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Biomedical subjects

D J Moore

Publications and source records attributed to D J Moore.

At least 55 records · Page 3Linked to original sources

Cisapride in the control of symptoms in infants with gastroesophageal reflux: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of cisapride in the treatment of uncomplicated gastroesophageal reflux in children younger than 36 months of age. STUDY DESIGN: A total of 95 patients satisfied the entry criteria and were randomly assigned to double-blind treatment with either cisapride (n = 50), 0.2 mg/kg 4 times daily, or placebo (n = 45) for 2 weeks. At the end of the 2-week treatment period, symptom diary and parental evaluation with repeat 24-hour pH study were performed. RESULTS: Sixty-eight patients completed the trial (38 in the cisapride group and 30 in the placebo group). There were no significant differences in the symptoms of crying, vomiting, or gagging; the overall symptom intensity score; or parental global evaluations. There was a significant difference (P <.03) in the percent time pH <4, the number of reflux episodes lasting more than 5 minutes, and the duration of the longest episode. No significant difference was demonstrated for the number of episodes with pH <4 or the reflux score. CONCLUSIONS: Cisapride was no better than placebo for relief of symptoms in children with uncomplicated gastroesophageal reflux. A beneficial effect was demonstrated in the cisapride group in relation to the measured parameters for esophageal acid exposure time.

Administration, Oral↗

Outcome of the first 100 femoropopliteal angioplasties performed in the operating theatre.

OBJECTIVES: To examine the factors influencing outcome and restenosis in an initial series of 100 infrainguinal angioplasties. DESIGN: Prospective study of angioplasties of the superficial femoral and popliteal arteries performed over a 42-month period. MATERIALS AND METHODS: One hundred consecutive angioplasties in 96 patients performed in the operating theatre between January 1993 and June 1996 were followed prospectively with clinical, ABI, and duplex assessment. Forty-four procedures were for disabling claudication and 56 for critical ischaemia. Stents were deployed in 30 limbs. RESULTS: Angioplasty was successful in 84 of 100 limbs. Cumulative patency of the entire group at 3, 6, 12 and 18 months was 78%, 60%, 53%, and 49% respectively, while excluding initial failures, gave patencies of 95%, 69%, 63%, and 58%, respectively. Claudicants with a 1-year patency of 64% did significantly better than patients with critical ischaemia (44% p < 0.05). Angioplasties performed during the initial 21 months had a 1-year patency of 42%, while those performed in the final 21 months had a 74% patency (p = N.S.). The patency for stented arteries was 66% vs. 49% for angioplasty alone (p = N.S.). The 2-year limb salvage rate was 91% in patents with critical ischaemia. Forty-six per cent of restenoses were asymptomatic. CONCLUSIONS: The results suggest that while angioplasty is useful in treating infrainguinal arterial disease, there is a learning curve, resulting in a high restenosis rate for occlusive and multilevel disease, while concomitant placement of stents may be beneficial.

Aged↗

Site-specific changes in transforming growth factor-alpha and -beta1 expression in colonic mucosa of adolescents with inflammatory bowel disease.

BACKGROUND: Transforming growth factors (TGF-alpha and -beta1) play important roles in intestinal growth and repair. To further understand their roles in the pathophysiology of inflammatory bowel disease (IBD), this study examined changes in their expression in colonic mucosa of adolescents with IBD. METHODS: TGF-alpha and -beta1 expression was examined by immunohistochemistry and in situ hybridization. RESULTS: TGF-gamma immunostaining and mRNA labelling appeared unchanged in the epithelium of specimens with active IBD. Similarly, expression of epithelial TGF-beta1 remained unaltered in IBD. However, the numbers of TGF-beta1-positive cells, including T cells, neutrophils, and monocytes/macrophages, in the lamina propria increased during disease activity. CONCLUSIONS: Adolescent IBD is characterized by a normal expression of TGF-alpha and -beta1 peptide and mRNA in the colonic epithelium but by an increased density of TGF-beta1-positive immune cells in the lamina propria during disease activity, suggesting a role in inflammatory modulation in IBD.

Adolescent↗

The sugar permeability test reflects disease activity in children and adolescents with inflammatory bowel disease.

