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Biomedical subjects

E M Messing

Publications and source records attributed to E M Messing.

At least 19 recordsLinked to original sources
PubMed2003

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Adult↗
PubMed2001

Localization of androgen receptor expression in human bone marrow.

Androgens have been shown to modulate the haematopoietic and immune systems and have been used clinically for stimulating haematopoiesis in bone marrow failure conditions. To identify the bone marrow cell types as potential targets of androgens, an androgen receptor (AR)-specific antibody was used to localize the AR in normal human bone marrow biopsies. The results show that AR was ubiquitously expressed in the bone marrow of both males and females. Furthermore, the AR expression pattern did not change with age. Stromal cells, macrophages, endothelial cells, myeloblasts, myelocytes, neutrophils, and megakaryocytes expressed AR. In contrast, AR was not detected in the lymphoid and erythroid cells, or in eosinophils. These results indicate that androgens may exert direct modulating effects on a wide spectrum of bone marrow cell types via AR-mediated responses.

Adolescent↗
PubMed2001

Automated noninvasive measurement of cyclophosphamide-induced changes in murine voiding frequency and volume.

PURPOSE: We developed an automated noninvasive method for studying bladder function in mice. Changes in voided volume and frequency accompanying cyclophosphamide-induced cystitis were measured using computerized digital balances. MATERIALS AND METHODS: Eight CRL CD-1 mice were given a solution of glucose and saccharin to increase urine output and studied during the dark cycle, when most voiding occurs. Urine fell directly onto electronic balance pans. The time and weight of each void was recorded. Computer programs adjusted for evaporative loss analyzed voiding data within and across sessions. After establishing stable voiding patterns 300 mg./kg. cyclophosphamide were administered intraperitoneally. The Wilcoxon signed rank test was done to compare median voided volumes, frequency and gm. per hour of urine produced before and after cyclophosphamide. RESULTS: We implemented an automated method for voiding studies in mice. After cyclophosphamide administration the number of voids per hour increased and voided volume decreased. Some mice had as much as a 70% decrease in bladder volume and a tripling of urinary frequency. Mice responded by a sustained elevation in frequency and decreased voided volume as early as 24 hours after cyclophosphamide administration or by a pattern of delayed toxicity. CONCLUSIONS: This noninvasive technique measures changes in mouse voiding patterns with great sensitivity and minimal effort. The method is applicable to murine models of interstitial cystitis, detrusor instability and other abnormal voiding states. It may be used for evaluating potential therapies for such conditions.

Animals↗
PubMed2001

Real-time US versus CT determination of pubic arch interference for brachytherapy.

PURPOSE: Part 1, to determine whether transrectal ultrasonography (US) enables accurate determination of pubic arch interference (PAI) for prostate brachytherapy (PBT); part 2, to compare the accuracy of transrectal US with that of computed tomography (CT) for PAI determination; and part 3, to determine the cost savings of PAI determination with transrectal US versus that with CT. MATERIALS AND METHODS: Part 1: The pubic arch was identified intraoperatively with transrectal US and compared with attempted needle passage (14 patients). Part 2: Planning CT with the patient supine was compared with planning transrectal US with patients in the dorsal lithotomy position (nine patients). Part 3: Cost savings were calculated for PAI determination with transrectal US versus that with CT (32 patients per group). RESULTS: Part 1: Transrectal US accurately showed the pubic arch relative to the prostate. Part 2: CT resulted in PAI overestimation by 11.8 mm. Part 3: Cost savings with transrectal US were $1,465 per patient. CONCLUSION: Transrectal US PAI determination is easily performed, intraoperatively useful, and accurate. CT can result in PAI overestimation. Reducing direct CT costs and the indirect costs of unnecessary hormonal therapy for false-positive PAI will reduce expense and improve patient care. Transrectal US should replace CT for PAI determination.

Aged↗
PubMed1999

Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer.

BACKGROUND: Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy. METHODS: Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy, with either goserelin, a synthetic agonist of gonadotropin-releasing hormone, or bilateral orchiectomy, or to be followed until disease progression. The patients were assessed quarterly during the first year and then semiannually. RESULTS: After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome. CONCLUSIONS: Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer.

Aged↗
PubMed1999

Intraoperative optimized inverse planning for prostate brachytherapy: early experience.

