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Biomedical subjects

C A Olsson

Publications and source records attributed to C A Olsson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Renal effects of CO2 insufflation: oliguria and acute renal dysfunction in a rat pneumoperitoneum model.

OBJECTIVE: To determine the mechanism by which oliguria develops during raised intra-abdominal pressure secondary to CO2 insufflation, we created a rat pneumoperitoneum model. METHODS: Male Sprague-Dawley rats (n = 67) were organized into three groups. Each group was subjected to abdominal pressures of 0 (control), 5, or 10 mm Hg, over one, two, and four hours. Fourteen additional rats underwent a two-hour period of 10 mm Hg insufflation pressure followed by desufflation to 0 mm Hg. Urine output (UO) and serum creatinine levels were measured both during insufflation at one, two, and four hours, and two, four, ten, and twenty-two hours following its release. These measurements were compared to control values at each time point. Ultrasonic flow probes placed around both the inferior vena cava (IVC) and abdominal aorta during insufflation characterized the effects of increased abdominal pressure on blood flow. The flow rate was determined at insufflation pressures of 0 (control, 100% flow) to 25 mm Hg. RESULTS: Rats subjected to 10 mm Hg pressure had significant decreases in UO (oliguria) compared to controls for up to four hours (P < 0.01). There were no significant differences in UO in the control or 5 mm Hg groups over each time interval. While a reduction in UO was observed at two, four, and ten hours postrelease, significance was achieved only at ten hours (P < 0.006). By twenty-two hours postrelease, no differences in UO were observed. Serum creatinine elevations declined two hours postdesufflation. IVC flow was reduced by 92.9 percent at 10 mm Hg, while arterial flow decreased by 46.4 percent. Flow was restored to preinsufflation levels after release of pneumoperitoneum. CONCLUSIONS: Oliguria can be produced in rats undergoing pneumoperitoneum. The renal effects of pneumoperitoneum are most likely related to renal vascular insufficiency from central venous compression.

Acute Disease↗
PubMed1994

Neurotrophic factors in the rat penis.

An intact nerve supply is essential for normal erectile function. We have undertaken a study to examine the presence and synthesis of growth factors of the penis that support neural function. Extracts were obtained from deskinned penises of Sprague-Dawley rats, aged 3, 6 and 10 weeks, representing prepubertal, pubertal and postpubertal states. Penile extracts were subjected to Northern blot analysis to evaluate expression of nerve growth factor-beta (beta-NGF)-mRNA, PC-12 bioassay to quantitate the nerve growth promoting activity and immunoassay to detect the amount of beta-NGF protein. These initial experiments showed a disproportionately abundant level of nerve growth promoting activity as compared with the levels detected with the immunoassay. The PC-12 bioassay is sensitive to both beta-NGF and fibroblast growth factors (FGFs). To further investigate these findings, the bioassay was conducted again after heparin chromatography, with beta-NGF receptor blockade, or with the addition of anti-beta-NGF, anti-basic-FGF, or anti-acidic-FGF. These studies confirmed that the abundant nerve growth promoting activity in the rat penis is due largely to basic FGF. In conclusion, the neurotrophin NGF is expressed in the rat penis at levels consistent with its expression in other peripheral tissues. Basic-FGF, on the other hand, has been detected at levels far in excess of NGF. Since erectile function is dependent on the integrity of the vascular structure and its intact innervation and since basic FGF presents as an abundant penile growth factor with both angiogenic and neurotrophic activities, basic FGF might play a significant role in erectile physiology.

Animals↗
PubMed1994

Detection and treatment of prostate cancer: perspective of the urologist.

We examine changes in the detection and treatment of prostate cancer from the perspective of the urologist. There has been an extraordinary increase in the incidence of prostate cancer (60% from 1990 to 1993). We calculated, based on data from the literature and assumptions about changes in urological practice, that 52% of newly diagnosed cases would be treated by radical prostatectomy in 1993. Extrapolating from the work of Catalona, we derived the number of office consultations, prostate biopsies and orchiectomies associated with the diagnosis and treatment of these tumors. Applying Health Care Financing Administration reimbursements to our figures, we calculated that each urologist would realize $45,370 for prostate cancer care in the Medicare population in 1993. If all patients 50 to 70 years old were screened by American Cancer Society and American Urological Association recommended algorithms, this projection would be $107,919. Despite this enormous economic impact of prostate cancer on the urologist, uncertainties remain concerning the appropriateness of screening and treatment for this disease. Only increased funding for basic research in prostate cancer will resolve these uncertainties.

