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Biomedical subjects

N A Scott

Publications and source records attributed to N A Scott.

At least 109 records · Page 6Linked to original sources
PubMed1990

Distinction of NPY receptors in vitro and in vivo. II. Differential effects of NPY and NPY-(18-36).

We have studied the hemodynamic effects of neuropeptide Y (NPY) and its COOH-terminal fragment NPY-(18-36) in conscious rats. Intra-arterial injection of NPY rapidly elevated systemic vascular resistance (SVR), which remained high for greater than 30 min. Cardiac output (CO) decreased, and it remained low for greater than 30 min. Accordingly, blood pressure rose only transiently and returned to base-line values within 5 min. The reduction of CO could be attributed to a decreased stroke volume with an only marginal reduction of heart rate. Thus a direct cardiodepressive effect of NPY rather than baroreflex activation appears to be the major cause of the reduced CO. In vitro experiments excluded the possibility that NPY has direct negative inotropic effects and suggest that its cardiodepressive action is caused by coronary vasoconstriction or by presynaptic inhibition of norepinephrine release. Intra-arterial injections of NPY-(18-36) caused different hemodynamic effects. NPY-(18-36) decreased CO in a manner similar to that seen with NPY but initially did not elevate SVR, resulting overall in a reduced blood pressure. Only later, when blood pressure was reduced, was an elevation of SVR observed, which could be associated with increased plasma levels of catecholamines, angiotensin II, vasopressin, and NPY. Thus NPY-(18-36) mimics the cardiac effects of NPY but does not elicit its vascular effects. As NPY-(18-36) discriminates between NPY receptor subtypes in vitro, we conclude that the cardiac and vascular effects of NPY are mediated by distinct receptor subtypes.

Animals↗
PubMed1990

Octreotide and gastrointestinal fistulae.

The place of somatostatin and its analogues in the management of gastrointestinal fistulae is reviewed, drawing attention to the difficulty of assessing treatments that influence spontaneous closure. Sixteen patients with gastric, small bowel, and pancreatic fistulae were randomized to receive octreotide injections (100 micrograms t.i.d.) or placebo for 12 days. Spontaneous fistula closure occurred in 7 at a mean of 37 days after entering the trial. A second study is underway with greater patient numbers recruited from peripheral hospitals and with an increased period of octreotide medication (21 days).

Adult↗
PubMed1989

Anal and ileal pouch manometric measurements before ileostomy closure are related to functional outcome after ileal pouch-anal anastomosis.

Anal canal length, and canal resting and squeeze pressures, ileal pouch capacity and pouch compliance were measured in 104 patients after ileal pouch-anal anastomosis but before ileostomy closure. The intention was to determine if such parameters were associated with late functional outcome after re-establishment of intestinal continuity. Functional outcome in terms of stool frequency (day and night), incontinence (day and night), perianal pad use, perianal skin irritation, and the use of constipating agents was assessed for all 104 patients 1 year or more (median 438 days) after ileostomy closure. A low mean anal sphincter resting pressure before ileostomy closure was associated with subsequent nocturnal incontinence (P less than 0.05) and, to a lesser extent, the need to use constipating agents (P = 0.08). Pouch compliance if low before ileostomy closure was associated with an increased frequency of nocturnal stool frequency after 1 year (P less than 0.05). Anal canal length, and sphincter squeeze pressure and pouch capacity before ileostomy closure were not related to subsequent functional outcome in these patients.

Adolescent↗
PubMed1989

Elevation of plasma neuropeptide Y levels in congestive heart failure.

PURPOSE: Our objectives were to assess whether plasma neuropeptide Y (NPY) levels are elevated in patients with congestive heart failure (CHF) and whether or not NPY levels can serve as a reliable indicator of sympathetic activity in CHF. PATIENTS AND METHODS: Plasma levels of the sympathetic neurotransmitters norepinephrine and epinephrine and of the sympathetic co-transmitter NPY were measured in 17 patients with CHF and 14 healthy control subjects at rest and after maximal exercise. RESULTS: Under resting conditions, plasma NPY and norepinephrine levels were elevated in patients with CHF compared with control subjects (551 +/- 48 pg/ml versus 311 +/- 22 pg/ml, p less than or equal to 0.001 for NPY, and 306 +/- 73 pg/ml versus 124 +/- 22 pg/ml, p less than or equal to 0.02 for norepinephrine). Plasma NPY correlated better with plasma norepinephrine than with epinephrine, indicating its origin from sympathetic nerve terminals. Acute stimulation of sympathetic activity by dynamic exercise increased plasma norepinephrine levels in control subjects and patients with CHF, but did not significantly alter the mean plasma NPY value in the latter group. CONCLUSION: NPY may play a role in the pathophysiology of CHF.

