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Biomedical subjects

P Sinclair

Publications and source records attributed to P Sinclair.

At least 37 records · Page 2Linked to original sources
PubMed1998

Optimization of acid suppression for patients with peptic ulcer bleeding: an intragastric pH-metry study with omeprazole.

OBJECTIVE: To study whether an intravenous infusion dose of omeprazole (80 mg + 8 mg/h) during 24 h can be subsequently reduced with maintained effect. Second, to study the effect of oral omeprazole 20 mg given once or twice daily up to day 10, after cessation of a 3-day intravenous infusion (80 mg + 8 mg/h). DESIGN: Prospective, randomized, partly blinded study. METHODS: Twelve Helicobacter pylori(+) patients and 12 H. pylori(-) subjects were included. In part I the patients received omeprazole, 80 mg + 8 mg/h, during 24 h followed by 8, 4 or 2 mg/h. In part II the subjects received 80 mg + 8 mg/h during 3 days followed by 20 mg omeprazole orally, once or twice daily until day 10. Intragastric pH was measured. RESULTS: All H. pylori(+) patients showed a rapid increase of intragastric pH with a mean intragastric pH of 6.7 during the second half of the first day. After the subsequent dose reduction, the mean pH decreased to 6.1-6.2. Patients continuing on 8 mg/h showed the best results. Likewise, all H. pylori(-) subjects showed a rapid and sustained reduction of intragastric acidity during the infusion. Subsequent dose reduction to 20 mg once daily led to a stable fraction of time with pH > 3 of 72%. CONCLUSIONS: Omeprazole given as a continuous infusion of 80 mg + 8 mg/h for 72 h followed by omeprazole 20 mg once daily raised the intragastric pH to and above levels alleged to allow haemostasis in patients with peptic ulcer bleeding and subsequent healing of the ulcer.

Adult↗
PubMed1998

From bench to bedside and back--report on the European Helicobacter pylori Study Group Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori.

The Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori was held in Lisbon, Portugal, from September 12 to 14, 1997. State-of-the-art reviews and research findings were presented to over 2000 participants. This review focuses on important new developments and serves as a rapid communication of clinically relevant material.

Drug Therapy, Combination↗
PubMed1997

Helicobacter pylori: from bench to bedside.

With the exponential increase in research in the field of Helicobacter pylori a paradigm shift has occurred. It is now recognized that H pylori is a chronic infection of the stomach causing inflammation. Some patients remain asymptomatic, while others may develop dyspepsia, duodenal or gastric ulcer, gastric cancer or a mucosa-associated lymphoid tissue lymphoma. However, the role of H pylori in contributing to nonulcer dyspepsia or nonsteroidal anti-inflammatory drug gastropathy remains controversial. An effective vaccine against H pylori is years away. Major interest has focused on the questions "who should be investigated and therefore treated" and "what is the latest gold standard for eradication of H pylori"? In Europe, guidelines have been developed to help the practitioner answer these important questions. Canadian guidelines will soon be available. For persons with known peptic ulcer disease there should be unequivocal acceptance that the good clinical practice of eradicating H pylori will result in substantial savings in health care expenses. The original 'classical triple therapy' (bismuth, metronidazole and tetracycline [BMT]) has now been surpassed by the combination of a proton pump inhibitor (PPI) plus two antibiotics (metronidazole plus clarithromycin; amoxicillin plus clarithromycin; or amoxicillin plus metronidazole), each given twice a day for one week. In Canada, the regimen of omeprazole plus one antibiotic (amoxicillin or clarithromycin) was approved recently but gives an eradication rate that is lower than the current target of 90%. According to the European (Mäastricht) recommendations, if a single treatment attempt with PPI plus two antibiotics fails, PPI plus BMT is recommended.

Antacids↗
PubMed1996

Clinical and scientific applications/advances in video imaging.

This paper discusses the current capabilities and limitations of video imaging. Probable future applications are suggested, including the use of video imaging as an adjunct for esthetic diagnosis and treatment planning and as a means of providing realistic representations to patients of probable treatment outcomes. The widespread use of video imaging to facilitate interactive informed consent and rapid interspecialty communication and transfer of data is predicted and discussed.

Communication↗
PubMed1996

t(9;13)(q34;q12) chromosomal translocation persisting 4 years post autologous bone marrow transplantation for secondary AML despite morphological remission.

A 42-year-old male patient with a history of occupational exposure to benzene presented with pancytopenia. His bone marrow showed evidence of trilineage dysplasia and cytogenetic analysis revealed a unique t(9;13)(q34;q12) translocation. Five months after diagnosis he developed secondary AML. He was treated with four courses of chemotherapy and an autologous bone marrow transplantation (BMT). Four years post-transplantation he remains in haematological and morphological remission though the cytogenetic abnormality is still present in all metaphases examined.

