Commentary: Helicobacter pylori--the story so far.
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Gastritis↗
Biomedical subjects
M Thomson
Publications and source records attributed to M Thomson.
Metacarpophalangeal pattern profile and bone age in Rett syndrome: further radiological clues to the diagnosis.
Hand radiographs of 100 girls representing 73% of the known Australian population of girls with Rett syndrome, age 20 years or less, were available for this study. Control radiographs were matched for age, sex, and laterality. Bone age was assessed against standard radiographs in Greulich and Pyle [1959: Radiographic Atlas of Skeletal Development of the Hands and Wrist, 2nd ed.]. A metacarpophalangeal pattern (MCPP) profile comparing the relative lengths of the hand bones with mean population norms by age was produced by converting the length of each of the 19 metacarpal and phalangeal bones into a Z score. In girls less than 15 years old, bone age was more advanced in Rett syndrome than in age-matched control girls (left hand P = 0.03, right hand 0.004), but was most advanced in the younger group and normalized with age. In Rett syndrome, the mean Z score for the 19 metacarpal and phalangeal bones was 1.0 in children under 5 years, -0.27 in those aged 5-11 years, and -1.7 in those aged 12 years and over. This variation between age groups was much greater than in the controls. The dips in the MCPP profile occurred at MC2 and D1, and the peaks at M5, P5, and M4. An MCPP profile may provide an additional aid to diagnosis in cases of Rett syndrome where all the criteria are not met, but in children under age 5 years, advanced bone age may be more helpful as a marker.
Adolescent↗
Comparison of pharmacokinetics of Neoral and Sandimmune in stable pediatric liver transplant recipients.
Cyclosporine (Sandimmune; Novartis Pharmaceuticals UK Ltd) is an effective immunosuppressive drug, but its lipid formulation and variable absorption may expose children to the risk of rejection during episodes of gastroenteritis after liver transplantation. Neoral (Novartis) is a microemulsified form of cyclosporine that may be better absorbed. In this study, the pharmacokinetic profiles of Neoral and Sandimmune were compared in stable children after liver transplantation to evaluate whether Neoral is more predictably absorbed. Eight children, 6 boys and 2 girls, with a mean age of 4.5 years (range, 1.2-12) were studied between 4 and 12 months after liver transplantation. Pharmacokinetic profiles were performed on each child by using the same dose (mg/kg) of Neoral or Sandimmune. Tmax, Cmax, Ctrough, and the area under the curve (AUC) were calculated and side effects were documented in children taking either drug for more than 3 months. Mean peak cyclosporine levels were higher and were achieved significantly sooner with Neoral (Cmax 790.5 +/- 216.5 ng/mL, P =.06; Tmax 1.8 +/- 1.0 hr, P =.01) than with Sandimmune (Cmax 589.4 +/- 313 ng/mL, Tmax 2.5 +/- 1.7 hr), implying more rapid and better absorption. There was no significant difference in overall drug exposure (AUC) and 12-hour trough levels between the two formulations (P >.05). Children with Roux-en-Y loop biliary anastomosis taking Neoral, however, showed greater increases in AUC (mean increase = 37%) than those with duct-to-duct anastomosis (mean increase = 16%). There was no correlation between 12-hour trough level and AUC for either Neoral (r2 = 0.48) or Sandimmune (r2 = -0.08); however, for both drugs, AUC correlated very well with the 2-hour post-dose level (r2 = 0.68 and 0.7, respectively). Hirsutism was reported in 4 of 6 children on Neoral and may be associated with higher peak levels. Neoral is more consistently absorbed than Sandimmune in children after liver transplantation and may be more effective prophylaxis against rejection. Because of the increased peak levels and drug exposure, which may influence side effects, particularly in children with Sandimmune malabsorption, we recommend a 1:0.75 dose conversion ratio in patients being converted from Sandimmune to Neoral.
Child↗
Recovery rates of regional sympathetic reinnervation and myocardial blood flow after acute myocardial infarction.
