Search PubMed⌕ Search

Biomedical subjects

Martin I Resnick

Publications and source records attributed to Martin I Resnick.

At least 19 recordsLinked to original sources

Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis.

It is hypothesized that oxalate plays an active role in calcium oxalate (CaOx) nephrocalcinosis and oxalate driven nephrolithiasis by interacting with the kidney. We developed an adjustable, nonprecursor, continuous infusion model of hyperoxaluria and CaOx nephrocalcinosis to investigate this hypothesis. Minipumps containing PBS or KOx (60-360 micromol/day; n = 5-7/dose) were implanted subcutaneously in male Sprague-Dawley rats on D0 and D6. Rats were killed on D13. Oxalate excretion and CaOx crystalluria were monitored by 20+4 h urine collections. Localization and content of intrarenal crystals were determined on frozen sections using polarization and microFTIR. Oxalate excretion was significantly elevated in all KOx rats (P < or = 0.005). CaOx crystalluria was most persistent in the 240-360 micromol/day KOx rats, but even 60 micromol/day KOx rats showed sporadic crystalluria. One hundred percent of KOx rats had CaOx nephrocalcinosis as confirmed by microFTIR. Most crystals were localized to the lumens of the corticomedullary collecting ducts. A few crystals are localized just under the papillar urothelium. The minipump model is the first model of hyperoxaluria to provide continuous infusion of oxalate. It permits control of the levels of hyperoxaluria, crystalluria and CaOx nephrocalcinosis. The level of sustained hyperoxaluria and CaOx nephrocalcinosis induced by treatment with 360 micromol/day KOx for 13D models the conditions frequently observed in jejunoileal bypass patients. Adjustments in the length of treatment and level of hyperoxaluria may allow this model to also be used to study the oxalate driven CaOx-nephrolithiasis common in patients with hyperoxaluria due to other causes.

Animals↗

Prostate imaging.

Explore the source record for details and available documents.

Diagnostic Imaging↗

The influence of chronic inflammation in prostatic carcinogenesis: a 5-year followup study.

PURPOSE: We investigated an association between chronic prostatic inflammation and prostate carcinogenesis. MATERIALS AND METHODS: Initial prostate needle biopsies from 177 patients with clinical parameters suspicious for malignancy were examined. We evaluated them for the presence and extent of chronic inflammation and other pathological findings. Findings in followup biopsies during the next 5 years were reviewed and correlated with the initial results. RESULTS: Two patients subset were identified, including 144 patients with and 33 without chronic inflammation in the initial biopsies. Additional pathological findings in some cases in each group included simple atrophy, high grade prostatic intraepithelial neoplasia, adenocarcinoma and atypical small acinar proliferation. Post-atrophic hyperplasia and proliferative inflammatory atrophy were noted only in patients with chronic inflammation. A significant association between serum prostate specific antigen and the degree of inflammation was observed in needle biopsies. In repeat biopsies within 5 years in patients with chronic inflammation 29 new cancers were diagnosed, representing a new cancer incidence of 20%. Of these cancers 6 occurred in patients in whom initial biopsies showed only chronic inflammation, 15 occurred in patients with initial post-atrophic hyperplasia/proliferative inflammatory atrophy lesions, 7 occurred in patients with initial high grade prostatic intraepithelial neoplasia and chronic inflammation, and 1 occurred in a patient with initial atypical small acinar proliferation and chronic inflammation. High grade prostatic intraepithelial neoplasia was newly discovered in 9 patients in the initial chronic inflammation group, of whom 7 had post-atrophic hyperplasia/proliferative inflammatory atrophy and 2 had simple atrophy and chronic inflammation in the initial biopsies. In contrast, in 33 patients initially showing no inflammation adenocarcinoma was subsequently found in 2 (6%). One of these patients had high grade prostatic intraepithelial neoplasia and the other had atypical small acinar proliferation on initial biopsies. CONCLUSIONS: Chronic inflammation may be a significant risk factor for prostatic adenocarcinoma.