Adult↗
PubMed1989

The cardiovascular actions of centrally administered neuropeptide Y.

The cardiovascular actions of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) were examined in conscious, unrestrained rats. A prolonged decrease in heart rate (HR) and a fall in mean arterial pressure (MAP) were obtained following i.c.v. administration of NPY (1 and 10 micrograms). Passive immunization with an antiserum directed against NPY confirmed that the slowing of HR following i.c.v. administration of NPY was mediated via a central nervous mechanism and not from leakage of NPY out of the brain. Administration of NPY into different brain parenchymal regions identified a putative site of action in the rostral region of the solitary tract. The mechanism of the decrease in HR caused by centrally administered NPY was investigated by i.c.v. administration of NPY to animals that were pretreated with agents that altered autonomic tone. Administration of NPY to atropine-treated animals produced a reversal of the atropine-induced tachycardia, suggesting that the NPY-induced decrease in HR was not due to augmented vagal tone. However, administration of NPY to animals pretreated with propranolol did not significantly lower HR below that obtained with propranolol alone. These data suggest that i.c.v. administration of NPY may cause a decrease in cardiac sympathetic outflow. The effects of centrally administered NPY on baroreflex function were studied. The changes in HR caused by NPY did not significantly alter baroreflex set-point or gain. These studies provide evidence that NPY acted within a brainstem region to decrease sympathetic nervous outflow, resulting in a decrease in HR and MAP.

Animals↗
PubMed1989

Synthesis and hypertensive activity of neuropeptide Y fragments and analogues with modified N- or C-termini or D-substitutions.

Porcine neuropeptide Y (NPY), NPY fragments, and analogues with D-Xaan, Ala9, D-Ala9, and Met17 substitutions or modifications to the C- or N-termini were synthesized. The synthesis and purification of these peptides was achieved by using routine laboratory strategies and techniques. The ability of these peptides to alter mean arterial pressure (MAP) and heart rate (HR) in conscious rats was monitored for 15 min following intraarterial administration. Potencies and efficacies of these peptides relative to NPY were determined by comparison of dose-response curves. Administration of 40 micrograms/kg NPY resulted in a rapid, though short-lived, rise in mean arterial pressure from a basal value of 107.0 +/- 2.6 to 157 +/- 5.5 mmHg (means +/- sem, n = 13). The ED50 (+/- SE) for this response was 3.04 +/- 0.88 micrograms/kg. Peptide YY (PYY) elicited a response that was similar in magnitude but with an ED50 (+/- SE, n = 3) of 0.76 +/- 0.24 micrograms/kg while porcine pancreatic polypeptide (pPP) was inactive when tested at 40 micrograms/kg (n = 4). Relative potencies for [Ac-Tyr1]NPY, [Ac-D-Tyr1]NPY, [des-amino-Tyr1] NPY, and [Me-Tyr1]NPY ranged from 1.1 to 2.2. Potencies relative to NPY for D-substitutions at positions 2-6 and 8-13 inclusive ranged from 0.1 to 1.0. Analogues with D-substitutions at positions 1-3 exhibited an extended duration of action. Analogues with D-substitutions at positions 33-35 inclusive were inactive at 40 micrograms/kg, and [D-Tyr36]NPY was 10-fold less potent than NPY, suggesting that the integrity of the C-terminal region is critical to the overall biological action of NPY. This conclusion is supported by studies with C- and N-terminal deletion peptides. NPY2-36 showed full intrinsic activity at 40 micrograms/kg and retains 40% of the hypertensive potency of NPY. There was a sequential decrease in efficacy upon further N-terminal deletion. In contrast to the finding with NPY2-36, modification of the C-terminus either from the native carboxamide to the free carboxylic acid or by deletion of the C-terminal residue resulted in analogues which were inactive at 40 micrograms/kg. These data indicate that an essentially full-length, C-terminally amidated NPY structure is required for the hypertensive activity observed in conscious rats upon intraarterial administration of NPY and NPY analogues.

Animals↗
PubMed1989

Carcinoma of the anal canal and flow cytometric DNA analysis.

