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Biomedical subjects

R Greenberg

Publications and source records attributed to R Greenberg.

At least 73 records · Page 4Linked to original sources

Frequent progesterone receptor immunoreactivity in tuberous sclerosis-associated renal angiomyolipomas.

Angiomyolipomas can occur sporadically or in association with tuberous sclerosis complex (TSC). TSC is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, kidney, and skin. Angiomyolipomas are more common in women than in men, suggesting a possible hormonal influence on tumor growth. In this study, 35 angiomyolipomas from 23 patients were immunostained with antibodies to estrogen receptor (ER) and progesterone receptor (PR). Eleven angiomyolipomas (31%) contained clusters of PR-immunoreactive smooth muscle cells. None contained ER-immunoreactive cells. Of the 21 tumors from patients with TSC, 11 (48%) were PR immunoreactive. All of the PR-immunoreactive angiomyolipomas were from women younger than 50 years of age, and all except one of these women had TSC. This study suggests that hormonal factors play a role in the pathogenesis of TSC-associated angiomyolipomas.

Adult↗

Metabotropic glutamate receptors prevent nitric oxide-induced programmed cell death.

Activation of metabotropic glutamate receptor (mGluR) subtypes can prevent neuronal injury through the signal transduction pathways of nitric oxide (NO). It is this link to NO free radical injury and subsequent DNA damage that is the most intriguing. We therefore examined whether neuronal protection through mGluR activation was dependent on the molecular mechanisms of programmed cell death (PCD). The NO generators sodium nitroprusside and 3-morpholino-sydnonimine were administered to induce NO toxicity in primary hippocampal neurons. PCD was documented by hematoxylin and eosin nuclear staining, DNA gel electrophoresis, transmission electron microscopy, and protein synthesis assays. Following NO exposure, PCD induction was rapid and robust in approximately 70% of the neuronal population. Activation of specific mGluR subtypes with 1S,3R-ACPD and L-AP4, agents that are neuroprotective against NO, significantly limited the progression of PCD. In contrast, antagonism of mGluRs with L-AP3 did not prevent the development of PCD. Induction of new protein synthesis, a common requisite for PCD, was evident following NO exposure, but did not appear to represent a principal pathway of modulation by the mGluR agonists. Our studies suggest that mGluR modulation of NO-induced PCD represents a primary molecular pathway responsible for neuronal survival. Further elucidation of the molecular mGluR signaling pathways may yield new insight into specific genetic regulatory mechanisms responsible for neuronal injury.

Animals↗

The structure of Selmer groups.

The purpose of this article is to describe certain results and conjectures concerning the structure of Galois cohomology groups and Selmer groups, especially for abelian varieties. These results are analogues of a classical theorem of Iwasawa. We formulate a very general version of the Weak Leopoldt Conjecture. One consequence of this conjecture is the nonexistence of proper Lambda-submodules of finite index in a certain Galois cohomology group. Under certain hypotheses, one can prove the nonexistence of proper Lambda-submodules of finite index in Selmer groups. An example shows that some hypotheses are needed.

Journal Article↗

[Diverticular disease of the appendix].

The incidence of appendiceal diverticulosis in pathologic specimens is 0.004-2.1%. Diverticular disease of the appendix is classified as congenital (true) or acquired (false). The clinical presentation differs from that of acute appendicitis. The average age is older, the pain is often intermittent, and while localized in the right lower abdominal quadrant, is of longer duration. No further treatment besides appendectomy is needed. Since a high rate of perforations, peritonitis and lower gastrointestinal bleeding have been reported as complications, it is recommended that in those with an incidental finding of diverticula of the appendix during surgery, that appendectomy be performed. It is not recommended to perform prophylactic appendectomy when diverticula of the appendix are found on barium enema.

Appendectomy↗

Phase II trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer.

PURPOSE: To evaluate the antitumor activity of 96-hour paclitaxel and daily oral estramustine phosphate (EMP) in patients with metastatic hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Thirty-four patients with adenocarcinoma of the prostate that progressed after one or more hormonal therapies and a trial of antiandrogen withdrawal were enrolled onto this phase II trial. Patients received paclitaxel 120 mg/m2 by 96-hour intravenous (i.v.) infusion on days 1 through 4 of each 21-day cycle, together with daily oral EMP 600 mg/m2/d, continuously. RESULTS: Four of nine patients with measurable disease had objective responses (one complete response [CR] and three partial responses [PRs]) in liver (two patients) or nodes (two patients) of 2, 6, 8, and 20 months' duration. Of 25 assessable patients with metastases limited to bone, 14 had a > or = 50% decline in pretreatment prostate-specific antigen (PSA) level sustained for at least 6 weeks and seven had a > or = 80% decline. Overall, 17 of 32 patients (53.1%) with elevated pretreatment PSA levels had a > or = 50% decline of PSA and nine (28.1%) had a > or = 80% decrease. The main toxicities (> or = grade 2) were nausea, fluid retention, and fatigue, which occurred in 33%, 33%, and 24.2% of patients. Median time to progression, based on increasing PSA level and other clinical criteria, was 22.5 weeks. The estimated median overall survival time is 69 weeks. CONCLUSION: The combination of EMP and 96-hour paclitaxel is an active regimen for patients with HRPC. These results further support the therapeutic strategy of combining agents that impair microtubule function by complementary mechanisms.

