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Biomedical subjects

F Lee

Publications and source records attributed to F Lee.

At least 145 records · Page 8Linked to original sources
PubMed1994

US-guided percutaneous cryoablation of prostate cancer.

A tailored approach to cryosurgery of prostate cancer is presented. The authors have performed 214 cryoprocedures to date with use of this protocol. The technique requires pretreatment with androgen ablation therapy, preoperative diagnosis and staging with ultrasound (US)-guided biopsies, and detailed knowledge of prostate and rectal anatomy. Five cryoprobes are placed in the prostate under US guidance in a configuration that depends on tumor location, sites of extracapsular extension, the size of the tumor, and gland geometry. Freezing starts anteriorly to keep from obstructing the ultrasound beam. Two freezes are performed at the known cancer site, and additional freezes are performed, if necessary, to include the remainder of the gland. Thermosensors enable monitoring of the cryosurgical ice ball and determination of the number of freezes. Cryosurgery is always performed by a urologist and a radiologist working together.

Cryosurgery↗
PubMed1994

Circadian variation of sustained ventricular tachycardia in patients with coronary artery disease and implantable cardioverter-defibrillators.

BACKGROUND: While previous studies using epidemiological data and ambulatory ECG monitoring have shown peak occurrence of sudden death and nonsustained ventricular tachycardia in the morning, none have examined circadian variation of potentially life-threatening ventricular tachycardia (VT), nor has any study observed circadian behavior of any arrhythmias in individuals followed longitudinally. We used the event memory of multiprogrammable implantable cardioverter-defibrillators to evaluate the circadian pattern of sustained VT over time. METHODS AND RESULTS: Data were reviewed from 32 consecutive patients with coronary artery disease and sustained VT who had received the Ventak PRX (CPI, Inc) cardioverter-defibrillator between May 1991 and August 1993 and had experienced at least one episode of VT terminated by their device. Mean follow-up was 14 +/- 7 months. Among the 2558 episodes recorded by the device logs, VT occurrence peaked between 6 AM and noon (P = .007 by ANOVA among four 6-hour time periods). Harmonic regression revealed a morning peak at 9 AM (P < .01). This morning peak occurred in patients with both frequent and infrequent events. Among 21 patients who experienced more than four VT events, 8 (38%) had an AM peak of VT occurrence (> 35% of VT between 6 AM and noon). Neither age, ejection fraction, event frequency, presenting arrhythmia, nor drug therapy distinguished patients who displayed the AM VT peak. CONCLUSIONS: In patients with coronary artery disease, sustained VT displays circadian variation with peak frequency in the morning, similar to that for sudden death. Individual patients who display specific patterns of circadian variation over time can be identified using defibrillator logs. Investigation of circadian variation of other phenomena to elucidate mechanisms of VT should focus on these patients.

Aged↗
PubMed1994

Characterization of spontaneous factor-independent cell lines derived from the human leukemic cell line TF-1: a dominant event.

Uncontrolled proliferation of acute myeloid leukemia (AML) cells is an important step during leukemogenesis. However, little is known about the mechanisms leading to growth autonomy. Studies using immortalized murine hematopoietic cell lines have suggested that autocrine production of growth factors, or the constitutive activation of molecules in growth factor signalling pathways, are involved. We have established six spontaneous factor-independent cell lines from the human growth factor-dependent TF-1 cell line. The factor-independent cells showed no detectable growth factor activity. Immunoblotting analyses of tyrosine phosphorylation, Raf-1 and extracellular signal-regulated kinase 2 (ERK-2) showed a similar pattern in all the cell lines including TF-1 cells. Furthermore, somatic-cell hybrids between TF-1 and the factor-independent cells grew in absence of growth factor. Taken together this data demonstrates that the factor independence in this system is dominant and suggests that the molecular event is located either downstream of the Raf-1 and MAP kinases pathway or on an alternative pathway. Finally, the karyotype analysis of one factor-independent cell line TF-1i1 and TF-1H- (G418 resistant, HAT sensitive TF-1 cells) and their hybrids demonstrated an unstable derivative chromosome [der(19) t(19;?) (q13.1;?)] which seemed to correlate with the factor-independence capacity. This model may help in our understanding of autonomous proliferation by human myeloid leukemias.

Acute Disease↗
PubMed1993

Characteristics of prostate cancers detected in a multimodality early detection program. The Investigators of the American Cancer Society-National Prostate Cancer Detection Project.