PURPOSE: To demonstrate the feasibility of an intraoperative inverse planning technique with advanced optimization for prostate seed implantation. METHODS AND MATERIALS: We have implemented a method for optimized inverse planning of prostate seed implantation in the operating room (OR), based on the genetic algorithm (GA) driven Prostate Implant Planning Engine for Radiotherapy (PIPER). An integrated treatment planning system was deployed, which includes real-time ultrasound image acquisition, treatment volume segmentation, GA optimization, real-time decision making and sensitivity analysis, isodose and DVH evaluation, and virtual reality navigation and surgical guidance. Ten consecutive patients previously scheduled for implantation were included in the series. RESULTS: The feasibility of the technique was established by careful monitoring of each step in the OR and comparison with conventional preplanned implants. The median elapsed time for complete image capture, segmentation, GA optimization, and plan evaluation was 4, 10, 2.2, and 2 min, respectively. The dosimetric quality of the OR-based plan was shown to be equivalent to the corresponding preplan. CONCLUSION: An intraoperative optimized inverse planning technique was developed for prostate brachytherapy. The feasibility of the method was demonstrated through an early clinical experience.

Algorithms↗
PubMed1999

Automated treatment planning engine for prostate seed implant brachytherapy.

PURPOSE: To develop a computer-intelligent planning engine for automated treatment planning and optimization of ultrasound- and template-guided prostate seed implants. METHODS AND MATERIALS: The genetic algorithm was modified to reflect the 2D nature of the implantation template. A multi-objective decision scheme was used to rank competing solutions, taking into account dose uniformity and conformity to the planning target volume (PTV), dose-sparing of the urethra and the rectum, and the sensitivity of the resulting dosimetry to seed misplacement. Optimized treatment plans were evaluated using selected dosimetric quantifiers, dose-volume histogram (DVH), and sensitivity analysis based on simulated seed placement errors. These dosimetric planning components were integrated into the Prostate Implant Planning Engine for Radiotherapy (PIPER). RESULTS: PIPER has been used to produce a variety of plans for prostate seed implants. In general, maximization of the minimum peripheral dose (mPD) for given implanted total source strength tended to produce peripherally weighted seed patterns. Minimization of the urethral dose further reduced the loading in the central region of the PTV. Isodose conformity to the PTV was achieved when the set of objectives did not reflect seed positioning uncertainties; the corresponding optimal plan generally required fewer seeds and higher source strength per seed compared to the manual planning experience. When seed placement uncertainties were introduced into the set of treatment planning objectives, the optimal plan tended to reach a compromise between the preplanned outcome and the likelihood of retaining the preferred outcome after implantation. The reduction in the volatility of such seed configurations optimized under uncertainty was verified by sensitivity studies. CONCLUSION: An automated treatment planning engine incorporating real-time sensitivity analysis was found to be a useful tool in dosimetric planning for prostate brachytherapy.

Algorithms↗
PubMed1999

Chromosome 9 monosomy by fluorescence in situ hybridization of bladder irrigation specimens is predictive of tumor recurrence.

PURPOSE: Bladder irrigation specimens are effective for sampling the urothelium for detection of recurrent bladder cancer. These specimens can be evaluated by cytology or quantitative techniques. Proliferation and ploidy changes are readily detected using deoxyribonucleic acid (DNA) cytometry. Tumor associated chromosomal aberrations can be assayed using fluorescence in situ hybridization (FISH). The prognostic values of DNA cytometry, and chromosome 9 and 9p21 FISH on exfoliated cells from bladder irrigation specimens from 61 bladder cancer patients were evaluated. MATERIALS AND METHODS: A total of 61 consecutive bladder irrigation specimens were obtained during cystoscopy. DNA cytometry was performed by image analysis. FISH was performed using a centromeric chromosome 9 probe and a cosmid contig (COSp16) probe to the CDKN2A/p16 tumor suppressor region of 9p21. Proportional hazards regression analysis was performed with statistical software to test the predictor variables of initial patient status (presence of tumor), COSp16 fraction (the proportion of COSp16 signals relative to centromeric probe signals), monosomic and hyperdisomic fractions of the chromosome 9 probe, and hyperdiploid fraction from DNA cytometry. Median time to recurrence was calculated using statistical software survival analysis. RESULTS: Initial patient status and monosomy of chromosome 9 were predictive of bladder cancer recurrence (p <0.0001 and p = 0.0073, respectively). The 11 patients with chromosome 9 monosomy fractions greater than 15% and a visible tumor had a median time to recurrence of 105 days. In contrast, only 8 of the 25 patients with chromosome 9 monosomy fractions less than 15% and no visible tumor had recurrence within 560 days. Median time to recurrence was 185 days for 6 patients with chromosome 9 monosomy fractions greater than 15% and no visible tumor, and 225 for 19 with chromosome 9 monosomy fractions less than 15% and a visible tumor. Hyperdiploid fraction was suggestive but not predictive of bladder cancer recurrence (p = 0.078). COSp16 and hyperdisomic fractions were not predictive of bladder tumor recurrence (p = 0.11 and p = 0.30, respectively). CONCLUSIONS: Chromosome 9 monosomy by FISH was predictive of bladder tumor recurrence. Furthermore, our findings support the hypothesis that losses of tumor suppressor genes on chromosome 9 are critical, perhaps initiating genetic events in bladder cancer.

