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Biomedical subjects

M A Rubin

Publications and source records attributed to M A Rubin.

At least 73 records · Page 4Linked to original sources

Whole mounted radical prostatectomy specimens do not increase detection of adverse pathological features.

PURPOSE: The optimal method to process radical prostatectomy specimens to maximize the detection of adverse pathological features is unclear and accurate staging is critical. We compare the ability of whole mounted sections to detect these features compared to partially submitted radical prostatectomy specimens. MATERIALS AND METHODS: A total of 93 consecutive radical prostatectomy specimens were processed as whole mounts. Tissue sections were analyzed and the pathological outcomes measured included Gleason score, surgical margin status, and presence or absence of extraprostatic tumor extension and/or seminal vesicle invasion. The pathological outcomes of the preceding cohort were compared to those of a similar cohort consisting of 554 men whose radical prostatectomy specimens were processed as partially submitted glands. RESULTS: A multivariate logistic regression analysis was performed to determine the effect of the method of tissue processing on the pathological outcomes. When considered alone or adjusted for various preoperative patient characteristics (prostate specific antigen, biopsy Gleason score and clinical stage), there were no significant differences in the ability of whole mounted specimens to detect the various outcomes compared to partially submitted specimens (all p >0.4). CONCLUSIONS: Whole mounted sampling of the radical prostatectomy specimen does not improve detection of adverse pathological features.

Histocytological Preparation Techniques↗

Common mutations in BRCA1 and BRCA2 do not contribute to early prostate cancer in Jewish men.

BACKGROUND: Families with a high incidence of hereditary breast cancer, and subsequently shown to have terminating mutations in BRCA1 or BRCA2, appear to have a higher incidence of prostate cancer among male relatives. We aimed to determine whether the common germline mutations of BRCA1 or BRCA2 in Ashkenazi Jewish men predisposed them to prostate cancer. METHODS: We examined genomic DNA from 83 (for BRCA1 185delAG) or 82 (for BRCA2 6174delT) Ashkenazi Jewish prostate cancer patients, most of whom were treated at a relatively young age, for the most common germline mutation in each gene seen in the Ashkenazi population. RESULTS: Our study should have been able to detect a 4-5-fold increase in the risk of prostate cancer due to mutation of BRCA1 or BRCA2. However, only one (1.15%; 95% confidence interval, 0-3.6%) of the patients was heterozygous for the BRCA1 mutant allele, and only two were heterozygous for the BRCA2 mutation (2.4%; 95% confidence interval, 0-6.2%). CONCLUSIONS: The incidence of each of the germline mutations in these prostate cancer patients closely matched their incidence (about 1%) in the general Ashkenazi Jewish population. This suggests that unlike cases of breast and ovarian cancers, mutations in BRCA1 or BRCA2 do not significantly predispose men to prostate cancer.

Adult↗

The detection of renal carcinoma cells in the peripheral blood with an enhanced reverse transcriptase-polymerase chain reaction assay for MN/CA9.

BACKGROUND: Using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, the authors previously determined the expression of MN/CA9 mRNA in renal cell carcinoma (RCC) and its absence in benign renal tissue. In the current study, the utility of an enhanced RT-PCR assay in the detection of renal carcinoma cells in the peripheral blood was assessed. METHODS: An enhanced MN/CA9 RT-PCR assay was applied to peripheral blood samples from a total of 96 patients. Forty-two patients had renal tumors, including 5 with benign renal lesions, 28 with localized RCC, and 9 with metastatic RCC. Fifty-four control patients without renal tumors were similarly tested. Pathologic staging for patients with localized cancer was T1N0M0 for 5, T2N0M0 for 9, and T3N0M0 for 14 patients. RESULTS: Cells expressing MN/CA9 were detected in 1 of 54 controls (1.8%) and in 18 of 37 cancer patients (49%). Thirteen of twenty eight patients (46%) with localized RCC and 5 of 9 (56%) with metastatic disease tested positive with the assay. No patient with a benign renal tumor exhibited MN/CA9 expression. All blood test results for patients with clear cell RCC were noted to be positive. No correlation was noted between MN/CA9 results and age, gender, or tumor grade. The differences in MN/CA9 results according to T classification were not statistically significant. CONCLUSIONS: The enhanced RT-PCR assay for MN/CA9 is a highly specific technique for detecting circulating renal carcinoma cells in the peripheral blood, and it may prove useful in the diagnosis and monitoring of RCC.