Using flow cytometric DNA analysis of paraffin embedded tissue, DNA histograms were successfully obtained from the anal cancers of 117 patients. DNA diploid patterns were given by 82 cancers (70%) and DNA non-diploid patterns by 35 cancers (30%): 15 DNA aneuploid, 20 DNA tetraploid. Well differentiated squamous cell cancers were mainly DNA diploid, while a larger proportion of poorly differentiated and small cell cancers were DNA non-diploid. The large majority of stage A cancers were DNA diploid. A greater proportion of tumours that had invaded through the anal sphincter or had lymph node metastases or distant spread were DNA non-diploid. Prognosis was slightly poorer for patients with DNA non-diploid cancers when compared to patients with DNA diploid tumours (P = 0.08) and significantly poorer for individuals with DNA aneuploid anal cancers (P = 0.037). However, in a multivariate analysis model, the DNA ploidy pattern of an anal cancer was not of independent prognostic significance alongside tumour histology and tumour stage.

Aged↗
PubMed1989

Thermic effect of parenteral nutrition in septic and nonseptic individuals.

This study compared the metabolic responses to parenteral nutrition in five septic and six nonseptic individuals. Oxygen uptake (VO2) was measured for 1 h preinfusion and during the first 2 h of parenteral nutrition infusion. While baseline VO2 was 19% higher in the septic compared with nonseptic patients (p less than 0.01), both groups responded similarly to nutrition: VO2 increased 25% and 27% above baseline in the nonseptic and septic groups, respectively (NS between groups). Respiratory quotient increased 9% in the nonseptic (p less than 0.01) and 5% in the septic (p less than 0.05) patients during infusion. Plasma glucose and insulin increased identically in both groups. Cortisol was consistently higher in the septic patients whereas glucagon decreased similarly in both groups with feeding. Norepinephrine increased 25% in response to the nutrition and remained elevated in the nonseptic group. The results illustrate the effect nutrient-induced thermogenesis may have in the energy balance of parenterally fed patients.

Adult↗
PubMed1989

Identification and nucleotide sequence of a gene in equine herpesvirus 1 analogous to the herpes simplex virus gene encoding the major envelope glycoprotein gB.

A gene in equine herpesvirus 1 (EHV-1; equine abortion virus) equivalent to the gB glycoprotein gene of herpes simplex virus (HSV) has been identified by DNA hybridization and nucleotide sequencing. A 4.3 kbp EHV-1 PstI-ClaI sequence (0.40 to 0.43 map units) contained an open reading frame flanked by appropriate control elements and was capable of encoding a polypeptide of 980 amino acids. This had 50 to 60% identity over a 617 amino acid conserved region with the gB gene products of HSV and three other alphaherpesviruses, and 20 to 30% identity with those of human cytomegalovirus and Epstein-Barr virus. Analysis of the amino acid sequence predicts a long signal peptide, hydrophobic and hydrophilic domains and N-glycosylation sites, and has identified a probable internal proteolytic cleavage site. The EHV-1 gB open reading frame appears to be overlapped at its 5' end by 135 nucleotides of the 3' end of an upstream open reading frame the potential translation product of which has approximately 50% identity with HSV gene ICP 18.5 and VZV gene 30 products.

Amino Acid Sequence↗
PubMed1988

Postoperative intra-abdominal and pelvic sepsis complicating ileal pouch-anal anastomosis.

In a series of 500 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis or polyposis coli, significant intra-abdominal or pelvic sepsis developed in 30 (6%). Among the patients who did not require laparotomy because they responded to treatment with antibiotics or local drainage (surgical or radiologically guided) or both, no pouches were excised and the ileostomy closure rate (92%) was similar to that for the patients who did not have sepsis. The 17 patients whose sepsis did require laparotomy had a high rate of pouch excision (41%) (p less than 0.0001) and a low rate of ileostomy closure (29%) (p less than 0.0001). Factors identified as possibly associated with severe sepsis included female gender and ulcerative colitis complicated by toxicity or malignancy.

Adult↗
PubMed1988

Perianal metastasis from a sigmoid carcinoma--objective evidence of a clonal origin. Report of a case.

A case is described in which flow cytometric DNA analysis of a sigmoid cancer and a subsequently diagnosed anal malignancy demonstrated the same DNA aneuploid pattern in both tumors. The ability to show, by this technique of DNA analysis, that an anal malignancy has seeded from a colon cancer could be important for future therapy. This is because the positive identification of such a deposit as a "dropped" metastasis would prevent inappropriately radical surgery.

Adenocarcinoma↗
PubMed1988

DNA aneuploidy in solitary colonic adenomas and the future risk of colorectal cancer.