OBJECTIVES: To investigate the relationship of intestinal permeability in children and adolescents with inflammatory bowel disease (IBD) to disease activity, disease extent, and response to therapy. STUDY DESIGN: Patients with new and established diagnoses of IBD (12 Crohn's disease [CD] and 18 ulcerative colitis [UC]) were studied. Intestinal permeability was evaluated by measuring with high-performance liquid chromatography 5-hour urinary excretion ratio of lactulose/L-rhamnose (L/Rh). RESULTS: In 8 of 9 patients with active CD, the L/Rh ratio was higher than the reference range (0.006 to 0.074, n = 36). In inactive CD (n = 3) the L/Rh ratio was within the reference range. In 6 of 7 patients with active extensive UC, the L/Rh ratio was elevated. In inactive extensive UC (n = 6) the normal permeability ratio was shown. In both active CD and active extensive UC, the frequency of elevated intestinal permeability was significantly greater than values in both inactive forms. The permeability ratio was normal in 4 of 5 patients with active left-sided colitis. In 5 of 7 patients (3 CD, 4 UC), repeat permeability values entered the reference range after acute phase therapy. Two patients with persistently elevated intestinal permeability (1 CD, 1 UC) had a disease flare-up within 6 months. CONCLUSIONS: Intestinal permeability is a marker of disease activity in CD and extensive UC. Serial permeability test may be useful in monitoring disease activity.

Adolescent↗

Can a total knee replacement prosthesis be made entirely of polymers?

We have prospectively studied 63 total knee replacements (TKR) in which the femoral component was polyacetal, and 138 TKRs in which the femoral component was conventional cobalt chrome. The tibial and patellar components were of ultrahigh molecular weight polyethylene (UHMWPE). Patients were followed-up for at least 10 years. In the polyacetal group, a number of patients have died or have been revised, for reasons unrelated to the presence of polyacetal. There were no instances of femoral component fracture, nor failure by wear. One postmortem specimen, retrieved at 9 years after surgery, showed no measurable polyacetal wear and negligible HDP wear. The histology of tissue in contact with polyacetal was indistinguishable from that adjacent to polymethyl methacrylate and UHMWPE in the same knee. We believe that polyacetal could be used for the femoral component of a TKR and that a further trial should be undertaken.

Acetals↗

Popliteal aneurysms: a 10-year experience.

BACKGROUND: Popliteal aneurysms account for 70% of peripheral arterial aneurysms and, if untreated, pose a serious threat to the affected limb. Debate continues about the best form of treatment especially for asymptomatic lesions. METHOD: We reviewed the computer records and charts of patients seen at this department with a diagnosis of popliteal aneurysm over the last 10 years. Patients who had not been seen within the last year were followed-up through their G.P. RESULTS: Twenty-four patients (M 23/F 1) presented with 40 popliteal aneurysms. The mean age was 63.5 +/- 9 years. Symptoms were present in 23 of the affected limbs while 17 were asymptomatic. Thirty were treated surgically and 10 followed with regular ultrasound. The mean diameter of the repaired aneurysms was 3.3 +/- 1 cm. Aneurysms < 2 cm were more likely to be asymptomatic. No limbs were lost in patients undergoing elective repair of popliteal aneurysms. The secondary patency and limb salvage rates at 3 years were 84% and 96% respectively. Conservative management of asymptomatic lesions < 2 cm was not complicated by the development of symptoms. CONCLUSIONS: Elective repair of popliteal aneurysms by exclusion and bypass is a safe, effective and durable technique. Small asymptomatic lesions can be safely managed with close follow-up.

Aneurysm↗

Bowel dysfunction in cystic fibrosis: importance of breath testing.

OBJECTIVE: To investigate the prevalence of carbohydrate malabsorption and bacterial overgrowth in children with cystic fibrosis (CF) and abnormal stool pattern referred for breath hydrogen testing. METHODS: Results from 89 tests using lactose, sucrose and lactulose in 54 children with CF were compared with 5430 tests on children with non-CF-related stool abnormalities. RESULTS: Children with CF were more frequently unable to ferment lactulose to hydrogen (39% vs. 20%, P<0.03); they had significantly longer oro-caecal transit times (mean 99 vs. 68 min, P<0.0003); they had a higher incidence of bacterial overgrowth (32% vs. 7%, P<0.003) and sucrose malabsorption (47% vs. 14.5%, P<0.004); but they had no increase in lactose malabsorption (40% vs. 31%). Children with bacterial overgrowth in both groups had longer transit times (CF 123 min, non-CF 108 min) compared to the non-CF children without overgrowth (68 min) and reference normal children (69 min). CONCLUSIONS: Bacterial overgrowth and carbohydrate malabsorption, particularly of sucrose, should be considered when assessing children with CF and abnormal stool patterns.

Breath Tests↗

Recurrent varicose veins.