Adult↗

Microvessel density in prostate cancer: lack of correlation with tumor grade, pathologic stage, and clinical outcome.

OBJECTIVES: Angiogenesis is believed to play an important role in tumor progression and metastasis. Previous studies have suggested that the microvessel density (MVD) of prostate tumors may be of prognostic value. This study investigated the reliability of assessing MVD in radical prostatectomy specimens and its value as an independent prognostic indicator in men with clinically localized prostate cancer. METHODS: One hundred radical prostatectomy specimens from 1993 to 1995 were randomly selected for this study. Thirteen cases were excluded because the patients had undergone neoadjuvant hormonal therapy or tissue blocks were unavailable. The median follow-up time was 36 months. Tumor blocks were immunostained using the endothelial-specific antibody CD31. MVD was counted in areas with the greatest microvessel immunostaining, which were designated "hot spots." MVD was analyzed for associations with clinical and pathologic factors. In a subset of 60 cases, the same observer repeated the counts three times. RESULTS: Intraobserver reliability for MVD counting was excellent (reliability coefficient 0.82), demonstrating that this method could be reproduced by a single observer. MVD was not associated with Gleason sum, tumor stage, surgical margin status, or seminal vesicle invasion. Of the 87 patients, 20 (23%) had a prostate-specific antigen (PSA) failure during a 36-month median follow-up time. As expected, Gleason sum and tumor stage were strong predictors of PSA failure, with risk ratios of 2.1 and 2.3, respectively. In contrast, MVD was not associated with PSA failure. CONCLUSIONS: MVD, as determined by CD31, can be reliably measured by a single observer, but it is not a useful prognostic indicator for men with clinically localized prostate cancer.

Aged↗

Perineural invasion on prostate needle biopsy: an independent predictor of final pathologic stage.

OBJECTIVES: To examine the significance of perineural invasion (PNI) in predicting pathologic findings in patients treated by radical prostatectomy, because a recent study concluded that PNI on needle biopsy has no independent predictive value. METHODS: Between 1993 and 1998, radical prostatectomy was performed in 319 consecutive patients. Prostate needle biopsies were reviewed in all cases. We compared PNI with other preoperative parameters, including digital rectal examination, PSA, and biopsy Gleason score, for the ability to predict tumor stage. Clinical records and pathologic findings were reviewed for all cases. Tumor stage was defined as either pT2 (organ confined) or pT3 (extraprostatic extension and/or seminal vesicle invasion). RESULTS: The median age was 61.4 years (range 40 to 75.6). Seventy-two percent of the 95 men with nonpalpable disease and 67% of the 224 men with palpable disease had organ-confined prostate cancer on final pathologic staging. Of 205 men with a Gleason score on biopsy of 6 or less, 159 (78%) had organ-confined disease compared with 59 (52%) of 114 with a Gleason score of 7 to 9 (P <0.001, chi-square test). PNI was identified in 77 (24%) of 319 patients, with 83% specificity and 40% sensitivity for Stage pT3 disease (odds ratio 3.49). Of men with pT3 disease on final pathologic staging, 18%, 27%, and 56% had preoperative PSA levels of 0 to 4, more than 4 to 10, and greater than 10 ng/mL, respectively (P <0.001, Mantel-Haenszel chi-square test). On multivariate analysis, PNI (P = 0.0031), PSA (P = 0.0004), and Gleason score (P = 0.0003) independently predicted stage (pT3 disease). CONCLUSIONS: PNI is an important preoperative predictor of pathologic stage and should be reported when adenocarcinoma is diagnosed on prostate needle biopsies.

Adult↗

Effects of lead on adenylate cyclase activity in rat cerebral cortex.

Lead decreased in a dose dependent manner the basal AC activity in membranes of rat cerebral cortex (IC50 = 2.5 +/- 0.1 microM). In membranes preincubated under basal conditions, AC activity was stimulated by approximately two and fourfold by 10 microM Gpp(NH)p or forskolin, respectively. Under basal conditions, lead (3 microM) inhibited enzyme activity up to 50%, but was not able to inhibit the Gpp(NH)p- or the forskolin-stimulated AC activity. However, in membranes preincubated with Gpp(NH)p (10 microM), lead (3 microM) had no significant effect on enzyme activity, but it partly blocked the stimulation of AC activity elicited by forskolin (10 microM). In membranes preincubated with 10 microM lead, the addition of 10 microM Gpp(NH)p or forskolin in the incubation medium did not stimulate AC activity. However, when added together in the incubation medium Gpp(NH)p + forskolin produced an increase in enzyme activity. In membranes preincubated with 10 microM lead + 10 microM Gpp(NH)p, Gpp(NH)p (10 microM) or forskolin (10 microM) added alone or in combination to the incubation medium did not stimulate AC activity. Moreover, under these latter conditions lead had no further effect on enzyme activity. These results indicate that lead may interact with G-proteins and with the catalytic subunit of cerebral cortical AC to produce inhibition of the enzyme activity.

