Biomedical subjects
Publications and source records attributed to B W Brown.
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.
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The monitoring of accumulating data in a clinical trial is a challenging endeavor, yet one that must be undertaken to fulfill the ethical responsibility to the participating subject. This paper, using the Nocturnal Oxygen Therapy Trial as an example, discusses three issues often faced by data monitoring committees. These are (1) the multiplicity of outcomes, (2) decisions about extension of the patient recruitment period in order to achieve specified sample size goals, and (3) problems in monitoring survival data with a lag in the reporting of events. The decision process can be quite complex and existing statistical methodology can at best serve as a guide in this decision process.
In six anaesthetized, non-pregnant ewes, uterine blood flow rates measured by monitoring the clearance of xenon (133Xe) from the lumen of the uterus were compared with estimates of endometrial and myometrial capillary blood flow obtained by the use of microspheres of 15 micron diameter (eleven comparisons). On analysis, seven of the 133Xe clearance curves indicated the occurrence of both a fast and a slow compartment of flow with flow rates approximating to the rate of capillary blood flow in the caruncular and inter-caruncular portions of the endometrium, respectively. In each of the remaining four curves which provided a single estimate of flow, the derived blood flow rate was similar to the rate of capillary blood flow in both the caruncular and inter-caruncular portions of the endometrium. No relationship existed between myometrial capillary blood flow and the flow rates derived from the 133Xe clearance curves.
Total uterine blood flow was measured with a tritiated water (TOH) diffusion method and with radioactive microspheres in six, conscious, pregnant ewes. With continuous infusion of TOH, equilibrium between the TOH concentration in utero-ovarian venous blood and arterial blood was attained within 50 min of the start of the infusion. The concentration of TOH in uterine and foetal tissue and in foetal blood water was the same as that in uterine venous water by 40 min; at this time, the concentration of TOH in the water of amniotic and allantoic fluids was 96% of that in uterine venous blood water. Estimates of total uterine blood flow obtained using TOH were highly correlated with those obtained with microspheres (r = 0.889, P less than 0.001, n = 8) and the corresponding mean (+/- s.e.m.) flow values obtained with the two techniques (1030.5 +/- 110.6 and 1006.2 +/- 100.0 ml min-1, respectively) did not significantly differ. The percentage of the total uterine blood flow passing through arteriovenous anastomoses ranged from 1.4 to 3.3%.
Patients with stages O and I malignant melanomas of the trunk and proximal limbs, having had wide excisions only without lymph node dissections, were reviewed to determine whether the presence or absence of muscle fasciae correlated with prognosis. Prior to 1969 most patients seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston with primary melanomas underwent wide excision of their lesions including muscle fasciae; however, after 1969 the fasciae were not resected in most patients. Records of 107 patients in whom fasciae were excised and 95 patients in whom fasciae were preserved, all with 5-year follow-up, were analyzed. Although a trend was present in favor of the patients in whom the fascia was removed (20% regional recurrence rate versus 25%), the incidence of subsequent recurrence, site of recurrence, and survival were not statistically different between the two groups. This review has not confirmed the hypothesis that the excision of muscle fasciae correlates with recurrence or survival in patients treated for primary malignant melanoma.
The pathologic material from 256 patients with malignant melanoma of the limb seen between 1955 and 1969 was reviewed to correlate the clinical course of the disease with the microstage, in an attempt to determine whether treatment factors affect the course of the disease. Rates of disease recurrence observed during the ten-year follow-up period were: Level II--19%, III--33%; IV--54% and V--94%, while for measured depths the recurrence rates were less than 0.5 mm--18%; 0.5 to 1 mm--26%; 1 to 1.5 mm--44%; 1.5 to 2 mm--49%; 2 to 3 mm--78% and greater than 3 mm--74%. For those patients with Level II melanomas, or Level III less than 1 mm, there was no difference in disease recurrence or survival, whether they were treated by wide local excision, with or without lymph node dissection, or by regional chemotherapy. For the more deeply invasive melanomas, rates of disease recurrence, survival and time to recurrence were all statistically better for those treated by regional therapy, confirming a treatment effect for malignant melanoma patients.
Blood flow rates to a hind limp preparation, consisting predominantly of muscle, were obtained with tritiated water (TOH) diffusion and radioactive microsphere technique in four conscious ewes (a total of seven comparisons). During the continuous infusion of TOH, equilibrium between muscle and its venous drainage was attained by 40--60 min after the start of the infusion. Total blood flow to the hind limb measured using TOH was corrected for arteriovenous anastomosis flow to provide a measure of capillary blood flow through the hind limb. The capillary blood flow rates so obtained using TOH were highly correlated with those measured directly in muscle with microspheres (ml min-1, r = 0.934; ml 100 g-1 min-1, r = 0.886, P less than 0.01, n = 7) and the corresponding mean flow values obtained with the two techniques (respectively, 104.6 +/- 15.1 v. 106.5 +/- 14.9 ml min-1 and 7.2 +/- 0.8 v. 7.3 +/- 0.8 ml 100 g-1 min-1) were not significantly different. There were substantial difference in the capillary blood flow rates for the individual muscles of the hind limb.
Vessels with histological features characteristic of arterio--venous anastomoses were found in the stroma but not in CL. In 5 conscious ewes at the mid-luteal stage of the oestrous cycle, ovarian blood flow was significantly greater (P less than 0.025) with microspheres of 50 than of 15 micrometers diameter in ovaries without CL (0.23 +/- 0.04 (s.e.m.) and 0.11 +/- 0.02 ml/min, respectively), but not in ovaries with CL (4.42 +/- 0.86 and 3.73 +/- 0.70 ml/min, respectively). In 5 similar but anaesthetized ewes, the portion of each ovarian artery within the ovarian vascular pedicle was bypassed with re-entrant catheters through which microspheres were perfused. A greater proportion (P less than 0.01) of 50 than of 15 micrometers microspheres was retained in ovaries with (90 and 79%) or without (82 and 45%) a CL. It is concluded that functional arterio--venous anastomoses are present in sheep ovaries.