Recurrence of varicose veins after treatment has been reported as being between 7% and 65%. During the five month period from August to December 1993, 400 operations on 265 patients were performed for varicose vein disease. Of these, 53 patients had presented with recurrent vein disease in 72 limbs (18%). All patients underwent Duplex scanning of their deep and superficial systems and sites of venous incompetence were identified. The sapheno-femoral junction (SFJ) was found to be incompetent in 52 limbs, of which 31 had previously undergone flush ligation. Sapheno-popliteal junction (SPJ) was incompetent in 33 limbs, while the long saphenous vein (LSV) was found to be incompetent in 67 cases. There were no major complications in this group. Minor complications occurred in 10 cases (14%), mainly in the form of thigh paraesthesia. The more common causes of recurrent disease have been identified and therefore, it should be possible to reduce its incidence. Duplex scanning is essential for any unit dealing with recurrence.

Adult↗

Adipocyte fatty acid-binding protein: interaction with phospholipid membranes and thermal stability studied by FTIR spectroscopy.

Fatty acid-binding proteins (FABPs) found in many tissues constitute a family of low molecular weight proteins that are suggested to function as intracellular transporters of fatty acids. Studies of the transfer kinetics of fluorescent anthroyloxy-labeled long-chain fatty acids from FABP to model membranes led to the suggestion that the FABPs, typically considered to be cytosolic proteins, could nevertheless interact directly with membranes [Wootan, M. G., et al. (1993) Biochemistry 32, 8622-8627]. In the current study, the interaction of the adipocyte FABP (A-FABP) with vesicles of various phospholipids has been directly measured and confirmed with FTIR spectroscopy. The strength of this interaction was inferred from the lowering of the gel-liquid-crystal phase transition temperature as monitored from temperature-induced variations in the acyl chain CH2 stretching frequencies and from the intensities of the components of the CH2 wagging progressions. A-FABP interacts more strongly with anionic phospholipids (phosphatidylserine and cardiolipin) than with zwitterionic phosphatidylcholine. Unsaturation in the acyl chains leads to a greater reduction in Tm (stronger lipid-protein interaction). In contrast, neutralization of A-FABP surface charges by acetylation considerably weakens the interaction. Comparison of the shifts in lipid melting temperatures with those induced by other proteins suggests that A-FABP behaves like a typical peripheral membrane protein. The degree of membrane interaction correlates directly with the rate of fatty acid transfer, suggesting that contact between A-FABP and membranes is functionally related to its fatty acid transport properties. As expected, the protein exhibits a predominantly beta-sheet structure. It was found to aggregate with increasing temperature. With the exception of minor differences between the pure and lipid-associated A-FABP in the 1640-1660 cm-1 region, both the protein structure and thermal stability appeared essentially unchanged upon interaction with the lipid.

Acetylation↗

Constitutive binding of the transcription factor interleukin-2 (IL-2) enhancer binding factor to the IL-2 promoter.

A positive regulatory element in the interleukin-2 (IL-2) promoter, designated the antigen receptor response element-2, is essential for the induction of IL-2 gene expression upon the binding of an inducible multiprotein complex of proteins known as nuclear factor of activated T cells. In the current study, we demonstrated that the winged-helix transcription factor IL-2 enhancer binding factor (ILF) is constitutively expressed in both resting and activated Jurkat cells and binds to two adjacent sequence motifs immediately downstream of the binding site for NFAT. One of these elements has a high degree of homology with consensus binding sites for a variety of winged-helix DNA binding proteins, and the second site functions to modulate ILF binding. Mutagenesis of each of the two sequence elements required for ILF binding decreased IL-2 promoter activity when assayed in transfection assays. Although ILF bound constitutively to the IL-2 promoter, it was not detected as a component of the NFAT complex. These results suggest that important regulatory sequences in the IL-2 promoter are bound by ILF and that this binding may be involved in the control of IL-2 gene expression.

Binding Sites↗

Lipid domains and orthorhombic phases in model stratum corneum: evidence from Fourier transform infrared spectroscopy studies.

A three component model for the lipid barrier of the stratum corneum (SC) consisting of ceramide III, cholesterol, and perdeuterated palmitic acid, has been characterized by Fourier transform infrared spectroscopy. At physiological temperature the CD2 scissoring mode of the palmitic acid methylenes, and the CH2 rocking mode of the ceramide methylenes, are each split into two components. This indicates that both components exist in separate, conformationally ordered phases, probably with orthorhombic perpendicular subcells. The magnitude of the splitting indicates that the domains are at least 100 chains in size. The thermotropic behavior of the CD2 stretching vibrations demonstrates that conformational disordering of the palmitic acid commences at 42 degrees C with a transition midpoint of 50 degrees C. The CH2 stretching frequency indicates the ceramide chains remain ordered until 50 degrees C then disorder with a midpoint of 67 degrees C. The results provide a molecular characterization for the complex low temperature (10-40 degrees C) dynamic behavior suggested by recent 2H NMR experiments.

