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1.
Ann R Coll Surg Engl ; 98(5): 320-3, 2016 May.
Article in English | MEDLINE | ID: mdl-27087324

ABSTRACT

INTRODUCTION: The aim of this study was to compare the efficacy of a gentamicin antibiotic intraoperative irrigation regimen (regimen A) with a povidone-iodine intraoperative irrigation regimen (regimen B) and to evaluate the ability of adjunctive local vancomycin powder (regimen C) to reduce the surgical site infection (SSI) rate following idiopathic scoliosis correction. METHODS: This was a retrospective, single centre, two-surgeon cohort study of paediatric scoliosis procedures involving 118 patients under the age of 18 years who underwent correction for idiopathic scoliosis over a period of 42 months. Patients' baseline characteristics, pseudarthrosis and rates of SSI were compared. RESULTS: Baseline characteristics were comparable in all three groups, with the exception of sex distribution. Over a quarter (27%) of patients with regimen B were male compared with 13% and 6% for regimens A and C respectively. Patients were mostly followed up for a minimum of 12 months. The SSI rate for both superficial and deep infections was higher with regimen A (26.7%) than with regimens B and C (7.0% and 6.3% respectively). The SSI rates for regimens B and C were comparable. No patients developed complications related to vancomycin toxicity, metalwork failure or pseudarthrosis. CONCLUSIONS: Wound irrigation with a povidone-iodine solution reduces SSIs following adolescent idiopathic scoliosis surgery. The direct application of vancomycin powder to the wound is safe but does not reduce the SSI rate further in low risk patients. Additional studies are needed to elucidate whether it is effective at higher doses and in high risk patient groups.


Subject(s)
Scoliosis/surgery , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Therapeutic Irrigation/methods , Therapeutic Irrigation/statistics & numerical data , Adolescent , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Female , Gentamicins/administration & dosage , Gentamicins/therapeutic use , Humans , Intraoperative Care/methods , Intraoperative Care/statistics & numerical data , Male , Povidone-Iodine/administration & dosage , Povidone-Iodine/therapeutic use , Retrospective Studies , Surgical Wound Infection/drug therapy , Vancomycin/administration & dosage , Vancomycin/therapeutic use
2.
Oncogene ; 34(28): 3711-27, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25241900

ABSTRACT

Glioblastoma is the most common and lethal primary malignant brain tumor in adults. The tumor suppressor gene PTEN is deleted, mutated or hypermethylated in more than 60% of glioblastoma cases resulting in hyperactivation of the phosphoinositide 3-kinase pathway, which leads to sustained PI(3,4,5)P3 signaling, and thereby hyperactivation of Akt and other effectors. PI(3,4,5)P3 is also hydrolyzed to PI(3,4)P2 by inositol polyphosphate 5-phosphatases such as SKIP, but the role this pathway has in glioblastoma is unknown. Microarray expression profiling of SKIP in human glioblastoma has revealed both increased and decreased SKIP gene expression. Here we have screened PTEN-deficient glioblastoma for SKIP protein expression by immunohistochemistry and report that SKIP expression is increased in some cases or decreased relative to normal brain. Using the U-87MG PTEN-deficient cell line we show that SKIP knockdown did not further enhance cell proliferation or survival. However, SKIP overexpression in U-87MG cells suppressed anchorage-independent cell growth and growth factor-induced PI(3,4,5)P3/Akt signaling. Although, SKIP knockdown did not affect cell proliferation or survival, cell migration was significantly retarded, associated with significantly increased PI(4,5)P2 signals, and decreased phosphorylation of the actin-regulatory protein cofilin, a PI(4,5)P2-binding protein. Notably, overexpression of SKIP also inhibited migration of U-87MG cells to a similar degree as observed with PTEN reconstitution, however, via distinct mechanisms. PTEN reconstitution promoted sustained lamellipodia generation and focal adhesion formation. In contrast, SKIP overexpression reduced sustained lamellipodia formation, talin incorporation into focal adhesions and recruitment of PI(4,5)P2-binding proteins to the plasma membrane. Notably, analysis of two independent ONCOMINE microarray data sets revealed a significant correlation between increased SKIP mRNA expression in glioblastoma and improved long-term survival. Therefore, SKIP expression in glioblastoma may affect the local invasion of PTEN-deficient tumors.


Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , PTEN Phosphohydrolase/genetics , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolism , Brain Neoplasms/enzymology , Brain Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Glioblastoma/enzymology , Glioblastoma/genetics , Humans , MAP Kinase Signaling System , Oligonucleotide Array Sequence Analysis , Survival Analysis
3.
J R Army Med Corps ; 157(4): 396-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22319986

ABSTRACT

Fragment embolisation following vascular injury is uncommon. The case of a 31 year old soldier, who sustained a penetrating fragment injury to the neck with distal arterial embolisation, is presented and the discussion illustrates both the importance of expedient assessment and management of cervical vascular injuries and of thorough correlation of clinical and radiological findings to avoid missed emboli.


Subject(s)
Brachiocephalic Trunk/injuries , Foreign-Body Migration/diagnosis , Military Personnel , Neck Injuries/diagnosis , Ulnar Artery , Wounds, Penetrating/diagnosis , Adult , Foreign-Body Migration/surgery , Humans , Male , Metals
4.
J Hosp Infect ; 72(4): 332-6, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19278752

ABSTRACT

In May 2003, two adult patients in an oncology unit were diagnosed with listeriosis, and sandwiches consumed in the hospital were identified as a common risk factor. Both patients were infected by the same strain of Listeria monocytogenes. Sandwiches collected from the hospital and external sandwich producer, as well as sites within the manufacturing environment, were contaminated by the same strain of L. monocytogenes. Sandwiches consumed in other hospitals have been associated with small clusters of listeriosis patients in the UK. This report describes the investigations following diagnosis of the two infections, and highlights a more general problem with sandwiches sold in hospitals.


Subject(s)
Disease Outbreaks , Foodborne Diseases/epidemiology , Foodborne Diseases/microbiology , Listeria monocytogenes/isolation & purification , Listeriosis/epidemiology , Listeriosis/microbiology , Bacterial Typing Techniques/methods , Cross Infection/epidemiology , Cross Infection/microbiology , Environmental Microbiology , Female , Food Microbiology , Hospitals , Humans , Listeria monocytogenes/classification , Middle Aged , United Kingdom
6.
J Bone Joint Surg Br ; 89(2): 253-7, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17322448

ABSTRACT

We performed a biomechanical study to compare the augmentation of isolated fractured vertebral bodies using two different bone tamps. Compression fractures were created in 21 vertebral bodies harvested from red deer after determining their initial strength and stiffness, which was then assessed after standardised bipedicular vertebral augmentation using a balloon or an expandable polymer bone tamp. The median strength and stiffness of the balloon bone tamp group was 6.71 kN (sd 2.71) and 1.885 kN/mm (sd 0.340), respectively, versus 7.36 kN (sd 3.43) and 1.882 kN/mm (sd 0.868) in the polymer bone tamp group. The strength and stiffness tended to be greater in the polymer bone tamp group than in the balloon bone tamp group, but this difference was not statistically significant (strength p>0.8, and stiffness p=0.4).


Subject(s)
Deer , Fractures, Compression/therapy , Kyphosis/therapy , Spinal Fractures/therapy , Animals , Biomechanical Phenomena , Bone Cements/therapeutic use , Catheterization , Cementation/methods , Dilatation/instrumentation , Dilatation/methods , Disease Models, Animal , Elasticity , Polymers , Stress, Mechanical , Weight-Bearing
8.
Clin Orthop Relat Res ; (388): 205-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11451121

ABSTRACT

Type III fractures of the tibial spine require open reduction and internal fixation when conservative treatment fails. The Acutrak cannulated screw system has been used successfully for arthroscopic reduction and fixation of these injuries. It was used in four children and two adults; all patients have returned to their preinjury exercise status. The use of a tent peg technique in children allows preservation of the proximal tibial physis, which prevents premature epiphysiodesis.


