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Biomedical subjects

J E Fowler

Publications and source records attributed to J E Fowler.

At least 37 records · Page 2Linked to original sources

Early results of a prospective study of hormone therapy for patients with locally advanced prostate carcinoma.

BACKGROUND: Locally advanced prostate carcinoma is usually not curable with surgery or radiation therapy. Primary hormone therapy is an alternative therapeutic option, but contemporary prospective studies of the outcomes of such therapy are not available. METHODS: The authors conducted a prospective, hospital-based study of gonadal androgen ablation with deferred antiandrogen therapy in 103 men with prostate carcinoma clinically classified as T3-4NXM0. The median potential follow-up was 51 months (range, 36-74 months), and the median period of observation was 43 months (range, 6-74 months). RESULTS: Each patient experienced regression of the primary tumor, and none experienced significant morbidity from the primary tumor during the study period. The projected 5-year cause specific, metastasis free, PSA disease free (no PSA elevation > 1.0 ng/mL after the beginning of antiandrogen therapy), and all-cause survival rates were 84%, 84%, 68%, and 58%, respectively. CONCLUSIONS: Primary hormone therapy is a reasonable treatment option for locally advanced prostate carcinoma in elderly men or in men with significant comorbid disease who request therapeutic intervention.

Aged↗

Fine needle aspiration biopsy of the penis: transitional cell carcinoma of the urinary bladder with mucinous differentiation.

We report a case of transitional cell carcinoma of the urinary bladder metastatic to the penis. The diagnosis was established by fine needle aspiration biopsy (FNAB). Malignant cells showed mucinous differentiation. Ancillary studies carried out in the FNA material as well as in the primary bladder carcinoma suggested transitional cell carcinoma with mucinous differentiation. FNAB proved to be effective in diagnosing a secondary neoplasm to the penis. Mucoid differentiation of urothelial cells can be seen in FNAB specimens and might pose a problem in differential diagnosis.

Biopsy, Needle↗

A randomized prospective study of transurethral electrovaporization vs laser ablation of the prostate in men with benign prostatic hypertrophy.

OBJECTIVE: A prospective randomized study comparing transurethral electrovaporization (TVP) vs laser ablation of the prostate was undertaken to compare the efficacy and safety of the procedures. METHODS: A total of 31 patients underwent treatment, with 20 patients receiving electrovaporization surgery and 11 patients undergoing laser treatment. Patients underwent initial evaluation consisting of an American Urological Association (AUA) symptom score, prostate specific antigen (PSA), uroflowometry, pressure flow, and transrectal ultrasound for prostate volume. Patients were seen in follow-up at 1, 3 and 6 months. RESULTS: A total of 31 patients with a 2:1 randomization of TVP to laser treatment were enrolled. The laser patients had a mean pre-operative AUA symptom score of 19.0 and scores of 9.0, 6.0 and 5.0 at 1-, 3- and 6-month follow-up. The TVP patients had a mean pre-operative symptom score of 22.0 and scores of 7.0, 8.0 and 5.0 at 1-, 3- and 6-month follow-up. Mean peak uroflow (PF) rate pre-operative was 10.7 for the laser group and 7.7 for the TVP group. At 1-, 3- and 6-month follow-up, mean PF rates of 13.3, 17.6 and 16.5 were present for the laser patients and 15.0, 17.5 and 14.2 for the TVP group. The differences were not statistically significant. There were 6 complications in the laser patients and 7 complications in the TVP group. Operative time was a mean of 27 min for the laser patients and 46 min for the TVP group, and the difference in operative time was statistically significant. CONCLUSION: At 6-month follow-up the improvement in symptoms score and peak flow rate are comparable in both treatment groups. The electrovaporization procedure required significantly longer to perform than the laser procedure. Long-term follow-up is required to see if these results remain sustainable for electrovaporization therapy.

Aged↗

Prostate cancer detection in candidates for open prostatectomy.

