PubMed Health⌕ Search

Biomedical subjects

J Ferrara

Publications and source records attributed to J Ferrara.

At least 19 recordsLinked to original sources
PubMed2002

Assessment of psychological distress in prospective bone marrow transplant patients.

Patient psychological distress is associated with many aspects of the bone marrow transplantation (BMT) process and has been linked with poor treatment outcomes. We assessed psychological distress in potential BMT candidates, and compared patient and nurse coordinator ratings of emotional distress at the time of initial BMT consultation. Fifty patients self-reported psychological distress using both the NCCN Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). Coordinators rated patient emotional distress using the DT and Coordinator Rating Scales that measure anxiety and depression. Fifty and 51% of patients self-reported clinically significant levels of emotional distress and anxiety, respectively, but only 20% self-reported clinically significant levels of depression. There was good correlation between ratings using the brief DT and the more comprehensive HADS. There was significant but only moderate agreement between patient and coordinator ratings of emotional distress and anxiety, with coordinators underestimating the number of patients with high levels of emotional distress. In addition, coordinator ratings of patient emotional distress primarily reflected anxiety, whereas anxiety and depression together only minimally accounted for patient self-reports of psychological distress. These findings suggest that: (1) the DT can be a useful screening device; (2) approximately half of patients at the time of initial consultation for BMT already experience significant levels of psychological distress; and (3) coordinators observe emotional distress primarily as anxiety, but patients experience psychological distress as something more than anxiety and depression.

Adult↗
PubMed2001

Clinical protocol. Purging of autologous stem cell sources with bcl-x(s) adenovirus for women undergoing high-dose chemotherapy for stage IV breast carcinoma.

High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. However, the bone marrow of such patients is often contaminated with tumor cells. Recently, we have found that a recombinant adenovirus vector that contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family), called the bcl-x(s) adenovirus, is lethal to cancer cells derived from epithelial tissues, but not to normal human hematopoietic cells. To determine the mechanism, by which this virus spares normal hematopoietic cells, we isolated normal mouse hematopoietic stem cells and infected them with an adenovirus that contains a beta-galactosidase minigene. Such cells do not express beta-galactosidase, indicating that hematopoietic stem cells do not express transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT.

Adenoviridae↗
PubMed2001

Pathways of lymphatic drainage from the breast.

BACKGROUND: The current standard for obtaining accurate sentinel lymph node (SLN) mapping is intraparenchymal lymphophilic dye/radiocolloid injection close to the breast tumor. We hypothesized that common lymphatic trunks drain both a large volume of breast parenchyma and skin and that intradermal or intraparenchymal routes flow to the same axillary node. METHODS: 99mTc-labeled filtered sulfur colloid was injected intradermally directly over the breast tumor in 119 patients. Blue dye was injected intraparenchymally in the same quadrant as the primary tumor (concordant quadrant) in 66 and in a discordant quadrant in 53 patients. During axillary exploration, both blue and gamma-emitting (hot) nodes were found. End points were SLNs that were hot and blue, either the same node or different nodes. RESULTS: In 62 (93.9%) of 66 of concordant quadrant and in 49 (92.5%) of 53 of discordant quadrant patients, the same SLN was both hot and blue (P = .99; Fisher's exact test). In eight cases in which two distinct nodes were blue and not hot and hot but not blue, the lymph nodes were very close to each other. CONCLUSIONS: The dermal and parenchymal lymphatics of the breast seemed to drain to the same axillary lymph nodes. Lymph from the entire breast seemed to drain through a small number of lymphatic trunks to one or two lymph nodes.

Aged↗
PubMed2001

Allogeneic stem cell transplantation reduces disease progression compared to autologous transplantation in patients with multiple myeloma.