Adenylyl Cyclases↗

Renal oncocytosis: a morphologic study of fourteen cases.

Diffuse renal involvement by numerous oncocytic nodules has rarely been described. We report 14 cases (19 specimens) with innumerable oncocytic nodules in the kidney. Invariably, these kidneys showed additional associated findings. We suggest the term renal oncocytosis for this entire morphologic spectrum. Six (43%) cases had histologically or radiologically proven bilateral involvement. Each specimen had at least one dominant tumor (2.0-10.5 cm) in addition to numerous other microscopic to macroscopic oncocytic nodules. Additional features observed were: interstitial pattern, with the oncocytic tubules and acini diffusely intermingling with and infiltrating between non-neoplastic parenchyma (one case); diffuse oncocytic change in the nonneoplastic tubules, cytologically difficult to separate from the oncocytic nodules (seven cases); and benign oncocytic cortical cysts (four cases). The dominant mass in 13 specimens was a renal oncocytoma and in two, a chromophobe renal cell carcinoma. In four specimens, the largest tumor was considered a hybrid tumor because of the presence of mixed histologic features of both tumor types. Most smaller nodules had the morphologic features of renal oncocytoma, but a few had the appearance of chromophobe renal cell carcinoma or nodules with hybrid features. We conclude that the presence of numerous oncocytic nodules may be associated with a wide spectrum of oncocytic changes in the kidney. The association of numerous renal oncocytoma-like nodules with lesions having a mixed morphology or a morphology of pure chromophobe renal cell carcinoma suggests that they may constitute a morphologic spectrum of oncocytic tumors and that renal oncocytoma and chromophobe renal cell carcinoma may arise from a common progenitor lesion.

Adenoma, Oxyphilic↗

Can perineural invasion on prostate needle biopsy predict prostate specific antigen recurrence after radical prostatectomy?

PURPOSE: We evaluated the role of perineural invasion identified on prostate needle biopsy as a predictor of prostate specific antigen (PSA) recurrence after radical prostatectomy. MATERIALS AND METHODS: Between 1993 and 1998 radical prostatectomy was performed in 319 consecutive patients. Prostate needle biopsies were reviewed in all cases. We compared perineural invasion with other preoperative parameters, including digital rectal examination, PSA and biopsy Gleason score, for the ability to predict PSA recurrence with recurrence defined as any serum PSA level greater than 0.2 ng./ml. RESULTS: Perineural invasion was identified on 77 of 319 preoperative prostate biopsies (24%). There was PSA recurrence in 46 patients (14.4%) at a mean followup of 25.4 months (range 0.2 to 62.1). Perineural invasion statistically correlated with PSA recurrence. Kaplan-Meier analysis revealed disease-free survival rates of 24 versus 64% when perineural invasion was and was not present in the prostate biopsy (p = 0.0003, log rank 12.92). Multivariate analysis demonstrated that perineural invasion (p = 0.012) and PSA (p = 0.005) were independent preoperative predictive factors of PSA recurrence. When perineural invasion was compared with postoperative parameters, including disease stage, surgical margins and seminal vesicle invasion, it was not an independent predictor because it closely correlated with tumor stage. CONCLUSIONS: Perineural invasion on preoperative prostate needle biopsy is a strong independent predictor of PSA recurrence in patients in whom prostate cancer was treated with radical prostatectomy.

Adult↗

Changes in biochemical disease-free survival rates as a result of adoption of the consensus conference definition in patients with clinically localized prostate cancer treated with external-beam radiotherapy.