PURPOSE: We determine the incidence of biopsy detectable prostate cancer in men with clinical benign prostatic hyperplasia (BPH) and prostate specific antigen (PSA) elevation who are candidates for open prostatectomy, and the histology of prostatic tissue of men who underwent surgery. MATERIALS AND METHODS: Sextant peripheral zone prostate biopsies were performed in 128 consecutive men with obstructive voiding symptoms who had digital rectal examination not suspicious for cancer, PSA greater than 4.0 ng./ml. and prostate volume 75 ml. or greater. Of the patients 59 also underwent transition zone biopsy. Median PSA was 9.9 ng./ml. (range 4.1 to 80.0), median prostate volume was 92 ml. (range 75 to 220), median PSA density was 0.10 ng./ml./ml. (range 0.03 to 0.80) and median percent free PSA in 43 patients was 23.6 (range 8.8 to 41.3). RESULTS: Of the 128 patients 16 (13%) had malignant biopsy including 1 who had cancer detected with transition zone biopsy only. Gleason score of tumors ranged from 4 to 8 (median 5). Of 57 patients who underwent prostatectomy 6 (11%) had stage T1a and 2 (4%) had stage T1b cancer. Among men without an indwelling urethral catheter due to acute urinary retention mean PSA, PSA density and percent free PSA were not significantly different in those with benign and malignant biopsies and/or prostatectomy specimens. CONCLUSIONS: Greater than 10% of men with PSA elevation who are potential candidates for open prostatectomy will have biopsy detectable prostate cancer. This diagnostic yield, while lower than that reported for unselect men with normal digital rectal examination and PSA elevation, may justify preoperative peripheral zone biopsy to avoid surgical misadventure during open enucleation. Among patients with benign peripheral zone biopsy there is a less than 5% prevalence of large volume tumors that may complicate open enucleation.

Aged↗

Clinical experience with the Storz Modulith SL 20 lithotriptor.

BACKGROUND: A Food and Drug Administration pre-market approval study evaluated the safety and effectiveness of the Storz Modulith SL 20 lithotriptor. METHODS: Protocol was a maximum of 2,000 shock waves per treatment and no more than three treatments per patient. Safety and effectiveness parameters were defined and followed. RESULTS: The overall success rate was 74.6% with a stone-free rate of 63.6%. No clinically or statistically significant adverse trends were noted acutely or in follow-up. CONCLUSIONS: The Storz Modulith SL 20 lithotriptor is a safe and effective device to treat renal and ureteral calculi in an outpatient setting using intravenous sedation/analgesia.

Adult↗

Electrovaporization of the prostate versus laser ablation of the prostate in men with benign prostatic hypertrophy: a pressure-flow analysis.

PURPOSE: To urodynamically assess the outcome results in a prospective cohort study of electrovaporization of the prostate (TVP) versus laser ablation of the prostate (LAP) in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A randomized cohort of 10 men were enrolled to undergo a TVP procedure and a second cohort of 10 patients to undergo LAP. Preoperatively and at the 6-month follow-up all patients underwent a pressure-flow urodynamic study. Transrectal ultrasound for prostatic volume was performed at the time of enrollment and at the 6-month follow-up. RESULTS: Preoperatively, all patients except 1 were in the obstructed or equivocal range according to the Abrams-Griffin nomogram. At the 6-month follow-up the mean maximum detrusor pressure (Pdet) maximum flow rate (Qmax) for both groups of patients moved into the equivocal range. The mean prostatic volume for the TVP patients decreased 20% in comparison to a 2% decrease in prostatic volume for LAP patients. Both groups experienced similar decreases in the American Urological Association (AUA) symptom scores and increases in peak flow rates at the 6-month follow-up. CONCLUSION: Both treatment groups demonstrated a relief in symptoms by urodynamic assessment and AUA symptom score. This was present even though both groups had only a minimal decrease in prostatic volume. A reduction in prostate volume does not appear to be a prerequisite for improvement of symptoms from BPH.