Adenocarcinoma↗

Resistance to antidepressant medications and short-term clinical response to ECT.

OBJECTIVE: Traditionally, it has been widely assumed that the likelihood of response to ECT is independent of the adequacy of previous treatment with antidepressant medications. However, recent research has raised the possibility that medication-resistant patients with depression have a poorer clinical ECT outcome than patients who have not failed previous adequate medication trials. METHOD: Medication resistance of 100 patients with primary, unipolar, nonpsychotic major depression was evaluated during the index episode with the Antidepressant Treatment History Form. Patients were recruited and treated with ECT at three sites; standardized ECT and clinical assessment procedures were used. Clinical outcome was assessed immediately and 1 week after completion of the ECT course. RESULTS: Patients who previously had failed one or more adequate antidepressant medication trials were less likely to respond to subsequent ECT than patients not known to be medication resistant. This finding held within each study site, whether clinical response was assessed categorically or in terms of the magnitude of symptomatic improvement and after the authors accounted for other potential predictors of clinical outcome. Resistance to heterocyclic antidepressants predicted poorer outcome after ECT, while resistance to selective serotonin reuptake inhibitors and monoamine oxidase inhibitors did not show significant predictive relations. CONCLUSIONS: While a substantial percentage of medication-resistant patients respond to ECT, clinical outcome in this group is inferior to that of patients without established medication resistance. The predictive power of medication resistance is generalizable across diverse clinical settings, particularly for heterocyclic antidepressants, which perhaps suggests an overlap in the mechanisms of actions of ECT and this medication class.

Aged↗

Galileo multispectral imaging of Earth.

Nearly 6000 multispectral images of Earth were acquired by the Galileo spacecraft during its two flybys. The Galileo images offer a unique perspective on our home planet through the spectral capability made possible by four narrowband near-infrared filters, intended for observations of methane in Jupiter's atmosphere, which are not incorporated in any of the currently operating Earth orbital remote sensing systems. Spectral variations due to mineralogy, vegetative cover, and condensed water are effectively mapped by the visible and near-infrared multispectral imagery, showing a wide variety of biological, meteorological, and geological phenomena. Global tectonic and volcanic processes are clearly illustrated by these images, providing a useful basis for comparative planetary geology. Differences between plant species are detected through the narrowband IR filters on Galileo, allowing regional measurements of variation in the "red edge" of chlorophyll and the depth of the 1-micrometer water band, which is diagnostic of leaf moisture content. Although evidence of life is widespread in the Galileo data set, only a single image (at approximately 2 km/pixel) shows geometrization plausibly attributable to our technical civilization. Water vapor can be uniquely imaged in the Galileo 0.73-micrometer band, permitting spectral discrimination of moist and dry clouds with otherwise similar albedo. Surface snow and ice can be readily distinguished from cloud cover by narrowband imaging within the sensitivity range of Galileo's silicon CCD camera. Ice grain size variations can be mapped using the weak H2O absorption at 1 micrometer, a technique which may find important applications in the exploration of the moons of Jupiter. The Galileo images have the potential to make unique contributions to Earth science in the areas of geological, meteorological and biological remote sensing, due to the inclusion of previously untried narrowband IR filters. The vast scale and near global coverage of the Galileo data set complements the higher-resolution data from Earth orbiting systems and may provide a valuable reference point for future studies of global change.

Africa↗

Activation of the metabotropic glutamate receptor is neuroprotective during nitric oxide toxicity in primary hippocampal neurons of rats.

Metabotropic glutamate receptors (mGluRs) can influence neuronal survival and have been shown to be neuroprotective during glutamate toxicity in retinal cells and in cortical neurons. The mechanisms that mediate protection by this group of receptors are not clear. Since nitric oxide (NO) production can lead to neuronal cell death during excessive glutamate release, we examined whether neuronal survival was directly linked to mGluR activity and the NO pathway. Treatment with the mGluR4 receptor subtype agonist, L-(+)-2-amino-4-phosphonobutyric acid, in hippocampal cell cultures protected neurons during NO exposure. Treatment with L-(+)-2-amino-3-phosphonopropionic acid, an antagonist of the mGluR1 receptor subtype and inhibitor of inositol trisphosphate formation, did not significantly alter neuronal survival during NO administration. We conclude that activation of the mGluR4 receptor protects hippocampal neurons from NO toxicity and that the mechanism of NO induced neurodegeneration does not appear to involve inhibition of the mGluR1 receptor subtype activity or the phosphoinositide system.