Aged↗
PubMed1994

Effect of dosing regimen on efficacy and safety of doxazosin in normotensive men with symptomatic prostatism: a pilot study.

OBJECTIVES: In this pilot study, the effect of dosing schedule on the efficacy and safety of the long-acting alpha 1-adrenergic blocker doxazosin (DOX) was evaluated in 48 consecutive, normotensive men (mean age, 61.2 years) with symptoms of prostatism. METHODS: In this titration to fixed dose study, patients were randomized into 1 of 4 treatment groups: (1) 4 mg DOX once in the AM (n = 12); (2) 4 mg DOX once in the PM (n = 12); (3) 8 mg DOX once in the AM (n = 12); and (4) 8 mg DOX once in the PM (n = 12). Parameters evaluated included Boyarsky symptom score (Sx), peak uroflow (Qmax), blood pressure, and occurrence of side effects. Once stabilized, patients were seen at 3-month intervals; follow-up ranged from 3 to 19 months (mean, 7.7). RESULTS: Clinical improvement as determined by Sx and Qmax was similar for AM and PM groups with either 4 or 8 mg of DOX. Mean decreases in Sx at 3 months were 4.6, 4.2, 5.1, and 5.2 and at 6 months were 4.7, 4.7, 5.3, and 5.4 for the 4 mg AM, 4 mg PM, 8 mg AM, and 8 mg PM, respectively. Mean peak uroflow at 3 months increased 2.7, 2.9, 3.2, and 3.3 mL/s and at 6 months increased 2.6, 3.0, 3.4, and 3.5 mL/s for the 4 mg AM, 4 mg PM, 8 mg AM, and 8 mg PM, respectively (p < 0.05). Six patients (13%) were dropped from the study because of side effects (2 for fatigue, 2 for headache, 2 for dizziness): 5 during the titration phase (4 mg AM: 2; 8 mg AM: 2; 8 mg PM: 1), and 1 during the treatment phase (8 mg AM). CONCLUSIONS: These data suggest that evening dosing does not diminish efficacy yet may enhance toleration of DOX. These preliminary results suggest that a larger prospective study is warranted to determine the optimal dosing and timing of DOX in the management of symptomatic benign prostatic hyperplasia.

Aged↗
PubMed1994

Reconstruction of urinary and gastrointestinal tracts in total pelvic exenteration: experience at Columbia-Presbyterian Medical Center.

OBJECTIVES: To examine the effectiveness of and complications from total pelvic exenteration (TPE) with maintenance of urethral and anal sphincter function for locally invasive tumors of the pelvis. METHODS: A retrospective review of 4 patients who have undergone TPE with urethral and anal sphincter preservation at Columbia-Presbyterian Medical Center in the last 2 years was performed with attention to perioperative morbidity and mortality, disease-free status, and need for further operative procedures. RESULTS: Two patients had colorectal adenocarcinoma, 1 had squamous cell carcinoma of the cervix, and 1 had prostate sarcoma. All had urinary tract reconstruction with orthotopic neobladder creation, and 3 of 4 had primary low rectal anastomoses for gastrointestinal reconstruction. One patient underwent creation of a J rectal pouch. One of 4 patients had received radiation therapy for the disease prior to surgery. There was no operative or perioperative mortality. Two of 4 patients required reoperation, 1 in the immediate postoperative period for repair of a left ureteral stricture, and the other 13 months postoperatively for repair of a rectal-neobladder fistula. With a mean follow-up of 25 months (range, 21 to 43 months), 3 of 4 patients are alive and free of disease. All living patients are continent of urine and 2 of 3 are continent of stool. CONCLUSIONS: Our experience confirms that TPE can be effective in controlling a variety of locally advanced pelvic tumors and can be performed in conjunction with simultaneous genitourinary and gastrointestinal reconstruction with minimal morbidity.

Adenocarcinoma↗
PubMed1993

An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density.

Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is < or = 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is < or = 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1-10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important.2_

Aged↗
PubMed1993

Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat.

