Biomedical subjects

M M Lieber

Publications and source records attributed to M M Lieber.

At least 109 records · Page 6Linked to original sources

PubMed1994

Correlation between urinary flow rate, voided volume, and patient age in a community-based population.

This investigation is unique in that is the first study to use a large number of randomly chosen men from the community to establish the relationship between: 1) urinary flow rate and voided volume, 2) urinary flow rate and patient age, 3) voided volume and patient age, and 4) the time to achieve peak urinary flow rate and patient age. The results clearly indicate that both the peak and mean urinary flow rate decreases with advancing age. The voided volume also diminishes with increasing age. The time required to achieve the peak urinary flow rate, however, appears to be independent of the patient's age. Irrespective of age, approximately 9 seconds are required to achieve the maximum urinary flow rate. Because the urinary flow rate is dependent upon both the quantity of urine voided and the patient's age, it is necessary to account for the influence of both parameters when establishing the "normal range" for peak urinary flow rate. To this end, nomograms estimating the peak urinary flow rate percentile as a function of voided volume and patient age have been generated and are included in this report. These nomograms, based on a large, randomly selected population, should make peak urinary flow rate a more reliable diagnostic modality for assessing bladder outlet obstruction. They also should be most useful to the practicing clinician when interpreting the results of a peak urinary flow rate determination for a patient presenting with symptoms of prostatism.

Adult↗

PubMed1994

DNA ploidy in prostate cancer: potential measurement as a surrogate endpoint biomarker.

Measurements of DNA ploidy have considerable promise for serving as surrogate endpoint biomarkers (SEBs) for prostate carcinoma. Studies of benign prostatic hypertrophy (BPH) tissue by flow cytometry (FCM), image analysis, and fluorescent in situ hybridization (FISH) for ploidy invariably show normal DNA content and chromosome numbers. In contrast, most aggressive prostate cancers are aneuploid, particularly when new, sensitive methodologies are applied. Certain tumors which have appeared to be DNA diploid by FCM can be shown to be aneuploid with only one or a few abnormal chromosomes by FISH studies. Certain cases of prostatic intraepithelial neoplasia (PIN) are also known to be aneuploid by FISH ploidy using alpha satellite probes for centromere counting. The latest data suggest abnormalities of chromosomes 7 and 8 are most frequently detected. Therefore, a surrogate endpoint assay which detects aneusomies of chromosomes 7 or 8 in histologically normal or dysplastic prostate tissue might serve as a very significant intermediate endpoint biomarker to identify neoplastic prostate cells on their way to becoming clinically aggressive prostate carcinomas.

Biomarkers, Tumor↗

PubMed1994

The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials.

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.

Anticarcinogenic Agents↗

PubMed1993

Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges.

OBJECTIVE: To define the characteristics of serum prostate-specific antigen (PSA) in a population of healthy men without clinically evident prostate cancer, but who are at risk for developing the malignancy. The influence of patient age and prostatic size on the serum PSA concentration was assessed in order to use PSA more appropriately to detect clinically significant prostate cancer at an early, potentially curable stage. DESIGN: Prospective, community-based study. PARTICIPANTS: Between December 1989 and March 1991, 2119 healthy men aged 40 to 79 years from Olmsted County, Minnesota, were entered into a prospective study to assess the natural history of benign prostatic hyperplasia. Of these, 537 (25%) were randomly chosen to participate in a detailed clinical examination that included a serum PSA determination (Tandem-R PSA assay), digital rectal examination, and transrectal ultrasonography. Four hundred seventy-one (88%) completed the prostatic evaluation and had no evidence of prostate cancer by any of these three diagnostic tests; these men formed the study population on which all analyses were performed. MAIN OUTCOME MEASURE: Serum PSA concentration, prostatic volume, and PSA density (serum PSA level/prostatic volume) as a function of patient age. RESULTS: The serum PSA concentration is correlated with patient age (r = .43; P < .0001) and prostatic volume (r = .55; P < .0001). Prostatic volume, in turn, is directly correlated with patient age (r = .43; P < .0001), whereas the PSA density value is only weakly correlated with patient age (r = .25; P < .001). For a healthy 60-year-old man with no evidence of prostate cancer, the serum PSA concentration increases by approximately 3.2% per year (0.04 ng/mL per year). The recommended reference range for serum PSA (95th percentile) for men aged 40 to 49 years is 0.0 to 2.5 ng/mL; for 50 to 59 years, 0.0 to 3.5 ng/mL; 60 to 69 years, 0.0 to 4.5 ng/mL; and 70 to 79 years, 0.0 to 6.5 ng/mL. CONCLUSIONS: The serum PSA concentration is directly correlated with patient age and prostatic volume, the latter of which also is directly related to age. Thus, rather than rely on a single reference range for men of all age groups, it is more appropriate to have age-specific reference ranges. These age-specific reference ranges have the potential to make serum PSA a more discriminating tumor marker for detecting clinically significant cancers in older men (increasing specificity) and to find more potentially curable cancers in younger men (increasing sensitivity).