Alanine↗

Phase II study of topotecan in metastatic hormone-refractory prostate cancer.

Systemic chemotherapy with currently available agents has not improved survival for patients with hormone refractory prostate cancer (HRPC), consequently, the evaluation of new agents is warranted. Topotecan is a specific inhibitor of topoisomerase I with broad antitumor activity in preclinical studies. The purpose of this phase II trial was to determine the objective response rate of topotecan administered as a 30 minute infusion for five consecutive days in men with metastatic HRPC. Thirty-four evaluable patients were treated with topotecan 1.1-1.5 mg/m2 as a 30 minute infusion daily for five days, repeated every three weeks until disease progression or unacceptable toxicity. Response was assessed with a combination of standard solid tumor response criteria and the serum prostate specific antigen (PSA) for patients with bidimensionally measurable disease, and by serial measurements of the PSA in patients with bone only (evaluable) disease. One of 13 patients (7.6%) with measurable soft tissue disease had a PR in nodal sites. Of 21 patients with only osseous metastases, 1 (4.7%) had improvement in bone scan. Six of the 34 evaluable patients (17.6%) had the serum PSA decrease by > or = 50% and 2 (5.8%) had PSA decreases of > or = 75%. Toxicity was chiefly hematologic with 66% of patients experiencing Grade 3 or 4 granulocytopenia. Thirty-nine percent of cycles required a delay to allow for hematologic recovery and ten patients required red cell transfusions. Non-hematologic toxicity, mainly nausea and alopecia, was mild. Topotecan administered at this dose and schedule has limited activity in patients with HRPC. Further trials of topo I inhibition in HRPC should utilize alternative schedules of topotecan (e.g., prolonged infusion) or other camptothecin analogs with more potent topo I inhibitory activity.

Aged↗

A comparative assessment of cryosurgical devices: application to prostatic disease.

OBJECTIVES: To determine the comparative freezing ability of the Cryotech (CT) and AccuProbe (CMS) cryosurgical systems. METHODS: Four conditions designed to model clinical situations were produced: (1) Single-probe performance in water at 17 degrees C; (2) five-probe performance in water at 17 degrees C; (3) single-probe performance in gel at 22 degrees C; and (4) single-probe performance in bovine liver. Parameters evaluated included temperatures at various time points (rates to and final low temperature), configuration of a freeze zone, and shaft freezing characteristics. In addition, isotherms were measured at predetermined distances from the center of the freeze zone. RESULTS: Both systems provided freezing of various media under operational conditions. In water, the CMS 3-mm probe delivered more rapid freezing temperature rates than the 3-mm CT probe, with a 110 degrees C difference in probe surface temperature. In gel, the CMS probe increased freeze volume fourfold versus a twofold increase for the CT probe. In bovine liver, there was nearly equivalent performance with respect to geometry of the freeze ball. Extrapolation of the CT cooling curve indicated temperature equivalence at 30 minutes. A larger shaft diameter 4.9-mm CT probe produced results similar to the CMS probe in all the tested media. In addition, the freeze configuration of the CMS probe was spherical; the CT configuration was more cylindrical. CMS probe (equivalent diameter) tip temperatures were on average 100 degrees C lower. CONCLUSIONS: Our tests demonstrated differences between the CMS and CT probe. The major differences are in the configuration of the freeze zone and shaft freezing. In equivalent conditions, the CMS 3-mm probe delivered more rapid cooling rates, a more spherical freeze ball, and lower absolute temperatures than the CT 3-mm probe. The larger CT probe produces equivalent freezing temperatures to the CMS probe, albeit with a more spherical shape. However, these in vitro systems may not adequately reflect varied prostate morphology. Further research is under way to determine if these differences affect relative efficacy of cryotherapy of the prostate.

Animals↗

Paclitaxel plus estramustine in metastatic hormone-refractory prostate cancer.

