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R Hurst

Publications and source records attributed to R Hurst.

At least 19 recordsLinked to original sources
PubMed2000

Restorative proctocolectomy with J-pouch ileoanal anastomosis.

Restorative proctocolectomy with ileoanal anastomosis, complemented by a pouch formed with the last foot of terminal ileum, is the procedure of choice for patients in need of surgical treatment for ulcerative colitis and familial polyposis. The procedure has undergone many technical modifications that have ensured a very high degree of continence and an acceptable number of daily bowel movements. Herein we describe the operative technique we use in the majority of our patients, a restorative proctocolectomy with hand-sewn J-pouch ileoanal anastomosis with protecting ileostomy. We also comment on the immediate postoperative care and on the long-term functional results.

Adenomatous Polyposis Coli↗
PubMed2000

Initial presentation with stage IV colorectal cancer: how aggressive should we be?

HYPOTHESIS: The appropriate surgical treatment of patients with colorectal cancer who are found on initial presentation to have stage IV disease is controversial. With presumed limited life expectancy, the role of primary colon or rectal resection has been questioned, as has the utility of synchronous hepatic resection. DESIGN: A retrospective chart review. SETTING: The University of Chicago Hospitals, Chicago, Ill, a tertiary-care referral center. PATIENTS: One hundred twenty patients were identified through The University of Chicago Hospitals Tumor Registry whose initial presentation showed stage IV colorectal cancer and who underwent laparotomy. MAIN OUTCOME MEASURES: The primary end points of the study were perioperative morbidity and mortality and overall survival. RESULTS: Median survival and 5-year survival were 14.4 months and 10%, respectively. Survival was greater for patients younger than 65 years than for those who were aged 65 years or older (18.3 vs 9.8 months; P = .007). Carcinomatosis was associated with significantly decreased survival when compared with less extensive stage IV disease (6.7 vs 18.1 months; P<.001). Patients who underwent any form of resection of hepatic metastases achieved a survival advantage over those with unresectable liver lesions (median survival, 29.6 vs 10.2 months; P<.001). Overall, 27 patients (22.5%) developed postoperative complications. Seven patients (5.8%) died during the postoperative period. CONCLUSIONS: Age of 65 years or older, carcinomatosis, and extensive (bilobar) liver involvement are associated with decreased survival and increased postoperative morbidity and mortality and may negate any potential benefit patients derive from resection of the primary lesion. A substantial number of patients with synchronous hepatic metastases have protracted survival that justifies resection of the primary colorectal tumor at initial presentation. Despite the presence of stage IV disease, resection of the primary tumor and, when feasible, liver metastases is indicated.

Adult↗
PubMed1999

Phospholipid hydroperoxide cysteine peroxidase activity of human serum albumin.

Human serum albumin (HSA) reduced the phospholipid hydroperoxide, 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl)-l-3-phosphatidylcholine (PLPC-OOH) to the corresponding hydroxy-derivative with a high apparent affinity (Km=9. 23+/-0.95 microM). Removal of bound lipid during purification increased this activity. At physiological concentration, HSA reduced the phospholipid hydroperoxide in the absence of a cofactor. However, in the presence of a cofactor (reductant), the rate of the reaction was increased. All of the major aminothiols in plasma could act as reductants, the best being the most abundant, cysteine (Km=600+/-80 microM). For every nanomole of PLPC-OOH reduced by HSA, 1.26 nmol of cystine was formed, indicating a reaction stoichiometry of 1 mol PLPC-OOH to 2 mol cysteine. We used chemical modification to determine which amino acid residues on HSA were responsible for the activity. Oxidation of thiol group(s) by N-ethylmaleimide led to a reduction in the rate of activity, whereas reduction of thiols by either dithiothreitol or the angiotensin-converting enzyme inhibitor, captopril, increased the activity. Both N-ethylmaleimide-modified HSA and dithiothreitol-treated HSA exhibited increased apparent affinities for PLPC-OOH. For a range of preparations of albumin with different modifications, the activity on PLPC-OOH was dependent on the amount of free thiol groups on the albumin (correlation coefficient=0.91). Patients with lowered albumin concentrations after septic shock showed lowered total plasma thiol concentrations and decreased phospholipid hydroperoxide cysteine peroxidase (PHCPx) activities. These results therefore show for the first time that HSA exhibits PHCPx activity, and that the majority of the activity depends on the presence of reduced thiol group(s) on the albumin.