Adenocarcinoma↗

Residual and recurrent disease following renal energy ablative therapy: a multi-institutional study.

PURPOSE: In this study we detail the incidence and pattern of residual and recurrent disease after radio frequency ablation or cryoablation of a renal mass and, using this information, determine reasonable minimum recommendations for when to perform surveillance imaging during year 1 after treatment. To our knowledge no evidence based guidelines exist for determining how or when followup abdominal imaging should be performed after renal energy ablative therapy. MATERIALS AND METHODS: We reviewed treatment and followup information of patients who underwent radio frequency ablation or cryoablation for a renal mass at 7 institutions. Postoperative monitoring was performed using a variety of surveillance schedules. RESULTS: Of 616 patients 63 were found to have residual or recurrent disease after primary radio frequency ablation (13.4%) or cryoablation (3.9%) for a median of 8.7% in 7 institutions. Most incomplete treatments (70%) were detected within the first 3 months. After salvage ablative therapy was rendered, therapy failed in only 4.2%. At a mean followup of 2 years patients with residual or recurrent disease had an overall survival rate of 82.5% and a 2-year metastasis-free survival rate of 97.4% for those with localized, unilateral renal tumors. CONCLUSIONS: In most cases initial treatment failure was detected within the first 3 months after treatment. Our findings support a minimum of 3 to 4 imaging studies in year 1 after ablative therapy, and at months 1, 3, 6 (optional) and 12.

Catheter Ablation↗

Choices.

Explore the source record for details and available documents.

Acute Disease↗

Intraprostatic lymphocyte profiles in aged wistar rats with estradiol induced prostate inflammation.

PURPOSE: We report LS phenotypes in aged Wistar rats (Charles Rivers, Wilmington, Massachusetts) with EPI. MATERIALS AND METHODS: EPI was induced in 36 to 40-week-old male rats by castration with subcutaneous injections of 17beta-estradiol (0.25 mg/kg daily) plus dihydrotestosterone propionate (2.5 mg/kg daily) in sesame oil for 30 days. Controls were sham castrated, aged rats that were injected with sesame oil. Prostate, spleen and blood LSs in aged and young (10 to 12-week-old) rats were identified by flow cytometry in a cluster of differentiation system. RESULTS: All prostates in 6, 17beta-estradiol plus dihydrotestosterone propionate treated rats and in 3 of 7 controls (43%) showed inflammation foci. All studied LSs in Aged-SPIs and Aged-EPIs were similar. Blood LSs in Aged-SPIs, Aged-EPIs, Aged-NPIs and Youngs showed no differences. Levels of lymphocytes bearing the natural killer marker were decreased, and levels of total T and CD4(+) T cells were increased in prostates with age. Intraprostatic and splenic levels of CD4(+) natural killer T cells were down-regulated significantly in Aged-SPIs and Aged-EPIs compared to those in Aged-NPIs and Youngs. Levels of CD45RC(+)CD4(+)alphabetaTCR(+) T cells were decreased 2-fold in the spleen and up-regulated 2-fold in the prostate of Aged-SPIs and Aged-EPIs compared to those in Aged-NPIs and Youngs. CONCLUSIONS: Similar LS features in Aged-SPIs and Aged-EPIs may indicate that the EPI model is appropriate for studies of the immune aspects of prostate inflammation. Imbalance between suppressive CD4(+) natural killer T cells and autoreactive CD45RC(+)CD4(+)alphabetaTCR(+) T cells in Aged-SPIs and Aged-EPIs may suggest their role in prostate inflammation in this model.

Age Factors↗

The impact of a negative (111)indium-capromab pendetide scan before salvage radiotherapy.