PURPOSE: The optimal definition of biochemical recurrence of prostate cancer after definitive radiotherapy remains elusive. Different institutions have developed their own definitions, and a consensus conference (CC) sponsored by the American Society for Therapeutic Radiology and Oncology has recently proposed another definition. This study compares the definition previously used at our institution with the definition proposed by the CC. METHODS: Two hundred and eight patients were treated for localized prostate cancer with conformal external-beam radiotherapy between 1989-1993 at our institution and followed for at least 24 months. Patients were categorized as failures according to our institutional definition and the CC definition. Our definition (CPMC) required two increases in serum prostate specific antigen (PSA) over at least a 3-month period with a final value of at least 1 ng/ml or a single value resulting in clinical intervention. The CC definition required three consecutive increases in PSA. This was modified to also consider those patients with one or two increases leading to clinical intervention as failures. Differences in the failure rates between the two definitions were evaluated and factors influencing these differences were explored. In an additional analysis, CC was modified such that patients with one or two PSA increases were censored at the time of the PSA prior to the increases (CC-II), rather than at the last PSA (CC). The median follow-up time was 31 months. RESULTS: There were 36 fewer failures according to CC (n = 96) compared with CPMC (n = 132) (p < 0.001). Twenty cases called failures by CPMC subsequently had a decrease in PSA ("false failures"). The other 16 patients have had two increases in PSA, but are awaiting their next follow-up visit to obtain a third PSA ("pending failures"). Analysis of factors predicting "pending failures" showed Gleason score to be the sole predictor of this change in status in multivariate analysis (p = 0.03) with patients with lower-grade tumors being more likely to change status (Gleason 2-6: 15% vs. Gleason 7-10: 1%). On the other hand, "false failures," compared to true failures, had a lower mean PSA nadir (1.7 ng/ml vs. 7.0 ng/ml, p < 0.001) and significantly smaller mean increases in PSA (1st increase: 0.6 ng/ml vs. 3.4 ng/ml, p = 0.006; 2nd increase: 0.4 ng/ml vs. 4.8 ng/ml, p = 0.002). In 85% (17 of 20) of these patients, at least one of the increases was < or = 0.3 ng/ml compared with 44% (42 of 96) of the true failures (p = 0.0008). CC-II resulted in a small decrease in BDFS rates compared with CC, but did not affect the overall difference between CC and CPMC. A modified definition that defines failure as two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml, or three consecutive increases would result in a "false" failure rate of only 3% (3 of 99) and identify 56% (54 of 96) of the true failures after only two PSA increases. CONCLUSION: The CPMC definition of two PSA increases can falsely identify patients as failures, particularly if the increases in PSA are small (i.e., < or = 0.3 ng/ml). The CC definition requiring three increases in PSA can falsely identify patients as disease-free when the time to failure is long relative to the follow-up time. We propose a that a definition that combines aspects of both definitions (two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml, or three consecutive increases) may be a better definition of biochemical failure.

Consensus Statements as Topic↗

Cyclin D1 expression in human prostate carcinoma cell lines and primary tumors.

BACKGROUND: The cyclin D1 gene is amplified and/or overexpressed in several types of human cancer, including cancers of the breast, esophagus, head, and neck. However, the role of cyclin D1 in prostate cancer has not been previously studied in detail. METHODS: Six human prostate cancer cell lines and cultures of normal human prostate cells were examined by Western and Northern blot analyses for levels of expression of the cyclin D1 protein and mRNA, respectively. Southern blot analyses were performed to examine possible amplification of this gene. Immunostaining for cyclin D1 was performed on 50 primary prostate cancer samples. RESULTS: Cyclin D1 protein was expressed at relatively high levels in all of the six human prostate cancer cell lines examined, but was not detected in the cultures of normal human prostate cells. The ALVA 41 cell line expressed the highest level of this protein. Relatively high levels of cyclin D1 mRNA were also found in all of the prostate cancer cell lines. Nevertheless, none of these cell lines revealed amplification of the cyclin D1 gene. Twelve of the 50 primary prostate cancer samples (24%) revealed regions of moderate to strongly positive staining for cyclin D1. CONCLUSIONS: The increased expression of cyclin D1 in several prostate cancer cell lines and in a subset of primary prostate cancer samples suggests that further studies on the expression of this gene and related genes may be of interest in understanding the pathogenesis of prostate cancer.

Blotting, Northern↗

Kaposi's sarcoma associated herpesvirus deoxyribonucleic acid sequences: lack of detection in prostatic tissue of human immunodeficiency virus-negative immunocompetent adults.