Adult↗

PubMed1993

A population-based study of health care-seeking behavior for treatment of urinary symptoms. The Olmsted County Study of Urinary Symptoms and Health Status Among Men.

OBJECTIVE: To determine the extent to which severity of urinary symptoms predicts a man's decision to seek medical care for urinary symptoms. DESIGN: Cross-sectional, population-based survey; the baseline component of a prospective cohort study. SETTING: Olmsted County, Minnesota (1990 population, 105,720), including the city of Rochester (population, 69,995) and surrounding rural townships. SUBJECTS: A population-based sample of men aged 40 to 79 years randomly selected within age- and residence-specific strata. INTERVENTION: A previously validated questionnaire that elicited information about the frequency and bother of urinary symptoms, sociodemographic information, and information regarding use of physician services in the last year. MAIN OUTCOME MEASURE: An affirmative response to any of 12 questions asking the subject if he had seen a physician in the last year because of specific urinary symptoms. MAIN RESULT: Symptom severity, whether measured by American Urologic Association frequency or bother score or by interference with daily activities, was a significant predictor of health care-seeking behavior for urinary symptoms, but was neither as sensitive nor as specific as would be ideal. After adjusting for symptom severity and sociodemographic characteristics, men aged 70 to 79 years were 4.6 times as likely (95% confidence interval, 2.1 to 10.1) as men aged 40 to 49 years to have sought health care because of urinary symptoms in the last year. CONCLUSION: While symptom severity is an important determinant of health care-seeking behavior for men with urinary symptoms, some additional factor or factors associated with age remain that may drive men to seek care for urinary symptoms. These factors may prove important in understanding the small-area variations in treatment of benign prostatic hyperplasia that have been noted by others.

Adult↗

PubMed1993

Natural history of prostatism: factors associated with discordance between frequency and bother of urinary symptoms.

The objective of this study was to assess the association between frequency and bother of urinary symptoms in a population-based cohort of men and to identify psychosocial factors that are related to reporting heightened or subdued bother relative to symptom frequency. The survey was conducted among men aged forty to seventy-nine years in Olmsted County, Minnesota, the baseline component of a prospective cohort study. Men were queried about the frequency of urinary symptom occurrence and the perceived bother associated with the symptoms. A regression analysis of American Urologic Association (AUA) bother scores on AUA frequency scores demonstrated a tight correspondence (r2 = 0.71). Men with bother scores greater than predicted from their frequency scores were more likely to have sought health care for their urinary symptoms than men whose bother was close to predicted (14 versus 5 percent, respectively). These men with heightened bother were older, poorer, more anxious, and had lower general psychologic well-being scores than the men whose bother was similar to that expected from their reported frequency. Men whose bother was lower than would be expected were less likely to have sought health care for urinary symptoms in the past year (3%) but were of similar age and socioeconomic status as compared with men whose bother was close to expected. These men, however, were more depressed than men whose bother was commensurate with reported frequency. While the men who reported greater bother than expected from their symptom frequency were more likely to have sought medical care for urinary symptoms in the past year, it is not clear whether this greater health-care-seeking behavior is because bother captures an additional component of urologic disease or is a manifestation of psychosocial differences.