PURPOSE: We determined the prognostic role, if any, of the ProstaScint (111)indium-capromab pendetide scan before salvage radiotherapy for biochemical recurrence after RP for localized prostate cancer. MATERIALS AND METHODS: We reviewed the records of 649 patients who underwent a ProstaScint scan from 1998 to 2004. A total of 44 patients were identified who had biochemical recurrence after RP and underwent a ProstaScint scan immediately before salvage radiotherapy. All patients received salvage radiotherapy to the prostatic bed unless pelvic lymph node uptake was identified on the scan, resulting in initial whole pelvic radiotherapy with 45 Gy, followed by a conformal boost to the prostate bed in 6. The median salvage radiotherapy dose to the prostate bed was 72 Gy. Patient demographics, pathological information, PSA values and ProstaScint results were collected retrospectively. The majority of ProstaScint scans were digitally fused with noncontrast pelvic computerized tomography images for interpretation. PSA progression after radiotherapy was defined using American Society for Therapeutic Radiation and Oncology criteria. RESULTS: At a mean followup of 22 months 43 of 44 patients (97%) experienced a PSA decrease after salvage radiotherapy with a mean PSA nadir of 0.16 ng/ml compared to a mean pre-radiotherapy PSA of 1.7 ng/ml. Of the 44 patients 15 (34%) showed post-radiotherapy PSA progression. When the entire cohort was analyzed, patients with negative ProstaScint scans had statistically lower post-radiotherapy PSA progression rates than patients with positive scans (1 of 10 or 10% vs 14 of 34 or 41%, p = 0.026). Patients with negative ProstaScint results were also statistically more likely to have a pre-radiotherapy PSA of less than 1.0 ng/ml (p = 0.005), no seminal vesicle involvement (p = 0.006), a greater mean PSA doubling time (p = 0.008) and received no hormone therapy (p = 0.003). When patients with pre-radiotherapy PSA less than 1.0 ng/ml were analyzed, a negative ProstaScint scan suggested but did not provide a statistically significant advantage over pre-radiotherapy PSA alone for predicting post-radiotherapy PSA progression (1 of 9 or 11% for negative vs 5 of 15 or 33% for positive scans, p = 0.20). CONCLUSIONS: Our early experience supports an improved prognosis in patients receiving salvage pelvic radiotherapy for biochemical recurrence after RP who have a negative pre-radiotherapy ProstaScint scan. However, this finding is not necessarily independent of pre-radiotherapy PSA.

Aged↗

Up-regulation of insulin-like growth factor binding protein-3 by apigenin leads to growth inhibition and apoptosis of 22Rv1 xenograft in athymic nude mice.

Epidemiological studies suggest that increased intake of fruits and vegetables may be associated with a reduced risk of prostate cancer. Apigenin (4', 5, 7,-trihydroxyflavone), a common dietary flavonoid abundantly present in fruits and vegetables, has shown remarkable anti-proliferative effects against various malignant cell lines. However, the mechanisms underlying these effects remain to be elucidated. We investigated the in vivo growth inhibitory effects of apigenin on androgen-sensitive human prostate carcinoma 22Rv1 tumor xenograft subcutaneously implanted in athymic male nude mice. Apigenin was administered to mice by gavage at doses of 20 and 50 mug/mouse/day in 0.2 ml of a vehicle containing 0.5% methyl cellulose and 0.025% Tween 20 in two different protocols. In the first protocol, apigenin was administered for 2 wk before inoculation of tumor and was continued for 8 wk, resulting in significant inhibition of tumor volume by 44 and 59% (P<0.002 and 0.0001), and wet weight of tumor by 41 and 53% (P<0.05), respectively. In the second protocol, administration of apigenin began 2 wk after tumor inoculation and continued for 8 wk; tumor volume and wet weights of tumor were reduced by 39 and 53% (P<0.01 and 0.002) and 31 and 42% (P<0.05), respectively. The tumor inhibitory effect of apigenin was more pronounced in the first protocol of extended treatment, which was associated with increased accumulation of human IGFBP-3 in mouse serum along with significant increase in IGFBP-3 mRNA and protein expression in tumor xenograft. Apigenin intake by these mice also resulted in simultaneous decrease in serum IGF-I levels and induction of apoptosis in tumor xenograft. Importantly, tumor growth inhibition, induction of apoptosis, and accumulation of IGFBP-3 correlated with increasing serum and tumor apigenin levels. In both studies, animals did not exhibit any signs of toxicity or reduced food consumption. In cell culture studies, apigenin treatment resulted in cell growth inhibition and induction of apoptosis, which correlated with increased accumulation of IGFBP-3 in culture medium and cell lysate. These effects were associated with significant reduction in IGF-I secretion; inhibition of IGF-I-induced cell cycle progression and insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, along with an increase in sub-G1 peak by apigenin. Further, treatment of cells with IGFBP-3 antisense oligonucleotide reversed these effects and attenuated apigenin-mediated inhibition of IRS-1 phosphorylation conferring inhibitory effects of apigenin on IGF-signaling. This study presents the first evidence that the in vitro and in vivo growth inhibitory effects of apigenin involve modulation of IGF-axis signaling in prostate cancer.

