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M Thomson

Publications and source records attributed to M Thomson.

At least 19 recordsLinked to original sources
PubMed2006

Sustainable use of continuous positive airway pressure in extremely preterm infants during the first week after delivery.

BACKGROUND: Early use of nasal continuous positive airway pressure (nCPAP) may reduce lung damage, but it is not clear how many extremely preterm infants can be cared for without mechanical ventilation on the first days after delivery. OBJECTIVES: To describe our experience of nCPAP in infants born at <27 weeks' gestation and to determine the chance of reintubation of this group of extremely preterm infants. METHODS: A retrospective, observational study examined the period from November 2002 to October 2003, when efforts were made to extubate infants to nCPAP at the earliest opportunity. Data were collected on all infants born at <27 weeks' and gestation admitted to The Neonatal Intensive Care Unit, Queen Charlotte's and Chelsea Hospital, London, UK. The chance of an individual infant requiring reintubation within 48 h of delivery was estimated, calculating the predictive probability using a Bayesian approach, and oxygen requirements at 36 weeks' postmenstrual age were examined. RESULTS: 60 infants, 34 inborn and 26 ex utero transfers, were admitted; 7 infants admitted 24 h after birth were excluded and 5 died within 48 h. The mean birth weight was 788 g and the gestational age was 25.3 weeks. Extubation was attempted on day 1 in 21 of 52 infants on ventilators and was successful in 14; and on day 2 in 14 of 35 and successful in 10 of infants extubated within 48 h of delivery survived to discharge. 5 of 23 infants on mechanical ventilation at 48 h of age were on air at 36 weeks postmenstrual age, and 12 of 26 of those were on nCPAP at 48 h of age. The probability of an individual baby remaining on nCPAP was 66% (95% CI 46% to 86%) on day 1 and 80% (95% CI 60% to 99%) on day 2. The smallest infant to be successfully extubated was 660 g and the youngest gestational age was 23.8 weeks. CONCLUSIONS: Extremely preterm infants can be extubated to nCPAP soon after delivery, with a reasonable probability of not requiring immediate reintubation.

Continuous Positive Airway Pressure↗
PubMed2006

High-magnification chromoscopic colonoscopy in ulcerative colitis: a valid tool for in vivo optical biopsy and assessment of disease extent.

BACKGROUND AND STUDY AIMS: Colonoscopy with mucosal biopsy is currently considered to be the "gold standard" investigation for the evaluation of disease activity and disease extent in ulcerative colitis. Conventional colonoscopic criteria are inadequate for assessing disease extent and for predicting clinical relapse, however. Histopathological markers of relapse, such as microscopic crypt abscess formation and mucin depletion cannot be identified using conventional endoscopy. The aim of this study was to evaluate the efficacy of high-magnification chromoscopic colonoscopy for the in vivo assessment of histopathological inflammation and disease extent using standardised endoscopic and histopathological criteria. PATIENTS AND METHODS: Total colonoscopy using the Olympus CF240Z magnifying colonoscope was performed prospectively in 325 consecutive patients with a known diagnosis of ulcerative colitis. A "biphasic" examination of all five colonic segments and the rectum was performed with conventional endoscopy followed by magnification imaging and biopsy. Disease activity was documented using Baron's classification, modified Saitoh criteria for magnification imaging, and Matts' histopathological grading. RESULTS: A total of 1800 images from 300 patients were analyzed (25 patients were excluded). The kappa coefficients of agreement between Saitoh's magnification criteria grades 1/2, 3/4, and 5/6 and Matts' histopathological grades 1/2, 3a/b, and 4/5 were 0.96, 0.62, and 0.51, respectively. Mild, moderate, and severe histopathological disease (Matts' grades 1/2, 3a - 4, and 5) were represented more accurately using Saitoh's criteria than by conventional Baron scores for all clinical parameters ( R = 0.976; P < 0.001). Magnification imaging was significantly better than conventional colonoscopy for predicting disease extent in vivo ( P < 0.0001). CONCLUSIONS: This is the largest prospective study and the only Western group to report on this application of magnification imaging. High-magnification imaging provides a sensitive and specific in vivo "virtual biopsy" in ulcerative colitis and so an instant biomarker for disease relapse, while accurately predicting disease extent. High-accuracy optical biopsy can limit the number of biopsies required, with significant cost savings for pathology services.