We describe early alterations in rat bladder gene expression which may relate to the development of diabetic bladder dysfunction in a streptozotocin model of inducible diabetes. Utilizing cDNA probes, the gene products sulfated glycoprotein-2 (SGP-2), transforming growth factor-beta (TGF-beta), beta-actin (beta-actin), N-ras and beta nerve growth factor (beta-NGF), were quantitated in bladders of male Sprague-Dawley rats at 1, 2, 4 and 6 weeks after induction of diabetes with streptozotocin (STZ). beta-actin and SGP-2 expression were transiently increased at 1 and 4 weeks after induction, respectively. TGF-beta was not altered over the period of the study. N-ras was reduced at all times compared with control rat bladders. Transcripts encoding beta-NGF were dramatically increased in STZ-treated rats at 4 weeks. None of these changes were seen in diuresis control group fed 5% sucrose. Our results suggest that during the early stages of diabetes, cellular hypertrophy, growth and remodeling are occurring concomitantly with cellular injury and programmed cell death. Furthermore, the transient increase in expression of beta-NGF mRNA may represent a compensatory response to the diabetic condition in an attempt to attract further innervation and revascularization.

Actins↗
PubMed1993

Transrectal hyperthermia in the management of men with prostatism: an algorithm for therapy.

Transrectal hyperthermia has been proposed as a potential treatment for benign prostatic hyperplasia (BPH). This report presents our initial experience in an ongoing clinical trial to evaluate the safety and efficacy of transrectal thermal therapy (TRTT) for symptomatic BPH. To date, 24 patients (mean age 60.6 years) have undergone TRTT. In all cases the initial investigations included pre-operative symptom score analysis, synchronous video/pressure/flow urodynamic studies and transrectal measurement of both the size of the prostate and the distance between the applicator and the prostatic urethra (AU). Twenty-one patients completed the study (mean follow-up 6.7 months). There was a significant reduction in symptom score (> 50%) in 14 patients and the peak urinary flow rate (Qmax) increased from 5.9 to 12.4 ml/s at 1 month, 12.7 ml/s at 3 months and 13.2 ml/s at 6 months. In 12 patients the decrease in symptom score and the increase in flow rate exceeded 50%. Five of the 6 patients who failed to respond to treatment had prostate volumes > 85 g; 4 had voiding detrusor pressures < 40 cm H2O and 5 had an AU distance > 2.5 cm. These preliminary results suggest that TRTT may be a potential therapeutic alternative in patients with mild to moderate symptoms of prostatism. However, patients with either lower detrusor pressures (< 40 cm H2O) or very large prostates are unlikely to show a beneficial response. We suggest that large prostates may preclude effective temperature distribution and therefore mitigate the potential therapeutic benefit.

Adult↗
PubMed1993

PSA density (PSAD). Role in patient evaluation and management.

Prostate Specific Antigen (PSA) is the most accurate serum marker for cancer of the prostate. However, sensitivity and specificity are suboptimal, especially at the intermediate levels between 4.1 and 10.0 ng/ml (monoclonal). For intermediate PSA levels, prostate specific antigen density (PSAD) provides unique information regarding the need for biopsy and the likelihood of prostate cancer. This article summarizes the utility of PSAD in diagnosing and treating prostate cancer.

Aged↗
PubMed1993

Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers.

The oncoprotein encoded by bc1-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lymphoma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intraepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bc1-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bc1-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.

Antibodies, Monoclonal↗
PubMed1993

[Radical cystectomy for cancer. Technic].

Radical cystectomy is the treatment of choice for invasive bladder cancer. Morbidity and mortality associated with this procedure have been reduced substantially as a result of advances in surgical techniques and instruments. The cystectomy technique described herein offers satisfactory exposure and hemostasis, thus providing optimal conditions for achieving high-quality urinary diversion.

Cystectomy↗
PubMed1992

Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle.

Castration initiates extensive apoptosis of the secretory epithelial cells lining the ducts of the rat ventral prostate, resulting in the striking regression of this male sexual accessory tissue. We had previously described the paradox of finding similar cascades of gene activity (c-fos greater than c-myc greater than hsp-70) induced during the early period of ventral prostate regression and during the regrowth of the ventral prostate gland initiated by testosterone replenishment. This common pattern of protooncogene expression during periods of predominant cellular apoptosis or proliferation caused us to examine further the possibility that the two cellular events occur through identical early molecular pathways. In the present study we demonstrate that apoptotic prostate epithelial cells incorporate bromodeoxyuridine into nuclear high-molecular-weight DNA prior to nuclear DNA fragmentation. The DNA synthetic activity occurs in coordination with a massive induction of proliferative cell nuclear antigen, a proliferation marker, in the nuclei of androgen-deprived prostatic epithelial cells. Moreover, this activity is also associated with the increased expression of mRNA encoding p53, a suppressor gene well known as a cell cycle-blocking agent. Our data indicate that quiescent (G0) prostate epithelial cells undergo apoptosis due to two sequential events initiated by testosterone depletion. The first event is the active reentry of these cells into the cell cycle. The second event is the apoptotic destruction resulting from the inability of the differentiated cells to successfully complete this cycle.

