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Biomedical subjects

C A Olsson

Publications and source records attributed to C A Olsson.

At least 109 records · Page 6Linked to original sources
PubMed1992

The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen.

Prostate specific antigen (PSA) is an extremely valuable tumor marker. However, its use in detection is limited by its low positive and negative predictive values. The ability of serum PSA to distinguish between benign and malignant prostatic conditions is particularly poor in the intermediate range of 4.1 and 10 ng./ml. by the Hybritech assay. We used transrectal ultrasound determined prostate volumes in a well characterized population of 533 men to form a serum PSA/prostate volume ratio called prostate specific antigen density (PSAD). The prevalence of cancer in the entire population was 18.4%. Discriminant analysis according to negative or positive outcome allowed for the construction of nomograms, which resulted in a PSAD defined cancer risk ranging from 3 to 100%. Predictive value nomograms created from PSAD may allow for a more individualized approach to evaluation of patients with intermediate levels of Hybritech serum PSA.

Aged↗
PubMed1992

Prostatic and periprostatic interstitial temperature measurements in patients treated with transrectal thermal therapy (local intracavitary microwave hyperthermia).

One of the questions raised regarding the use of transrectal thermal therapy in the treatment of benign prostatic hyperplasia (BPH) is whether there is a uniform and safe temperature distribution within the prostate. Our study represents the first attempt in humans to map the interstitial thermal distribution in the prostate during transrectal thermal therapy. With the patient under local anesthesia and under ultrasound guidance, a transperineal 3-point thermocouple was placed into various areas of the prostate in 15 patients. Prostatic-urethral thermocouple distance ranged from 1 to 3 cm. A urethral catheter containing a 5-point linear array thermocouple was placed and the balloon was inflated so that the proximal point was at the bladder neck and the remaining points were at 1 cm. intervals along the prostatic urethra. Power (25 watts) was delivered via the Primus (Technomatix) transrectal microwave applicator with simultaneous cooling of the rectal mucosa (between 12 and 14C). Treatment was delivered for 60 minutes and temperatures were recorded. In the prostatic substance a maximal temperature of 45C was observed during the heat-up phase and this decreased as the vasoactive response occurred. Temperature along the prostatic urethra varied between 40 and 43C and never exceeded 44C. A similar distribution of temperature was registered in the thermocouple points in the prostatic substance. The anticipated thermal dose of 41.5 +/- 1C for 60 minutes was achieved in the prostatic substance as measured by the sensors in the prostatic urethra and interstitial sensors. The results suggest that transrectal thermal therapy delivers a uniform and safe distribution of heat in the prostatic substance and urethra. Clinical trials are currently underway to ascertain the efficacy of transrectal thermal therapy in the management of BPH.

Adult↗
PubMed1992

Analysis of continent versus standard urinary diversion.

The seemingly high complication and re-operation rates associated with continent urinary diversion have led some to criticize its morbidity and question its role in reconstructive urological surgery. We therefore reviewed our experience with all patients undergoing either continent or standard urinary diversion performed by 3 urological surgeons during a specified 3-year period. In 73 consecutive patients (22 continent urinary diversion, 51 standard urinary diversion), no significant difference was demonstrated with respect to the number of post-operative in-hospital days, complication rate, re-operation rate and operative mortality rate between the 2 groups. While those undergoing continent diversion were on average younger and healthier than their counterparts receiving standard diversion, stratification of patients in each group according to age and a pre-operative "fitness" score showed no significant difference in operative mortality or major morbidity between comparable patients in each group. The mean post-operative length of hospital stay was, however, 3 days shorter for the youngest and fittest patients receiving standard versus continent urinary diversion.

Adult↗
PubMed1992

Urinary diversion.