Aged↗

Trends in diagnosis of stage T1a-b prostate cancer.

PURPOSE: Stage T1a-b prostate cancer comprised about 44% of newly diagnosed local prostate cancer cases in the United States before the advent of medical and minimally invasive treatments for symptomatic benign prostatic hyperplasia (BPH) and before the widespread use of prostate specific antigen (PSA) testing in men with BPH. Information about the impact of these advances on detection of T1a-b cancer is not available. MATERIALS AND METHODS: Prevalence of T1a-b prostate cancer was determined in 1,554 consecutive men who underwent surgical prostatectomy for suspected BPH at a Veterans Affairs Medical Center from 1985 through 1996. Since 1991 a PSA blood test was obtained routinely before surgery and patients with PSA greater than 4.0 ng./ml. usually underwent ultrasound guided prostate biopsy. RESULTS: The number of T1a-b cancer cases was relatively stable during 1985 to 1990 but declined from 36 in 1990 to 9 in 1996. There were no temporal trends in proportion of prostatectomy patients with T1a-b cancer and the decline in cancer detection paralleled less frequent use of surgical prostatectomy for treatment of BPH. The proportion of prostatectomy patients with T1a-b cancer was similar in 1985 to 1990 and in 1991 to 1996 but the percentage of Gleason 7 to 10 cancers declined from 26 in 1985 to 1990 to 10 in 1991 to 1996 (p < 0.0001). PSA and PSA density of evaluable patients with cancer were significantly greater than in evaluable patients with BPH. Of 105 patients with PSA greater than 4.0 ng./ml. who underwent preoperative prostate biopsy 16 (15%) had T1a-b cancer. CONCLUSIONS: The less frequent use of surgical prostatectomy at our institution has produced marked decline in detection of T1a-b cancer. If representative of national trends this experience suggests that many men with obstructive voiding symptoms and T1a-b cancer will remain undiagnosed and that periodic monitoring to identify unsuspected cancer is important in men who are treated with medical or minimally invasive therapies for BPH. Decline in detection of T1a-b cancer may also confound the accuracy of projected incidence rates of local prostate cancer in the United States.

Aged↗

Prostate specific antigen in black and white men after hormonal therapies for prostate cancer.

PURPOSE: Prostate cancer deaths usually result from proliferation of the androgen independent malignant phenotype, and in the United States the survival of black men with metastatic cancer is less favorable than that of white men. We compared prostate specific antigen (PSA) functions after hormonal therapies in men of both races to investigate potential differences in the biology of androgen independent cancer. MATERIALS AND METHODS: The PSA nadir after gonadal androgen withdrawal was determined in 217 black and 188 white men with localized or metastatic cancer. The time to PSA elevation and PSA doubling time were determined in 62 black and 27 white men with biochemical relapse. Biochemical response to deferred flutamide treatment and flutamide withdrawal was assessed in 87 and 11 black and 30 and 10 white men, respectively. RESULTS: There were no significant racial differences in the PSA nadir when controlled for clinical stage and pretreatment PSA, or in PSA doubling time when controlled for clinical stage, PSA nadir and month of PSA elevation. The biochemical response to deferred flutamide therapy and flutamide withdrawal was the same in black and white men. CONCLUSIONS: The burden and growth rate of androgen independent cancer estimated from PSA functions after gonadal androgen withdrawal, and the impact of deferred antiandrogen therapy on the serum PSA are similar in black and white men. These findings suggest that racial differences in the biology of androgen independent carcinoma do not contribute to the inferior survival of black men with metastatic prostate cancer.

Aged↗

Plant cell morphogenesis: plasma membrane interactions with the cytoskeleton and cell wall.

