PubMed Health⌕ Search

Biomedical subjects

R Connelly

Publications and source records attributed to R Connelly.

At least 19 recordsLinked to original sources
PubMed2001

Prostate biopsy protocols: 3D visualization-based evaluation and clinical correlation.

OBJECTIVES: Systematic needle core biopsy is commonly used for the diagnosis of prostate cancer by urologists worldwide. As accurate and early diagnosis will result in more and better options for treatment, it is critical that the best possible protocols for biopsy be used clinically. In this study, we develop three-dimensional (3D) modeling and simulation technologies to evaluate most of the biopsy protocols in current clinical use, and correlate the results with those from clinical cases. MATERIALS AND METHODS: Using deformable modeling techniques, 3D computerized prostate surface models were reconstructed from step-sectioned, whole-mounted radical prostatectomy specimens with localized prostate cancer. A 3D computer simulation system was developed to accurately depict the anatomy of the prostate and all individual tumor foci. A user-friendly interface was developed in the system so that a physician can easily and interactively use it for prostate needle core biopsy. A total of 281 prostate models were reconstructed, and 18 biopsies were performed by a urologist on each model to determine the detection rates of seven different biopsy protocols. Clinical biopsies from 35 patient cases were also reviewed and correlated with the simulation results. RESULTS: The most commonly used sextant biopsy had only a 71.5% detection rate, while rates for the 10-pattern and 12-pattern protocols were much higher (96.4% and 97.2%, respectively). Even the lateral 4-pattern protocol performed better than the sextant protocol, with a detection rate of 89.3%. The lateral sextant biopsy protocol (using sites similar to, but more lateral than, those in the sextant protocol) achieved a rate of 92.5%. Although the rate of the 14-pattern biopsy was a little higher (97.5%), it used four more biopsies to achieve this increase, which, according to McNemar's test, is not statistically significant when compared to results with the 10-pattern protocol. The 5-region protocol, which uses 12 biopsies, had a detection rate of 89.7%. Transition zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. The clinical correlation also confirmed that the 10-pattern protocol was significantly superior to the traditional sextant biopsy pattern. CONCLUSIONS: The 10-pattern biopsy protocol was the most optimized among all the protocols evaluated. This protocol supplemented the sextant biopsy protocol with four more lateral biopsies in the mid and apical sites on both sides.

Biopsy, Needle↗
PubMed1999

Allelic loss on chromosome 6Q in primary prostate cancer.

Molecular genetic analyses of human prostate cancer (CaP) has revealed frequent loss of specific chromosome regions suggesting the presence of putative tumor suppressor gene(s) (TSG) on these chromosome loci whose inactivation may play a role in prostate tumorigenesis. To understand the role of 6q alterations in CaP, we have undertaken a comprehensive analysis of proximal 6q. Genomic DNA from tumor and normal prostate tissues from radical prostatectomy specimens of 38 patients were analyzed by polymerase chain reaction (PCR) for 13 polymorphic microsatellite loci on 6q. Allelic losses of 1 or more polymorphic loci were detected in 11 of 38 patients (29%). Six of 11 tumors showing any 6q deletion were found to have allelic losses at D6S1056 and D6S300 loci. Our results revealed a 1.5 megabase interval between D6S1056 and D6S300 at 6q16.3-21 as the minimal region of deletion, which may contain the putative TSG involved in prostate tumorigenesis. One of the tumor samples demonstrated homozygous deletion at a distal location D6S314 (6q23-24), suggesting another locus potentially associated with CaP. Although the relationship of 6q loss of heterozygosity (LOH) with various clinico-pathologic variables, i.e., cancer recurrence or pathologic stage, did not reveal a statistically significant association, the risk for 6q LOH to non-organ confined (pT3) disease was 5-fold higher than for organ confined disease.

Adult↗
PubMed1997

Prostate-specific antigen-detected prostate cancer (stage T1c): an analysis of whole-mount prostatectomy specimens.

