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Biomedical subjects

D Sutton

Publications and source records attributed to D Sutton.

At least 19 recordsLinked to original sources
PubMed1992

The effect of relaxin on tissue expansion.

Relaxin is a 56-amino acid polypeptide that produces relaxation of the pubic ligament. Ten young male pigs were implanted with tissue expanders and osmotic pumps. The pumps in five animals contained recombinant human relaxin to produce a serum relaxin level of 1 ng/mL. The other five pumps contained saline. Repeated measurements of the pressure-volume expansion curves showed a significant decrease in the pressure needed to fill the expanders in the relaxin group compared with the control group. Dermal thickness in the control group and epidermal thickness in both control and experimental groups were increased on histomorphometric measurement. No adverse effects were seen in the relaxin group. Relaxin facilitates tissue expansion in pigs without affecting dermal thickness.

Animals↗
PubMed1992

Constitutive expression of the beta-phaseolin gene in different tissues of transgenic alfalfa does not ensure phaseolin accumulation in non-seed tissue.

Phaseolin is a glycoprotein that constitutes the major storage protein in bean seeds. The phaseolin gene promoters function in a seed-specific manner. In an attempt to understand if events following transcription of the gene also contribute to the seed-specific accumulation of the phaseolin protein, we studied the effect of substituting the constitutive CaMV-35S promoter for the beta-phaseolin gene promoter on expression of the phaseolin gene in different plant organs. A chimeric gene consisting of the 35S promoter, the coding sequence of the beta-phaseolin gene (all five introns and six exons) and the 3'-flanking region of the beta-phaseolin gene, was introduced into alfalfa via Agrobacterium tumefaciens. While all organs examined shared high levels of phaseolin transcripts, the only organ that showed significant accumulation of the phaseolin protein were the mature seeds. Co-migration of the major immunoreactive polypeptides from the non-seed organs with the authentic beta-phaseolin polypeptides on SDS-PAGE indicates that the protein in non-seed organs undergoes correct post-translational processing and modification, but are more unstable in a non-seed environment.

DNA, Recombinant↗
PubMed1992

Cortical region of interest definition on SPECT brain images using X-ray CT registration.

We present a method for brain single photon emission computed tomography (SPECT) analysis based on individual registration of anatomical (CT) and functional (133Xe regional cerebral blood flow) images and on the definition of three-dimensional functional regions of interest. Registration of CT and SPECT is performed through adjustment of CT-defined cortex limits to the SPECT image. Regions are defined by sectioning a cortical ribbon on the CT images, copied over the SPECT images and pooled through slices to give 3D cortical regions of interest. The proposed method shows good intra- and interobserver reproducibility (regional intraclass correlation coefficient approximately 0.98), and good accuracy in terms of repositioning (approximately 3.5 mm) as compared to the SPECT image resolution (14 mm). The method should be particularly useful for analysing SPECT studies when variations in brain anatomy (normal or abnormal) must be accounted for.

Blood Flow Velocity↗
PubMed1992

A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group.

Sixty-three patients with crescentic glomerulonephritis (cellular crescents in greater than 50% of glomeruli) were considered for a prospective randomized trial comparing intravenous methylprednisolone, prednisone, and azathioprine with and without plasma exchange. Of 32 patients who fulfilled the inclusion criteria for this study, 16 were randomly assigned to receive drug therapy (control) and 16 to receive plasma exchange as well. The randomization was stratified for initial need of dialysis, and the presence of oliguria and sclerosis. Renal pathology was similar in the two groups of patients. There was no significant difference in the number of patients initially on dialysis who were able to discontinue it during the study (2/7 control v 3/4 plasma exchange), whereas no control but two plasma exchange-treated patients started dialysis during the study. Serum creatinine at randomization was similar in the two groups: 769 +/- 486 mumol/L (8.7 +/- 5.5 mg/dL) in the control group versus 643 +/- 275 mumol/L (7.3 +/- 3.1 mg/dL) in the plasma exchange group. There was no significant difference between the two groups in mean serum creatinine, change in serum creatinine, change in reciprocal, or change in logarithm of serum creatinine at 1, 3, 6, or 12 months following randomization. Power calculation, assuming a 20% difference would be clinically relevant, was 0.94 at 12 months. There was significant morbidity in both groups; there were two deaths within 1 year of randomization, both of pulmonary infection and both in the plasma exchange group. We conclude that plasma exchange offers no additional therapeutic benefit to patients with idiopathic rapidly progressive glomerulonephritis (RPGN) who are not dialysis-dependent at presentation.