Questionnaires, mailed to approximately 30,000 dentists and an equal number of dental assistants requesting information regarding professional exposure to anesthetics and health problems, showed an increased incidence of neurologic complaints in dental professionals who worked with nitrous oxide. The most striking differences were noted in individuals reporting symptoms of numbness, tingling, and/or muscle weakness. For dentists heavily exposed to nitrous oxide, the rate of these complaints was 4-fold greater than for nonanesthetic-exposed dentists. For dental assistants heavily exposed to nitrous oxide, a 3-fold increase in these same complaints was noted. In view of recent evidence that nitrous oxide abuse may lead to polyneuropathy, the results suggest that occupational exposure to nitrous oxide by both dentists and dental assistants may be associated with similar neuropathy.
Between 1975 and 1978, 51 patients with favorable histology non-Hodgkin's lymphomas, pathologic stage III-IV, were treated prospectively on a randomized treatment protocol. Treatment options were single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP), or fractionated whole body irradiation followed by low dose involved field irradiation. The median follow-up interval in this group of patients is not 41 mo. Actuarial survival is excellent, 84% at 4 yr for the entire group, with similar survival observed for each of the three treatment options. Initial complete remission rates (64%, 88%, and 71%) were not significantly different in the three treatment arms. Frequent relapse after initial remission induction was noted, however, with a freedom from relapse at 4 yr of only 25%. The toxicities of the three therapies were acceptable. Acute complications of therapy were most numerous in the group of patients treated with CVP; however, long-term hematologic depression was most commonly observed in patients treated with whole body irradiation. In general, hematologic complications were more frequent among patients who had marrow involvement and intact spleens at the time of initial therapy. The relationship of this study to other clinical trials in the management of patients with advanced stage favorable histology lymphomas and its implications for future clinical trials are discussed.
As many as 2% of all pregnant women undergo surgery during gestation, but there are few reports of the effects of anesthesia and surgery on fetal outcome. The present paper presents information on 287 women who had surgery during pregnancy. Surgery during early pregnancy was associated with a significant increase in the rate of spontaneous abortion compared to the rate in a control group that did not have surgery. There were no differences in the incidence of congenital abnormalities in this offspring of women who had surgery during early pregnancy. The data suggest that elective surgery be deferred during early pregnancy to minimize potential fetal loss.
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Uterine blood flow rates were obtained with a Krypton (85Kr) clearance technique and with radio-active microspheres in six anaesthetized, non-pregnant ewes (a total of ten comparisons). 85Kr was administered, via a catheter, into the abdominal aorta and beta-emissions were detected with a catheter-type semi-conductor detector probe situated in the lumen of a uterine horn. In seven instances, the 85Kr clearance curve had only one component while in the remaining three instances the curves could be resolved into two components. The flow rates derived from the single component curves and the mean flow rates calculated from the curves with two components were of the same order as, and highly correlated with, estimates of capillary blood flow obtained with microspheres for either the caruncles, the inter-caruncular endometrium or the total endometrium (r = 0.832, r = 0.822 and r = 0.841, respectively, P less than 0.005). There was no correlation between the flow rates obtained with the 85Kr technique and estimates of myometrial capillary blood flow obtained with microspheres.
A mail survey of 30,650 dentists and 30,547 chairside assistants grouped according to occupational exposure to inhalation anesthetic and sedatives in the dental operatory indicated increased general health problems and reproductive difficulties among respondents exposed to anesthetics. For male dentists who were heavily exposed to anesthetics, the increase in liver disease was 1.7-fold, kidney disease was 1.2-fold, and neurological disease was 1.9-fold. For wives of male dentists who were heavily exposed to anesthetics, the increase in spontaneous abortion rate was 1.5-fold. Among female chairside assistants who were heavily exposed to anesthetics, the increase in liver disease was 1.6-fold, kidney disease was 1.7-fold, and neurological disease was 2.8-fold. The increase in spontaneous abortion rate among assistants who were heavily exposed was 2.3-fold. Cancer rates in women heavily exposed to inhalation anesthetics were increased 1.5-fold but this finding was not statistically significant (P = .06). Separate analysis of the data for disease rates and birth difficulties by type of inhalation anesthetic indicates that in both dentists and chairside assistants chronic exposure to nitrous oxide alone is associated with an increase rate of adverse response.
Changes in the mean velocity of ovarian arterial blood flow during the oestrous cycle were monitored in 5 ewes by the use of doppler ultrasonic transducers chronically implanted around the ovarian arteries. In arteries supplying ovaries with a corpus luteum (CL), the velocity was minimal from Day -1 to Day 2 inclusive (Day 0 = day of oestrus), increased steadily until Day 13 (-4) and then declined precipitously. In contralateral arteries supplying ovaries without a CL, the velocity remained at a consistently low level throughout the oestrous cycle. In each ewe, arterial blood velocity to the ovary with a CL and progesterone levels in peripheral plasma were highly correlated; within-individual correlations falling between r = 0.830 (P < 0.001, n = 15) and r = 0.936 (P < 0.001, n = 15). The changes in the velocity of the arterial supply to the ovulatory ovary and the pattern to that for weight of luteal tissue in similar ewes.
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