BACKGROUND: Clinical and pathological staging of prostate cancer has been, and remains, problematic. Since prostate-specific antigen (PSA)-detected tumors are often discerned during "screening," what are their significance? METHODS: We analyzed 67 consecutive patients with stage T1c prostate cancer undergoing radical prostatectomy at our institution from August 1, 1991-September 12, 1995, and who had whole-mount specimen processing. Diagnosis was determined in all cases by transrectal ultrasound-guided biopsy. RESULTS: The mean age of our patients was 63 years, and the mean PSA at time of diagnosis was 8.6 ng/ml (median, 7.2 ng/ml). There was organ-confined cancer in 31/67 (46%) patients; 17/67 (25%) had periprostatic fat infiltration, and of these 5(7%) had seminal vesicle involvement. Thirty-one of 67 (46%) had positive surgical margins. Twenty-two (33%) had a Gleason sum of > or = 7 in the final pathological specimen. Insignificant tumors (dominant tumor volume < 0.20 cc) were found in only 4 cases. Smaller tumors were more likely to be found when the PSA was < 10 ng/ml. Multifocal disease was found in 64/67 (96%) prostate specimens. CONCLUSIONS: This study adds impetus to the growing realization that nonpalpable prostate cancer, detected because of elevated PSA, is rarely insignificant. Our findings add further emphasis to the fact that patients diagnosed by PSA elevation have, for the most part, significant cancer that should be treated aggressively.

Aged↗
PubMed1992

Geographic/ethnic differences in human herpesvirus-6 antibody patterns.

Serum samples from healthy adults in four geographic/ethnic groups (Ghanaian Blacks, Malaysian Chinese, Malaysian Indians and United States Caucasians) were tested under code for antibodies to human herpesvirus-6 (HHV-6). The prevalence and titer of HHV-6 antibody in the healthy Ghanaians were significantly higher than in the Malaysian Chinese; United States Caucasians and Malaysian Indians had intermediate prevalence and titer of antibodies. Thus far, no specific differences in HHV-6-associated diseases have been noted between geographic/ethnic groups with these marked variations in antibody patterns.

Adult↗
PubMed1992

Self-employment and providing child care.

This paper considers self-employment and providing child care as occupational strategies that can lower the cost of child care. If the ability to care for one's own children while engaged in market work is important to mothers with young children, we predict that women with young children will be more likely to choose to be self-employed or to be a child care provider than women without young children. The analysis provides strong support for this hypothesis. The results show that the presence of young children is an important factor in choosing self-employment and in choosing to be a child care provider. Finally, simulations are presented which show that a woman's choice among these sectors is quite sensitive to the number and ages of her young children.

Adult↗
PubMed1990

Characterization of the cytolytic activity of CD4+ and CD8+ tumor-infiltrating lymphocytes in human renal cell carcinoma.

Previously we showed that IL2 expanded tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma mediated non-major histocompatibility complex-restricted cytotoxicity. Phenotypic analysis showed that cultured TILs were composed mostly of T-lymphocytes with varying numbers of CD4+, CD8+, and CD56+ (Leu19+) populations. Here we compared the cytolytic activity of the two predominant TIL subsets, CD3+CD4+ and CD3+CD8+, to that of the CD56+ populations. Using magnetic beads coated with antibodies to either CD4 or CD8, CD3+CD4+, and CD3+CD8+ TILs were isolated in a highly enriched form (greater than 92%) and could be expanded for over 40 days in vitro with 1000 units/ml IL2. In a 4-h 51Cr release assay the CD4+ and CD8+ TILs showed minimal lytic activity, whereas unseparated cells exhibited significant levels of non-major histocompatibility complex-restricted cytotoxicity. The lytic activity seen in the 4-h assay with unseparated TILs appeared to be related to the presence of CD56+ populations. With one exception none of the purified CD4+ or CD8+ TILs expressed any significant levels of CD56, while the unseparated TILs contained varying numbers of CD3+CD56+ and CD3-CD56+ populations. Cell-sorting experiments verified that the CD56+ populations were responsible for most of the lytic activity in 4 h even though CD3+CD56- cells represented the predominant cell type. Although CD3+CD56- TILs were minimally lytic in 4 h, we show here that both CD3+CD4+ and CD3+CD8+ subsets displayed substantial cytotoxicity in long-term assays. In the 18-h 51Cr release assay 5 of 6 CD4+ and 2 of 3 CD8+ TILs were lytic for the autologous tumor. In two cases, restimulation with the autologous tumor induced augmented cytolytic activity of TIL subsets and in one case induced lytic activity in 4 h. The cytotoxic activity of TIL subsets was further examined using a 72-h assay in which TILs were cocultured with a confluent layer of tumor cells. The degree of cytotoxicity was quantitated by measuring the amount of crystal violet dye that was incorporated by tumor cells which remained after the incubation period. CD4+ and CD8+ TILs typically caused greater than a 50% reduction of tumor cells in 3 days and the level of reduction was increased when IL2 was added to the cultures. All the CD4+ and CD8+ subset preparations were cytotoxic in the 3-day assay even though some were not lytic for certain targets in the 18-h 51Cr release assay.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