Bilirubin↗
PubMed1999

Brain metastasis after immunotherapy in patients with metastatic melanoma or renal cell cancer: is craniotomy indicated?

The purpose of this study was to evaluate the outcome of surgical treatment of brain metastasis in patients with metastatic melanoma or renal cell cancer after interleukin-2 (IL-2) therapy. A retrospective analysis was conducted at the Surgery Branch, National Cancer Institute. All patients with a diagnosis of metastatic melanoma or renal cell cancer who received IL-2 from January 1, 1985 to January 1, 1996 (n = 1385) were screened for the development of brain metastasis. Forty patients underwent surgical treatment of brain metastasis that developed after initiating IL-2 therapy. Thirty-six were rendered free of disease after resection of a single metastasis and were the focus of this study. Twenty-two of the 36 patients achieved a clinical response (10 complete responses and 12 partial responses) at extracranial sites of disease after IL-2-based immunotherapy and before the development of brain metastasis. The median disease-free interval in the brain after resection of a single metastasis was 21, 7, and 3 months for patients achieving a complete response, partial response, and no response (CR, PR, and NR) to IL-2 therapy, respectively. The median survival after craniotomy for these three groups of patients was 23, 17, and 7 months, respectively. The disease-free interval in the brain and the overall survival after craniotomy were significantly longer for patients achieving a CR to previous immunotherapy when compared with patients achieving a PR or NR. Of the 10 patients who had achieved a prior CR, 8 remained disease free in the brain at last follow-up, 6 remained alive beyond 1 year, and 3 > 4 years. Twenty-five patients experienced neurologic symptoms before craniotomy and all had complete resolution of their symptoms after surgery. Surgical treatment of single brain metastasis in patients with metastatic melanoma or renal cell cancer is indicated in carefully selected patients. The benefits of resection include palliation of symptoms and the potential for a prolonged disease-free interval in the brain.

Adult↗
PubMed1999

Evaluating cardiovascular disease prevention programs in African American communities.

This article reports on an evaluation of community cardiovascular disease prevention projects. The evaluation protocol involved a monitoring system for documenting community activities. It showed improvements in cardiovascular disease prevention services, community actions, planned products, and new or modified community programs to prevent cardiovascular disease. Reports from focus group sessions provided analyses of participants' perceived behaviors and satisfaction with eight community-based cardiovascular disease prevention projects in African American communities. Modest improvements in blood pressure, blood cholesterol, dietary intake, and physical activity among a convenience sample of participants in the community were noted.

Adult↗
PubMed1998

Cloning, functional expression and purification of endo-beta-galactosidase from Flavobacterium keratolyticus.

Endo-beta-galactosidase (EC 3.2.1.103) is an enzyme that hydrolyzes internal endo-beta-galactosyl linkages in keratan sulfate, and glycoconjugates with N-acetyl-lactosamine repeating units. Here, we report the cloning of the endo-beta-galactosidase-encoding gene from Flavobacterium keratolyticus, its expression in Escherichia coli and the purification of the enzyme. The enzyme was purified over 15000-fold to apparent homogeneity. The purified endo-beta-galactosidase consists of a single band of about 43kDa on SDS-PAGE and has a specific activity of 148micro/mg. Based on peptide sequences derived from the purified enzyme, a full-length clone encoding endo-beta-galactosidase was isolated from F. keratolyticus genomic DNA. The gene contains a single open reading frame coding for a protein of 422 amino acid residues with a putative N-terminal signal peptide. Its authenticity was confirmed by colinearity of deduced amino acid sequences with the peptide sequences, and synthesis of enzyme in E. coli.

Amino Acid Sequence↗
PubMed1998

Porcine cartilage transplants in the cynomolgus monkey. III. Transplantation of alpha-galactosidase-treated porcine cartilage.