Subject(s)
Arthroscopy , Bone Screws , Fracture Fixation, Internal/instrumentation , Tibial Fractures/surgery , Adult , Child , Equipment Design , Humans , Middle Aged
9.
Plant Mol Biol ; 39(5): 927-32, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10344198

ABSTRACT

A detailed analysis of the currently available Arabidopsis thaliana genomic sequence has revealed the presence of a large number of open reading frames with homology to the stigmatic self-incompatibility (S) genes of Papaver rhoeas. The products of these potential genes are all predicted to be relatively small, basic, secreted proteins with similar predicted secondary structures. We have named these potential genes SPH (S-protein homologues). Their presence appears to have been largely missed by the prediction methods currently used on the genomic sequence. Equivalent homologues could not be detected in the human, microbial, Drosophila or C. elegans genomic databases, suggesting a function specific to plants. Preliminary RT-PCR analysis indicates that at least two members of the family (SPH1, SPH8) are expressed, with expression being greatest in floral tissues. The gene family may total more than 100 members, and its discovery not only illustrates the importance of the genome sequencing efforts, but also indicates the extent of information which remains hidden after the initial trawl for potential genes.


Subject(s)
Arabidopsis/genetics , Genes, Plant , Genome, Plant , Papaver/genetics , Plant Proteins , Plants, Medicinal , Pollen/genetics , RNA, Plant/genetics , RNA, Plant/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment
11.
Psychopharmacology (Berl) ; 102(2): 239-42, 1990.
Article in English | MEDLINE | ID: mdl-2177205

ABSTRACT

Mice withdrawn from exposure for 14 days to ethanol inhalation showed the expected signs of ethanol withdrawal including convulsive behaviour. Injection of chlormethiazole (100 mg/kg) 5 h after the start of withdrawal, at the time that the convulsive behaviour was near maximal, resulted in the virtual disappearance of the withdrawal-induced behaviour within 30 min, with its reappearance by 60 min. A dose of chlormethiazole of 40 mg/kg was without effect. The time course of the effect of chlormethiazole (100 mg/kg) in the withdrawal test was similar to its effect in raising seizure threshold and decreasing locomotor activity. Chlormethiazole did not alter in vitro binding of [3H]-PN 200-110 to the dihydropyridine sensitive Ca2+ channel. Chlormethiazole, a drug used clinically to treat ethanol withdrawal, has therefore been shown to be effective in this animal model of withdrawal. Dihydropyridine calcium antagonists are also active in the model but chlormethiazole is likely to work by a different mechanism and it is suggested that this may be by increasing GABAergic function.


Subject(s)
Chlormethiazole/pharmacology , Ethanol/toxicity , Substance Withdrawal Syndrome/drug therapy , Animals , Calcium Channels/drug effects , Calcium Channels/metabolism , Chlormethiazole/therapeutic use , Dihydropyridines/pharmacology , Isradipine , Male , Mice , Motor Activity/drug effects , Oxadiazoles/metabolism , Seizures/physiopathology
12.
Br J Pharmacol ; 99(1): 41-6, 1990 Jan.
Article in English | MEDLINE | ID: mdl-1691944