The patient facing cystectomy now has the opportunity to select various forms of urinary diversion. Although not all of the newer techniques have stood the test of time, preliminary results indicate that these continent diversions should be considered safe and effective. These procedures definitely alter the patient's lifestyle, resulting in a significantly better adjustment to the need for bladder removal. With experience, these procedures can be performed with morbidity rates very similar to those encountered with ileal conduit diversion. As with any procedures, however, appropriate patient selection and surgical training are imperative.

Carcinoma, Transitional Cell↗
PubMed1992

Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia.

A multiparametric analysis to demonstrate that even brief periods of arterial clamping can initiate extensive cell loss in a rat kidney through the process of apoptosis during the 48-hour period after reperfusion was performed. Microscopic examination of rat renal tissues subject to a 5-, 30-, or 45-minute period of complete ischemia showed the presence of apoptotic bodies both within and occasionally between renal tubules, appearing as early 12 hours after reperfusion, and increasing in numbers at 24 hours. Furthermore, DNA extracted from such reperfused renal tissue demonstrated the appearance of a distinct "ladder" pattern of DNA fragments after electrophoresis in agarose gels, a phenomenon commonly associated with cells undergoing apoptosis and in contrast to the predominant smear pattern obtained after electrophoresis of DNA extracted from necrotic renal tissue. Finally, messenger RNA (mRNA) encoding sulfated glycoprotein-2, a gene product previously identified to apoptotic renal cells, was found to be highly expressed in the 30-minute arterial clamped rat kidney after 24 hours of reperfusion, but was not detectable in mRNA extracted from renal tissue after 24 hours chronic infarction. This study demonstrates that a combination of morphologic, biochemical, and molecular markers can be used to distinguish predominant modes of cell death in varying forms of tissue injury. Application of these analytical techniques to renal vascular injury has distinguished that brief periods of complete ischemia initiates a form of cell death (apoptosis) during a subsequent reperfusion phase that is drastically different from cellular necrosis induced by prolonged severe ischemia.

Animals↗
PubMed1991

Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications.

We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

SGP-2 expression as a genetic marker of progressive cellular pathology in experimental hydronephrosis.

The onset of hydronephrosis following unilateral ureteral obstruction is associated with the induced expression of RNA and proteins encoded by the SGP-2 gene. SGP-2 expression has been shown to demarcate mammalian cells undergoing apoptosis. Using in situ hybridization, the cellular localization of SGP-2 expression in the obstructed kidney was determined as a means to study the various phases involved in the progression of hydronephrosis. Within 30 minutes of obstruction, SGP-2 mRNA expression was localized to the adventitial layers of the hilar arteries and intrarenal arterioles. Increasing time of obstruction resulted in the notable absence or depletion of this layer. In addition, the pattern of SGP-2 expression changed with time to the collecting ducts and distal tubules. This study identifies the vascular support tissue of the kidney as the initial site of reaction and potential cell death following ureteral obstruction. We believe that this observation may be of importance in explaining the early alterations in blood flow associated with hydronephrosis.

Animals↗
PubMed1990

Chromosomal assignment of the human homologue encoding SGP-2.

Although originally characterized as a constitutively expressed gene product in mammalian Sertoli cells, sulfated glycoprotein-2 (SGP-2) has gained widespread attention due to its remarkably rapid and sizable induction in numerous types of mammalian cells undergoing apoptosis, or programmed death. In order to identify the chromosomal assignment for the human homologue of SGP-2, we performed Southern blot analysis of Bgl II restricted genomic DNA extracted from a panel of cloned hamster-human hybrid cell lines and screened for the presence of restriction fragments homologous to SGP-2. The results of this analysis indicate that the human homologue of SGP-2 resides on chromosome 8.

Animals↗
PubMed1990

Flow cytometric analysis of localized adenocarcinoma of the prostate: the use of archival DNA analysis in conjunction with pathological grading to predict clinical outcome following radical retropubic prostatectomy.