PURPOSE: A recent study argued that Kaposi's sarcoma associated herpesvirus is ubiquitous, as reflected by the frequent detection of its deoxyribonucleic acid (DNA) sequences in the prostatic tissue of healthy Italian men. Because these findings are discordant with serological data, our objective was to reassess the prevalence of this virus in prostate tissue from immunocompetent men. MATERIALS AND METHODS: Normal tissue samples from 45 human immunodeficiency virus-negative men undergoing radical prostatectomy for prostate carcinoma were snap frozen. DNA was extracted from normal noncancerous tissue. DNA was confirmed to be polymerase chain reaction amplifiable. Then, using multiple primer sets, extracted prostatic DNA was blinded, polymerase chain reaction amplified and screened for Kaposi's sarcoma herpesvirus by Southern blot. RESULTS: Kaposi's sarcoma herpesvirus DNA sequences were not detected in either the 45 prostatic DNA or in blinded internal negative controls, but they were consistently identified in all positive internal controls. CONCLUSIONS: Since Kaposi's sarcoma herpesvirus was undetectable in any of the prostatic samples despite high assay sensitivity, it is unlikely that the prostate serves as a reservoir for this virus in immunocompetent North American men. These findings also suggest that Kaposi's sarcoma herpesvirus is not ubiquitous.

Adult↗

Acute and chronic resistive exercise increase urinary chromium excretion in men as measured with an enriched chromium stable isotope.

Both exercise and chromium exert beneficial effects on insulin function. The mechanism by which exercise improves insulin response may involve an alteration in Cr metabolism. To determine the effects of acute and chronic resistive exercise on urinary Cr losses, we measured the effects of acute resistive exercise and 16 wk of resistive exercise training on urinary Cr losses of 10 men 53-63 y of age. Subjects consumed diets in compliance with the American Heart Association Phase I diet with a Cr content of 30 +/- 4 microg/d. Sixteen weeks of resistive exercise training led to approximately 40% increases in upper and lower body strength, increases in fat-free mass and decreases in the percentage of body fat. An enriched stable isotope of Cr, 53Cr, was employed to differentiate the exogenously administered Cr from the native endogenous Cr. Both acute and chronic resistive exercise increased 53Cr losses. These data demonstrate that the improvements in body composition due to resistive exercise are associated with increased urinary Cr losses that are consistent with increased absorption.

Adipose Tissue↗

Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications.

Cribriform neoplasia of the prostate can be recognized easily. However, controversy persists regarding terminology, particularly with the intraductal spread of cribriform neoplasia; some consider this "intraductal carcinoma," whereas consensus meetings defined these lesions as high-grade cribriform prostatic intraepithelial neoplasia (HGCP). This study attempts to identify the incidence and clinical significance of HGCP and cribriform carcinoma (CC) by evaluating 114 radical prostatectomy specimens. Cases were divided into three histologic groups for statistical analysis: (1) pure acinar carcinoma: infiltrating acinar carcinoma without evidence of cribriform neoplasia; (2) CC: acinar carcinoma with CC; and (3) HGCP: acinar carcinoma with HGCP. High-grade cribriform prostatic intraepithelial neoplasia was defined as the presence of neoplastic cells spanning the entire lumen in a cribriform configuration in which a basal cell layer could be shown by immunohistochemistry. Similar areas in which no basal cell layer could be seen were diagnosed as CC. The incidence of cribriform neoplasia was 38% (43 of 114). The incidences of HGCP and CC were 13% (15 of 114) and 25% (28 of 114), respectively. Univariate analysis showed a strong association between HGCP and CC both and several preoperative and final pathology results, including digital rectal examination, pathology tumor stage, extraprostatic extension, surgical margin positivity, high Gleason sum (GS), and high tumor volume. Kaplan-Meier analysis showed HGCP to have a 61% cumulative prostate-specific antigen (PSA) failure rate in contrast with CC and pure acinar cancer, which had cumulative PSA failure rates of 15% and 13%, respectively (p = 0.0001, log-rank test). Multivariate Cox's proportional-hazards analysis found preoperative serum PSA, GS, tumor stage, and volume to be important predictors of PSA failure. In a second regression model that included serum PSA, GS, and pathology tumor stage, HGCP was an independent predictor of PSA failure. Both HGCP and CC are closely associated with several poor prognostic indicators, including advanced pathology tumor stage, a high GS, and serum PSA. Multivariate analysis showed HGCP as an independent prognostic indicator. The close association between high tumor volume and HGCP supports the theory that the development of HGCP is a late event in tumor progression, more compatible with the intraductal spread of tumor than dysplasia.