Adult↗
PubMed1992

Diagnostic implications of detection of proteinase K-resistant protein in spleen, lymph nodes, and brain of sheep.

Brain, spleen, and selected lymph nodes from sheep with clinical signs of scrapie were analyzed for presence of proteinase K-resistant protein (PrP-res). Diagnosis of scrapie on the basis of detection of PrP-res was compared with diagnosis on the basis of histologic evaluation of the brain from clinically affected or exposed sheep. Proteinase K-resistant protein was found in every brain that was histologically positive for scrapie, and in addition, was found in the brain of several clinically positive sheep that were not diagnosed as scrapie-positive by histologic evaluation. Proteinase K-resistant protein was also found in 87% of the spleens and lymph nodes from sheep that had PrP-res detected in brain homogenates. Therefore, analysis of sheep brain, spleen, or lymph nodes for PrP-res provided a diagnostic approach that was superior to histologic examination alone for detection of naturally scrapie agent-infected sheep.

Animals↗
PubMed1992

Target antigens of anti-platelet antibodies in patients with steroid-resistant ITP of recent onset. Canadian Apheresis Study Group.

Recent application of Western blotting procedures in the detection of anti-platelet antibodies has permitted more refined definition of reactivity. We report on the results of anti-platelet antibody assays in a series of 19 patients with recently diagnosed (less than 6 months duration) steroid-resistant, idiopathic thrombocytopenia purpura (ITP). At presentation, six of the 19 patients had a positive test for platelet-associated IgG (PAIgG) as measured by the direct radial-immunodiffusion (RID) assay, whereas three of the 19 were positive with the direct-platelet-suspension-immunofluorescence test (DPSIFT). The indirect-platelet-suspension-immunofluorescence test (IPSIFT) demonstrated antibodies in seven of the sera. Following Western blot (WB) analysis, the serum of 7/19 patients (only three of which were positive in the IPSIFT) could be shown to react with platelet antigens. Two patterns were seen: in four cases there were bands of apparent molecular weights of 60,000, 55,000 and 50,000; in the other three samples, a single band near 90,000 was demonstrated. Unlike the situation reported for chronic ITP, no reactivity was seen against higher molecular weight antigens other than the 'non-specific' binding at apparent molecular weight 200,000 which is also seen with normal sera. The data suggest that antibodies reacting against specific platelet antigens are present in the serum of some patients with recent onset ITP.

Adult↗
PubMed1992

Bile acid malabsorption in patients with post-vagotomy diarrhoea.

75SeHCAT scanning was evaluated as a means of detecting bile acid malabsorption in patients with postvagotomy diarrhoea. Seven day 75SeHCAT retention ratios were measured in five patients with unequivocal post-vagotomy diarrhoea. The results were compared with an age matched group of asymptomatic control patients (n = 4) each of whom had previously undergone truncal vagotomy and drainage and a further group of normal volunteers (n = 6). The median 75SeHCAT retention ratios in patients with post-vagotomy diarrhoea was 2% (range 0-9%). In contrast, the median 75SeHCAT retention ratios in asymptomatic controls was 29% (range 26-61%) and 28% (range 19-70%) in normal volunteers. These results demonstrate that there is gross bile salt malabsorption in patients with post-vagotomy diarrhoea and that 75SeHCAT scanning is an effective screening test in these patients.

Adolescent↗
PubMed1992

Pulmonary embolism in total hip and knee arthroplasty. Risk factors in patients on warfarin prophylaxis and analysis of the prothrombin time as an indicator of warfarin's prophylactic effect.

This study was designed to identify those total arthroplasty patients at high risk for embolism even while on a proven warfarin prophylactic regimen and to identify the measure of anticoagulation that would be most efficacious in the prevention of pulmonary embolism (PE). A series of 2348 total arthroplasty patients had a preoperative perfusion scan and a postoperative ventilation/perfusion scan. All patients were placed on a low-dose warfarin protocol. Eighty-one patients were identified as having a PE by pulmonary arteriography (incidence of 3.4%). Of these, 89% were asymptomatic and no case was fatal. A control group of 159 patients without PE was used for comparison. Patients older than 65 years of age with a history of genitourinary infection were identified as being at higher risk of PE while on a proven warfarin prophylactic program. These patients may need additional prophylactic measures to reduce the risk of PE. In contrast, patients with a history of phlebitis, PE, obesity, or varicosities were not at excess risk for PE while on warfarin prophylaxis; therefore, no additional prophylactic measures are required. All prothrombin time profiles were within the prophylactic range. Therefore, the actual prothrombin time may not be the critical determinant of the level of anticoagulation or prophylaxis achieved.