Flow cytometric DNA analysis was performed on the colonic adenomas of 24 patients who had resection of an invasive colorectal carcinoma subsequent to polypectomy. The incidence of DNA aneuploidy among these adenomas was only 13 percent. Thus, simple recognition of colonic adenomas as being DNA diploid or DNA aneuploid is unlikely to be helpful for identifying patients with adenoma who are at high risk for developing a future colorectal carcinoma.

Aneuploidy↗
PubMed1988

Identification of major antigenic proteins of bovine herpesvirus 1 and their correlation with virus neutralizing activity.

The polypeptides of an Australian isolate of bovine herpesvirus 1 were analysed by polyacrylamide gel electrophoresis, and Western blotting was used to identify those polypeptides which reacted most strongly with sera from infected animals. Approximately 20 polypeptides ranging in molecular weight from 11,000 to 240,000 daltons (11-240K) were identified by 35S-methionine labelling of virus and approximately half of these classed as glycoproteins using 14C-mannose and 3H-glucosamine incorporation into infected cells. Convalescent sera from cattle all reacted strongly with glycoprotein bands at 85 and 70K, with most sera also recognizing another band at 140-150K. The intensity of bands on the Western blot analyses was found to correlate well with neutralization titres of individual serum samples, indicating the involvement of these proteins in virus neutralization. The importance of the 70K glycoprotein was supported by the finding that, of 12 monoclonal antibodies studied, those 3 with the strongest neutralizing activity, were those which recognized a band at 70K in Western blot experiments.

Animals↗
PubMed1987

Colorectal cancer. Dukes' stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern.

Flow cytometric DNA histograms of colorectal carcinomas from 264 patients were evaluated for the association of tumor site, Dukes' stage, tumor grade, and preoperative carcinoembryonic level with patient survival. The DNA nondiploid carcinomas were significantly more common from the left (descending and sigmoid) colon and the rectum. A poorer prognosis was found for patients with DNA nondiploid cancers than for patients with DNA diploid cancers. This was particularly true for patients with Dukes' stages B2 and C tumors with a small number (one to three) of lymph nodes with metastatic deposits. The DNA nondiploid cancers also had a relatively poorer prognosis in patients with unresectable disease. In a Cox multivariate analysis model, the DNA pattern was an independent prognostic variable for this group of 264 patients with resected colorectal carcinoma.

Carcinoembryonic Antigen↗
PubMed1987

The relative prognostic value of flow cytometric DNA analysis and conventional clinicopathologic criteria in patients with operable rectal carcinoma.

The DNA histograms of resected rectal carcinomas from 121 patients were compared, along with a detailed clinicopathologic assessment of the same tumors, with the incidence of postresection tumor recurrence and patient survival over an extended period of 15-year follow-up. A poorer prognosis was found for patients with DNA aneuploid and DNA tetraploid rectal cancers as compared with patients with DNA diploid cancers. In addition, local tumor recurrence was twice as common among patients with DNA nondiploid rectal carcinomas. The DNA pattern of a rectal carcinoma was an independent prognostic variable in a Cox's multivariate analysis model. DNA nondiploid rectal carcinomas had a statistically significant increased incidence of vascular invasion, tumor fibrosis, and high Dukes' stage.

Aged↗
PubMed1987

Flow cytometric DNA patterns from colorectal cancers--how reproducible are they?

The heterogeneity of DNA ploidy patterns within individual colorectal carcinomas was investigated by analyzing 261 different samples from 30 fresh colorectal cancers. The results of DNA analysis of multiple superficial cup biopsy specimens, of multiple full-thickness fresh tumor slices, and of nuclei extracted from paraffin-embedded pathologic archival specimens with use of the Hedley technique were compared. The same DNA ploidy pattern was found in all specimens of 19 (63%) of the 30 tumors studied. Minimal heterogeneity for DNA ploidy pattern was noted in seven carcinomas (23%), and moderate to marked heterogeneity was found in an additional four tumors (13%). The DNA pattern of a full-thickness specimen from 79% of the carcinomas studied was the same when samples were obtained from any one of five possible sites. In addition, the DNA ploidy pattern of the majority of the carcinomas could have been accurately predicted by flow cytometric DNA analysis of superficial cup biopsy specimens. These results demonstrate that most colorectal carcinomas are DNA ploidy homogeneous. Therefore, measurement of this tumor property can be used in future clinical research studies with some degree of confidence.

Colonic Neoplasms↗
PubMed1985

Self-inflicted shotgun wounds of the abdomen.

Three cases of self-inflicted wounds of the abdomen caused by a long-barrelled shotgun are described. The difficulties encountered and the appropriate surgical management are discussed.

Abdominal Injuries↗