This study compares the probability of disease progression, progression-free survival, and overall survival between patients undergoing an allogeneic or autologous transplant for multiple myeloma using an identical preparative regimen. Patients received a preparative regimen of TBI, busulfan, and cyclophosphamide followed by an allogeneic or autologous transplant. In the allogeneic group (n = 21), six patients received bone marrow and 15 received G-CSF mobilized PBSC; all autologous patients (n = 35) received PBSC mobilized with cyclophosphamide and G-CSF. Allogeneic donors were HLA-identical (n = 20) or one-antigen mismatched (n = 1) siblings. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (n = 10), tacrolimus/methotrexate (n = 6), cyclosporine/methotrexate (n = 4), or cyclosporine (n = 1). The groups were evenly matched for gender, pretransplant therapy, disease status at time of transplant, myeloma subtype, and time from diagnosis to transplant. The median age was significantly lower in the allogeneic group (48 vs 55 years, P < 0.01). In the allogeneic group the probabilities of developing acute GVHD grade II-IV and chronic GVHD were 55% and 82%, respectively. The Kaplan-Meier probability of disease progression was significantly lower in the allogeneic group (11% vs 64%, P < 0.001) compared to the autologous group. Although progression-free (60% vs 30%, P = 0.19) and overall survival at 2 years (60% vs 42%, P = 0.39) favored the allogeneic group, this did not reach statistical significance. Within the allogeneic transplant group, patients age 50 years or under had a 3-year overall survival significantly higher when compared to older patients (79% vs 29%, P = 0.03). Using identical preparative regimens, allogeneic transplantation reduced disease progression compared to autologous transplantation for myeloma. This suggests that allogeneic transplantation induces a graft-versus-myeloma (GVM) effect.

Actuarial Analysis↗
PubMed2001

Double dose-intensive chemotherapy with autologous stem cell support for relapsed and refractory testicular cancer: the University of Michigan experience and literature review.

Testicular cancer patients refractory or in relapse after primary chemotherapy have < or =25% 5-year progression-free survival with salvage. To improve prognosis, patients entered a phase I/II tandem dose-escalation trial of carboplatin (1500-2100 mg/m(2)) and etoposide (1200-2250 mg/m(2)) with ABMT. Patients were eligible for a second cycle if disease progression was absent and performance status allowed. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. At the time of ABMT, 10 were chemosensitive, four were chemoresistant, and 10 were absolutely refractory to platinum. Disease status (no. patients) at transplant: primary refractory disease (six), first relapse (10), second relapse (eight), third relapse (five). Fifteen (52%) received both transplants. Treatment-related mortality was 10%. Best response after ABMT included: two CR, one CR surgically NED, five PR, three PR surgically NED, seven SD, and eight PD. Eight (28%) patients are continuously progression-free a median 60 months (range, 31-93) from first ABMT. Three seminoma patients remain progression-free. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. Eighteen relapses occurred a median of 4 months after ABMT I (two late relapses at 28 and 44 months). The median PFS and OS for the whole group are 4 and 14 months, respectively. Patients with relapsed/ refractory testicular cancer benefit most from ABMT if they have platinum-sensitive disease in first relapse. Patients who do poorly despite ABMT have a mediastinal primary site, true cisplatin-refractory disease, disease progression prior to ABMT, and/or markedly elevated betaHCG at ABMT. New treatment modalities are needed for the latter group.

Adolescent↗
PubMed2000

Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation.

Currently, limited data exist on the role of tacrolimus (FK506) in pediatric allogeneic marrow transplantation. Forty-one patients who received tacrolimus as prophylaxis were reviewed, with a median age of 9 years (range 0.2-16 years). Twenty-one patients underwent related donor transplants and 20 underwent unrelated donor transplants. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous i.v. infusion. When clinically possible, patients were switched to oral therapy in two divided doses, at four times the intravenous dose. Tacrolimus levels were monitored twice a week, and dosages adjusted to maintain serum levels 5-15 ng/ml. Common adverse effects included hypomagnesemia (98%), hypertension (49%), nephrotoxicity (34%), and tremors (32%). Less common side-effects (<10% cases) included seizures and hyperglycemia. The median time to ANC recovery (ANC >500 x 106/l) was 15 days. For the related donor group, the incidence of grade II-IV acute GVHD was 33%, and grade III-IV GVHD 19%. For the unrelated donor group, the incidence of grade II-IV acute GVHD was 55%, and grade III-IV GVHD 30%. Overall, tacrolimus therapy was well tolerated as prophylaxis for acute GVHD in pediatric patients undergoing allogeneic transplantation.

Actuarial Analysis↗
PubMed1999

Detection of prostatic specific membrane antigen messenger RNA using immunobead reverse transcriptase polymerase chain reaction.