Analysis of Variance↗
PubMed1991

Macaque anteroventral cochlear nucleus: developmental anatomy.

The development of the anteroventral cochlear nucleus (AVCN) in fetal and infant monkeys (Macaca nemestrina) was analyzed for gross morphologic changes together with growth-related modifications in constituent cell size and cell distribution. Rapid and extensive prenatal volumetric changes were followed by slow and limited postnatal volumetric changes. The time course of packing density and cell size changes paralleled the volumetric changes. At each age the packing density along the rostrocaudal axis of the AVCN was constant except in the youngest specimens (mid- to late-fetal), where local variations occurred. Similarly, the size of AVCN cells along the rostrocaudal axis remained approximately constant at any given age. In comparison with the human and mouse, the macaque exhibits relatively less pronounced postnatal change in overall volume and cellular growth features.

Animals↗
PubMed1991

Abnormal esophageal transit in patients with typical reflux symptoms but normal endoscopic and pH profiles.

There is a small, well-known cohort of patients who, despite classic reflux symptoms, have a normal esophageal pH profile and endoscopic picture. The treatment of these patients has proved problematic. In an attempt at determining the pathophysiology of this subgroup, we investigated the esophageal transit, using the radiolabeled solid bolus esophageal egg transit technique, in 58 such patients: 25 males, 33 females, mean age 39.5 years (range: 13 to 65 years). The egg transit was normal in 31 (53.4%) patients. In the remaining 27 (46.6%) patients, the condensed image analysis showed the following specific abnormal transit patterns: "step" delay pattern, demonstrating segmental hold-up in mid- or distal esophagus in 16 (59.3%); nonspecific delay in 6 (22.2%); oscillatory pattern in 3 (11.1%); and total nonclearance during the study period (4 minutes) in 2 (7.4%) patients. The patients with abnormal transit patterns had demographic parameters and symptom scores similar to those found in patients with normal transit. This study shows that almost 50% of patients with reflux symptoms and negative pH and endoscopy have abnormal esophageal transit, and almost two thirds of these patients display segmental transit delay in the lower half of the esophagus. The effect on symptomatology by prokinetic agents in the patient subgroup needs evaluation.

Adolescent↗
PubMed1991

An opioid pancreatic peptide produces ileal muscle inhibition and naloxone-reversible analgesia.

The opioid activity of immunoreactive beta-endorphin-like peptide extracted from pork pancreas duplicates the effects of morphine and synthetic beta-endorphin when measured by inhibition of isolated guinea pig ileal muscle response to electro-stimulation in vitro and by morphine-like analgesia following intravenous injection in the mouse. These responses are reversed by the opiate antagonist naloxone, indicating that a potent opioid mu receptor binding ligand is present in pancreatic extract. These findings imply a pancreatic source of plasma immunoreactive beta-endorphin that may explain a number of physiological and behavioral effects generally attributed to hypophyseal beta-endorphin alone.

Analgesics↗
PubMed1991

Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: preliminary report of a phase II study.

Twenty-two patients with refractory intermediate- or high-grade non-Hodgkin's lymphoma were treated with dexamethasone 10 mg every six hours and ifosfamide 1 g/m2, cisplatin 25 mg/m2, etoposide 100 mg/m2 (DICE), and mesna uroprotection daily x4 every 3 to 4 weeks. Pretreatment with prochlorperazine and metoclopramide was given to prevent nausea and vomiting. Eighteen men and four women, aged 21 to 74 years (median age, 65) have received a total of 64 cycles. Seventeen patients had stage IV, one had stage III, and four patients had stage II disease. Seven patients had B symptoms and 11 had marrow involvement. Only two patients had had more than one previous chemotherapy regimen. Median time from last chemotherapy to DICE was 7 months (range 1 to 41). Two patients who suffered early treatment-related deaths (from sepsis) were classified as nonresponders. Six of 22 patients (27%) achieved complete remission (2 to 22+ months), and 11 (50%) had partial remissions (1 to 8+ months) for an overall response rate of 77%. Median survival has not been reached yet, and 12 patients are alive 1 to 22 months from the start of treatment. Nine patients had nadir granulocyte counts less than 0.5 x 10(9)/L; six required RBC transfusions and five, platelet transfusions. The platelet nadir was less than 50 x 10(9)/L in 13 patients. Four patients had microscopic hematuria, two had grade 3 gastrointestinal toxicity, and one had a transient episode of delirium and blurred vision.