Adolescent↗
PubMed2006

"Salvage" endoscopic mucosal resection in the colon using a retroflexion gastroscope dissection technique: a prospective analysis.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and submucosal dissection can provide curative endoscopic therapy for Paris type I/II adenomas and node-negative early cancer. No studies have addressed the technical feasibility of retroflexion endoscopic dissection methods for luminal "salvage" therapy in patients considered unresectable using conventional forward-viewing resection. PATIENTS AND METHODS: Colonoscopy using an Olympus GIF-XQ240 gastroscope was carried out in 76 patients with Paris type I/II adenomas, early colorectal cancer (CRC), or laterally spreading tumors (LSTs) when the index endoscopist considered the lesion to be unresectable due to retrograde fold involvement. Endoscopic mucosal resection (EMR) and submucosal dissection were carried out using a complete retroflexion technique. Endoscopic and miniprobe 20-MHz or 12.5-MHz ultrasound follow-up data were collected prospectively up to 24 months after the index resection. RESULTS: Cecal intubation or cannulation to the neoterminal ileum was achieved in 76 (100 %) cases. Forty lesions (53 %) were classified in accordance with the Paris criteria as Is; 16 (21 %) as type II; 10 (13.5 %) as LST-G; and 10 (13.5 %) as LST-NG. Eight lesions (10 %) were excluded from EMR on the basis of endoscopic ultrasound criteria, with 68 of the 76 lesions (89 %) meeting the criteria for endoluminal resection. The median intubation time was 16 min (range 3-32 min). The median resection times were 98 min (range 30 - 242 min), 36 min (range 10-60 min), 172 min (range 20 - 240 min), and 60 min (range 10-116 min) for Paris Is, II, LST-G, and LST-NG lesions, respectively. LST-G morphology was associated with a high median submucosal injection volume in comparison with all other Paris types ( P < 0.05) and with a prolonged resection time ( P < 0.01). Sixty-one patients (94 %) completed the surveillance protocol. Higaki recurrence criteria were met in seven patients (11 %), with six undergoing successful adjunctive endoluminal resection. After 24 months of follow-up, the "cure" rate with endoscopic resection was 60 out of 61 (98 %). CONCLUSIONS: This is the first prospective study to address the safety and medium-term efficacy of retroflexion endoscopic resection in the colon. When appropriate exclusion criteria are applied, selected patients can receive curative resection using the retroflexion technique. "Salvage" endoluminal therapy may therefore be possible in such cases when surgical resection would otherwise have been required.

Adenoma↗
PubMed2005

Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in the gp41 region of different HIV-1 genetic forms from T20 naive patients.

BACKGROUND: The natural occurrence of primary resistance mutations in reverse transcriptase (RT) and protease (PR) genes of HIV-1 isolates from untreated patients has been reported and it may have important implications for the response to drug treatment. It is predictable that the same occurs in the HR1 region of gp41 sequence from patients who have never received T20 therapy, and in this regard it would be important to know not only the mutation frequencies at HR1 region but also the natural polymorphisms at resistance-associated positions present in the absence of this drug. OBJECTIVES: The objectives of this study are to investigate the existence of natural resistance-associated mutations to T20 in HR1 gp41 region corresponding to different HIV-1 genetic forms from T20 naive patients and to determine their prevalence. STUDY DESIGN: Two hundred HIV-1 gp41 sequences were included: subtype B: 164 (81.3%); subtype A: 15 (8.2%); subtype G: 10 (4.6%); subtype F: 6 (3.5%); subtype C: 3 (1.8%); subtype K: 1 (0.6%); and subtype D: 1 (0.6%). We analyzed the resistance-associated mutations previously described: Q32H/R, G36D/S, I37V, V38A/M, Q39R/H, Q40H, N42T/D/Q/H, N43D/S/K/Q, L44M, L45M, R46M and V69I. RESULTS: Natural resistance mutations to T20 were found at a high frequency: 10.5%, corresponding to 9.1% in subtype B and 16.7% in non-B subtype samples. Polymorphisms were more frequent in non-B and recombinant forms than in subtype B (p<0.001). Different substitutions were related to subtypes: N42S in subtypes A, B, G and C, but not in F, Q56R in subtype A from CRF02_AG, and L54M in subtype B from CRF14_BG. CONCLUSIONS: To our knowledge this is the first study describing natural-resistance to T20 among different HIV-1 subtypes, warranting a study of the biological significance of this mutations and their clinical relevance. The detection of differences between subtypes may have an influence on the rate and patterns of resistance in patients undergoing T20 treatment.

