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Biomedical subjects

R J Kryscio

Publications and source records attributed to R J Kryscio.

At least 55 records · Page 3Linked to original sources

Properties of Tango's index for detecting clustering in time.

Tango proposed an index for detecting disease clustering in time applicable to grouped data obtained from a population that remains fairly stable over the study period. In this paper, we show that Tango's index is a two-dimensional U-statistic having an asymptotic normal distribution. To apply this result in the finite sampling situation, an Edgeworth expansion is used and is shown to be at least as accurate as Tango's best result in approximating the tails of his test statistic under the null hypothesis. This is extended to show that the Edgeworth expansion can be used to approximate the power of Tango's test statistic under selected alternatives to randomness. A power study based on simulations is conducted to compare the power of Tango's index to that of three of its competitors.

Demography↗

A morphology index based on sonographic findings in ovarian cancer.

A morphology index based on morphologic characteristics of ovarian tumors was developed. Specific categories included tumor volume, wall structure, and septal structure. A point scale (0-4) was developed within each category with the total points per evaluation varying from 0-12. Sonograms on 121 patients undergoing exploratory laparotomy for ovarian masses were evaluated using this index. Eighty ovarian tumors had a morphology index score < 5, and all were benign (negative predictive value, 1.000). In postmenopausal patients, a morphology index score > or = 5 had a positive predictive value for malignancy of 0.45. All ovarian malignancies had significant abnormalities in wall structure and all had a total volume in excess of 10 cm3. The findings of the present investigation indicate that the morphology index is a cost effective adjuvant method which significantly increases the specificity and positive predictive value of transvaginal sonography. The routine application of a morphology index to screening sonography should decrease the amount of diagnostic surgery performed in order to detect each case of ovarian cancer.

Adolescent↗

Thromboxane receptor antagonism and synthase inhibition in cerebral ischemia.

Thromboxane A2 (TXA2) is a proaggregatory vasoconstrictor that may suppress regional cerebral blood flow (rCBF) during postischemic hypoperfusion. This study was undertaken to determine if rCBF could be elevated by postischemic treatment with a TXA2 receptor antagonist, SQ29,548, given alone or in combination with 1-benzylimidazole (1-BI), a thromboxane synthase inhibitor. Wistar rats were subjected to 30 min of reversible forebrain ischemia and treated with SQ29,548 or an SQ29,548/1-BI combination during 60 min of reperfusion. Cerebral TXB2, the stable metabolite of TXA2, was 1.33 +/- 0.91 ng mg brain protein-1 in animals treated with SQ29,548 and exposed to ischemia, compared to 1.15 +/- 0.32 in ischemic controls (p = NS). Administration of SQ29,548/20 mg kg-1 1-BI reduced cerebral TXB2 to 0.20 +/- 0.25 (p < or = 0.01). Regional CBF was depressed significantly in ischemic controls compared to sham-ischemic animals (p < or = 0.01 in all regions except for p < or = 0.05 in diencephalon) and was not altered by treatment with SQ29,548. Rats given the SQ29,548/1-BI combination showed an overall increase in rCBF that did not reach statistical significance when compared to ischemic controls. However, rCBF in hippocampus and diencephalon of animals given the drug combination was significantly greater than in rats treated with SQ29,548 alone (p < or = 0.05).

Animals↗

Monoaminergic and cholinergic synaptic markers in the nucleus basalis of Meynert (nbM): normal age-related changes and the effect of heart disease and Alzheimer's disease.