BACKGROUND: Few data are available to describe the clinical and pathologic characteristics of prostate cancers detected through early detection programs. The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multimodality, multicenter study of the feasibility of early prostate cancer detection using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). One hundred fifty-six prostate cancers are available from this project for analysis. METHODS: The ACS-NPCDP is a prospective, comparative study of a cohort of 2,999 men between 55 and 70 years of age not suspected of having prostate cancer. DRE, TRUS, and PSA are performed for each subject on an annual basis for as long as 5 years. Biopsies are performed on the basis of recommendations from DRE or TRUS results. Although elevated PSA alone was not typically a basis for biopsy, in some instances biopsies were recommended because of the degree of elevation in PSA. Diagnoses are confirmed by participating pathologists and by pathologic analysis. RESULTS: A small proportion of cancers detected were advanced in terms of the clinical stage at time of diagnosis. A total of only six cancers were stage C1 to D1, and five of these were preexisting cancers detected at the first examination. Cancers detected by DRE tended to be more advanced than those found on the basis of only TRUS or PSA. A large proportion of patients received curative therapy, involving radical prostatectomy for 67.9% and radiation therapy for 17.9%. Of 100 men presumed to have organ confined disease and treated by prostatectomy, 64 actually proved to have localized cancer, a rate of upstaging of 36.0%. PSA level and PSA density were associated with the detection of organ confined cancer, but several advanced cancers had PSA levels in the normal range, limiting the usefulness of these measures for staging. CONCLUSIONS: The cancers resulting from this multimodality detection effort represented a spectrum of pathologic findings. These data, however, suggest that early detection interventions in men not suspected to have prostate cancer will yield tumors with a favorable stage distribution that are likely to benefit from treatment. Further follow-up evaluation is needed to determine whether these benefits are reflected in long-term mortality and survival experience.

Aged↗
PubMed1993

Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells.

We have used two in vitro models to identify genes whose expression may serve as markers of lineage commitment during the development of hematopoietic stem cells. One system involves the development in vitro of blastocyst-derived embryonic stem cells into embryoid bodies. The second involves culturing of day 3.5 blastocysts in vitro under conditions that support their development into yolk saclike cysts. In both cases, hematopoietic cells arise in a manner that closely mimics the normal process occurring in the yolk sac of the early mouse embryo. We have focused our analysis on the expression of mRNAs for 15 hematopoietic growth factor receptor genes and other genes expressed in a hematopoietic lineage-specific manner. Although some growth factor receptor genes are apparently expressed constitutively during in vitro development, there are several classes of genes that undergo a highly consistent pattern of induction in both model systems. Genes induced early include those encoding the shared beta subunits of the interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors; those induced at intermediate times include the c-fms, G-CSF receptor, and CD34 genes; and a gene induced late during in vitro development is the IL-7 receptor gene. The defined temporal order for the expression of these genes suggests that they may be useful as markers for multiple stages in the development of different hematopoietic cell lineages during embryogenesis.

Animals↗
PubMed1993

American Cancer Society--National Prostate Cancer Detection Project. Results from multiple examinations using transrectal ultrasound, digital rectal examination, and prostate specific antigen.

BACKGROUND: The American Cancer Society-National Prostate Cancer Detection Project is a prospective study of the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). Two thousand nine hundred ninety-nine men not previously suspected of having prostate cancer have been entered on study in ten participating clinical centers. METHODS: The study protocol requires these men to undergo testing with the three detection methods under investigation on an annual basis for up to 5 years. Data currently are available on 1972 men who have completed protocol requirements for two sequential series of examinations. RESULTS: At the first visit, it was recommended that 16.5% of subjects undergo biopsy based on the TRUS and/or DRE findings. Seventy-three (3.7%) men were found to have cancer after the first series of examinations. When the 1899 men who did not have cancer were reexamined, in 11.4%, a biopsy was recommended, and an additional 33 (1.7%) cancers were detected. Cancer detection rates were higher in older men, and the sensitivity of TRUS was higher than that of DRE at both examinations. The positive predictive values (PPV) of TRUS and DRE varied significantly depending on the PSA level; PPV decreased at the second examination. Positive findings during the second examination were associated with elevated PSA levels during the earlier visit and rising PSA levels between examinations. Analyses of the 106 cancers detected currently showed a preponderance of early-stage cancer and low Gleason scores. CONCLUSIONS: It may be possible to increase the early detection of prostate cancer by periodic examination by a combination of detection modalities.

Aged↗
PubMed1993

Staging of early prostate cancer: a proposed tumor volume-based prognostic index.

