initial tumor response as opposed to estimation of long-term response. In this study, the validity of initial response rates to predict long-term responses was examined for tumors treated with radiotherapy alone compared with heat combined with radiotherapy. A total of 130 pet animals with either squamous cell carcinomas, melanomas, fibrosarcomas, mammary adenocarcinomas, or mast cell sarcomas were randomized to receive either radiation alone (XRT) or heat + radiation (delta + XRT). Responses to treatment were evaluated by response rates and response duration. The complete response (CR) rates were consistently higher for delta + XRT than for XRT across different histology groups. The combined therapy led to prolonged tumor response in all histological subgroups except melanomas, which had a longer response duration when treated with XRT alone (p = 0.043). This was in spite of a relatively high CR rate in that group (100% versus 12.5% for delta + XRT and XRT, respectively). In contrast, while no significant improvement in CR rate was observed for dermal squamous cell carcinomas treated with delta + XRT (XRT = 52.9%; delta + XRT = 68.8%), a significant improvement in response duration was noted (p = 0.002). These are two examples where CR rate did not predict long-term response. When all histological subgroups were combined (except melanomas), the CR rate was higher (p less than 0.001), and response duration was prolonged (p = 0.031) for delta + XRT compared to XRT alone.
Animals↗
Preliminary results of a phase III trial of spontaneous animal tumors to heat and/or radiation: early normal tissue response and tumor volume influence on initial response.
A Phase III randomized trial was initiated to test the relative efficacies of heat alone, radiation alone and heat plus radiation using spontaneous malignancies in pet animals. Heat alone was inferior to the other two treatment arms as demonstrated by a significantly higher non-response rate and shorter response duration. The ratio of complete response rates (CR) for heat plus radiation to radiation alone or the thermal relative risk (TRR) was greater for tumors greater than 10 cm3 as compared to those less than 10 cm3 (TRR = 4.8 and 1.4, respectively). The overall TRR for complete responses was 2.3. The CR data for the combined therapy arm indicate at least an additive effect between heat and radiation for small tumors but most likely a synergistic effect in the larger tumor group. Based on the data currently available, no significant difference in response duration is observed between the two radiation arms, although a nonsignificant advantage to the combination therapy exists. Normal tissue effects were evaluated by incidence of full moist desquamation within the irradiated volume, late fibrosis and bone necrosis. Since the radiation skin dose depended upon the technique being used it was possible to estimate the dose to achieve moist desquamation in 50% of the animals (DD50) by a logistic regression model as being 3728 +/- 344 rad for radiation alone. Significant lowering of the DD50 was not observed for the addition of heat to radiation. Low patient numbers where intact skin was heated prevented an accurate analysis of the effect, however.
Animals↗
Risk factors and angiographic coronary artery disease: a report from the coronary artery surgery study (CASS).
The findings for 14 risk variables were correlated with the results of coronary arteriography in 8807 patients registered in the interinstitutional Coronary Artery Surgery Study (CASS). Discriminant-function analysis revealed that age, sex, cigarette smoking and the level of blood cholesterol best distinguished between the groups with (6688 patients) and without (2119 patients) coronary artery disease. A family history of coronary artery disease and the presence of hypertension or diabetes were of addition, but less, discriminating value. The relative risk for coronary artery disease in patients with the combination of cigarette smoking and an elevated cholesterol level was high (> 4) in females age 55 years or younger and in males age 35 years or younger. Few females age 45 years or younger (seven of 97) had coronary artery disease when both of these risk factors were absent. In spite of these correlations, only limited gains accrued from the use of discriminant-function analysis in correctly allocating patients into disease and nondisease groups. This indicates that, while certain factors are significantly correlated with coronary arteriographic findings, their value for predicting the presence of coronary artery disease is limited.
Adult↗
Local control and distant metastases in primary canine malignant melanomas treated with hyperthermia and/or radiotherapy.
Forty-three dogs with primary malignant melanoma were randomized to receive radiotherapy alone (XRT) or hyperthermia plus radiotherapy (delta + XRT). Tumour responses were analysed in terms of complete response rates, rate of one year disease free survival and the incidence and time to develop distant metastasis. The frequency of complete responses (CR) was greater with adjuvant heat (76 per cent vs 21 per cent for XRT; P = 0.001). A trend towards an improvement in one year disease free survival was observed with delta + XRT (23.8 per cent) as compared with XRT (7.7 per cent), but the difference was not statistically significant. The frequency of distant metastases was not different between the two treatments. Descriptors of intratumoural temperatures achieved during therapy indicated that higher CR rates could be achieved with higher minima. When minima were less than and greater than 20 Equivalent minutes at 43 degrees C (Eq43) the CR rates were 64 and 90 per cent, respectively. One year disease free survival rates and frequencies of distant metastases seemed to be correlated with the intratumoural temperatures as well. This was reflected in analyses examining temperature minima and maxima. Examination of patterns of failure suggested that the most plausible explanation for the correlation between intratumoural temperature and metastases was the high local failure rate (70 per in the heated group). The results of this study emphasize the need for further investigation of the influence of local hyperthermia as a part of curative therapy on the frequency of distant metastases.
Animals↗