Adult↗

PubMed1993

Flow cytometric DNA ploidy pattern for predicting metastasis of clinical stage I nonseminomatous germ cell testicular tumors.

The best treatment of patients with clinical Stage I nonseminomatous germ cell testicular tumors (NSGCTT) remains controversial. Archival formalin-fixed paraffin-embedded testicular tumor specimens from 23 patients diagnosed between 1977 and 1988 were available for analysis. All patients had clinical Stage I NSGCTT, and the specimens were prepared using Hedley's technique and propidium iodide staining prior to flow cytometric ploidy analysis. Tumors from 3 patients (13%) were classified as DNA diploid; the remaining 20 tumors had DNA aneuploid patterns. Eleven patients had retroperitoneal lymph node dissection (RPLND); 2 (18%) were upstaged to pathologic NSGCTT Stage IIA, and 1 had a subsequent relapse in the contralateral testicle. Among 12 patients in the surveillance protocols, 3 (25%) had tumor recurrence. All patients who were either upstaged to pathologic NSGCTT Stage IIA or had tumor recurrence while under surveillance had DNA aneuploid patterns. The 3 patients with DNA diploid tumor patterns had been in the surveillance protocols. To date, with fifteen months minimum follow-up, none has had tumor recurrence. Such data suggest that flow cytometric DNA ploidy analysis, when used as an adjuvant to more traditional prognostic parameters, may help to identify a group of patients with clinical Stage I NSGCTT at very low risk for recurrence and perhaps well-suited for surveillance management.

Adult↗

PubMed1993

The prevalence of prostatism: a population-based survey of urinary symptoms.

To establish the age-specific prevalence of urinary symptoms among a community-based cohort of men, a randomly selected sample of men were screened and invited to participate in a longitudinal survey of urinary symptoms. The population of Olmsted County, Minnesota, as enumerated by the Rochester Epidemiology Project, formed the sampling base for this study. Men between 40 and 79 years old with no history of prostate or other urological surgery, and who also were free of conditions associated with neurogenic bladder were invited to participate. A previously validated questionnaire was completed by the subject. Urine flow measures, current medications and family histories of urinary disease were also obtained. Nonresponse corrected scores for a composite of obstructive symptoms showed moderate to severe symptomatology among 13% of the men 40 to 49 years old and 28% of those older than 70 years. Prostatism is a highly prevalent symptom complex among unselected men in the community. The specific urinary symptoms of nocturia, weak stream, restarting, urgency and sensation of incomplete emptying are strongly age-related and, therefore, may be predictive of a prostatic disease process.

Adult↗

PubMed1993

Use of fluorescent in situ hybridization for deoxyribonucleic acid ploidy analysis of prostatic adenocarcinoma.

Fluorescent in situ hybridization using 2 chromosome specific centromere probes was evaluated as a method of ploidy analysis in touch preparations from 50 radical prostatectomy specimens. Tumors were classified as aneuploid by fluorescent in situ hybridization when nuclei had an abnormal copy number (aneusomic) for either chromosome centromere 8 or 12. Tetraploid tumors were defined as those with 4 copies (tetrasomic) of chromosome centromeres 8 and 12. The fluorescent in situ hybridization ploidy patterns were compared to the deoxyribonucleic acid (DNA) ploidy patterns subsequently obtained by flow cytometry on the same tissue following paraffin embedding. Concordant fluorescent in situ hybridization and flow cytometry ploidy classification was obtained in 82% of the cases (p < or = 0.0001). Of 7 aneuploid tumors 3 were identified by both methods. Trisomy 8 was detected by fluorescent in situ hybridization in 3 cases that were classified as DNA diploid (2 tumors) and DNA tetraploid (1 tumor). Conversely, flow cytometry detected aneuploidy (hypotetraploidy) in 1 tumor when the fluorescent in situ hybridization results were consistent with tetraploidy. Overall, fluorescent in situ hybridization was more sensitive in aneuploidy detection (6 of 7 cases) than flow cytometry (4 of 7). Of 19 tetraploid cases 5 had discordant fluorescent in situ hybridization and flow cytometry results. However, all 5 cases contained low levels of tetraploidy and the discrepant results were most likely due to the limits of precision of 1 or both methods. In conclusion, we demonstrated that fluorescent in situ hybridization ploidy analysis can be rapidly performed on fresh touch preparations of prostate tissue. This preliminary study demonstrates that the ploidy result determined by fluorescent in situ hybridization correlates well with that obtained by flow cytometry. More complete fluorescent in situ hybridization studies of prostate carcinoma will require additional probes for other chromosomes.