Adaptor Proteins, Signal Transducing↗

Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model.

BACKGROUND: Cancer progression is usually facilitated by independent growth signals that may lead to increased cell survival and evasion of apoptosis. Phosphatidylinositol 3'-OH kinase (P I3 K)-Akt and transcription factor NF-kappaB are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis, and oncogenesis. Although P I3 K-Akt and NF-kappaB have been implicated in the development and progression of prostate cancer, expression of these molecules during progression of autochthonous disease has not been elucidated. METHODS: Prostate cancer growth and progression in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and male non-transgenic littermates were observed by magnetic resonance imaging (MRI). Expression patterns of P I3 K-Akt, NF-kappaB, I kappaB, and associated signaling molecules during different stages of cancer progression in these mice were examined by Western blot analysis, electrophoretic mobility shift assay (EMSA), enzyme-linked immunoabsorbent assay (ELISA), kinase assay, and immunohistochemistry. RESULTS: Sequential MRI and gross analysis of prostate gland exhibited increasing prostate volume associated with the development and progression of prostatic adenocarcinoma in TRAMP mice, compared to male non-transgenic littermates. Differential protein expression of P I3 K, phosphorylated-Akt (Ser 473), I kappa Balpha and its phosphorylation, IKK kinase activity, NF-kappaB/p65, p50, DNA binding, and transcriptional-regulated genes, viz., Bc l2, cyclin D1, MMP-9, and VEGF were observed during prostate cancer progression in TRAMP mice, compared to male non-transgenic littermates. Expressions of these molecules were significantly increased during cancer progression observed at 24 and 32 weeks of age. CONCLUSIONS: Differential expression pattern of P I3 K-Akt, NF-kappaB and I kappaB during prostate cancer progression in TRAMP mice suggest that these molecules represent potential molecular targets for prevention and/or therapeutic intervention.

Adenocarcinoma↗

How do residents manage personal finances?

BACKGROUND: We examined three research questions: How do residents' debts and savings compare to the general public? How do surgical residents' financial choices compare to other residents? How may institutions help residents' personal financial decisions? METHODS: The Survey of Consumer Finances was modified and piloted tested to elicit financial information. The instrument was completed by 612 residents at 8 programs. RESULTS: Only 60% of residents budgeted expenses, and 25% and 10% maintained cash balances <611 dollars and unpaid credit card balances >10,000 dollars, respectively. Compared with controls, residents held greater median ratios of debt to household income (2.46 vs. 1.06, P <0.0001), fewer assets to income (0.64 vs. 2.28, P <0.0001), less net wealth to income -1.43 vs. 0.90, P <0.0001), and lower retirement savings balance to household income (0.01 vs. 0.12, P <0.0001). Surgery residents were the least financially conservative group. Mean annual resident contributions to retirement accounts were $1532 higher at institutions with versus without retirement plans (P <0.01). CONCLUSIONS: Resident debts are higher and savings lower than the general public. This behavior is most common among surgery residents. Residents save more for retirement when they are eligible for tax-deferred retirement plans. Graduate medical programs should instruct residents on financial management.

Adult↗

The healthy rat prostate contains high levels of natural killer-like cells and unique subsets of CD4+ helper-inducer T cells: implications for prostatitis.