Amino Acid Sequence↗
PubMed2005

Lung function in immature baboons with respiratory distress syndrome receiving early caffeine therapy: a pilot study.

AIM: The cardiopulmonary effects of early caffeine therapy in surfactant-treated immature baboons were measured. METHODS: Nine 125-d (term = 185 d) baboons receiving caffeine citrate at 1 and 12 h age as part of a pilot study on the use of nasal CPAP at 24 h were compared to six untreated animals destined for prolonged ventilator support. All received surfactant prior to their first breath and again at 6 h age. Serial physiologic and ventilatory parameters were recorded. Lung mechanics were measured by body plethysmography. Data were compared from 1 through 24 h age. RESULTS: There were no between-group differences in any study variables prior to caffeine therapy at 1 h age. Airway resistance (RA) was significantly lower in caffeine-treated compared to non-caffeine-treated animals at 12 and 24 h age [median (range)12 h: 47 (35-107) cm H2O/l/s to 135 (120-259) cm H2O/l/s; and 24 h: 93(60-137) cm H2O/l/s to 211 (86-235) cm H2O/l/s; p < 0.05]. Respiratory system compliance (CRS) was higher in caffeine-treated compared to non-caffeine-treated animals at 18 and 24 h age [median (range) 18 h: 0.60 (0.29-1.58) ml/cm H2O/kg to 0.39 (0.33-0.46) ml/cm H2O/kg; and 24 h: 0.68 (0.36-1.20) ml/cm H2O/kg to 0.36 (0.33-0.55) ml/cm H2O/kg; p < 0.05]. Ventilatory efficiency index and arterial/alveolar ratio significantly improved in caffeine-treated animals over the 24-h study period (p < 0.05, repeated measures ANOVA). CONCLUSIONS: In this pilot study, early caffeine treatment, combined with prophylactic surfactant therapy, was associated with better lung function during the initial 24 h of life. This combined approach may facilitate earlier extubation or prophylactic efforts to support infants on nasal CPAP. Randomized, controlled investigation is warranted.

Animals↗
PubMed2005

Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by combined intraluminal impedance/pH.

BACKGROUND: Gaviscon Infant (GI) has been recommended for gastro-oesophageal reflux (GOR) in infants. Its efficacy has not been examined with a physiologically appropriate denominator to define the degree of GOR. AIM: To investigate the influence of Gaviscon Infant on GOR in infants using combined pH and intraluminal impedance measurement. METHODS: Twenty infants (mean age 163.5 days, range 34-319 days) exclusively bottle fed, with symptoms clinically suggestive of GOR, underwent 24 hour studies of intra-oesophageal 6 channel impedance and dual channel pH monitoring, during which six random administrations (3+3) of Gaviscon Infant (625 mg in 225 ml milk) or placebo (mannitol and Solvito N, 625 mg in 225 ml milk) were given in a double blind fashion. Impedance/pH reflux data were recorded and analysed blind by one observer. RESULTS: The median number of reflux events/hour (1.58 v 1.68), acid reflux events/hour (0.26 v 0.43), minimum distal or proximal pH, total acid clearance time per hour (time with pH below pH 4), and total reflux duration per hour were not significantly different after GI than after placebo. Reflux height was marginally lower after GI (median 66.6% v 77.3% oesophageal length) compared with placebo. CONCLUSIONS: Results showed a marginal but significant difference between Gaviscon Infant and placebo in average reflux height, and raises questions regarding any perceived clinical benefit of its use.