Adenocarcinoma↗

PubMed1993

Natural history of prostatism: urinary flow rates in a community-based study.

Urinary flow rates were measured in a randomly selected community sample of more than 2,000 men 40 to 79 years old with no history of prostate surgery, prostate cancer or certain other diseases known to interfere with normal voiding. Peak urinary flow rates decreased from a median of 20.3 ml. per second in men 40 to 44 years old to 11.5 ml. per second for men 75 to 79 years old, while voided volumes decreased from a median of 355.5 to 222.5 ml. for the same age ranges. Peak flow rates of less than 10 ml. per second were found in 6% of the men aged 40 to 44 years, increasing to 35% among men aged 75 to 79 years. Urological standards for peak urinary flow rate should be based on community data, and should account for age and voided volume. Our study may serve as the starting point for the development of community-based flow rate normal ranges. Nomograms are given to permit estimating flow rate percentiles as a function of age and voided volume.

Adult↗

PubMed1993

Similar levels of urological symptoms have similar impact on Scottish and American men--although Scots report less symptoms.

Urinary symptoms and the extent to which they interfere with living activities were compared in 2 community-based investigations that enrolled men 40 to 79 years old who were randomly sampled from Olmsted County, Minnesota (2,119) and the Forth Valley of Scotland (1,385). Both investigations included symptom questions with wording that is nearly identical to that of the American Urological Association (AUA) symptom index. Following AUA scoring conventions we grouped scores into mild (AUA score 0 to 7), moderate (score 8 to 19) and severe (score 20+) categories. Minnesota men had symptoms that were more frequent, more bothersome and caused greater interference with living activities than did Scottish men of comparable age (p < 0.0002). However, within each symptom score category, the extent to which symptoms interfered with living activities was essentially the same in both populations. Although there appear to be important differences in urinary symptom prevalence between Scotland and Minnesota, the AUA symptom index provides a consistent measure of the extent to which urinary symptoms interfere with living activities in both populations. These findings support use of the AUA symptom index in the diagnostic evaluation of men with benign prostatic hyperplasia.

Adult↗

PubMed1993

Influence of patient age on the serum PSA concentration. An important clinical observation.

Although PSA is a most valuable tool for the practicing physician, it lacks sufficient sensitivity and specificity for detecting early prostate cancer to be the perfect tumor marker. The parameters PSAD and PSA velocity are useful attempts to make PSA a better tumor marker, but they likewise are not always reliable on an individual basis. There is now evidence from several investigations that the serum PSA concentration in healthy men without clinical evidence of prostate cancer increases with advancing age. This is primarily attributable to the concomitant increase in prostate size over the same time period. As a result, age-specific reference ranges have been determined and have the potential to make PSA a more sensitive tumor marker for men less than 60 years of age and a more specific tumor marker for men beyond 60 years of age. If one utilizes the age-specific reference ranges for serum PSA, it appears that PSAD can be eliminated as a parameter in the diagnostic evaluation of patients suspected of having prostate cancer. Thus, a new algorithm utilizing age-specific reference ranges has been developed.

Adult↗

PubMed1993

Renal oncocytoma.