BACKGROUND: The implication of an arrhythmogenic role for infarction-induced disruption of regional myocardial sympathetic nerve activity has led to a search for noninvasive methods to study regional sympathetic nerve activity in patients after infarction. METHODS AND RESULTS: By using positron emission tomography, we measured the time course of myocardial hypoperfusion with [13N]-ammonia retention and sympathetic innervation with [18F]-6-fluorodopamine within the infarct zone in 10 patients at 2 weeks, 3 months, and 6 months after a first-onset Q-wave myocardial infarction. The time course for reestablishment of global cardiac autonomic function was also determined by measuring the power spectrum of heart rate variability with an autoregressive technique. The average infarct defect size as determined by the fractional uptake of [13N]-ammonia was 17.22% +/- 5.95% of the left ventricular myocardium. The fractional uptake of [18F]-fluorodopamine in the infarct zone was similar, at 15.83% +/- 4.45% (not significant). There was a significant increase (14% to 15%; P <.05) in myocardial blood flow and [18F]-fluorodopamine uptake to the infarct zone between 2 weeks and 3 months, with no further change between 3 months and 6 months. However, the average rate of loss (t1/ 2 hour) of [18F]- fluorodopamine continued to decrease between 2 weeks and 6 months. This paralleled a continuing fall in the low-frequency to high-frequency autospectral power ratio throughout the 6 months after infarction. CONCLUSIONS: This study demonstrates a modest increase in myocardial blood flow and evidence for sympathetic reinnervation to the infarct zone between 2 weeks and 3 months after acute myocardial infarction. Despite a flow-dependent effect on the uptake of [18F]-fluorodopamine by 3 months, there is a suggestion that restoration of sympathetic activity within the infarct zone continues between 3 months and 6 months after acute myocardial infarction.
Adult↗
Hepatitis C virus-like particles synthesized in insect cells as a potential vaccine candidate.
BACKGROUND & AIMS: Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. Successful vaccine development is crucial in controlling global HCV infection. We have previously described the generation of HCV-like particles (HCV-LPs) in insect cells using a recombinant baculovirus containing the complementary DNA of the HCV structural proteins. These HCV-LPs had similar morphological and biophysical properties as the putative virions. In this study, we analyzed the structural features, antigenic composition, seroreactivity, and immunogenicity of purified HCV-LPs. METHODS: HCV-LPs were analyzed by electron microscopy and antibody immunolabeling and precipitation. An enzyme-linked immunosorbent assay (ELISA) using HCV-LPs was developed. The humoral response to HCV-LPs in mice was studies by core and envelope ELISAs, Western immunoblotting, and immunofluorescence. RESULTS: Structural and antigenic compositions of HCV-LPs were shown to be similar to those of putative HCV virions. Using the HCV-LP ELISA, high-titer anti-HCV antibodies were detected in individuals infected with various HCV genotypes. In vivo, HCV-LPs elicited a humoral response broadly directed against HCV structural proteins. CONCLUSIONS: HCV-LPs resemble HCV virions and are capable of inducing a humoral response targeted against various regions of HCV structural proteins, suggesting that HCV-LPs may be promising as a potential vaccine candidate.
Animals↗
Are endoscopic biopsies of small bowel as good as suction biopsies for diagnosis of enteropathy?
BACKGROUND: Endoscopy is increasingly used in paediatric practice for diagnosis of enteropathy, although the quality of grasp forceps-obtained biopsy specimens required for reliable diagnosis has been questioned in comparison with suction capsule biopsy specimens. This study prospectively compared the diagnostic suitability of grasp forceps biopsy versus suction biopsy in the same patient during the same procedure. METHODS: A double-port paediatric suction biopsy capsule was front-loaded onto an endoscope and directed to the fourth part duodenum-proximal jejunum for biopsy sampling. Subsequently, three grasp biopsy specimens were taken from the same region. All biopsies were coded, photographed, and measured for area, using computed morphometry. A single blinded histopathologist assessed sample adequacy for diagnosis. Twenty-nine patients were enrolled (age range, 8-185 months). RESULTS: On three occasions the suction capsule failed to fire, and on four occasions only one sample was obtained. Three grasp biopsy specimens were obtained on each occasion by endoscopy, and the first two were used for comparison with suction biopsy samples. Median total area of individual biopsy samples obtained by the two procedures was not different (21.3 vs. 22.5 mm2; P = 0.027). Muscularis mucosae was obtained more commonly with grasp biopsies (P<0.001), and no difference was observed for the presence of three or more villus-crypt units, degree of haemorrhage, or optimal orientation. Two suction biopsy procedures and one grasp biopsy procedure were inadequate for diagnosis. CONCLUSIONS: Endoscopic grasp biopsies are perfectly adequate for the assessment of small intestinal histology. In addition, endoscopy affords advantage in diagnosis of other upper gastrointestinal disease with avoidance of radiologic screening involved with the suction capsule technique.
Adolescent↗
Post-MI care in general practice.
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Cardiac Care Facilities↗
What are guanosine triphosphate-binding proteins doing in mitochondria?