Alginates↗
PubMed2005

A covenant with the status quo? Male circumcision and the new BMA guidance to doctors.

This article offers a critique of the recently revised BMA guidance on routine neonatal male circumcision and seeks to challenge the assumptions underpinning the guidance which construe this procedure as a matter of parental choice. Our aim is to problematise continued professional willingness to tolerate the non-therapeutic, non-consensual excision of healthy tissue, arguing that in this context both professional guidance and law are uncharacteristically tolerant of risks inflicted on young children, given the absence of clear medical benefits. By interrogating historical medical explanations for this practice, which continue to surface in contemporary justifications of non-consensual male circumcision, we demonstrate how circumcision has long existed as a procedure in need of a justification. We conclude that it is ethically inappropriate to subject children-male or female-to the acknowledged risks of circumcision and contend that there is no compelling legal authority for the common view that male circumcision is lawful.

Attitude of Health Personnel↗
PubMed2004

Diagnostic role of upper gastrointestinal endoscopy in pediatric inflammatory bowel disease.

BACKGROUND: Discrimination between ulcerative colitis (UC) and Crohn disease (CD) may be difficult on ileo-colonoscopy alone because of a lack of definitive lesions. Retrospective studies show upper gastrointestinal endoscopy may be helpful in confirming diagnosis in such cases. AIMS: To prospectively determine importance of upper gastrointestinal endoscopy in diagnosis of inflammatory bowel disease (IBD) and assess factors predictive of upper gastrointestinal involvement in IBD. METHODS: All pediatric patients were enrolled prospectively and consecutively over a 2-year period and investigated with an ileo-colonoscopy and barium meal follow-through. Children with procto-sigmoiditis, later confirmed histologically to be typical of UC, were excluded from the study. The remainder underwent upper gastrointestinal endoscopy. The protocol and methodology were determined a priori. RESULTS: 65 children suspected of IBD underwent colonoscopy. Of the total, 11 had recto-sigmoiditis with typical macroscopic appearances of UC; once this was confirmed on histology these patients were excluded from the study. Of the 54 children (males, 31; median age, 11.1 years) remaining, 23 were initially diagnosed with CD on ileo-colonoscopy and 18 (33%) were diagnosed with UC. The diagnosis remained ambiguous in 13 (six colonic, four ileo-colonic, three normal colon) on clinical, radiologic and histologic grounds. Upper GI endoscopy helped to confirm CD in a further 11 (20.4%). Two patients were diagnosed with indeterminate colitis. Upper gastrointestinal inflammation was seen in 29 of 54 (22 CD; 7 UC ). Epigastric and abdominal pain, nausea and vomiting, weight loss and pan-ileocolitis were predictive of upper gastrointestinal involvement (P < 0.05). However, 9 children with upper gastrointestinal involvement were asymptomatic at presentation (31%). Overall upper gastrointestinal tract inflammation was most common in the stomach (67%), followed by the esophagus (54%) and duodenum (22%). CONCLUSIONS: Upper gastrointestinal tract endoscopy should be part of the first-line investigation in all new cases suspected of IBD. Absence of specific upper gastrointestinal symptoms do not preclude presence of upper gastrointestinal inflammation.

Adolescent↗
PubMed2004

De novo initiation pocket mutations have multiple effects on hepatitis C virus RNA-dependent RNA polymerase activities.