BACKGROUND: Studies on transplantation of porcine meniscus and articular cartilage into monkeys are important for evaluating the possible use of such tissues in humans. In addition, such studies shed light on the chronic xenograft rejection process in primates. Transplantation of porcine cartilage into cynomolgus monkeys for 2 months results in a many-fold increase in anti-Gal activity and in a strong cellular inflammatory response of T lymphocytes and macrophages within the implants. The objective of this study was to determine whether elimination of Galalpha1-3Galbeta1-4GlcNAc-R (alpha-gal epitopes) from the xenograft may alter the immune response and the inflammatory reaction. METHODS: Porcine meniscus and articular cartilage specimens were treated with recombinant alpha-galactosidase (100 U/ml), and the absence of alpha-gal epitopes was assessed by the binding of the monoclonal anti-Gal antibody M86. The treated cartilage specimens were transplanted into the suprapatellar pouch of cynomolgus monkeys. The immune response to cartilage was monitored in the serum and the inflammatory reaction was assessed in the xenografts, which were explanted after 2 months. RESULTS: Incubation with alpha-galactosidase resulted in complete removal of alpha-gal epitopes from the cartilage. The increase in anti-Gal activity in the transplanted monkeys was marginal. However, most monkeys produced antibodies to antigens specific to porcine cartilage. The inflammatory response within the alpha-galactosidase-treated xenografts was much lower than in nontreated cartilage and the proportion of T lymphocytes within the cellular infiltrates was greatly reduced. CONCLUSIONS: Treatment of cartilage xenografts with alpha-galactosidase successfully removes alpha-gal epitopes from porcine cartilage. Transplantation of the treated cartilage results in the production of only anti-porcine cartilage-specific antibodies and a reduced inflammatory response consisting primarily of macrophages infiltrating into the cartilage.

Animals↗
PubMed1998

Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferases.

Human glutathione transferases (GSTs) from Alpha (A), Mu (M) and Theta (T) classes exhibited glutathione peroxidase activity towards phospholipid hydroperoxide. The specific activities are in the order: GST A1-1>GST T1-1>GST M1-1>GST A2-2>GST A4-4. Using a specific and sensitive HPLC method, specific activities towards the phospholipid hydroperoxide,1-palmitoyl-2-(13-hydroper oxy-cis-9, trans-11 -octadecadienoyl)-l-3-phosphatidylcholine (PLPC-OOH) were determined to be in the range of 0.8-20 nmol/min per mg of protein. Two human class Pi (P) enzymes (GST P1-1 with Ile or Val at position 105) displayed no activity towards the phospholipid hydroperoxide. Michaelis-Menten kinetics were followed only for glutathione, whereas there was a linear dependence of rate with PLPC-OOH concentration. Unlike the selenium-dependent phospholipid hydroperoxide glutathione peroxidase (Se-PHGPx), the presence of detergent inhibited the activity of GST A1-1 on PLPC-OOH. Also, in contrast with Se-PHGPx, only glutathione could act as the reducing agent for GST A1-1. A GST A1-1 mutant (Arg15Lys), which retains the positive charge between the GSH- and hydrophobic binding sites, exhibited a decreased kcat for PLPC-OOH but not for CDNB, suggesting that the correct topography of the GSH site is more critical for the phospholipid substrate. A Met208Ala mutation, which gives a modified hydrophobic site, decreased the kcat for CDNB and PLPC-OOH by comparable amounts. These results indicate that Alpha, Mu and Theta class human GSTs provide protection against accumulation of cellular phospholipid hydroperoxides.

Binding Sites↗
PubMed1997

Cloning and expression of a novel mammalian homolog of Drosophila transient receptor potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein.

Hormonal stimulation of Gq-protein coupled receptors triggers Ca2+ mobilization from internal stores. This is followed by a Ca2+ entry through the plasma membrane. Drosophila Trp and Trpl proteins have been implicated in Ca2+ entry and three mammalian homologues of Drosophila Trp/Trpl, hTrp1, hTrp3 and bTrp4 (also bCCE) have been cloned and expressed. Using mouse brain RNA as template, we report here the polymerase chain reaction-based cloning and functional expression of a novel Trp, mTrp6. The cDNA encodes a protein of 930 amino acids, the sequence of which is 36.8, 36.3, 43.1, 38.6, and 74. 1% identical to Drosophila Trp and Trpl, bovine Trp4, and human Trp1 and Trp3, respectively. Transient expression of mTrp6 in COS.M6 cells by transfection of the full-length mTrp6 cDNA increases Ca2+ entry induced by stimulation of co-transfected M5 muscarinic acetylcholine receptor with carbachol (CCh), as seen by dual wavelength fura 2 fluorescence ratio measurements. The mTrp6-mediated increase in Ca2+ entry activity was blocked by SKF-96365 and La3+. Ca2+ entry activity induced by thapsigargin was similar in COS cells transfected with or without the mTrp6 cDNA. The thapsigargin-stimulated Ca2+ entry could not be further stimulated by CCh in control cells but was markedly increased in mTrp6-transfected cells. Records of whole cell transmembrane currents developed in response to voltage ramps from -80 to +40 mV in control HEK cells and HEK cells stably expressing mTrp6 revealed the presence of a muscarinic receptor responsive non-selective cation conductance in Trp6 cells that was absent in control cells. Our data support the hypothesis that mTrp6 encodes an ion channel subunit that mediates Ca2+ entry stimulated by a G-protein coupled receptor, but not Ca2+ entry stimulated by intracellular Ca2+ store depletion.