Current staging of early prostate cancer separates patients into two groups: those with palpable and non-palpable tumors. Such staging relies on digital rectal examination in making this separation, despite the low sensitivity, low specificity, and low positive predictive value of this method. As an alternative, tumor volume may be useful for staging because of its powerful prognostic ability and its potential to be assessed clinically due to recent advances in imaging techniques such as transrectal ultrasound. In this study, we evaluate the utility of tumor volume in predicting progression of early prostate cancer based on the composite published evidence from nine pathologic studies of serially-sectioned prostates. Logistic regression revealed that tumor volume was a good positive predictor of all measures of tumor progression. There was a 10 percent probability of capsular invasion in tumors measuring about 0.5 cm3; 10 percent probability of seminal vesicle invasion in tumors measuring about 4.0 cm3; and 10 percent probability of metastases in tumors measuring about 5.0 cm3. These composite results suggest that tumor volume is a significant predictor of cancer progression. A volume-based prognostic index is proposed as an adjunct to staging for early prostate cancer.

Humans↗
PubMed1993

The role of transrectal ultrasound-guided staging biopsy and androgen ablation therapy prior to radical prostatectomy.

Radical prostatectomy is the most common therapy for localized prostate cancer. Unfortunately, resection is associated with positive surgical margins in 35-50% of cases. We report the use of ultrasound-guided staging biopsies to stage tumors preoperatively with greater accuracy. We also report the use of androgen ablation therapy (AAT) as an adjunct to radical prostatectomy in an attempt to downstage tumors preoperatively and decrease the incidence of positive margins. Between 1 June 1991 and 31 July 1992, 131 patients underwent radical prostatectomies, 119 of whom underwent AAT before surgery and 12 of whom did not. Specimens were examined for the presence of positive surgical margins, extracapsular extension, and perineural invasion. Cases pretreated with AAT had a 9.2% positive surgical margin rate compared with 33% in untreated subjects. Extracapsular extension was seen in 22 of 119 (18.5%) of AAT, and 5 of 12 (41.7%) of non-AAT, cases. Perineural invasion was nearly 3 times less likely in AAT patients. Moreover, perineural invasion was significantly less marked in AAT patients. We present a subset of 11 patients who were definitively proven as pathologic stage C cancer by transrectal ultrasound (TRUS)-guided needle biopsy. These cases had prostate cancer intermixed with fatty tissue and pigmented seminal vesicle epithelium, elements not found in the prostate. In this selected stage C subset, gland shrinkage, evidence of downstaging, and tumor obliteration were seen after AAT. We conclude that TRUS-guided staging biopsy can definitively stage prostate cancer as stage C when tumor is intermixed with extraprostatic elements, and AAT appears to decrease the incidence of positive surgical margins by tumoral necrosis and selective perineural kill. We believe that these findings demonstrate the antitumor effects of AAT and deserve further scrutiny in a large randomized clinical trial.

Androgen Antagonists↗
PubMed1993

Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy.

Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex). The positive margins decreased from 35.3% in the group undergoing prostatectomy alone to 11.5% in the group of men who received combination therapy before radical prostatectomy. In 41 apical tumors, the incidence of positive margins decreased from 50% in the control group to 18.6% in the combination therapy group. In stage C disease, the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5% after 3 months and 16.7% after 6 months. Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients. However, the initial results obtained in the present study are very encouraging.

Aged↗
PubMed1993

Differential effect of HTLV infection and HTLV Tax on interleukin 3 expression.

To characterize the interactions between human T-cell leukemia virus (HTLV) infection and cellular gene expression, we examined the expression of the lymphokine interleukin 3 (IL-3) in the presence and absence of HTLV infection. IL-3, like granulocyte-macrophage colony-stimulating factor (GM-CSF), is produced by activated but not resting T cells, but although GM-CSF is constitutively expressed in HTLV-infected T cells IL-3 mRNA cannot be detected in either unstimulated or mitogen-stimulated HTLV-infected cells by polymerase chain reaction (PCR) analysis. In contrast, transient co-transfection studies with an IL-3 promoter-CAT reporter gene and an HTLV-II Tax expression construct demonstrate that Tax can transactivate the IL-3 promoter in HTLV-uninfected T cells. To determine whether differences in IL-3 promoter-binding proteins present in HTLV-infected and uninfected T cells account for this discrepancy, DNAase I footprinting of the IL-3 promoter was performed. Although crude nuclear extracts from both cell types protected the IL-3 sequences located between base pairs -168 and -125, the sequences between -125 and -103, which contain the lymphokine consensus sequences CK-1 and CK-2, were protected by extracts from HTLV-infected but not HTLV-uninfected T cells. Deletion of the region containing the CK-1 and CK-2 sequences from an IL-3 promoter CAT construct resulted in a sixfold rise in promoter activity in HTLV-infected but not uninfected T-cell lines, indicating that this region participates in the repression of IL-3 gene expression in HTLV-infected T cells.