The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) has several distinct biochemical activities, including initiation of RNA synthesis by a de novo mechanism, extension from a primed template, nontemplated nucleotide addition, and synthesis of a recombinant RNA product from two or more noncovalently linked templates (template switch). All of these activities require specific interaction with nucleoside triphosphates (NTPs). Based on the structure of the HCV RdRp bound to NTP (S. Bressanelli, L. Tomei, F. A. Rey, and R. DeFrancesco, J. Virol. 76:3482-3492, 2002), we mutated the amino acid residues that contact the putative initiation GTP and examined the effects on the various activities. Although all mutations retained the ability for primer extension, alanine substitution at R48, R158, R386, R394, or D225 decreased de novo initiation, and two or more mutations abolished de novo initiation. While the prototype enzyme had a K(m) for GTP of 3.5 microM, all of the mutations except one had K(m)s that were three- to sevenfold higher. These results demonstrate that the affected residues are functionally required to interact with the initiation nucleotide. Unexpectedly, many of the mutations also affected the addition of nontemplated nucleotide, indicating that residues in the initiating NTP (NTPi)-binding pocket are required for nontemplated nucleotide additions. Interestingly, mutations in D225 are dramatically affected in template switch, indicating that this residue of the NTPi pocket also interacts with components in the elongation complex. We also examined the interaction of ribavirin triphosphate with the NTPi-binding site.

Hepacivirus↗
PubMed2004

Early interactions of Salmonella enterica serovar typhimurium with human small intestinal epithelial explants.

BACKGROUND: Salmonella enterica serovar typhimurium (S typhimurium) causes invasive gastroenteritis in humans, a disease involving significant penetration of the intestinal mucosa. However, few studies have been undertaken to investigate this interaction directly using differentiated human gut tissue. AIMS: To investigate the early interactions of an enteropathogenic strain of S typhimurium with human intestinal mucosa using human intestinal in vitro organ culture (IVOC). METHODS: Wild-type and mutant derivatives of S typhimurium TML were used to compare interactions with cultured human epithelial cells, bovine ligated loops, and human intestinal IVOC. RESULTS: S typhimurium TML was shown to attach to cultured Caco-2 brush border expressing cells and cause tissue damage and fluid accumulation in a ligated bovine loop model.S typhimurium TML bound predominantly to the mucus layer of human IVOC explants during the first four hours of IVOC incubation. From four to eight hours of IVOC incubation, small but characteristic foci of attaching and invading S typhimurium TML were detected as clusters of bacteria interacting with enterocytes, although there was no evidence for large scale invasion of explant tissues. Ruffling of enterocyte membranes associated with adherent Salmonella was visualised using electron microscopy. CONCLUSIONS: Human IVOC can be used as an alternative model for monitoring the interactions between S typhimurium and human intestinal epithelium, thus potentially offering insight into the early stages of human Salmonella induced gastroenteritis.

Animals↗
PubMed2004

Endoluminal gastroplication in children with significant gastro-oesophageal reflux disease.

AIMS: To describe paediatric experience, and to assess complications and therapeutic effectiveness of the use of endoluminal gastroplication in children with gastro-oesophageal reflux disease (GORD) refractory to, or dependent on, proton pump inhibitors. METHODS: Seventeen (five male) consecutive children/adolescents (median (range) age 12.4 (6.1-15.9) years, median (range) weight 46.0 (16.5-87.5) kg) with GORD either dependent for more than 12 months on proton pump inhibitors or non-responsive to medical treatment underwent endoscopic gastroplication using a flexible endoscopic sewing device (EndoCinch). Three plications were placed in gastric tissue below the lower oesophageal sphincter. Drug dose requirement, pH measurements, daily symptom severity and frequency, and validated reflux (QOLRAD) and general gastrointestinal (GSRS) quality of life scores were compared before and after endoscopic gastroplication. RESULTS: All patients showed post-treatment improvement in symptom severity, frequency, and quality of life scores (p<0.0001). Three patients with recurrent symptomatic GORD had a repeat procedure within six weeks and did well subsequently. At up to 33 months of follow up (median 23), 14/17 patients remained off all antireflux medications, and 14/17 had maintained their symptomatic improvement. All pH parameters improved and had returned to normal values in 14/16 patients post-treatment and in 6/9 after one year of follow-up: in particular the reflux index had decreased from a median of 16.6% (0.9-67%) to 2.5% (0.7-15.7%) (p<0.0001) six weeks and 4.3% (2.2-20.6) (p<0.02) 12 months post-procedure. The only complication observed was gastric bleeding in one patient due to previously undiagnosed coagulopathy, which spontaneously resolved. CONCLUSIONS: Endoluminal gastroplication is an effective and safe procedure in children/adolescents with significant GORD refractory to, or dependent on, medical anti-GORD therapy.