Because plants are composed of immobile cells, plant morphogenesis requires mechanisms allowing precise control of cell expansion and cell division patterns. Cortical domains, localized in response to directional cues, are of central importance in establishing cell polarity, orienting cell division, and determining daughter cell fates in a wide variety of prokaryotic and eukaryotic organisms. Such domains consist of localized macromolecular complexes that, in plant cells, provide spatial control of cell expansion and cell division functions. The role of the cytoskeleton, plasma membrane, and targeted secretion to the cell wall in the spatial regulation of cell morphogenesis in plants is discussed in light of recent results from model organisms, including brown algal zygotes (e.g. Fucus). A general model, emphasizing the importance of cortical sites and targeted secretion, is proposed for morphogenesis in higher plant cells based on current knowledge and principles derived from analysis of the establishment of a stable cortical asymmetry in Fucus. The model illustrates mechanisms to direct the orientation of an asymmetric division resulting in daughter cells with different fates.

Animals↗

Sectors expressing the homeobox gene liguleless3 implicate a time-dependent mechanism for cell fate acquisition along the proximal-distal axis of the maize leaf.

The longitudinal axis of the maize leaf is composed of, in proximal to distal order, sheath, ligule, auricle and blade. The semidominant Liguleless3-O (Lg3-O) mutation disrupts leaf development at the ligular region of the leaf midrib by transforming blade to sheath. In a previous study, we showed that leaf sectors of Lg3 mutant activity are cell nonautonomous in the transverse dimension and can confer several alternative developmental fates (Fowler, Muehlbauer and Freeling (1996) Genetics 143, 489-503). In our present study we identify five Lg3 sector types in the leaf: sheath-like with displaced ligule (sheath-like), sheath-like with ectopic ligule (ectopic ligule), auricle-like, macro-hairless blade and wild-type blade. The acquisition of a specific sector fate depends on the timing of Lg3 expression. Early Lg3 expression results in adoption of the sheath-like phenotype at the ligule position (a proximal cell fate), whereas later Lg3 expression at the same position results in one of the more distal cell fates. Furthermore, sheath-like Lg3 sectors exhibit a graded continuum of phenotypes in the transformed blade region from the most proximal (sheath) to the most distal (wild-type blade), suggesting that cell fate acquisition is a gradual process. We propose a model for leaf cell fate acquisition based on a timing mechanism whereby cells of the leaf primordium progress through a maturation schedule of competency stages which eventually specify the cell types along the proximal to distal axis of the leaf. In addition, the lateral borders between Lg3 'on' sectors and wild-type leaf sometimes provide evidence of no spreading of the transformed phenotype. In these cases, competency stages are inherited somatically.

Gene Expression Regulation, Plant↗

Genetic analysis of mutations that alter cell fates in maize leaves: dominant Liguleless mutations.

The three major components of the maize leaf are the blade, the sheath, and at their junction, ligular region. Each exhibits specific cell types and organization. Four dominant Liguleless (Lg) mutations (Lg3-O, Lg4-O, Lg*347, and Lg*9167) in at least three different genes cause a similar morphological phenotype in leaves, although each mutation affects a distinct domain of the blade. Mutant leaves display regions of altered cell fate in the blade, accompanied by elimination of ligule and auricle at their wild-type positions and development of ligule and auricle in the blade at the borders of the altered regions. The affected blade cells are transformed into sheath-like cells, as determined by morphological and genetic tests. Lg4-O expressivity is highly dependent on genetic background. For example, two different backgrounds nay specify converse patterns of phenotypic expression. Lg4-O expressivity is also affected by the heterochronic mutation Teopod2 (Tp2). Gene dosage experiments indicates Lg4-O is a neomorph. Interactions between recessive lg mutations (which eliminate ligular structures) and the dominant Lg mutations suggest that the lg+ genes act after the Lg mutations. Lg3-O and Lg4-O act semidominantly, and interact with each other and with other mutations in the Knotted1 (Kn1)-like family (a family in which dominant mutant alleles cause blade to sheath transformation phenotypes). These interactions suggest that the above Kn1-like mutations may function similarly in the leaf. We discuss the similarities between the Lg mutations and the other mutations of the Kn1-like family, which led us to postulate that Ig3 and Ig4 are members of a growing family of kn1-like (knox) homeobox genes that are identified by dominant mutant alleles causing leaf transformation phenotypes. We also propose that certain key characteristics of this family of dominant neomorphic mutations are important for generating meaningful morphological changes during evolution.