Base Sequence↗
PubMed1992

Predicted prostate specific antigen results using transrectal ultrasound gland volume. Differentiation of benign prostatic hyperplasia and prostate cancer.

METHODS: The diagnostic performance of transrectal ultrasound (TRUS) gland volume and prostate specific antigen (PSA) results were evaluated in 204 men consecutively scheduled to undergo transurethral prostatic resection (TUR). RESULTS: Nonpalpable prostate cancer was detected by TRUS alone in 18% (29 of 161) and by TUR alone in 9% (14/161), for an overall cancer incidence of 27%. A predicted PSA value (TRUS gland volume x 0.20 ng/ml/g = polyclonal PSA) was used for comparison with serum PSA for each patient. TRUS positive predictive value improved from 52% to 86% when serum PSA exceeded the predicted value. The specificity and positive predictive value of PSA at 2.5 ng/ml were 23% and 37%, respectively, which increased to 88% and 72%, respectively, when serum PSA exceeded the predicted value. CONCLUSIONS: Predicted PSA values produce decision levels near the 95th percentile for each patient and assist individual biopsy decisions better than grouped gland volume ranges. Wider application of TRUS and PSA in any clinical setting or early detection program is now possible.

Aged↗
PubMed1992

The relationship of prostate-specific antigen to digital rectal examination and transrectal ultrasonography. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The participating institutions of the American Cancer Society National Prostate Cancer Detection Project did 520 biopsies on 2425 men over a 3.5-year period. A total of 88 cancers were confirmed pathologically, 93% of which clinically were organ confined. In 324 men (62.3%), a recommendation for biopsy was made based solely on the results of transrectal ultrasonography (TRUS); in 69 patients (13.3%), solely on the digital rectal examination (DRE); in 116 patients (22.3%), on abnormal DRE and TRUS examinations; and in 11 patients (2.1%), in whom DRE and TRUS were normal, on elevated prostate-specific antigen (PSA) levels. The TRUS was abnormal in 80.6% of men found to have cancer, and the PSA level and DRE were abnormal for 67% and 50% of cancers, respectively. The influence of PSA level on cancer detection increased as the serum level increased above 4 ng/ml. The positive predictive values of both the DRE and TRUS were influenced significantly by the presence of an elevated PSA level (P = 0.044 and P less than 0.001, respectively). The results of this ongoing multicenter study support the following statements: (1) the prostate cancer detection rate is influenced by this diagnostic triad and (2) the detection rate of organ-confined disease can be improved substantially by early detection programs.

Aged↗
PubMed1992

Prostate-specific antigen levels in 1695 men without evidence of prostate cancer. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The American Cancer Society National Prostate Cancer Detection Project is a prospective, multidisciplinary, and multicenter trial to assess the potential for early detection of prostate cancer by transrectal ultrasonography (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen assay (PSA). By November 1990, 2805 men between the ages of 55 and 70 years with no known signs or symptoms of prostate cancer were enrolled in the study, which is planned to run for 5 years. Annual TRUS, DRE, and PSA tests were done on these subjects, and biopsies were recommended for suspicious lesions when detected. To study the performance of PSA testing in presumed normal subjects, all men were eliminated who had (1) prostate cancer detected on their initial examinations and proven by biopsy or (2) cancer detected during the year or subsequent examinations. Additionally, all men with TRUS or DRE findings that were interpreted as suspicious for cancer but who are being followed and have not yet had biopsies done were removed from this series. This left a unique, extensively screened group of 1695 men who were free of prostate cancer, as far as could be determined. Analyses of the PSA levels in this large population in the appropriate age range for increasing risk of prostate cancer revealed several important findings. First, there was a direct relationship between serum PSA levels and estimated prostate volume for both the currently available monoclonal and polyclonal PSA assays. Individuals with benign prostatic hyperplasia and larger gland volume have a higher normal limit of PSA than men with normal gland volume. Second, analyses showed no relationship between age and PSA levels or between symptoms of prostatism and PSA levels independent of gland enlargement. It was concluded that volume-adjusted upper limits of normal PSA can be determined for different levels of specificity desired. This information may be applicable to the use of PSA in men not already suspected of having prostate cancer and may increase its effectiveness as a tool for early detection.

Age Factors↗