Adolescent↗
PubMed2004

Massive pulmonary haemorrhage as a cause of death in the neonate--a retrospective review.

OBJECTIVES: To examine massive pulmonary haemorrhage as an independent factor and as a co-factor in neonatal mortality by analysing the associated factors, with the purpose of identifying predisposing characteristics. DESIGN: A retrospective study reviewing 32 neonates who died of pulmonary haemorrhage. Data were extracted from the 2001 King Edward VIII Hospital (KEH) neonatal death records. Relevant obstetric and neonatal variables were used in the data analysis. SETTING: KEH, a tertiary care institute, provides secondary and tertiary services and functions as a referral centre for surrounding clinics and hospitals. RESULTS: Pulmonary haemorrhage occurred in 32 of 260 neonatal fatalities (12.3%). All cases of pulmonary haemorrhage fell into the low-birth-weight category (< 2,500 g), and 26 of the infants (81.25%) died during the early neonatal period. A gestational age of 28-32 weeks was recorded in 27 cases (87%) and 19 (60%) showed adequate growth for gestational age. Three infants had pulmonary haemorrhage as a primary cause of death. In the remaining 29, pulmonary haemorrhage was secondary to a variety of causes. Obstetric information revealed that 29 mothers (93.5%) experienced obstetric complications, viz. pre-eclampsia/eclampsia syndrome 21 (64.5%), abruptio placentae 5 (16.1%) and previous pregnancy losses 9 (29%). Seven babies were ventilated and 2 were diagnosed with patent ductus arteriosus. CONCLUSION: The study revealed more well-grown babies than expected. Complications of pregnancy hypertension, abruptio placentae and previous pregnancy losses were more frequently associated with pulmonary haemorrhage in these neonates. The majority of babies suffering pulmonary haemorrhage were not associated with intensive care management.

Adult↗
PubMed2003

Use of unlicensed and off-label medications in paediatric gastroenterology with a review of the commonly used formularies in the UK.

BACKGROUND: Use of unlicensed and off-label medications is common in hospital based paediatric practice. Whilst inpatient prescription can be closely monitored within the hospital setting, it is subspecialties like paediatric gastroenterology, caring for chronically ill children on an outpatient basis that require administration of regular medications in the community. Local practitioners rely on available paediatric formularies or information provided by the tertiary unit for monitoring and dispensing further prescriptions. AIM: To assess the proportion of unlicensed and off-label medications prescribed in a paediatric gastroenterology unit to children discharged to the community and assess adequacy of information about these medications in commonly used British formularies. METHODS: All prescriptions prescribed over a six-month period (Jan-Jul 2002) either in the paediatric gastroenterology outpatient department or for children discharged home after an inpatient stay, were retrieved from the pharmacy database. The main outcome measures were to assess the proportion of medications prescribed for unlicensed or off-label use. RESULTS: 308 patients received 777 prescriptions of which 384 (49%) were for unlicensed or off-label use. Of these 291 (76%) were off-label; 208 in relation to indication and 83 to child's age. 93 of the prescribed medications were unlicensed; 37 were due to manipulation of formulation. Of the commonly used formularies in the UK, only 'Medication for Children(R)' contained dosage information on more than half (9/13) of the most often prescribed off-label/unlicensed medications in paediatric gastroenterology. CONCLUSIONS: Use of unlicensed and off-label medications remains a problem in paediatric practice. Until licensing laws change and more drugs are licensed in children, paediatric gastroenterologists remain responsible for provision of information to families, local practitioners, nurses and pharmacists. Of the commonly used formularies, 'Medicines for Children' is the most detailed and comprehensive, and should be available to all general practitioners and pharmacists in the UK. Clear communication between specialist units and local practitioners is imperative to ensure safe and effective prescribing to children.