Alleles↗

Neointimized Gore-Tex graft for ureteral prosthesis in the dog.

OBJECTIVES: To determine the feasibility of replacing a ureteral segment with a neointimized Gore-Tex graft. METHODS: Seven adult mongrel dogs underwent a two-stage operative procedure. The first procedure involved arterializing the graft to stimulate spread of a luminal neoendothelium by transmural capillary growth. Eight weeks after the initial procedure, a segment of the ipsilateral ureter was replaced with a segment of the neointimized graft. RESULTS: Histologic evaluation of a portion of the graft removed during the second procedure demonstrated transmural neocapillary ingrowth in all grafts; however, there was no neoendothelial growth on the luminal surface. In 5 dogs the graft was occluded with blood clot and was not suitable for a ureteral prosthesis. In 2 dogs the graft was patent and was successfully incorporated into the urinary system. After 1 year of observation, both of these dogs maintained a patent ureter and had no evidence of hydronephrosis on intravenous urogram. CONCLUSIONS: These data demonstrate that a Gore-Tex graft can be used as a ureteral prosthesis in the dog. The importance of preliminary arterialization, however, remains to be determined.

Animals↗

Mosaic analysis of the liguleless3 mutant phenotype in maize by coordinate suppression of mutator-insertion alleles.

Liguleless3-O (Lg3-O) transforms the leaf blade, auricle and ligule into sheath around the midrib region. We conducted a genetic mosaic analysis of the Lg3 phenotype to determine the site of Lg3 gene action. Combining the Mutator (Mu) suppressible Lg3-Or211 and a1-mum2 alleles in a Mu-active background generated a stock wherein somatic loss of Mu activity resulted in anthocyanin-marked clonal sectors expressing Lg3 in the leaf. Lg3-Or211 plants appear wild type in a Mu-active line, but Mu-inactive plants express a severe Lg3 phenotype. We observed four sector classes: wild type, sheath-like with ligule displacement, sheath-like with ectopic ligule, and auricle-like. The mutation does not cause transformation to a specific cell or regional identity. Lg3-Or211 activity in the mesophyll alters wild-type epidermal cell fates; activity in epidermis seems functionless. Lg3 mutant activity has a nonautonomous, cell-layer-specific function in the transverse dimension. In the lateral dimension, sectors of Lg3 mutant phenotype can exhibit either cell-autonomous or nonautonomous effects. Our work demonstrates that mosaic analysis by coordinate suppression of Mu-induced alleles is useful for analyzing the cell autonomy of genetically defined functions.

Alleles↗

Survival in blacks and whites after treatment for localized prostate cancer.

PURPOSE: Racial differences were assessed in all cause and disease related actuarial survivals after treatment for localized prostate cancer. MATERIALS AND METHODS: We studied 148 black and 209 white men with clinical stages T1b to 4NXMO prostate cancer treated with surgery or radiation therapy between 1980 and 1991 at a Veterans Affairs medical center. RESULTS: After a median potential followup of 96 months, there were no significant differences in the all cause, cause specific, metastases-free, clinical disease-free or prostate specific antigen disease-free survivals in 109 black and 167 white men with stages T1b to 2 cancer treated with surgery or radiation therapy, or in 39 black and 42 white men with stages T3 to 4 cancer treated with radiation therapy. CONCLUSIONS: Race appears to have no impact on the stage specific actuarial survivals in men with localized prostate cancer treated with surgery or radiation therapy in an equal access health care system.

Actuarial Analysis↗