Fifty-four specimens from patients undergoing radical prostatectomy for clinically confined prostate cancer between 1983 and 1987 were reviewed to determine the potential for flow cytometric (FCM) analysis of DNA ploidy and replication rate to predict disease recurrence. Each specimen was deparaffinized for FCM analysis and the pathology slides were reviewed by a single pathologist. FCM characteristics were correlated with pathological grade and stage, and both were correlated with disease status. In this series of patients, routine FCM analysis of DNA ploidy and replication rate failed to significantly enhance the ability of standard histopathological grading to predict disease recurrence in patients having clinically localized prostate cancer. Aneuploid tumors pathologically confined to the prostate did not appear to negatively affect prognosis.

Adenocarcinoma↗
PubMed1990

Ureteral reconstruction and bypass: experience with ileal interposition, the Boari flap-psoas hitch and renal autotransplantation.

A total of 18 patients underwent an operation for extensive ureteral loss from 1980 to 1986. The indications included recurrent calculi, retroperitoneal fibrosis, surgical trauma and tumor. Of the patients 10 had construction of an ileal ureter (4 had bilateral reconstruction), 6 had creation of a psoas hitch with a Boari bladder tube and 2 were treated by autotransplantation. Mean duration of followup was 4.8 years. The procedure was successful in 17 patients. There were no apparent differences among the groups. Selection criteria and potential complications are discussed with regard to each technique. These procedures provide an excellent means for reconstruction of the urinary tract in patients who have failed other treatments.

Adult↗
PubMed1990

Characterization of the products of a gene expressed during androgen-programmed cell death and their potential use as a marker of urogenital injury.

Regression of the rat ventral prostate gland following castration is accompanied by the induced expression of messenger RNA encoding Testosterone Repressed Prostate Message-2 (TRPM-2). Subsequent studies have shown that this gene is also induced during renal injury. In each of these tissues, the TRPM-2 RNA products are expressed by cells undergoing programmed death as a result of the hormonal stimuli or the traumatic insult. In an attempt to characterize this gene and its products, we partially sequenced complementary DNAs for TRPM-2 isolated from a recombinant library constructed using RNA of a hydronephrotic kidney. The sequence of these clones showed close homology with the sulfated glycoprotein-2 (SGP-2/clusterin) gene, expressed constitutively by mammalian Sertoli cells. Antibody recognition studies confirm this homology. Antiserum made against rat clusterin recognized TRPM-2 encoded polypeptides in extracts of regressing rat ventral prostate glands. Western blot analysis allowed us to demonstrate large increases in the concentration of these proteins in extracts of regressing ventral prostate gland and in rat serum and urine during the acute period of prostatic regression. These results indicate that proteins are synthesized from the large amount of TRPM-2 RNA produced by dying prostate cells and imply that these proteins are shed into the serum and urine. Based on the intense synthesis of TRPM-2 gene products by dying cells in the urogenital tract and the ability to assay for these products in serum and urine, we suggest that an assay for TRPM-2 products might allow us to monitor the extent of cellular damage associated with specific urogenital disease states.

Animals↗
PubMed1990

Influence of retinoids on bladder cancer growth as detected by primary tissue culture.

The ability of the retinoid compounds, all-trans and 13-cis, to inhibit the growth of bladder tumour cells was investigated in primary tissue culture. A significant decrease in tumour growth was evident in 9 human bladder cancer patients. Since retinoid compounds are able to delay the progression or induction of tumours in primary tissue culture, their trial use as intravesical agents may be warranted.

Cell Division↗
PubMed1990

Immediate induction of c-fos and c-myc transcripts following unilateral nephrectomy.

Unilateral nephrectomy in the rat results in contralateral compensatory renal growth. The immediate molecular events which occur in the remaining renal unit were studied by examining RNA isolated from these kidneys. Northern blot analysis was used to analyze the expression of the growth-related (c-fos and c-myc) genes during the 1-hour period following unilateral nephrectomy. Both c-fos and c-myc band transcripts were detected within 15 min after nephrectomy. The immediate, transient induction of these genes in the remaining renal unit mimics that seen during proliferative stimulation of cultured cells and may play a role in modulating the eventual compensatory growth response.