Renal oncocytomas are believed to arise from the intercalated cells of the renal collecting tubules. Specific chromosomal abnormalities, which differentiate oncocytomas from renal cell carcinomas, have been found. Renal oncocytomas exist and behave differently from renal cell carcinomas. Urologic clinical judgement and surgical practice must evolve to keep pace with the knowledge that oncocytomas and renal cell carcinomas are different diseases.

Adenoma↗

PubMed1992

Stage D1 prostate cancer treated by radical prostatectomy and adjuvant hormonal treatment. Evidence for favorable survival in patients with DNA diploid tumors.

BACKGROUND: Stage D1 disease is found in at least every sixth patient undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer (PC). Previous recommendations for monotherapy using surgery, radiation, or systemic therapy alone for Stage D1 disease have usually been associated with a poor outcome in regard to progression and survival. Unlike other pathologic stages, D1 disease treated with RRP is mainly related to DNA ploidy pattern in regard to all end points (progression and survival) and immediate adjuvant hormonal treatment (AHT) rather than to the usual pathologic variables, including the number of positive nodes. METHODS: Complete DNA ploidy information was available in 370 patients with Stage D1 disease (age range, 40-77 years; mean, 64 years) undergoing RRP with or without AHT with a follow-up of up to 22 years (mean, 5 years). RESULTS: Overall, 80% of all DNA ploidy classes (diploid, 37%; tetraploid, 46%; and aneuploid, 17%) had AHT that highly significantly delayed progression for diploid (P less than 0.0001) more than tetraploid (P less than 0.0001) and more than aneuploid (P less than 0.0001) tumors. Significant prolongation of the disease-free interval might have improved the quality of life for tetraploid and aneuploid patients. Survival (crude and cause-specific) was significantly (P = 0.02) improved only for diploid patients who received AHT but not for tetraploid and aneuploid patients. This was due to the significantly accelerated death rate after progression in those patients with early AHT for tetraploid and aneuploid (but not diploid) tumors. Delayed (on progression only) AHT resulted in high progression rates for all DNA ploidy classes (aneuploid greater than tetraploid greater than diploid); e.g., 21 of 30 diploid patients progressed and 6 patients died from disease at a median of 31.5 months in spite of immediate hormone treatment on progression. RRP and AHT for patients with Stage D1 disease resulted in a highly significant delay in overall progression (76% at 10 years) and excellent local control, depending on DNA ploidy pattern (diploid greater than tetraploid greater than aneuploid) compared with a treatment regimen without AHT (24% overall nonprogression); only 20% of all patients with AHT are projected to die of disease at 10 years. Disease in diploid patients (37%) treated with AHT rarely progressed and those patients are unlikely to die of disease in 10 years or less; delayed (on progression) hormone treatment for diploid patients seemed ineffective. Inclusion of values for prostate specific antigen led to a higher failure rate on progression, and this is dependent on DNA ploidy class (diploid greater than tetraploid greater than aneuploid). CONCLUSION: Only patients with nondiploid tumors should be entered into prospective studies using innovative adjuvant treatment protocols to improve survival.

Adult↗

PubMed1992

The clinical significance of nuclear DNA ploidy pattern in 184 patients with pheochromocytoma.

Flow cytometric nuclear DNA analysis was performed on paraffin-embedded tissue samples taken from 184 patients with pheochromocytoma and paraganglioma treated between 1960 and 1987. The Hedley technique was used for measurement of nuclear DNA content. Thirty-five percent of the tumors were DNA diploid, 33% showed a DNA tetraploid pattern, and 32% had DNA aneuploid pattern. Familial pheochromocytoma and associated endocrine or neoplastic disorders were more common among patients with DNA nondiploid tumors. Eighty-four percent of the tumors that invaded blood vessels and all patients with regional or distant metastases had tumors classified as DNA tetraploid or DNA aneuploid. Of 22 patients who had disease progression, 21 (95%) had tumors with abnormal DNA ploidy pattern (P less than 0.001). All 12 patients who died of cancer-related disease had abnormal DNA ploidy; none of the patients with DNA diploid tumor (n = 64) have died of pheochromocytoma (P less than 0.01). These results suggest that nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pheochromocytoma and paraganglioma.