Ambulatory Care↗
PubMed2003

Parathyroid hormone-related peptide modulates signal pathways in skin and hair follicle cells.

Parathyroid hormone-related protein (PTHrP) is secreted by skin epithelial cells and is thought to play an important role in the development and function of the hair follicle. It was hypothesized that PTHrP binds to receptors in dermal papilla cells and modulates intracellular signaling systems in these cells. We tested the effects of PTHrP on protein synthesis, protein kinase A (PKA) and protein kinase C (PKC) activities as well as tyrosine phosphorylation in rat vibrissa dermal papilla and capsular fibroblast cells. Cells were cultured in the presence or absence of the N-terminal peptide PTHrP1-34 for 48 h and detergent extracts prepared. Proteins were separated by electrophoresis. Phosphotyrosine and the PTH/PTHrP receptor immunoreactivity was identified by Western blot analysis. PKC and PKA activities in the cells were measured using colorimetric enzyme assays. Extracts of both dermal papilla cells and capsular fibroblasts displayed immunoreactivity to the PTH/PTHrP receptor. Electrophoresis showed that PTHrP treatment reduced the density of a 50-kDa protein in dermal papilla cells but not in capsular fibroblasts. Media conditioned by the cells showed similar changes, indicating that the PTHrP-modulated 50-kDa protein was secreted. Furthermore, 2-D gel electrophoresis indicated that the protein had a number of phosphorylation sites. Western analysis with antiphosphotyrosine antibodies confirmed a significant decrease in the intensity of a phosphorylated 50-kDa protein in papilla cells and papilla cell-conditioned medium. PKC and PKA activities of papilla cells were unaffected by PTHrP. However, activities of PKC were increased and PKA reduced in capsular fibroblasts following peptide treatment. These cell-specific effects showed that endogenous PTHrP may activate different intracellular pathways in mesenchymal cells of skin and elicit changes in levels of locally secreted proteins that specifically modulate normal follicular function.

Animals↗
PubMed2002

Evidence of undiscovered cell regulatory mechanisms: phosphoproteins and protein kinases in mitochondria.

The finding that mitochondria contain substrates for protein kinases lead to the discovery that protein kinases are located in the mitochondria of certain tissues and species. These include pyruvate dyhydrogenase kinase, branched-chain alpha-ketoacid dehydrogenase kinase, protein kinase A, protein kinase Cdelta, stress-activated kinase and A-Raf as well as unidentified kinases. Recent evidence suggests that mitochondrial protein kinases may be involved in physiological processes such as apoptosis and steroidogenesis. Additionally, the novel finding of low-molecular-weight GTP-binding proteins in mitochondria suggests the possibility that these may interact with mitochondrial protein kinases to regulate the activity of mitochondrial effector proteins. The fact that there are components of cellular regulatory systems in mitochondria indicates the exciting possibility of undiscovered systems regulating mitochondrial physiology.

Animals↗
PubMed2002

Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study.

The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.

Alleles↗
PubMed2002

Refeeding syndrome with enteral nutrition in children: a case report, literature review and clinical guidelines.

Refeeding syndrome is a potentially fatal complication of the nutritional management of severely malnourished patients. The syndrome almost always develops during the early stages of refeeding. It can be associated with a severe derangement in electrolyte and fluid balance, and result in significant morbidity and mortality. It is most often reported in adults receiving total parenteral nutrition (TPN), although refeeding with enteral feeds can also precipitate this syndrome. We report what we believe to be the first case of refeeding syndrome in an adolescent with newly diagnosed Crohn's disease. This developed within a few days of starting exclusive polymeric enteral nutrition. A systematic literature review revealed 27 children who developed refeeding syndrome after oral/enteral feeding. Of these, nine died as a direct result of complications of this syndrome. We discuss the implications of this syndrome on clinical practice and propose evidence-based guidelines for its management.

Adolescent↗