Aged↗

Effect of lead acetate on neurobehavioral development of rats.

We investigated the effects of lead exposure during the pre- and postnatal period on the neurobehavioral development of female Wistar rats (70-75 days of age, 120-150 g) using a protocol of lead intoxication that does not affect weight gain. Wistar rats were submitted to lead acetate intoxication by giving their dams 1.0 mM lead acetate. Control dams received deionized water. Growth and neuromotor development were assessed by monitoring daily the following parameters in 20 litters: body weight, ear unfolding, incisor eruption, eye opening, righting, palmar grasp, negative geotaxis, cliff avoidance and startle reflex. Spontaneous alternation was assessed on postnatal day 17 using a T maze. The animals' ability to equilibrate on a breaker rim was measured on postnatal day 19. Lead intoxication was confirmed by measuring renal, hepatic and cerebral lead concentration in dams and litters. Lead treatment hastened the day of appearance of the following parameters: eye opening (control: 13.5 +/- 0.6, N = 88; lead: 12.9 +/- 0.6, N = 72; P < 0.05), startle reflex (control: 13.0 +/- 0.8, N = 88; lead: 12.0 +/- 0.7, N = 72; P < 0.05) and negative geotaxis. On the other hand, spontaneous alternation performance was hindered in lead-exposed animals (control: 37.6 +/- 19.7; lead: 57.5 +/- 28.3% of alternating animals; P < 0.05). These results suggest that lead exposure without concomitant undernutrition alters rat development, affecting specific subsets of motor skills.

Analysis of Variance↗

Fas ligand is constitutively secreted by prostate cancer cells in vitro.

LNCaP, DU145, and PC3 prostate carcinoma cells secrete the 27-kDa soluble Fas ligand (sFasL) into their local environment. sFasL arises from the 40-kDa membrane-bound form (mFasL), which can be found on the cell surface in the LNCaP line, as demonstrated by monoclonal antibody staining. mFasL was also found in extracts of all three cell lines, as demonstrated by Western blotting. FasL mRNA was detected not only in the cell lines, but in the normal prostate as well. sFasL protein could also be detected immunohistochemically in prostate secretions and in human semen. Cleavage of mFasL to sFasL could be inhibited by several matrix metalloprotease inhibitors without a change in the cellular levels of FasL. Prostate-derived sFasL is biologically active, as demonstrated by its induction of apoptosis in Fas-positive Ramos cells, which was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Mitoxantrone induces cellular apoptosis in all three prostate cancer cell lines. Mitoxantrone treatment and doxorubicin treatment also cause up-regulation of Fas, the cell surface receptor for FasL, in LNCaP cells, but not in DU145 or PC3 cells. Furthermore, the up-regulation of Fas expression by mitoxantrone at a high concentration was potentiated by hydrocortisone. When FasL interacts with its Fas, the Fas-bearing cell undergoes apoptosis. When LNCaP cells were treated with mitoxantrone and incubated with an anti-FasL monoclonal antibody, apoptosis was partially blocked. This not only further suggests that the sFasL is biologically active, but that the up-regulation of Fas in the presence of sFasL accounts, in part, for the cytotoxicity of mitoxantrone.

Anti-Inflammatory Agents↗

Intrahippocampal GMP administration improves inhibitory avoidance performance through GABAergic and glutamatergic mechanisms in rats.

Guanidino compounds play specific physiological and pathological roles in the central nervous system. We investigated the effect of an intrahippocampal infusion of GMP (a guanidino compound) administered immediately post-training on the inhibitory avoidance learning paradigm in rats. Bilateral intrahippocampal micro-injection of GMP (0-30 nmol) caused a dose-dependent increase in test step-down latencies which was completely reversed by intrahippocampal co-administration of muscimol or baclofen (GABA agonists) or preadministration (15 min pre-training, i.p.) of MK-801 (an NMDA antagonist). These results provide evidence for a participation of GABA and NMDA receptors in the GMP-induced increase in the test step-down latencies.

Animals↗

Ultrasound in the evaluation and management of blunt abdominal trauma.

Failure to detect intraabdominal injury in the patient with blunt trauma may result in significant morbidity and mortality. The diagnosis of abdominal injury remains a clinical challenge. Presented here is a review of recent literature comparing ultrasound with diagnostic peritoneal lavage and computed tomography in the evaluation of blunt abdominal trauma.

Abdominal Injuries↗