The present study was performed to detect circulating prostatic carcinoma (PC) cells using a novel three-step immunobead reverse transcriptase (RT) polymerase chain reaction (PCR) assay for prostatic specific membrane antigen (PSMA) messenger RNA (mRNA). The sensitivity and specificity of this technique was assessed and the incidence of immunobead RT-PCR positivity correlated with progressive metastatic disease and serum prostatic specific antigen (PSA) levels. Fifty peripheral blood (PB) samples from 46 patients with PC were incubated with magnetic beads coated with Ber-EP4 antibody directed against the human epithelial antigen a membrane antigen widely expressed by epithelial cells. The epithelial cell-enriched magnetic fraction was then subjected to mRNA isolation using oligo-deoxythymidine (dT) magnetic beads. Nested RT-PCR for PSMA was performed on the mRNA oligo-dT complex and the identity of the RT-PCR products was confirmed by Southern blotting. Twenty-one PB samples from 8 control subjects without PC were also evaluated. Three-step immunobead PSMA RT-PCR was able to detect one PC cell per 1 mL of PB. The positivity rate of the RT-PCR assay was significantly higher (11 of 25; 44%) in patients with metastatic tumor than in patients with non-metastatic disease (1 of 21; 5%) (P = 0.003). In patients with metastatic PC, RT-PCR positivity was much higher in patients with progressive disease (10 of 13; 77%) than in patients with responding or stable disease (1 of 12; 8%) (P = 0.001). There was a statistically significant correlation between immunobead PSMA PCR positivity and high levels of serum PSA (P = 0.005). All control subjects without PC tested negative for PSMA PCR. The three-step immunobead RT-PCR for PSMA can detect circulating PC cells with high specificity and sensitivity. Preliminary data show a strong correlation between immunobead PCR positivity, the presence of progressive metastatic disease, and high levels of serum PSA.

Antigens, Surface↗
PubMed1999

Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma.

PURPOSE: To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process. RESULTS: The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (<80%), high serum lactate dehydrogenase (> 1.5 times upper limit of normal), low hemoglobin (< lower limit of normal), high "corrected" serum calcium (> 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months. CONCLUSIONS: Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.

Adult↗
PubMed1999

Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer.

The INK4A gene maps to the 9p21 region and was initially described [M. Serrano et al., Nature (Lond.), 366: 704-707, 1993; A. Kamb et al., Science (Washington DC), 264: 436-440, 1994] as encoding a 148-amino-acid protein termed p16. The p16 protein associates exclusively with Cdk4 and Cdk6, inhibiting their complexation with D-type cyclins and the consequent phosphorylation of pRb. This contributes to cell cycle arrest. The purpose of the present study was to evaluate patterns of p16 expression in a well-characterized cohort of prostatic adenocarcinomas while exploring potential associations between alterations of p16 and clinicopathological variables. Normal and malignant tissues from 88 patients with prostate carcinoma were examined. In situ hybridization and immunohistochemistry assays were used to determine the status of the INK4A exon 1alpha transcripts and levels of p16 protein, respectively. Associations between altered patterns of expression and clinicopathological variables, including pretreatment prostate-specific antigen (PSA) level, Gleason grade, pathological stage, and hormonal status, were evaluated using the Mantel-Haenszel chi2 test. Biochemical (PSA) relapse after surgery was evaluated using the Kaplan-Meier method and the log-rank test. Levels of p16 expression and INK4A exon 1alpha transcripts in normal prostate and benign hyperplastic tissues were undetectable. However, p16 nuclear overexpression was observed in 38 (43%) prostate carcinomas, whereas the remaining 50 (57%) cases showed undetectable p16 levels. Overexpression of p16 protein was found to correlate with increased INK4A exon 1alpha transcripts. Moreover, p16 overexpression was associated with a higher pretreatment PSA level (P = 0.018), the use of neoadjuvant androgen ablation (P = 0.001), and a sooner time to PSA relapse after radical prostatectomy (P = 0.002). These data suggest that p16 overexpression is associated with tumor recurrence and a poor clinical course in patients with prostate cancer.

Adenocarcinoma↗
PubMed1999

Inactivation of the p53 pathway in prostate cancer: impact on tumor progression.