Adult↗
PubMed1991

Evidence for hypomotility in non-ulcer dyspepsia: a prospective multifactorial study.

A prospective multifactorial study of symptoms and disturbance of gastrointestinal function has been undertaken in 50 patients with non-ulcer dyspepsia. Objective tests including solid meal gastric emptying studies, gastric acid secretion, E-HIDA scintiscan for enterogastric bile reflux, and hydrogen breath studies were carried out in all patients and validated against control data. Gastroscopy and biopsy were carried out in non-ulcer dyspepsia patients only. Non-ulcer dyspepsia patients were categorised on the basis of predominant symptoms as: dysmotility-like dyspepsia (n = 22); essential dyspepsia (n = 14), gastro-oesophageal reflux-like dyspepsia (n = 11); and ulcer-like dyspepsia (n = 3). In the total non-ulcer dyspepsia population, solid meal gastric emptying was delayed (T50 mean (SEM) = 102 (6) minutes (patients) v 64 (6) minutes (controls), (p less than 0.01) and high incidences of gastritis (n = 26) and Helicobacter pyloridis infection (n = 18) were found. An inverse correlation was observed between solid meal gastric emptying and fasting peak acid output (r = -0.4; p less than 0.01). Indeed gastric emptying was particularly prolonged in eight patients (T50 mean (SEM) = 139 (15) minutes) with hypochlorhydria. In the non-ulcer dyspepsia population oral to caecal transit time of a solid meal was delayed (mean SEM = 302 (14) minutes (patients) v 244 (12) minutes (controls) (p less than 0.01]. Seven patients had a dual peak of breath hydrogen suggestive of small bowel bacterial overgrowth. No association was observed between symptoms and any of the objective abnormalities. This multifactorial study has shown that hypomotility, including gastroparesis and delayed small bowel transit, is common in non-ulcer dyspepsia and may be related to other disorders of gastrointestinal function. No relation between symptoms and disorders of function, however, has been shown.

Adult↗
PubMed1991

Effect of daily etidronate on the osteolysis of multiple myeloma.

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.

Aged↗
PubMed1990

Synthesis and antiviral activity of 9-alkoxypurines. 1. 9-(3-Hydroxypropoxy)- and 9-[3-hydroxymethyl)propoxy]purines.

Reaction of hydroxyl-protected derivatives of hydroxyalkoxyamines (3a,b,c) with either 4,6-dichloro-2,5-diformamidopyrimidine (5) or 4,6-dichloro-5-formamidopyrimidine (31) and subsequent cyclization of the resultant 6-(alkoxyamino)pyrimidines (6, 17, 32, 35) by heating with diethoxymethyl acetate afforded 9-alkoxy-6-chloropurines (7, 18, 33, 36), which were converted subsequently to 9-(3-hydroxypropoxy)- and 9-[3-hydroxy-2-(hydroxymethyl)propoxy] derivatives of guanine, 2-amino-6-chloropurine, 2-amino-6-alkoxypurines, 2-aminopurine, 2,6-diaminopurine, adenine, hypoxanthine, and 6-methoxypurine (8, 12, 13, 19-21, 23-26, 34, 37-39). Carboxylic acid esters (9-11, 14-16, 27-29) and a cyclic phosphate derivative (22) of the 9-(hydroxyalkoxy)guanines (8, 21) and 2-amino-9-(hydroxyalkoxy)purines (13, 26) were also prepared. The guanine derivatives (8, 21) showed potent and selective activity against herpes simplex virus types 1 and 2 and varicella zoster virus in cell cultures and 8 is more active than acyclovir. Although without significant antiviral activity in cell cultures, the 2-aminopurines (13, 14-16, 26-29) and 2-amino-6-alkoxypurines (12, 23-25) are well absorbed after oral administration to mice and are converted efficiently to the antiviral guanine derivatives (8, 21) in vivo.

Acyclovir↗