Amino Acid Sequence↗
PubMed1997

A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2.

The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B. Despite differences in urine flow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). The overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2.

Adult↗
PubMed1996

trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry.

SUMMARY: Capacitative calcium entry (CCE) describes CA2+ influx into cells that replenishes CA2+ stores emptied through the action of IP3 and other agents. It is an essential component of cellular responses to many hormones and growth factors. The molecular basis of this form of Ca2+ entry is complex and may involve more than one type of channel. Studies on visual signal transduction in Drosophila led to the hypothesis that a protein encoded in trp may be a component of CCE channels. We reported the existence of six trp-related genes in the mouse genome. Expression in L cells of small portions of these genes in antisense orientation suppressed CCE. Expression in COS cells of two full-length cDNAs encoding human trp homologs, Htrp1 and Htrp3, increased CCE. This identifies mammalian gene products that participate in CCE. We propose that trp homologs are subunits of CCE channels, not unlike those of classical voltage-gated ion channels.

Amino Acid Sequence↗
PubMed1996

Characterization of recombinant alpha-galactosidase for use in seroconversion from blood group B to O of human erythrocytes.

Alpha-Galactosidase (alpha-GAL) purified from green coffee bean cleaves the terminal galactose residues from the surface of group B erythrocytes, thereby converting these cells serologically to group O cells. Such enzymatically converted red cells have been transfused into group A and O recipients as part of the first phase of FDA-approved clinical trials. Recently we expressed the recombinant alpha-GAL (r)alpha-GAL) in large quantities in a methylotrophic yeast strain Pichia pastoris and purified the protein to apparent homogeneity by chromatography on a macro prep S50 column. Purified (r)alpha-GAL, migrating as a single band of 41 kDa on a SDS-PAGE, appears to be identical to its native counterpart in specific activity (32 U/mg) and kinetic parameters (K(m) =0.363 mM and V(max) = 46.9 U/mg). Both enzymes demonstrate the same pH profile in the pH range from 2 to 9, with an optimal pH at 6.4 when tested with the substrate p-nitrophenol-alpha-D-galactopyranoside. Furthermore, as with its native counterpart, (r)alpha-GAL specifically cleaves alpha-linked terminal galactose residues from group B red cells without affecting other major antigens on the red cell surface. In addition, we developed a method for using RT-PCR to detect possible DNA contamination in the purified protein preparation, which is one of the concerns for in vivo studies. Thus, with a simple procedure for over-expression and purification of (r)alpha-GAL from P. pastoris culture, one can readily obtain the enzyme needed for large-scale sero-conversion of red cells.

ABO Blood-Group System↗
PubMed1996

Spinal dural arteriovenous malformations. Intraoperative evoked potential evidence for pathophysiology. A case report.

STUDY DESIGN: This case report details intraoperative evoked potential changes during surgical removal of a T8 dural arteriovenous malformation. OBJECTIVES: The pattern of changes in somatosensory-evoked responses during surgical correction of spinal dural at arteriovenous malformation can illuminate the pathophysiologic process behind the clinical symptoms. SUMMARY OF BACKGROUND DATA: Arteriovenous malformation of the spinal dura can manifest with multiple symptoms, including progressive myelopathy and pain. The pathophysiologic process behind these symptoms could be either direct compression of the spinal cord by the arteriovenous malformation, ischemia resulting from the cord, or increased venous pressure. METHODS: To investigate these hypotheses further, the results of posterior tibial evoked potentials obtained during surgical removal of a T8 dural arteriovenous malformation were analyzed. RESULTS: At baseline, the cortical (P40) potential was markedly prolonged bilaterally. During surgery, just after the dura was opened, a marked increase was observed in the latencies of the P40 and P60 components of the evoked response on the right, which began to resolve as soon as the arteriovenous malformation was occluded. Only minimal changes were seen on the left. CONCLUSIONS: These results are most consistent with the increased venous pressure hypothesis for the pathogenesis of neurologic symptoms in dural arteriovenous malformations.