Adrenal Gland Neoplasms↗

PubMed1992

DNA ploidy: early malignant lesions.

The nuclear DNA content of prostate cancer specimens, both needle biopsies and aspiration biopsy specimens as well as transurethral resection (TUR) chips and radical prostatectomy specimens, can now be reliably measured by standardized methods of flow and static image cytometry. For prostate carcinomas of every clinical stage (A1-D2), DNA diploid tumors have a better prognosis than tumors of a similar stage and grade which are non-diploid. Of particular importance to this symposium is the fact that DNA diploid stage D1 and D2 tumors treated early by androgen deprivation generally have a remarkably good prognosis. In contrast, those patients with DNA non-diploid tumors progress early despite androgen deprivation. Such a result suggests that DNA ploidy can be used to identify prostate cancers which are potentially sensitive to hormonal manipulation. Additional investigations from several groups indicate that early stage prostate malignant lesions, for example stages A1, A2, B1, and B2, are generally DNA diploid (about 75%). Swedish data suggest a steady progression of prostate cancer from early diploid to tetraploid, to non-tetraploid aneuploid, to multiple stemline aneuploid tumors with time and advancing stage. Taken together, these data suggest that the earliest detectable prostate carcinomas should be overwhelmingly DNA diploid. A large majority of these patients with early tumors should be candidates for "chemoprevention" by pharmacologic methods which reduce the effective androgen stimulation of prostate tumor cells.

Androgens↗

PubMed1992

Chemoprevention of prostate cancer: guidelines for possible intervention strategies.

The "natural history" of prostate cancer may bedevil the development of guidelines for chemoprevention interventions. Can strategies be designed to direct agents to those lesions which have the potential to develop localized extension that may become symptomatic or metastatic disease? Of necessity our interventions will focus on the identification and quantification of appropriate biomarkers as intermediate endpoints, although no reliable endpoints for prostate cancer have yet been identified. The reduction of prostate cancer incidence may be the ultimate objective, but a decrease in the progression of microfocal or "latent" cancer may well be just as effective as prevention when the age of the target population and competing causes of death are taken into account. Early intervention strategies must focus on the analysis of the interactions of the chosen chemopreventive agents upon precancerous and cancerous cellular dynamics in the prostate. Whether the requirements of such molecular epidemiology necessitate a more deliberate strategy of Phase II studies or a high risk-high gain strategy of a broad Phase III study is open to debate. Factorial designs for proposed randomized chemoprevention trials may be desirable to test multiple chemopreventive agents simultaneously, provided knowledge of the biochemical synergism of the agents is solid. Stratification of study participants by degree of risk will ameliorate concerns regarding the precision targeting of lesions at different stages in the precancer/cancer continuum.

Androstenes↗

PubMed1992

Prognostic profile for patients with pheochromocytoma derived from clinical and pathological factors and DNA ploidy pattern.

Eighty-eight patients with pheochromocytoma and paraganglioma treated over a 28 year period (1960-1987) were studied. Based on clinical course, they were divided into three prognostic groups: benign (n = 57); multiple (n = 12); and metastatic (n = 19). Using clinical data, histopathologic findings, and tumor nuclear DNA content a prognostic profile for each group was constructed. The following variables were studied: age, familial pheochromocytoma, associated endocrine or neoplastic disorders, number and location of the lesion at diagnosis, size of the tumor, and the nuclear DNA ploidy pattern. Of these prognostic factors the most significant to predict a future malignant clinical course were large size and local tumor extension at time of surgery. Family history of pheochromocytoma, associated endocrine disorders, and young age at presentation predicted multiplicity. Old age, absence of familial pheochromocytoma or related endocrine disorders and DNA diploid tumors seem to be favorable findings. Using these variables in combination may be helpful for early identification of patients with malignant, multiple, or benign pheochromocytoma and paraganglioma.

Adrenal Gland Neoplasms↗