Biophysical Phenomena↗

Conformational order of specific phospholipids in human erythrocytes: correlations with changes in cell shape.

Acyl chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) and dimyristoyphosphatidylserine (DMPS-d54) were incorporated into human erythrocytes. Light microscopy demonstrated that erythrocytes incubated with an equimolar mixture of DMPC-d54/DMPS or DMPC/DMPS-d54 remained mostly discocytic whereas cells incubated with either DMPC-d54 or DMPS-d54 alone became echinocytic or stomatocytic, respectively. Cells in which the aminophospholipid translocating protein was inhibited became echinocytic when incubated with DMPS-d54. Fourier transform infrared (FTIR) spectroscopy was used to monitor conformational order in the acyl chains of the incorporated phospholipid, as detected through the asymmetric CD2 stretching vibrations in the intact cells. In cells incubated with equimolar mixtures of DMPC-d54/DMPS or DMPC/DMPS-d54, the deuterated species exhibited no thermotropic phase transitions but revealed chain order intermediate between the gel and liquid-crystal states. In contrast, DMPS-d54 incorporated into the outer leaflet of echinocytic erythrocytes was conformationally ordered while the same species incorporated into the inner leaflet of stomatocytic erythrocytes was highly disordered at all temperatures studied. Finally, DMPC-d54 incorporated into the outer leaflet of echinocytic erythrocytes exhibited a phase transition, suggesting that this species persists in domains. These data indicate that the acyl chain conformational order of specific phospholipids in the intact human erythrocyte is changed with alterations in cell morphology.

Dimyristoylphosphatidylcholine↗

Tandem balloon dilatation for childhood achalasia.

BACKGROUND: There are no previous reports of tandem balloon dilatation in childhood achalasia. OBJECTIVE: To report the treatment of four cases of paediatric achalasia using tandem balloon dilatation of the lower oesophageal sphincter. A review of the literature since 1986 was undertaken to compare outcomes of balloon dilatation and surgery. MATERIALS AND METHODS: A retrospective review of the patients diagnosed with this condition and treated at our institution over the past 6 years: all four patients were treated by balloon dilatation of the lower oesophageal sphincter using two or three balloons in tandem. The definition of technical success was demonstration of a waist at 1-1.5 atmospheres of inflation pressure followed by abolition of the waist at higher pressures. Where this was unable to be achieved using a single balloon, two or three balloons in tandem were used. RESULTS: No patient required oesophagomyotomy, and symptomatic control has been good to excellent in three of four patients. No significant side effects were encountered. CONCLUSIONS: Balloon dilatation and surgery have similar success rates in paediatric achalasia. Because of the low morbidity associated with balloon dilatation, the procedure should be considered as first line treatment of this condition. If the lower oesophageal sphincter is stretched insufficiently using a single balloon, tandem balloon dilatation should be utilised.

Catheterization↗

Lower extremity bypass for critical ischemia using synthetic conduit and adjuvant vein cuff.

The use of an interposition cuff of vein placed at the distal anastomosis between synthetic bypass conduit and outflow vessel has been advocated to improve patency of lower extremity bypass grafts. Over a three-year period we have performed 43 such bypass procedures: to the above knee popliteal artery (n = 3); below knee popliteal (n = 13), and infrapopliteal arteries (n = 27). There were 20 females and 23 males having a mean age of 70 years (48-84 years). Fifteen patients were hypertensive, 15 were diabetic, and 25 had a history of tobacco use. All cases required limb salvage for rest pain (n = 25), gangrene (n = 10), or ulceration (n = 8) in the absence of suitable autologous vein. Nineteen operations followed a previous failed bypass. Patients were reviewed at six-month intervals. The operative mortality was 8% and two-year primary and secondary patency were 40% and 55%, respectively. Cumulative patency rates were better for first-time grafting procedures than for patients who had undergone previous attempts at limb salvage (60% versus 22%). Two-year limb salvage was 60%. During the same time period, two-year primary and secondary patency rates were 54% and 67%, respectively for autogenous vein. Although the numbers are small these results support the use of an adjuvant vein cuff when employing synthetic grafts. A prospective study of vein versus synthetic graft plus cuff should be undertaken.

Aged↗