To determine the potential role of p53 inactivation in prostate cancer, we studied a well characterized cohort of 86 patients treated with radical prostatectomy. We analyzed patterns of p53, mdm2, and p21/WAF1 expression by immunohistochemistry. Results were then correlated with clinicopathological parameters of poor outcome, including time to PSA relapse. In addition, data were also correlated with proliferative index, as assessed by Ki67 antigen detection. p53-positive phenotype, defined as identification of nuclear immunoreactivity in > 20% of tumor cells, was observed in 6 of 86 cases (7%). An association was observed between p53-positive phenotype and decreased time to PSA relapse (P < 0.01). mdm2-positive phenotype, defined as > or = 20% of tumor cells displaying nuclear immunoreactivity, was observed in 28 of 86 cases (32.5%). mdm-2-positive phenotype was found to be associated with advanced stage (P = 0.009). p21-positive phenotype, defined as > 5% of tumor cells with nuclear immunoreactivity, was observed in 28 of 86 cases (32.5%). An association was observed between p21-positive phenotype and high Ki67 proliferative index (P = 0.002). Patients with p21-positive phenotype had a significant association with decreased time to PSA relapse (P = 0.0165). In addition, a significant association was found between p21-positive phenotype and coexpression of mdm2 (P < 0.01). Forty-three of 86 cases (50%) were found to have one or more alterations, and patients with any alteration were found to have a higher rate of PSA relapse (P < 0.01). It is our hypothesis that a pathway of prostate cancer progression involves p53 inactivation caused by mdm2 overexpression and that p21 transactivation in this setting is due to an alternative signaling system, rather than through a p53-dependent mechanism.

Aged↗
PubMed1997

Probing the structure and function of the estrogen receptor ligand binding domain by analysis of mutants with altered transactivation characteristics.

We have developed a genetic screen for the yeast Saccharomyces cerevisiae to isolate estrogen receptor (ER) mutants with altered transactivation characteristics. Use of a "reverse" ER, in which the mutagenized ligand binding domain was placed at the N terminus of the receptor, eliminated the isolation of truncated constitutively active mutants. A library was screened with a low-affinity estrogen, 2-methoxyestrone (2ME), at concentrations 50-fold lower than those required for activation of the unmutagenized ER. Several mutants displaying enhanced sensitivity to 2ME were isolated. We further characterized a mutant carrying the substitution L536P, which was located immediately N terminal to the AF-2-activating domain of the receptor. Amino acid 536 corresponds to a ligand contact residue in retinoic acid receptor gamma, suggesting that key contact points are conserved among receptors. Introduction of L536P into the original ER cDNA isolate HE0, which contains the substitution G400V, rendered the receptor more sensitive to a variety of agonists. When introduced into the wild-type ER HEG0, L536P also rendered the receptor more sensitive to agonists, and, in addition, induced high levels of constitutive activity that could be inhibited by antiestrogens. Estrogens containing a keto substitution in the steroid D ring, but not those containing a hydroxyl group, were full agonists of L536P-HEG0. Limited proteolytic analysis suggested that the L536P substitution, which is located immediately N terminal to the AF-2 domain, induces a conformational change in the ER that partially mimics binding by hormone. Both HEG0 and L536P-HEG0 formed complexes with hsp90 in vitro, indicating a lack of correlation between interaction with hsp90 in vitro and hormonal regulation of ER transactivation in vivo. This supports the idea that a factor(s) acting downstream of hsp90 is important for controlling activity of the hormone-free receptor.

Amino Acid Sequence↗
PubMed1997

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

PURPOSE: To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). PATIENTS AND METHODS: Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. RESULTS: One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. CONCLUSION: Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.

Adolescent↗
PubMed1997

High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes.

PURPOSE: To identify clinical factors predictive of treatment outcome after high-dose chemotherapy (HDC) for Hodgkin's disease and to develop a prognostic model for progression-free and overall survival. PATIENTS AND METHODS: 102 patients with relapsed or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide and autologous marrow and/or peripheral blood progenitor cell support. Median follow-up of survivors is 4.1 years (1.8-7.5 years). Factors potentially important for treatment outcome were examined in univariate analysis, and Cox regression with forward selection was performed. A prognostic model was developed. RESULTS: Poorer progression-free and overall survival were associated with nodular sclerosis histology, abnormal performance status, progressive disease at HDC, more than one extranodal site of disease, and shorter time from initial diagnosis to HDC. These factors and the presence of B symptoms at relapse also predicted for decreased overall survival. Progressive disease immediately prior to HDC, more than one extranodal disease site, and abnormal performance status retained significance for both progression-free and overall survival in multivariate analysis. Progression-free and overall survival are 42% (95% confidence interval, CI, 34 to 53) and 65% (95% CI 54 to 73) at three years. A model based on number of risk factors present divides patients into low, intermediate, and high risk groups with three-year actuarial survival of 82%, 56%, and 19% respectively. Treatment outcome for patients treated with HDC at first chemotherapy relapse was not significantly different from that of the group overall (p > 0.3). CONCLUSIONS: Asymptomatic patients with Hodgkin's disease involving at most one extranodal site whose disease is controlled by conventional dose chemotherapy or radiation therapy at the time of HDC have good outcomes after this therapy. Presence of increasing numbers of risk factors are associated with poorer outcomes. Results of HDC compare favorably to those of standard dose salvage therapy. These data can be used to estimate likely outcomes in patients undergoing HDC for Hodgkin's disease, to identify potential candidates for innovative therapies, and to evaluate strategies for the optimal use of HDC in Hodgkin's disease.