PURPOSE: Chronic nonbacterial prostatitis spontaneously develops in aged Lewis and Wistar rats but not in Sprague-Dawley rats. We report the unique profile of lymphocyte subsets present in the healthy Sprague-Dawley rat prostate. MATERIALS AND METHODS: We compared enzymatic and mechanical methods of intraprostatic lymphocyte isolation in healthy 8 to 10-week-old Sprague-Dawley rats. Mechanical isolation was chosen because of its superior preservation of surface antigens. Intraprostatic lymphocyte subsets were analyzed by flow cytometry. RESULTS: Levels of prostatic alphabetaTCR+ T cells were similar and levels of prostatic B cells were decreased 5 to 10-fold compared with those found in other tissues (p </=0.005). Unexpectedly two-thirds of the total prostatic lymphocytes expressed the natural killer (NK) marker CD161a+. They were divided equally between NK (CD161a+alphabetaTCR) and NKT (CD161a+alphabetaTCR+) cells. Of prostatic CD161a+ cells 50% to 60% were also CD8+. Levels of NKT cells were dramatically lower in other tissues (p </=0.005) and they never accounted for more than 8% of total lymphocytes. The prostate contained lower levels of CD4+ T cells than all tissues except the liver (p </=0.005) and higher levels of CD8+ T cells than any other tissue studied (p </=0.05), resulting in an inverted CD4-to-CD8 ratio. CD45RC+CD4+alphabetaTCR+ T cells and CD161a+CD4+alphabetaTCR+ NKT cells were elevated in the prostate (p </=0.02). CONCLUSIONS: The healthy rat prostate contains an unusually high proportion of NK and NKT cells. The balance between the CD45RC+CD4+alphabetaTCR+ T cells, which initiate the cell mediated immune response, and CD4+ NKT cells, which can suppress autoimmunity, may be a key in understanding the resistance of Sprague-Dawley rats to chronic nonbacterial prostatitis.

Animals↗

A novel computer based expert decision making model for prostate cancer disease management.

PURPOSE: We propose a strategic, computer based, prostate cancer decision making model based on the analytic hierarchy process. We developed a model that improves physician-patient joint decision making and enhances the treatment selection process by making this critical decision rational and evidence based. MATERIALS AND METHODS: Two groups (patient and physician-expert) completed a clinical study comparing an initial disease management choice with the highest ranked option generated by the computer model. Participants made pairwise comparisons to derive priorities for the objectives and subobjectives related to the disease management decision. The weighted comparisons were then applied to treatment options to yield prioritized rank lists that reflect the likelihood that a given alternative will achieve the participant treatment goal. Aggregate data were evaluated by inconsistency ratio analysis and sensitivity analysis, which assessed the influence of individual objectives and subobjectives on the final rank list of treatment options. RESULTS: Inconsistency ratios less than 0.05 were reliably generated, indicating that judgments made within the model were mathematically rational. The aggregate prioritized list of treatment options was tabulated for the patient and physician groups with similar outcomes for the 2 groups. Analysis of the major defining objectives in the treatment selection decision demonstrated the same rank order for the patient and physician groups with cure, survival and quality of life being more important than controlling cancer, preventing major complications of treatment, preventing blood transfusion complications and limiting treatment cost. Analysis of subobjectives, including quality of life and sexual dysfunction, produced similar priority rankings for the patient and physician groups. Concordance between initial treatment choice and the highest weighted model option differed between the groups with the patient group having 59% concordance and the physician group having only 42% concordance. CONCLUSIONS: This study successfully validated the usefulness of a computer based prostate cancer management decision making model to produce individualized, rational, clinically appropriate disease management decisions without physician bias.

Brachytherapy↗

A simple procedure for isolating microgram quantities of biologically active bikunin from human urine.