Combination antimicrotubule therapy with estramustine phosphate (EMP) and vinblastine has reproducible activity in metastatic hormone-refractory prostate cancer (HRPC) with an objective response rate of 31%. Although paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion was inactive in HRPC, 0.5 to 1.0 nmol/L concentrations of paclitaxel combined with EMP exerted synergistic cytotoxicity in DU-145 androgen-independent human prostate cancer cell lines. Based on these results, we treated 24 patients with HRPC using the combination of paclitaxel 120 to 140 mg/m2 by 96-hour intravenous infusion every 3 weeks plus daily oral EMP at 600 mg/m2/d. Of seven patients with measurable soft tissue metastases, three have attained partial responses and a fourth patient is nearing partial response status. Of 16 patients with bone-only disease evaluated by change in serum prostate-specific antigen levels, 11 patients (68.8%) have had decreases of > or = 50% from pretreatment baseline. The prostate-specific antigen decrease has exceeded 80% in six of 16 (37.5%) patients. For all 23 evaluable patients, the prostate-specific antigen has decreased by > or = 50% in 15 (65.2%) and by > or = 80% in eight (34.7%). Grade 4 leukopenia occurred in one of 21 patients treated at the paclitaxel dose of 120 mg/m2/96 hr and one of three patients treated at 140 mg/m2/96 hr. The incidence of nausea (50%) and peripheral edema (37.5%) was similar to that associated with single-agent EMP. These results demonstrate that 96-hour paclitaxel plus EMP is active in HRPC and provide further evidence that the rational combination of antimicrotubule agents leads to synergistic antitumor activity in HRPC.

Adenocarcinoma↗

Fluctuations in serum amylase in patients with macroamylasemia.

OBJECTIVE: To report wide fluctuation of serum amylase in patients with macroamylasemia. It has generally been considered to remain constant. METHODS: Over the past 16 y, 18 patients have been diagnosed with macroamylasemia in our GI department. Of these, four patients were followed up with serial serum amylase determinations for a period of less than 1-4 y. Serum amylase was measured by the "Phadebas amylase test." Serum macroamylase was measured by "PEG precipitation technique." RESULTS: There was a wide fluctuation of serum amylase in three out of four patients. In the fourth patient, more persistent hyperamylasemia was noted during the shorter observation period. CONCLUSION: Marked fluctuation in serum amylase, ranging from 115 to 1160% in this study, may occur in patients with macroamylasemia. The reasons for these fluctuations are not clear but may be due to association-dissociation of amylase with serum proteins at variable time intervals. This fluctuation, especially when the amylase becomes normal (as in cases 1 and 3), may lead to confusion in differentiating macroamylasemia from other causes of hyperamylasemia.

Acquired Immunodeficiency Syndrome↗

Phase I study of paclitaxel and estramustine: preliminary activity in hormone-refractory prostate cancer.

Estramustine phosphate is a unique antimitotic agent that binds to tubulin and microtubule-associated proteins. Preclinically, estramustine combined with other microtubule inhibitors, like vinblastine or paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), produced additive or greater antimitotic and cytotoxic effects. Clinically, the estramustine/vinblastine combination has significant activity in hormone-refractory prostate cancer. We have begun a phase I study of paclitaxel by 96-hour continuous infusion every 3 weeks combined with daily oral estramustine (600 mg/m2). Eighteen patients with refractory solid tumors have received paclitaxel doses ranging from 80 to 140 mg/m2. Grade 3 or 4 granulocytopenia occurred in one of seven and two of four patients treated at the 120- and 140-mg/m2 dose levels, respectively. The latter two patients experienced grade 3 mucositis and had mean plasma paclitaxel levels exceeding 0.1 mumol/L. Other toxicities, principally nausea and hepatic function abnormalities, have been mild. The apparent steady-state concentrations of paclitaxel 100 and 120 mg/m2 administered with estramustine are similar to those reported for single-agent paclitaxel administered as a 96-hour infusion at doses of 100 and 120 mg/m2. In contrast, at the 140 mg/m2 dose level, paclitaxel concentrations increased throughout the infusion, and steady state was not reached in three of the four patients treated. Objective responses have been observed in two of three patients with adenocarcinoma of the esophagus and in two patients with hormone-resistant prostate cancer and measurable soft tissue metastases. Two additional patients with prostate cancer have been treated with the estramustine/paclitaxel combination, one achieving a major response and the other stable disease. The recommended phase II dose for 96-hour infusional paclitaxel with daily oral estramustine is at least 120 mg/m2. Studies to determine the effect of estramustine on paclitaxel pharmacokinetics are continuing. The antitumor activity observed merits phase II studies of this combination in hormone-resistant prostate cancer and other malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Neuroimaging of meningeal disease.

In the past two decades, the advent of CT and MRI has made a considerable impact on the evaluation of meningeal diseases, conditions once regulated to cytological, histopathological, or postmortem analyses alone. This article reviews the imaging findings in various meningeal processes with particular attention to the anatomic definition of the meningeal layers and their relationship to the development of meningeal pathology and consequent imaging characteristics.

Central Nervous System Diseases↗