TIL from renal-cell carcinoma: restimulation with tumor influences proliferation and cytolytic activity.

TIL were cultured from human renal-cell carcinoma (RCC) in 1,000 U/ml rIL2 and restimulated with autologous tumor in efforts to establish which conditions would best expand the number of lymphocytes cytotoxic for autologous tumor. Greater cell yields resulted from multiple restimulations of TIL with autologous tumor. In most instances, these TIL lysed autologous tumor better than TIL grown in rIL2 alone. Enhanced proliferation was seen also after restimulation of TIL with allogeneic RCC as well as with tumor cells of non-renal origin. Although in some instances lysis of autologous tumor appeared to be specific, restimulation with autologous tumor did not consistently result in the generation of specific cytolytic T cells. Attempts to culture more specific cytolytic T cells by using 50 U/ml rIL2 were successful in expanding TIL with enhanced lytic activity; however, this activity was not specific for autologous tumor. The phenotype of the tumor-restimulated TIL generally did not change. In most of the TIL cultures, CD3+CD4+ cells were predominant with low numbers of CD3+Leu19+ cells and minimal numbers of CD3-Leu19+ cells. Thus, the cytotoxic response to tumor was mediated by T cells and not NK cells. Overall, our data indicate that restimulation of TIL with autologous tumor may be beneficial for growing larger numbers of cells which have increased lytic activity and for prolonging the presence of lytic activity among the expanded TIL.

Adult↗
PubMed1989

Characterization of two cell lines with distinct phenotypes and genotypes established from a patient with renal cell carcinoma.

Two human renal carcinoma cell lines have been established from the same patient. One cell line (CCF-RC1) was obtained from the primary tumor and the second (CCF-RC2) was established from cells of the renal vein effluent of the perfused tumorous kidney. Although they were established from the same patient, the cell lines differed in certain biological properties. They have been passaged up to 50 times in vitro for about two years. Each has an epithelial morphology and exhibits mutilayering. Cell cycle time of CCF-RC1 and CCF-RC2 was 34 and 36 h, respectively. They exhibited anchorage independent growth, and the plating efficiency of CCF-RC2 in soft agar was higher than that of CCF-RC1. Both lines induced tumors in nude mice at the site of s.c. injection closely resembling the original tumor in histological examination. Electron microscopic features of both tumors in nude mice were consistent with epithelial origin. Doubling time of CCF-RC1 and CCF-RC2 in nude mice was 11 and 12 days, respectively. CCF-RC1 and CCF-RC2 have hypotetraploid karyotype and modal numbers of 83 and 73, presenting two and three marker chromosomes, respectively. Immunocytology with commercial monoclonal antibodies against renal carcinoma (URO-3) and cytokeratin (Mac 6) showed positive reactions with both lines, suggesting that these cell lines derived from renal epithelium. A murine monoclonal antibody (2E11) was generated against CCF-RC2 by the hybridoma technique; 2E11 reacted with CCF-RC2, but not with CCF-RC1. These cell lines may provide a useful model for the study of tumor heterogeneity and its relationship to metastasis.