The discovery of GTP-binding proteins in mitochondria is a recent event. These regulatory proteins may be participating in membrane fusion and thereby playing important roles in the physiology of the mitochondrion. So far, it has been proposed that GTP-binding protein mediated membrane fusion may be involved in protein import, steroid hormone production and mitochondrial amalgamation during spermatogenesis.
Animals↗
The genomic sequence of defective interfering Semliki Forest virus (SFV) determines its ability to be replicated in mouse brain and to protect against a lethal SFV infection in vivo.
We have recently cloned and sequenced two genomes of defective interfering (DI) Semliki Forest virus (SFV), DI-6 (2146 nt), and DI-19 (1244 nt). These are similar in that both contain two large central deletions (encompassing the 5' part of the nsP1 gene and the 3' part of the nsP2 gene and all of the structural genes), and all the sequence of the latter is represented in the genome of SFV DI-6. RNA was transcribed from both and transfected into SFV-infected BHK-21 cells. RT-PCR analysis of tissue culture fluid harvested 18 h after transfection suggested that SFV DI virions had been rescued from the cloned genomes. Unlike the genomes of noncloned DI SFV, these genomes bred true for at least 7 serial passages. Cloned DI-6 and DI-19 viruses interfered to a similar extent with the multiplication of SFV in cultured cells, but only DI-19 protected mice from a lethal intranasal dose of SFV. Further investigation by RT-PCR analysis showed that DI-19 but not DI-6 genomes were replicated in mouse brain after direct intracerebral injection of DI virus together with an excess of infectious helper SFV. Thus the replication and hence antiviral activity of two closely related DI SFV genomes appears to be exquisitely sequence specific and cell specific. These findings mark a significant step on the way to using DI genomes as antivirals and also may explain why so few animal-protecting DI viruses have been identified.
Alphavirus Infections↗
Efficacy of Neoral in the immediate postoperative period in children post-liver transplantation.
Cyclosporine (Sandimmune) is an effective immunosuppressive drug but may be poorly absorbed in the early postoperative period after liver transplantation, exposing the recipient to an increased risk for rejection. Neoral is a new oral formulation of cyclosporine that uses a mixture of surfactant, lipophilic, and hydrophilic solvents to permit microemulsification that leads to potentially better absorption. This oral drug has not been evaluated in children immediately posttransplantation. The aim of this study was to evaluate the pharmacokinetics, bioavailability, and safety of Neoral during the first week post-liver transplantation in children. Twelve children, 8 boys and 4 girls, with a median age of 2.6 years (range, 1 to 8 years) were administered Neoral within 12 hours posttransplantation. Pharmacokinetic profiles were performed over a 12-hour period on each child on days 1, 3, and 5 and twice-daily trough levels were obtained on days 2, 4, 6, and 7. The maximum concentration (Cmax), time to reach Cmax (Tmax), 12-hour trough levels, and area under the curve were calculated, and rejection episodes and adverse events were documented over a 12-week period. Neoral was well absorbed, even on the first postoperative day. After the introduction of enteral feeding, the peak levels increased (Cmax, 655 ng/mL) and were achieved significantly sooner (Tmax, 2 hours). There was no significant difference in drug exposure between days 1, 3, and 5 (P > .05). The incidence of acute rejection was 25% and hypertension was reported in 4 of 12 patients during the first week. Neoral was well absorbed in the early post-liver transplantation period, provided effective immunosuppression, and was not associated with a high incidence of adverse events or toxicity. The introduction of enteral feeding improved absorption.
Area Under Curve↗
Purification of a toxic factor from Arabian Gulf catfish epidermal secretions.
The Arabian Gulf catfish, Arius bilineatus (Valenciennes) secretes a proteinaceous epidermal secretion when threatened or injured. A toxic factor has been isolated and purified from the crude extract (crude skin toxin) of these secretions by a combination of gel filtration on Sephacryl S-300 and preparative discontinuous polyacrylamide gel electrophoresis. The purified skin toxin has a molecular weight of 39,000 Da and an isoelectric point (pI) of 5.45. Injection of the purified skin toxin into rabbits i.v. and determination of the LD50 indicated that the protein had been purified approximately 30 fold by these procedures. Injection of the purified skin toxin into rabbits caused agitation, convulsions and death within 5 min. Analysis of plasma levels of lactate dehydrogenase, glutamate-oxaloacetate transaminase and glutamate pyruvate transaminase in injected rabbits indicated that the skin toxin caused cardiac and liver damage to the animals.
Alanine Transaminase↗
Prostanoid synthesis in whole blood cells from fish of the Arabian Gulf.