Neurotransmitter markers for acetylcholine, serotonin (5-HT), and dopamine (DA) were measured in autopsied human nucleus basalis of Meynert (nbM) from nondemented individuals without heart disease (non-HD) (age range, 4-84 years; n = 77), nondemented individuals with heart disease (HD) (age range, 57-92 years; n = 23), and individuals with Alzheimer's disease (AD) (age range, 59-92 years; n = 22). No significant differences in any chemical marker were found between age-matched HD and non-HD individuals. The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and [3H]spiperone binding were regionally distributed within the nbM in control (non-HD) subjects less than 54 years of age. The activity of AChE, 5-[3H]HT binding, and the content of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT were regionally distributed in the nbM in non-HD, HD, and AD subjects more than 54 years of age. The binding of [3H]spiperone was regionally distributed in the nbM in HD and AD subjects more than 54 years of age, only. Activity of ChAT and AChE, content of 5-HT, 5-HIAA, and DA, binding of 5-[3H]HT, and the turnover number for DA (ratio of HVA/DA) all decreased with increasing age in the non-HD control population. The content of HVA, binding of [3H]spiperone, and the turnover number for 5-HT (ratio of 5-HIAA/5-HT) did not change with increasing age. Significant reductions in ChAT and AChE activities were found in AD nbM compared with postmortem interval- and age-matched HD and non-HD individuals. The reduction of 5-HT and 5-HIAA content and [3H]spiperone binding in individuals with AD of all ages suggests a loss of functional serotonergic innervation of the nbM. Dopaminergic synaptic markers were less affected in AD nbM, although turnover numbers for both DA and 5-HT were increased in AD. Receptor upregulation in response to presynaptic deficits did not occur for DA or 5-HT.

Acetylcholinesterase↗

Transition from benign to malignant epithelium in mucinous and serous ovarian cystadenocarcinoma.

The slides of all patients with ovarian cystadenocarcinoma treated at the University of Kentucky Medical Center from 1966-1990 were reviewed. Fifty-four serous tumors and 42 mucinous neoplasms were identified for further study. Benign epithelium adjacent to an area of borderline or malignant epithelium was observed in 74 tumors (79%) and a site of epithelial transition was noted in 38 cases (40%). The presence of associated benign epithelium was more common in borderline or well-differentiated lesions and in patients with early-stage disease. These findings are consistent with epidemiologic and molecular genetic data and suggest that certain benign serous or mucinous ovarian tumors have the potential for malignant transformation. Removal of these tumors, particularly in postmenopausal women, should result in a subsequent reduction in the frequency of ovarian cancer.

Adolescent↗

Endometrioid carcinoma of the ovary and endometriosis: the association in postmenopausal women.

Histologic material from 42 patients with endometrioid carcinomas of the ovary was reviewed. Ovarian endometriosis was present in 11 cases (26%) and 8 of these patients were postmenopausal. The exact site of transition from benign to malignant epithelium was observed in 4 cases. The clinical characteristics of patients with associated endometriosis were not significantly different from those without this finding except that endometriosis was present only in patients with Grade 1 or Grade 2 carcinomas. These data suggest that ovarian endometriosis in the postmenopausal patient has the potential to undergo malignant transformation and, when detected, should be removed surgically.

Adenocarcinoma↗

Predictive value of specimen histology after preoperative radiotherapy in the treatment of bulky/barrel carcinoma of the cervix.

One hundred thirty-four patients with bulky and barrel-shaped cervix cancers were treated with preoperative radiation to 40-45 Gy, intracavitary therapy using Cs-137 or Cf-252 and extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) 4-6 weeks after radiotherapy. Outcome of therapy was traced for patients with residual tumor (positive) in the hysterectomy specimen and those who had no residual tumor (negative) in the specimens. All specimens were studied by a set protocol to carefully evaluate the TAHBSO specimen for gross or residual tumor. Ninety-two percent of the patients with negative specimens survived 5 years, but this dropped to 71% if the specimen was positive. These findings were observed in both the Cs-137- and Cf-252-treated patients. Patients with negative specimens failed mainly in distant sites, whereas those with positive specimens failed locally and distantly. Patient survival was less in patients with positive specimens. There was no difference in outcomes for adenocarcinoma and squamous cell carcinomas. The specimen histological findings have predictive value in patients treated with preoperative radiation and surgery.

Actuarial Analysis↗

A review of californium-252 neutron brachytherapy for cervical cancer.

Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron-enhancing chemicals.

Adenocarcinoma↗

Preoperative radiation therapy followed by extrafascial hysterectomy in patients with stage II endometrial carcinoma.