Acute Disease↗
PubMed1996

Excision technique for chondrodermatitis nodularis helicis.

This painful nodule of the ear commonly recurs at the tips of the excision ellipse. To minimize this risk, a smooth transition from the normal helical rim to the defect can be achieved by undermining between the skin and cartilage at the ends of the ellipse and trimming the cartilage spikes.

Ear Cartilage↗
PubMed1993

True telomeric translocation in a baby with the Prader-Willi phenotype.

We report on a baby with a nonreciprocal de novo unbalanced translocation between chromosomes 12 and 15. Her karyotype was 45,XX, -12, -15, +der(12)t(12;15)(pter-->qter::q13-->qter). The paternal origin of the 15q11-13 region was shown by DNA marker studies and, consistent with this, the baby had the Prader-Willi (PWS) phenotype. The breakpoint on 12q was distal to D12S11 (lambda MS43) which maps to 12q24.3-qter. Fluorescent in situ hybridization using the oligonucleotides (TTAGGG)7 and (AATCCC)7 showed that the 12q telomere was still present within the translocated chromosome. Thus, the translocation was within or onto the end of the telomere of 12q. This unusual translocation is further evidence of an unexplained instability of the 15q11-13 region.

Chromosome Banding↗
PubMed1993

On the functions of the yeast COX10 and COX11 gene products.

COX10 and COX11 are nuclear genes of Saccharomyces cerevisiae whose products are localized in mitochondria and are required for the synthesis of cytochrome oxidase. Genes homologous to COX10 are present in at least four different bacterial cytochrome oxidase operons. The bacterial gene, termed cyoE, has recently been proposed to code for a farnesyl transferase that converts protoheme to heme O (Saiki et al. (1992), Biochem. Biophys. Res. Commun. 189, 1491-1497). In this communication we report that the COX10 protein, like the product of cyoE is needed for heme A synthesis. Analyses of the heme constituents in a cox11 mutant indicate the absence of heme A and presence of a novel heme with chromatographic properties indistinguishable from those of heme O. This evidence suggests that the COX11 protein may be another heme A biosynthetic enzyme involved in forming the formyl group at position 8 of the porphyrin ring.

Alkyl and Aryl Transferases↗
PubMed1992

Relation between diameter and flow in major branches of the arch of the aorta.

In the analysis of arterial branching the classical "cube law' has provided a working model for the relation between the diameter of a blood vessel and the flow which the vessel carries on a long-term basis. The law has shown good agreement with biological data, but questions remain regarding its applicability to all levels of the arterial tree. The present study tests the hypothesis that the cube law may not be valid in the first few generations of the arterial tree, where vessel capacitance and gross anatomy may play important roles. Biological data have shown some support for this hypothesis in the past but the heterogeneity characteristic of past data has not allowed a conclusive test so far. We present new data which have been obtained from the same location on the arterial tree and in sufficient number to make this test possible for the first time. Also, while past tests have been based primarily on correlation of the measured data with an assumed power law, we show here that this can be misleading. The present data allow a simpler test which does not involve correlation and which leads to more direct conclusions. For the vessels surveyed, the results show unequivocally that the relation between diameter and flow is governed by a 'square law' rather than the classical cube law. Coupled with past findings this suggests that the square law may apply at the first few levels of the arterial tree, while the cube law continues from there to perhaps the precapillary levels.

Adult↗
PubMed1992

Association of autosomal dominant cleft lip and palate and translocation 6p23;9q22.3.

Orofacial clefting (OFC) is genetically complex in that no single gene defect is responsible for all forms. We have identified a family who exhibit autosomal dominant orofacial clefting together with some features of ectodermal dysplasia. In this family there is concordance between these features and an apparently balanced translocation t(6;9)(p23;q22.3) which raises the possibility that a locus for one form of orofacial clefting may be located at one of the translocation breakpoints. Fluorescent in situ hybridization has shown that a candidate gene for OFC, which maps to distal 6p, is located on the derived chromosome 9 in affected individuals from this family. Further characterization of the translocation breakpoints and of their relationship with the candidate gene will determine whether a gene important for normal facial and/or ectodermal development is disrupted in this family.

Adult↗
PubMed1991

Origin of the brachiocephalic trunk, left carotid, and left subclavian arteries from the arch of the human aorta.