The ability to synthesise prostaglandins and thromboxane from 14C-labelled arachidonic acid was investigated in 11 species of fish from the Arabian Gulf. Cyclooxygenase activity was assessed in washed whole blood cells. Arachidonic acid and its metabolites were extracted and separated on silicic acid columns and thin layer chromatography (silica gel G). Total capacity to convert [14C]arachidonic acid to prostanoids varied from 1 to 35% among the 11 fish species studied. Gray shark (Chiloscyllium griseum) blood cells had the highest capacity (37 +/- 0.4%) to convert arachidonate into prostanoids and two species of catfish (Arius bilineatus and A. thalassinus) exhibited greater than 10% capacity to convert [14C]arachidonate into prostanoids. The major prostanoid synthesised by the two catfish (A. bilineatus and A thalassinus) was 6-keto PGF1 alpha, a stable metabolite of prostacyclin, PGI2. In contrast, A. teunispinis synthesised thromboxane B2, a stable metabolite of thromboxane A2. Thromboxane B2 (TXB2) was the major product synthesised by all three species of shark studied (Chil. griseum, Carcharhinus plumbeus, Carch. melanopterus), with 6-keto PGF1 alpha a minor product. Other fish studied showed a varied pattern of prostanoid synthesis. The synthesis of these prostanoids was almost completely blocked by preincubation of the whole blood cells from catfish and shark with indomethacin (0.5 microM) suggesting the involvement of cyclooxygenase-mediated prostanoid synthesis.
6-Ketoprostaglandin F1 alpha↗
Dietary fat manipulation and signal transduction in ovine skin.
Protection of dietary lipids in a protein matrix prevents biohydrogenation in ruminants and increases the availability of polyunsaturated fatty acids. This alters the composition of the tissue lipids, including the membrane phospholipids, which are important substrates for signal transduction. This study investigates the effects of a diet containing protected fatty acids on the activities of key intracellular kinases in the skin. Two groups of six sheep were offered either a control diet or one containing protected cottonseed, a source of linoleic acid (C18:2), for 3 months. Skin was taken from August to October, and analysed for protein kinase C (PKC), protein kinase A (PKA), mitogen-activated protein kinase (MAPK), phosphotyrosine activity and epidermal growth factor (EGF) receptor content. Skin and wool samples were also taken to measure changes in the fibre characters and follicle function. At the end of the experiment, the mean linoleic acid content of skin phospholipids from sheep fed the protected diet was twice that of the controls. In both groups, PKC activity was significantly elevated in skin taken during September and October compared with August values. However, activities measured in the experimental sheep were higher than in controls. This coincided with a decline in wool production. PKA activity decreased significantly in both groups between August and October. MAPK activities did not alter during the experiment. Western analyses did not reveal differences in phosphotyrosine-positive or EGF receptor bands between the groups.
Animals↗
Effects of aqueous extract of onion on the liver and lung of rats.
The toxic effects of oral and intraperitoneal administration of onion extracts on lung and liver tissue of rats were investigated. Oral or intraperitoneal administration of low doses of onion (50 mg/kg) to rats had little effect on lung and liver tissues when compared to control animals. In contrast, administration of high doses of onion (500 mg/kg) resulted in apparent histological changes in lung and liver tissues of rats. Intraperitoneal administration of the high dose of onion was more damaging to lung and liver tissue than oral administration and resulted in a 25% rate of mortality in this treatment group. These results suggest that low doses of onion are nontoxic and may be administered with few ill effects.
Animals↗
Dyspepsia in infants and children.
Pathological processes and diseases of the upper gastrointestinal tract have become increasingly recognized over recent years as childhood entities responsible for a variety of upper gastrointestinal symptoms previously labelled as functional or non-organic. The term 'dyspepsia' is an adult one whose definition requires clarification before use in the paediatric context, but it encompasses age-dependent symptoms such as feed-associated irritability in the infant, peri-umbilical pain in the younger child, and heart-burn, nausea, and indigestion in the older child as in adults. The possible organic conditions giving rise to such symptoms are multiple and multiorgan and include: gastro-oesophageal reflux; peptic ulcer disease; upper gastrointestinal Crohn's disease; antroduodenal motility disorders; pancreatitis; cholecystitis; cholelithiasis; biliary dyskinesia; and abdominal migraine. However, Munchausen syndrome by proxy must not be forgotten. Non-ulcer dyspepsia, it is now clear, has a basis in altered gastroduodenal motility and may be amenable to propulsion agents. In many individuals the dyspeptic symptoms of recurrent abdominal pain may be altered by psychotherapeutic intervention. Indeed there remains a proportion of children who undoubtedly have a behavioural or psychological base to their complaint. Nevertheless, with the recent increase in diagnostic yield from improved technical investigative aids available to paediatrics in the last 5-10 years, it is clear that the responsibility of the paediatrician to the child to find a cause of their symptoms is paramount. The variety of presenting features, possible causes of these symptoms, and appropriate investigation and treatment will be discussed, and management algorithms based on published literature and personal practice will be offered.