Seventy-four patients with Stage II endometrial cancer were treated by a combination of preoperative radiation therapy followed by extrafascial hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling at the University of Kentucky Medical Center from 1967 to 1988. All patients had histologically confirmed endometrial cancer with involvement of the endocervix. The cell types and numbers of the tumors treated were as follows: adenocarcinoma, 58; adenoacanthoma, six; adenosquamous carcinoma, nine; and clear cell carcinoma, one. Preoperative radiation consisted of 4500 cGy external therapy followed by one intracavitary implant providing an additional 2000 cGy to point A. Surgery was done 4 to 6 weeks after completion of radiation therapy. Five patients (7.1%) had paraaortic lymph node metastases. Four were treated with extended-field radiation therapy and one with platinum-based combination chemotherapy. After treatment, the patients were followed at regular intervals from 2 to 22 years (mean, 5.4 years). Eleven patients (15%) had recurrent cancer, with the vagina and upper abdomen being the most common sites of spread. The estimated 5-year and 10-year disease-free survival rates of these patients are 88% and 76%, respectively. Cell type, depth of myometrial invasion, and lymph node status were the most important prognostic variables in the patients evaluated. These data confirm that the combination of preoperative radiation therapy and surgery produces excellent long-term survival in patients with Stage II endometrial cancer.

Adenocarcinoma↗

Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography.

From November 1987 to January 1991, 1300 postmenopausal women underwent screening with transvaginal sonography (TVS). Women eligible for screening were all asymptomatic with no known ovarian tumors. Ovarian volume was calculated using the prolate ellipsoid formula, and a value in excess of 8.0 cm3 was considered abnormal. Ovarian abnormalities were detected in 33 women (2.5%), and 27 underwent exploratory laparotomy. Ovarian tumors were noted in all 27 patients, including 2 primary carcinomas and 14 serous cystadenomas. The two women with ovarian carcinomas had normal results of pelvic examinations and normal serum CA-125 levels. Both women had Stage I disease, and are alive and well after conventional therapy. TVS was time efficient, easy to perform, and well-accepted by patients. Currently, there are more than 3000 patient years of follow-up in the screened population, and there have been no deaths due to ovarian cancer. A multi-institutional trial to determine the efficacy of TVS as a screening method for ovarian cancer is indicated.

Adenocarcinoma↗

Measuring the severity of disease clustering using Tango's index.

Tango [Biometrics 40:15 (1984)] proposed an index for detecting disease clustering in time applicable to grouped data obtained from a population that remains fairly stable over the study period. This index has received considerable attention in the literature including the suggestion that it be used to detect the space-time clustering of diseases and the suggestion to use similar test statistics to detect disease clustering in space and/or time while accounting for a changing population size over the study period. This paper concerns the related question of measuring the severity of the disease clustering once it has been determined that cases are not randomly distributed over space and/or time. A family of alternatives to randomness is proposed in which space and/or time versions of Tango's index are sufficient statistics for the parameters measuring the severity of the clustering. For the special case of temporal clustering, an unbiased estimator of the clustering parameter and its sampling variance is derived, and a particularly simple interpretation of this estimator is suggested. These latter results are based on some asymptotic approximations due to Tango [Biometrics 46:351 (1990)]. An application to the trisomy data given by Wallenstein [Am. J. Epidemiol. 111:367 (1980)] is discussed.

Cluster Analysis↗

Specimen findings and survival after preoperative 252Cf neutron brachytherapy for stage II cervical carcinoma.

Twenty-seven patients with operable Stage II cervical cancer with a mean diameter tumor of 8.0 cm were studied in a feasibility study using preoperative 252Cf implants plus whole-pelvis radiation to 45 Gy followed by extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy 4 to 6 weeks later. Hysterectomy specimens were studied by a set protocol. With the protocol used, 13/27 (51%) specimens and abdominal stagings were negative for residual tumor. The survival rate for the patients with negative findings was 93% at 5 years. In 14/27 (49%) patients the specimens were positive for residual tumor. In contrast, the 5-year survival rate for this group was 46% (P less than 0.001). In these patients several interrelated factors were determined to be of importance, i.e., (1) tumor size greater than 8 cm in maximum diameter, (2) positive or negative residual tumor status, and (3) total dose of radiation given. Survival was lower for larger tumors and specimens were more likely to show residual tumor. A lower treatment dose led to more positive specimens, as well as to poorer survival. While the patients with Stage II disease fared very well when negative specimens were found, further prospective studies of the appropriate treatment for those with positive tumor specimens are needed.