Animals↗
PubMed1989

Gene activity during the early phase of androgen-stimulated rat prostate regrowth.

Androgenic steroids regulate the proliferation rate of normal and malignant prostate cells. In order to investigate the molecular basis of this control, we utilized Northern and Western blot techniques to measure changes in the expression of individual genes during the early phase of prostate regrowth. Vestigial ventral prostate glands of 7-day castrated rats showed increased numbers of replicating cells within 12 h of continuous pharmacological testosterone replacement as demonstrated by flow cytometric procedures. The period prior to the onset of proliferative enhancement was accompanied by the sequential induction of a variety of transcripts encoding gene products often associated with cell growth. Within 1 h of treatment, mature mRNA transcripts for c-fos were induced 6-fold, returning to control levels by 2 h. Other genes showed transiently elevated transcript levels after 2 h (c-Ha-ras, c-Ki-ras) or after 8 h (c-myc,c-myb, beta-actin, and Mr 70,000 heat shock protein) of testosterone replacement. Expression of the polypeptide encoded by c-Ha-ras was coordinately enhanced (2-fold) during this period, but not to the levels of the transcript (20-fold induction). Transcripts encoding basic fibroblast growth factor were increased 16 h and later, subsequent to the earlier enhancement in the proliferation rate. By placing these genes in a defined temporal order with regard to their expression in response to testosterone, we have constructed a map of gene activity during early prostate regrowth. This map shows a number of genes, the products of which might participate in the mechanism by which androgens induce mitogenesis of prostate cells.

Animals↗
PubMed1989

Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of urinary bladder: cause for concern.

Twenty-one patients with high-stage transitional cell carcinoma (TCC) of the bladder were treated with a combination of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC). There was a minimum follow-up of thirty-six months (range 36-45) in all patients. Patients were divided into three groups: 10 patients with recurrent TCC post radical cystectomy, 6 patients staged as T3/T4 or N1 treated in a neo-adjuvant setting, and 5 patients who received adjuvant M-VAC four weeks post radical cystectomy. The overall initial response rate in patients with measurable disease was 68 percent (11 of 14), complete response rate 31 percent, and partial response rate 37 percent. There was no response in 31 percent. The durability of response in this series was very disappointing with all complete responders having recurrence of disease, with duration of responses ranging from eight to twenty-one months. Of the 5 patients who received M-VAC as adjunctive therapy, only 1 remains disease-free; the other 4 patients experienced disease progression four to seventeen months postoperative, and all have died. There was one drug-associated death due to nadir sepsis, and myelosuppression occurred in 12 patients. While M-VAC seems to be the best protocol currently available, the real durability of response is most disappointing.

Aged↗
PubMed1989

Gene expression in response to acute unilateral ureteral obstruction.

Acute unilateral ureteral obstruction results in differential growth characteristics of both the ipsilateral and contralateral kidney. The obstructed kidney undergoes cellular atrophy following an initial phase of interstitial proliferation while the contralateral kidney hypertrophies. To evaluate the molecular events occurring in both kidneys after obstruction, we examined the expression of growth related (c-fos, c-myc, cH-ras, HSP 70), cell maintenance (beta-actin), and cellular damage (TRPM-2) genes at the mRNA level. In the contralateral kidney an early and transitory induction of c-fos and c-myc expression occurred while a bimodal induction was noted in the obstructed kidney. The patterns of cH-ras, HSP 70 and actin expression also differed in both kidneys. Induction of TRPM-2 was noted only in the obstructed kidney. Rapid gene activation is evident in both the contralateral and obstructed kidney following unilateral ureteral obstruction. The patterns of expression are distinct and may reflect the cellular response to stress (cell death and stromal proliferation) in the obstructed kidney versus a response to a systemic stimulus resulting in cellular hypertrophy in the contralateral kidney.

Acute Disease↗