OBJECTIVE: To report a simple, relatively rapid protocol to isolate biologically active bikunin from human urine using ion-exchange-trypsin affinity chromatography. Bikunin is a protease inhibitor which has been shown to play a role in various processes, including inhibition of calcium oxalate crystallization, the regulation of proliferation and modulation of carcinogenesis. The unavailability of the purified protein has hampered studies on bikunin's expanding role in these processes. MATERIALS AND METHODS: Female human urine was dialysed (15 kDa threshold) and crudely fractionated with a double-saturated ammonium sulphate precipitation. The first precipitation was with 35% saturated ammonium sulphate, and the supernatant was harvested, and the second with 90% saturated ammonium sulphate, and the precipitate collected. The protein mixture was then passed over Sepharose SP-fast-flow cation exchange and Sepharose Q-fast-flow anion exchange columns connected in series. The final purification was with a trypsin-affinity column which selectively bound bikunin. RESULTS: This procedure could recover 1 microg of bikunin per 2 mL of urine, and the final product was essentially free of contaminating inter-alpha-trypsin inhibitor heavy chains or bikunin-heavy chain conjugates. Product purity was confirmed by two-dimensional polyacrylamide gel electrophoresis combined with silver staining or Western blot. All isolations contained the 17 kDa minimally glycoslyated/sulphated form of bikunin and the 28 kDa form of bikunin. Some preparations also contained 33-48 kDa forms of bikunin. The protein cores of all three proteins were confirmed to be bikunin by mass spectrometry and Western blot. Harvested bikunin retained its trypsin inhibitory activity (L-benzoylarginine-p-nitroanilide assay). Preparations containing the 33-45 kDa form had two to three times more trypsin inhibitory activity than preparations without this band. CONCLUSIONS: This novel ion exchange-trypsin affinity chromatography protocol uses only two chromatographic steps. The product consists of three isomers of biologically active bikunin, free of contaminating heavy chains or bikunin-heavy chain conjugates. The ready availability of purified bikunin should facilitate future studies of bikunin's emerging role in urolithiasis, proliferation and carcinogenesis.

Calcium Oxalate↗

Update on fused capromab pendetide imaging of prostate cancer.

The primary objective of this overview is to apprise clinical urologists and oncologists of the current state of fused multimodality imaging of prostate cancer, which can be applied to optimize treatment by ensuring that a patient's disease is characterized as well as current imaging technology permits. The focus of this study is the monoclonal antibody capromab pendetide, which targets prostate specific membrane antigen (PSMA), a type II membrane glycoprotein strongly associated with prostate cancer. Identifying where capromab pendetide uptake occurs can be done accurately if this functional imaging modality is combined with a modality that provides anatomic detail, such as computed tomography (CT) or magnetic resonance imaging (MRI). Image fusion, or coregistration, which is overlaying the functional images of capromab pendetide uptake on the anatomic CT or MRI images, provides a detailed map of cancer localization inside and outside the prostate gland. This same principle of fusing functional images on anatomic images is the basis for enormous growth of positron emission tomography with CT during the past 2 years. Positron emission tomography imaging has a different functionality base than does capromab pendetide, and thus the 2 modalities should be complementary. However, the key to both functional imaging modalities is accurate fusion with anatomic images, which is illustrated in our case reports. The cases cited demonstrate the need to optimize every phase of imaging from patient preparation to reading and reporting increased PSMA concentration seen on the fused images. Reference is also made to applying capromab pendetide/CT fused imaging to radiation therapy planning.

Aged↗

Prostate cancer: appraisal, coping, and health status.

The purpose of this study was to identify how cognitive appraisal and types of coping affect the health status of men with prostate cancer. Lazarus and Folkman's model of stress and coping guided this correlational, cross-sectional study. The convenience sample was composed of 131 men with prostate cancer who completed the Cognitive Appraisal of Health Scale, the Ways of Coping Checklist, and the Short-Form Health Survey using mailed questionnaires. Participants who appraised more harm or loss experienced worse physical and mental health. When participants perceived their diagnosis as posing more harm or loss or a greater threat, they were more likely to use emotion-focused coping. When the diagnosis was perceived as a challenge, men were more likely to use more problem-focused coping. The findings of this study enable health care providers to be more attentive to the psychosocial needs of prostate cancer patients.

Adaptation, Psychological↗