Brachytherapy↗

A randomized trial of surgery in the treatment of single metastases to the brain.

To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.

Adult↗

Phenotypic and functional properties of B lymphocytes from aged mice.

Phenotypic and functional properties of B lymphocytes from individual young and old mice of different inbred strains were studied. B lymphocyte subpopulations defined by the ratios of the densities of cell surface IgM and IgD were found to be altered with age. However, such alterations in B cell subsets were found only in 30-40% of the old mice. B cell mitogenic responses to anti-mu and anti-Lyb2 antibodies were decreased in a majority of DBA/2 mice. Proliferative responses to LPS and anti-mu were reduced only in a minority of CBA/Ca mice but there was a very good correlation in the responsiveness of the old mice to LPS and anti-mu. The anomalous properties of the individual old mice of these inbred strains may be due to a heterogeneity in the effects of aging or due to environmental influences.

Aging↗

31P spectroscopy in experimental embolic stroke: correlation with infarct size.

Serial 31P nuclear magnetic resonance spectra were acquired from the brain in 19 rats following microsphere embolization of the right internal carotid artery. The brains were sectioned and stained with 2,3,5-triphenyltetrazoline chloride 6 h post-embolization to visualize infarcted areas. There was a narrow dosage range for the effect of embolism measured by maximum decline in pH at 20 min, mortality, and infarct size. This narrow range effect may be due to occlusion of collateral channels by the 16 micron microspheres. There was a strong correlation between decline in pH at 20 min post-embolization and infarct size (r2 = 0.76); this decline was the best early marker for eventual infarct in our study. This animal model for macroscopically heterogenous brain ischemia may be useful for the evaluation of therapeutic interventions in stroke, and as an aid in the interpretation of phosphorus spectra from mixed volumes of ischemic and non-ischemic brain.

Adenosine Triphosphate↗

The efficacy of laser therapy in the treatment of cervical intraepithelial neoplasia.

The efficacy of carbon dioxide laser therapy in the treatment of cervical intraepithelial neoplasia (CIN) was evaluated in 253 patients treated at the University of Kentucky Medical Center from 1984 to 1987. All patients had histologically confirmed CIN and were treated in an outpatient setting. Parameters examined included severity of neoplasia, presence of koilocytosis on biopsy, depth of laser ablation, and the number of cervical quadrants involved by CIN. Following therapy, patients were examined at 3-month intervals from 12 to 48 months (mean 18 months). Eighty-nine per cent of patients were successfully treated with one laser ablation and all patients were cured of disease with two treatments. Over 70% of patients initially failing therapy had CIN III or greater than or equal to 3 quadrant disease. The most significant predictor of failure was lesion size. Only 74% of women with 3 or 4 quadrant disease were successfully treated with one treatment. No patient experienced postoperative infection or bleeding requiring treatment. These data confirm that carbon dioxide laser therapy is a safe and highly effective treatment method for all forms of CIN.

Adult↗

Interobserver variation in ovarian measurements using transvaginal sonography.

Ultrasound examination of ovarian size and morphology has been proposed as a screening method for ovarian carcinoma. A screening test must give consistent results when performed by different examiners to reliably determine the sensitivity and specificity of the test. This study was designed to evaluate interobserver variation in ovarian size measurements using transvaginal sonography. Two examiners independently measured 86 ovaries in three planes and ovarian volumes were calculated using the prolate ellipsoid formula. The correlation coefficient between the ovarian volume measurements made by each examiner was 0.960. These results indicate that interobserver variation in ovarian volume measurements is extremely low as determined by transvaginal sonography.

Adult↗