Adult↗
PubMed1996

Adrenomedullin is inactivated in the lungs of neonatal piglets.

Adrenomedullin, a novel 52 amino acid peptide normally present in adult human plasma, has been shown to induce systemic hypotension in the adult rat, pig and cat, and in the new-born piglet. Little is known about the site (s) of adrenomedullin inactivation in adults or neonates. Groups of five 0-2-day old and 2-week old anaesthetized piglets were prepared to enable continuous monitoring of cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, mean systemic vascular resistance and mean pulmonary vascular resistance. In both age groups, injections of human adrenomedullin1-52 into the left atrium produced significant (P < 0.05) reductions in mean systemic arterial pressure and mean pulmonary artery pressure. Although injections of similar doses of human adrenomedullin1-52 into the right atrium produced significant (P < 0.05) decreases in mean pulmonary artery pressure, there were no appreciable alterations in mean systemic arterial pressure in either age group. These results suggest that the systemic vasodilator properties of human adrenomedullin1-52 are reduced upon first pass through the pulmonary circulation in 2-week old piglets, a phenomenon that is present at birth.

Adrenomedullin↗
PubMed1995

Autonomic control of the regional hemodynamic response to scald.

Ultrasonic flow probes were placed around the ascending aorta and each femoral artery of dogs to record cardiac index and femoral blood flow, respectively. Intravenous hexamethonium (n = 5) produced 30% decreases in systemic mean arterial pressure and in cardiac index, and a 14% increase in femoral blood flow, effects that waned over time, consistent with the half-life of the agent. Without hexamethonium, hind paw scalding with boiling water for 5 sec (n = 5) caused a marked increase in ipsilateral femoral artery blood flow (70.7 +/- 8.9 ml/min pre-burn vs 243.7 +/- 23.7 ml/min 5 min post-burn) that persisted for the 3 hr observation period. Contralateral femoral blood flow, systemic mean arterial pressure, and cardiac index were unchanged. Compared to burn only dogs, pre-burn treatment with hexamethonium (n = 6) blunted the femoral vasodilator response to burn (78.8 +/- 9.7 ml/min pre-burn vs 116.5 +/- 7.5 ml/min 5 min post-burn). These data suggest that postganglionic autonomic nerves are at least partially responsible for mediation of the regional vasodilator response to thermal injury.

Animals↗
PubMed1995

Femoral vasodilation to cromakalim is blocked by U37883A, a non-sulphonylurea that selectively inhibits KATP channels.

The purpose of the present study was to determine the effects of U37883A, a non-sulphonylurea inhibitor of KATP channels, in the femoral vascular bed of the anaesthetized dog. Administration of U37883A, 4-morpholinecarboxamidine-N-1-adamentyl-N"-cyclohexyl hydrochloride (2.5 mg kg-1, i.v.), significantly inhibited the femoral vasodilator response to intra-femoral arterial injection of cromakalim, an activator of KATP channels. In contrast, U37883A had no effect on the femoral vasodilator responses to nitroglycerin, isoprenaline, 5-HT, or 5-carboxamidotryptamine, suggesting this agent is a novel and selective inhibitor of hindlimb vasodilation induced by KATP-channel activation. Since U37883A did not significantly alter baseline femoral blood flow and femoral vascular resistance, the present data suggest that KATP channels do not contribute, in large measure, to regulating the canine femoral vascular bed under resting conditions in-vivo.

Adamantane↗