Animals↗
PubMed1989

Is the ANA guilty of paternalism in its guidelines on withdrawing or withholding food and fluid?

The ANA Committee on Ethics's Guidelines on Withdrawing or Withholding Food and Fluid (1988) delineates those circumstances under which withholding is normally permissible. The Guidelines direct nurses to respect the wishes of competent adults. What of adults who are considered incompetent? Can they make decisions to refuse food and fluids? The Guidelines ask nurses to judge patient competence and the merit of the reasons behind the decisions. This suggests paternalism. A more appropriate role of the nurse might be to focus on helping the patient to make a decision, rather than on the merit of the decision itself.

American Nurses' Association↗
PubMed1988

An aging society: implications for health care needs and impacts on allied health practice.

The first report of the National Task Force on Gerontology and Geriatric Care Education, excerpted herein, raises many more questions than it answers. Through its broad-brush articulation of the health care needs of older people, the report sets the environment for gauging the impact of these needs on allied health practice. Responses to a number of the implications for health care needs are now underway, yet much remains undone. In the coming year the task force will develop an action plan that addresses directly the many implications for allied health.

Aged↗
PubMed1983

Immunotherapy of a murine renal cancer.

A preliminary study of the response to various immunotherapy models in a spontaneous murine nal cell carcinoma model is reported. Tumor cells were implanted intrarenally and nephrectomy performed at a later time. Specific immunotherapy using irradiated whole tumor cells plus complete Freund's adjuvant and a crude membrane preparation plus the same adjuvant were compared to nonspecific immunotherapy with adjuvant alone. In the 1st of 2 response criteria examined, there was a statistically significant decrease in tumor growth following hind limb rechallenge in those animals immunized with the membrane preparation plus adjuvant (p less than 0.01). This form of therapy also produced a statistically significant (p = .024) increase in survival in a second experimental model in which locally recurrent tumor was induced. Whole irradiated cells plus adjuvant slightly enhanced tumor growth, while adjuvant alone had no effect. Treatment with adjuvant alone did, however, result in an increase in the incidence of pulmonary metastases in both groups of animals. The practical and theoretical applicability of a membrane preparation vaccine in human tumors is discussed.

Adenocarcinoma↗
PubMed1980

Lack of positive results of a physiologically based treatment of amblyopia.

Recent reports have described marked improvement of visual acuity in amblyopic eyes of young children following monocular exposure to square-wave gratings presented at a variety of spatial frequencies and orientations for as little as 7 minutes. We sought to confirm and expand on these investigations, with emphasis on single-session results. Sixteen juvenile and 11 adult amblyopes and 26 control subjects were used. Visual acuity was determined before and after a 7-minute stimulation period using an E-chart that controlled for contour interaction. The 50% visual acuity threshold corrected for guessing was computer calculated by probit analysis. Results show that frequency, range, and magnitude of changes (either increases or decreases) in visual acuity following stimulation were approximately the same (< +/- 10% Snell-Sterling) in both amblyopic and control groups. These findings suggest that brief exposure to the grating patterns had little if any beneficial effect on visual acuity in amblyopic eyes.

Adolescent↗
PubMed1977

Comparative studies on immunity to EBV-associated antigens in NPC patients in North America, Tunisia, France and Hong Kong.

This study compared the relative antibody titers to EBV-related antigens in patients with nasopharyngeal carcinoma (NPC) and controls from a high-incidence (Hong Kong), an intermediate incidence (Tunisia), and two low-incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti-virus capsid antigen (VCA), anti-early antigen (EA), anti-soluble antigen by complement-fixation (CF) and antibody-dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven-fold (816 vs 11.5) for EA antibody and more than three-fold (359.7 vs 95.4) for VCA anti-body (p less than 0.01). A two-fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p less than 0.01) and a three-fold difference (2657.7 vs 870.9, p less than 0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well.

Antibodies, Viral↗