We measured branching angles of the brachiocephalic trunk, left carotid, and left subclavian arteries at their points of origin from the arch in 117 human specimens. We compared the measured angles with theoretical values commonly used in the study of arterial branching, and examined possible correlations with age and with the presence of atherosclerotic lesions. The results may be useful in the modelling and analysis of hemodynamic factors in the pathogenesis of vascular disease at these junctions and may be of some interest in clinical angiography. The junctions are important gateways for blood supply to the head and upper limbs and often are involved with lesions that affect blood supply to the brain.

Adolescent↗
PubMed1991

De novo ring chromosome 3: a new case with a mild phenotype.

We report an 18 year old female with a de novo ring chromosome 3 found after investigation for short stature. Her karyotype was interpreted as 46,XX, r(3)(p26.2q29). Her phenotype is milder than previously reported cases and illustrates the mild end of the spectrum of the ring chromosome 3 phenotype.

Adolescent↗
PubMed1990

Isolation of four forms of acetone-induced cytochrome P-450 in chicken liver by h.p.l.c. and their enzymic characterization.

The purpose of this study was to purify and characterize the forms of cytochrome P-450 induced in chicken liver by acetone or ethanol. Using high performance liquid ion-exchange chromatography, we were able to isolate at least four different forms of cytochrome P-450 which were induced by acetone in chicken liver. All four forms of cytochrome P-450 proved to be distinct proteins, as indicated by their N-terminal amino acid sequences and their reconstituted catalytic activities. Two of these forms, also induced by glutethimide in chicken embryo liver, appeared to be cytochromes P450IIH1 and P450IIH2. Both of these cytochromes P-450 have identical catalytic activities towards benzphetamine demethylation. However, they differ in their abilities to hydroxylate p-nitrophenol and to convert acetaminophen into a metabolite that forms a covalent adduct with glutathione at the 3-position. Another form of cytochrome P-450 induced by acetone is highly active in the hydroxylation of p-nitrophenol and in the conversion of acetaminophen to a reactive metabolite, similar to reactions catalysed by mammalian cytochrome P450IIE. Yet the N-terminal amino acid sequence of this form has only 30-33% similarity with cytochrome P450IIE purified from rat, rabbit and human livers. A fourth form of cytochrome P-450 was identified whose N-terminal amino acid sequence and enzymic activities do not correspond to any mammalian cytochromes P-450 reported to be induced by acetone or ethanol.

Acetaminophen↗
PubMed1990

Continuum analysis of common branching patterns in the human arch of the aorta.

A model is proposed for describing common variations in the arrangement of branches on the arch of the human aorta, and the model is used to analyze data from 123 human arches. The analysis allows the observed variations to fall freely along a continuous spectrum, rather than be confined to discrete categories as is commonly done at present. The results thus describe these variations in a more natural way and throw some new light on their likely source.

Aorta, Thoracic↗
PubMed1989

Immunochemical detection of different isoenzymes of cytochrome P-450 induced in chick hepatocyte cultures.

This study investigated whether the same cytochrome P-450 (P-450) isoenzymes were inducible in cultures of chick-embryo hepatocytes as in the liver of chicken embryos. We purified two isoenzymes of cytochrome P-450 from the livers of 17-day-old-chick embryos: one of molecular mass approx. 50 kDa induced in vivo by the phenobarbital-like inducer glutethimide, and the second of approx. 57 kDa induced by 3-methylcholanthrene. Rabbit antiserum against the 50 kDa protein inhibited benzphetamine demethylase activity in hepatic microsomes (microsomal fractions) from glutethimide-treated chick embryo. Antiserum to the 57 kDa protein inhibited ethoxyresorufin de-ethylase activity in hepatic microsomes from methylcholanthrene-treated chick embryo. Cultured chick hepatocytes were treated with chemicals known to induce isoenzymes of P-450 in rodent liver. The induced P-450s were quantified spectrophotometrically and characterized by immunoblotting and enzyme assays. From these studies, chemical inducers were classified into three groups: (i) chemicals that induced a P-450 isoenzyme of 50 kDa and increased benzphetamine demethylase activity: glutethimide, phenobarbital, metyrapone, mephenytoin, ethanol, isopentanol, isobutanol, lindane, lysodren; (ii) chemicals that induced a P-450 isoenzyme of 57 kDa and increased ethoxyresorufin de-ethylase activity: 3-methylcholanthrene and 3,3',4,4'-tetrachlorobiphenyl; and (iii) the mono-alpha-substituted 2,3',4,4',5-pentabromobiphenyl, which induced both proteins and both activities. The immunochemical data showed that chick-embryo hepatocytes in culture retain the inducibility of glutethimide- and methylcholanthrene-induced isoenzymes of P-450 that are inducible in the liver of the chicken embryo.

Animals↗