Aged↗
PubMed1996

Endorectal color Doppler imaging of primary and recurrent rectal wall tumors: preliminary experience.

OBJECTIVE: The purpose of our study was to assess whether color Doppler imaging is a useful adjunct to endorectal sonography in evaluating rectal wall neoplasms and in distinguishing recurrent or residual tumor from postoperative changes. MATERIALS AND METHODS: Thirty-two patients underwent endorectal sonography with color Doppler imaging for one of two indications: evaluation and staging of a suspected primary rectal wall cancer, or distinguishing tumor recurrence from postoperative scarring in patients with previously resected lesions. Rectal wall lesions were evaluated for hypervascularity, and their corresponding flow patterns were graded from 0 to 4. Local tumor staging with endorectal sonography and color Doppler imaging was performed before the results of pathological staging were available. RESULTS: Ninety-five percent of patients with malignant rectal wall tumors demonstrated hypervascularity during color Doppler imaging. In 61% of patients with rectal cancers, prominent perirectal vessels were identified supplying the tumor and were never identified in patients with benign lesions. Endorectal sonography alone correctly identified perirectal fat invasion with a 100% sensitivity and an 83% specificity. Color Doppler imaging during endorectal sonography correctly identified perirectal fat invasion with a sensitivity of 91% and a specificity of 83%. Of the 8 patients with previously resected lesions (five adenomas and three cancers), two patients had recurrent tumor, and both of these demonstrated grade 3 abnormality. Six patients with biopsy-proven fibrosis only had grades of 0 or 1. CONCLUSIONS: Both benign and malignant rectal wall tumors demonstrate abnormal intratumoral hypervascularity when seen with color Doppler imaging. Advanced rectal cancers (T3 or greater) are also associated with abnormal perirectal vascularity. Color Doppler imaging during endorectal sonography does not appear to improve discrimination of benign from T2 (or less) rectal wall cancers, nor does it appear to improve the ability to locally stage rectal wall cancers during endorectal sonography. However, endorectal sonography with color Doppler imaging may add significant information in distinguishing recurrent tumor from postsurgical scarring.

Female↗
PubMed1996

Rectal carcinoma: are we making a difference?

Evaluation of preliminary results at our institution revealed an improvement in survival of patients treated for rectal cancer from 1950-1988. A study was conducted to analyze responsible factors. A total of 335 patients with accurate staging and follow up for at least 5 years or until death were reviewed retrospectively. Of the 335 patients, 295 (88%) were treated by surgical resection, abdominal perineal resection (APR) (n=179), and anterior resections (n=105), the most common procedures. Operative mortality for patients with curable disease (n=188) was 18 per cent (n=34), which has significantly decreased from 24 per cent (n=28) (1950-1969) to 8 per cent (n=6) (1970-1988), (P < 0.01). Operative mortality for APR and anterior resection was 22 per cent (n=29) and 8 per cent (n=5), respectively. Mortality for APR decreased from 28 per cent (1950-1969) to 10 per cent (1970-1988) (P < 0.02) accounting for most of the improvement. Of the 335 patients, 142 (42%) presented with stage IV disease, which decreased from 54 per cent (n=47) (1950s) to 22 per cent (n=10) (1980s), P < 0.01. The overall 5-year survival was 19 per cent (n=64), with a corresponding increase per decade from 13 per cent (1950s) to 43 per cent (1980s), (P < 0.001). Of the remaining 188 patients, 41 had involved surgical margins and decreased 5-year survival of 8 per cent when compared to patients with clear surgical margins (37%) P < 0.01). Multifactor analysis revealed that stage of disease at presentation, involved surgical margins, and operative mortality were significant independent variables. Earlier stage at presentation and improved operative management increased the survival of patients with rectal cancer at our institution.

Cause of Death↗