Abdominal Pain↗
Detection of 8-epi prostaglandin F2alpha in an extract of epidermal secretion of the catfish from the Arabian Gulf.
We provide herein mass spectrometric evidence for the existence of F2 isoprostanes in an epidermal secretion of the catfish from the Arabian Gulf. The compounds were extracted, purified by thin layer chromatography (TLC) and derivatized into the pentafluorobenzyl trimethylsilyl (PFB-TMSi) derivatives and quantified using SIM-negative ion gas chromatography-mass spectrometry based on the addition of tetradeuterated 8-epi PGF2alpha as internal standard prior to sample workup. Freshly collected secretions from the male catfish contained 5.63 and 4.17 ng/ml (two determinations) and from the female catfish 3.60 and 3.81 ng/ml (two determinations) of free 8-epi PGF2alpha. The level of these compounds increases approximately 8-fold upon storage of the extract at -20 degrees. In view of the potent reported actions of F2 isoprostanes on vasoconstriction and as thromboxane receptor antagonists, the presence of isoprostanes in the catfish secretions may contribute to the reported ulcer healing properties of these secretions.
Animals↗
Vertebrate genome evolution and the zebrafish gene map.
In chordate phylogeny, changes in the nervous system, jaws, and appendages transformed meek filter feeders into fearsome predators. Gene duplication is thought to promote such innovation. Vertebrate ancestors probably had single copies of genes now found in multiple copies in vertebrates and gene maps suggest that this occurred by polyploidization. It has been suggested that one genome duplication event occurred before, and one after the divergence of ray-finned and lobe-finned fishes. Holland et al., however, have argued that because various vertebrates have several HOX clusters, two rounds of duplication occurred before the origin of jawed fishes. Such gene-number data, however, do not distinguish between tandem duplications and polyploidization events, nor whether independent duplications occurred in different lineages. To investigate these matters, we mapped 144 zebrafish genes and compared the resulting map with mammalian maps. Comparison revealed large conserved chromosome segments. Because duplicated chromosome segments in zebrafish often correspond with specific chromosome segments in mammals, it is likely that two polyploidization events occurred prior to the divergence of fish and mammal lineages. This zebrafish gene map will facilitate molecular identification of mutated zebrafish genes, which can suggest functions for human genes known only by sequence.
Animals↗
The systemic stress response to thermal injury in children.
OBJECTIVE: Thermal injury is extremely stressful, but data characterizing the endocrine stress response to this injury in children are sparse. The objective of this study was to measure the effects of thermal injury on the levels of stress hormones in children and to assess the temporal changes associated with them. PATIENTS: Twenty-three children, 13 girls and 10 boys aged between 5 months and 12 years 3 months (mean, 2 years 11 months), with burns covering 10-61% of their body surface (mean, 20.5%) were studied during the first 5 days following injury. MEASUREMENTS: The levels of arginine vasopressin, angiotensin II, cortisol, adrenaline, noradrenaline and dopamine were measured in sequential blood samples obtained from thermally injured children on admission and at specified time intervals during the 5 days of the investigation. RESULTS: At admission the concentrations of all the hormones were high, and varied widely between individual patients. The geometric mean and 95% confidence intervals of admission hormone levels were as follows: arginine vasopressin 18.3 (8.3-40.7) pmol/l; angiotensin II 122.0 (56.0-266.2) pmol/l; cortisol 650.6 (473.0-895.0) nmol/l; dopamine 1.0 (0.1-8.0) nmol/l; adrenaline 6.4 (3.2-12.5) nmol/l and noradrenaline 2.3 (1.3-4.3) nmol/l. Although the concentrations of arginine vasopressin and cortisol returned to normal 24 to 36 h after admission, the levels of angiotensin II, adrenaline and dopamine fluctuated and remained higher than normal throughout the study (108 h). CONCLUSIONS: Thermal injury results in the release of abnormally high levels of stress hormones in children. Although there are similarities between some of the data reported here and those reported in adults, higher levels of adrenaline and lower levels of noradrenaline than reported in adults suggest important differences too. These differences may need to be taken into account in the management of burn-injured children.
Angiotensin II↗