Adult↗
PubMed1999

Effect of angiotensin converting enzyme inhibition on the Doppler waveform in dogs with renal artery stenosis.

Our objective was to investigate whether the angiotensin converting enzyme inhibitor enalaprilat improves detection of hemodynamically significant renal artery stenoses in dogs. Renal artery stenoses of 50 to 99% were surgically created unilaterally in five dogs. Doppler ultrasonographic evaluation was performed at baseline (no stenosis), after creation of the stenosis, and after the administration of enalaprilat. The resistive index increased in the nonstenotic kidney (P < 0.01) but not in the stenotic kidney after administration of enalaprilat. The difference in resistive indices between nonstenotic and stenotic kidneys increased significantly (P < 0.05) after administration of enalaprilat. Measurement of the resistive index after administration of an angiotensin converting enzyme inhibitor in humans may improve the performance of Doppler ultrasonography in detecting hemodynamically significant renal artery stenoses.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

DNA cytometry and chromosome 9 aberrations by fluorescence in situ hybridization of irrigation specimens from bladder cancer patients.

OBJECTIVES: To determine the sensitivity and specificity of combining fluorescence in situ hybridization (FISH) measurement of chromosome 9 and DNA cytometry of bladder irrigation specimens in the detection of bladder cancer. METHODS: Bladder irrigation specimens were obtained from 37 normal control patients and 317 bladder cancer patients during cystoscopic examinations. Bladder cancer patients were sampled in the absence of observable tumor (256 specimens) and concurrently with tumor (204 specimens). Chromosome 9 copy number was determined on a cellular basis by FISH, and cellular DNA content was determined by Feulgen DNA staining and image cytometry. RESULTS: Sensitivity of chromosome 9 FISH was 42% for all tumors and was not correlated to transitional cell carcinoma tumor grade, while the sensitivity of DNA cytometry was 55% and improved with increasing grade from 38% for grade 1 to 90% for grade 3 tumors. The results of FISH and DNA cytometry were combined, resulting in specificity of 92% and sensitivity of 69% for grade 1, 76% for grade 2, and 97% for grade 3 tumors. CONCLUSIONS: The lack of increase with grade in the percentage of positive specimens by FISH supports the hypothesis that chromosome 9 aberrations are critical events in bladder tumorigenesis for many patients. These data demonstrate the presence of cells in irrigation specimens with specific genomic lesions of chromosome 9 and DNA content. Combining FISH on chromosome 9 and DNA cytometry provides an increase in sensitivity to transitional cell carcinoma over either test alone.

Carcinoma, Transitional Cell↗
PubMed1997

Loss of the CDKN2A/p16 locus detected in bladder irrigation specimens by fluorescence in situ hybridization.

PURPOSE: We measured the CDKN2A/p16 tumor suppressor gene locus in bladder irrigation specimens and correlated the measurement with the clinical status of patients with bladder cancer. MATERIALS AND METHODS: Irrigation specimens were obtained at cystoscopy from 10 normal controls, 21 patients with bladder cancer in whom no concurrent bladder tumor was seen and 23 patients with bladder tumors. Deoxyribonucleic cytometry and fluorescence in situ hybridization measurements were made. One fluorescence in situ hybridization probe was specific to the chromosome 9 centromere and the other, COSp16, targeted the CDKN2A/p16 region on chromosome 9p21. Three rates were calculated, including the hyperdiploid fraction from deoxyribonucleic acid cytometry, disomic fraction from the 9 centromere count and COSp16F, the frequency of COSp16 in association with 9 centromere. Specimens were classified as positive or negative for each of these rates using cutoff points based on previous studies and the distribution of values obtained for the normal control specimens. RESULTS: Hyperdiploid fraction values were positive (greater than 8%) in 1 normal and 1 nontumor specimen. Ten specimens from patients with tumor showed elevated hyperdiploid fraction values. In 4 nontumor and 13 tumor irrigation specimens the chromosome 9 disomic fraction values were positive (less than 80%). COSp16F was positive (less than 83%) for 18 nontumor irrigation specimens and 18 tumor irrigation specimens. One normal, and 39 of 44 nontumor and tumor irrigation specimens were positive by at least 1 test. CONCLUSIONS: COSp16 loss is measurable in irrigation specimens and it correlates with clinical status. This assay may prove useful in screening for and managing bladder cancer.

DNA, Neoplasm↗