Animals↗
PubMed1992

The predictive value of flow cytometry and urinary cytology in the followup of patients with transitional cell carcinoma of the bladder.

To determine the predictive value of flow cytometric deoxyribonucleic acid (DNA) ploidy and urine cytology in patients with superficial transitional cell carcinoma of the bladder, a retrospective analysis was performed on 181 patients who presented for evaluation of presumed superficial transitional cell carcinoma of the bladder. Of the patients 91 were confirmed to have superficial transitional cell carcinoma and were systematically followed with cystoscopy, flow cytometry and urine cytology from 1984 until 1989. They underwent 637 evaluations (mean 7 evaluations per patient). At initial evaluation, flow cytometry had 81% sensitivity and 57% specificity, while urine cytology was 75% sensitive and 94% specific. During the followup flow cytometry was 76% sensitive and 36% specific. Urine cytology was less sensitive (40%) but more specific (81%) than flow cytometry in followup evaluation. These results were similar whether intravesical chemotherapy or bacillus Calmette-Guerin was administered. To ascertain whether false positive flow cytometry represented early detection of recurrent transitional cell carcinoma not apparent at cystoscopy, patients with positive flow cytometry and urine cytology were followed longitudinally. False positive flow cytometry and urine cytology were equally predictive of recurrent transitional cell carcinoma progressively with time. However, for any given examination flow cytometry was more likely to detect and predict recurrent transitional cell carcinoma. At 4 years the bladder transitional cell carcinoma incidence for false positive flow cytometry and urine cytology was 87% and 84%, respectively.

Adult↗
PubMed1992

Renal growth factor expression during the early phase of experimental hydronephrosis.

Unilateral ureteral obstruction in the rat leads to hydronephrosis of the affected kidney and renal cell deletion through the process of apoptosis. We studied this experimental model to determine whether acute alterations in renal growth factor expression might be involved in the initiation of the apoptotic response. Northern blot analysis of hydronephrotic, contralateral and sham operated kidney polyadenylated messenger ribonucleic acid (mRNA) was performed to quantitate the expression of mRNA encoding the growth factors epidermal growth factor, transforming growth factor-beta and insulin-like growth factor II during the first 48 hours following ureteral obstruction. Although the expression of the insulin-like growth factor II mRNA was unchanged by ureteral obstruction, the expression of epidermal growth factor mRNA rapidly declined in the obstructed kidney during this period. The loss of epidermal growth factor expression was further confirmed by an immunocytochemical staining procedure that demonstrated high concentrations of epidermal growth factor in control renal tubules and a drastic loss of this staining in obstructed renal tubules. In contrast, expression of transforming growth factor-beta mRNA increased in the obstructed kidney. We believe that the altered growth factor environment of the hydronephrotic kidney might be an initiating factor in the onset of renal apoptosis associated with this condition.

Animals↗
PubMed1992

Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer.

Isolated prostate specific antigen (PSA) determinations in asymptomatic individuals have not demonstrated sufficient sensitivity and specificity to be useful in the routine evaluation of prostate disease. To enhance the accuracy of serum PSA we have used a quotient of serum PSA and prostate volume, which we refer to as prostate specific antigen density (PSAD). Prostate volume in this study was calculated from magnetic resonance imaging determinations of benign prostatic hypertrophy (BPH) or from the dimensions of the surgical specimen of cancer using the formula, length x width x depth x 0.5 = volume. A total of 61 patients with prostatic disease clinically confined to the prostate glands (41 with prostate cancer undergoing radical prostatectomy and 20 with BPH) was evaluated. The mean PSAD for prostate cancer was 0.581 while that for BPH was 0.044 (p less than 0.002). No patient with BPH had a PSAD of greater than 0.117 and only 1 patient had a density of 0.1 or greater. Of 34 patients with a PSAD of 0.1 or greater 33 had prostate cancer. Only 2 of the 41 prostate cancer patients and 14 of the BPH patients had a PSAD of 0.05 or less. There were 11 patients with a PSAD of greater than 0.05 and less than 0.1, including 6 with prostate cancer (1 with P0 disease) and 5 with BPH. Of the 6 prostate cancer patients 5 had a PSA of 4.0 or less and among the 5 patients with BPH 4 had a serum PSA of greater than 4.0 and 1 had a PSA of greater than 10. These results suggest that PSAD may be useful in distinguishing BPH and prostate cancer.

Antigens, Neoplasm↗