ABSTRACT

1. The effects of calcium antagonists on behaviour mediated by 5-hydroxytryptamine (5-HT) have been studied in rats and mice together with an investigation of the effects of these drugs on 5-HT synthesis in rat brain and endogenous 5-HT release from brain slices. 2. Administration of felodipine (35 mg kg-1 i.p.) to rats pretreated with tranylcypromine (20 mg kg-1, i.p.) resulted in the animals displaying the complete 5-HT-mediated behavioural syndrome (including head weaving, reciprocal forepaw treading and hind limb abduction) 75 min later. No evidence was obtained for the rate of 5-HT synthesis in brain regions differing between control and felodipine-treated rats. 3. Pretreatment with felodipine (10 or 35 mg kg-1) enhanced the 5-HT-mediated behavioural syndrome induced by injection of tranylcypromine and L-tryptophan. The rate of 5-HT accumulation in the brain was similar in both groups. Administration of Bay K 8644 (1 mg kg-1, i.p.) did not prevent the enhanced behaviour induced by felodipine (10 mg kg-1). 4. The 5-HT behavioural syndrome induced by injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was unaltered by either acute injection of felodipine (35 mg kg-1) or administration of felodipine twice daily for 3 days. 5. Felodipine (10 microM), verapamil (10 microM) and Bay K 8644 (10 microM) did not alter either basal release of endogenous 5-HT from slices prepared from frontal cortex or hind brain, or release following addition of K+ at a concentration of 20 mM, or 35 mM. 6. Verapamil (25mgkg-', i.p.), nicardipine (25mgkg-1, i.p.) and nifedipine (20mgkg-1, i.p.) all markedly inhibited the 5-HT2 receptor-mediated head twitch response in mice produced by injection of 5- methoxy-N,N-dimethyl-tryptamine (5-MeODMT). Felodipine had the same effect with an ED50 of 2.6mgkg-'. Bay K 8644 did not reverse this effect. Both verapamil (IC50:2.5 microM) and nicardipine (IC50:8 microM) were 5-HT2 antagonists as indicated by inhibition of [3H]-ketanserin binding in mouse frontal cortex. However felodipine and nifedipine antagonized 5-HT2 receptor binding only in the millimolar range.7. Hydralazine (5mg kg 1, i.p.) induced the 5-HT behavioural syndrome in tranylcypromine pretreated rats, enhanced the tranylcypromine/L-tryptophan behavioural syndrome, inhibited 5-MeODMT-induced head twitch behaviour in mice and was not a 5-HT2 receptor antagonist. 8. These data indicate that at a high dose, Ca2+ antagonists produce complex changes in 5-HT function in rodents which are similar to those produced by lithium administration. The data with hydralazine suggest that the effects seen are not related to an action at Ca2 + channels.


Subject(s)
Brain Chemistry/drug effects , Calcium Channel Blockers/pharmacology , Hydralazine/pharmacology , Serotonin/metabolism , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology , 8-Hydroxy-2-(di-n-propylamino)tetralin , Animals , Behavior, Animal/drug effects , Felodipine/pharmacology , Hydroxyindoleacetic Acid/metabolism , Male , Methoxydimethyltryptamines/pharmacology , Mice , Mice, Inbred C57BL , Rats , Receptors, Serotonin/drug effects , Receptors, Serotonin/metabolism , Serotonin/biosynthesis , Species Specificity , Tetrahydronaphthalenes/pharmacology , Tranylcypromine/pharmacology , Tryptophan/pharmacology
14.
Int J Lepr Other Mycobact Dis ; 52(1): 1-6, 1984 Mar.
Article in English | MEDLINE | ID: mdl-6368424

ABSTRACT

During treatment of multibacillary leprosy with the combination rifampin (RMP) 600 mg, ethionamide (ETH) 500 mg, and either dapsone (DDS) or clofazimine (CLO) 100 mg, hepatotoxicity was observed in 4.5% of 596 patients. Hepatitis appeared after 5-186 days, with a mean of 93 days and a median of 76 days. Mortality was 26%. ETH and DDS or CLO were administered daily in all regimens in which hepatitis occurred. RMP was given either daily or daily during the first two weeks or eight weeks, followed by a once-weekly dose. It is concluded that the combination RMP + ETH is the toxic component. In some patient groups there was a high correlation of toxicity with age. A regimen in which RMP was administered only twice a week during three months was not accompanied by hepatotoxicity. Future studies should show if reduction of the daily dose of ETH or reduction of the duration of the administration of RMP + ETH might reduce the incidence of hepatotoxicity while conserving the efficacy.


Subject(s)
Chemical and Drug Induced Liver Injury/etiology , Ethionamide/administration & dosage , Leprosy/drug therapy , Rifampin/administration & dosage , Adolescent , Adult , Child , Clinical Trials as Topic , Clofazimine/adverse effects , Dapsone/adverse effects , Drug Therapy, Combination , Ethionamide/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Rifampin/adverse effects
16.
Am J Med Genet ; 14(3): 445-52, 1983 Mar.
Article in English | MEDLINE | ID: mdl-6859096

ABSTRACT

We describe a baby with external and internal anomalies of the Majewski form of the short rib-polydactyly (SRP) syndromes. Previously unreported abnormal vertebral bodies, delayed ossification of the sternum and fibulae, and a diencephalic hamartoma are noted. These abnormalities and minimal histologic abnormality at the chondro-osseous junction suggest that this syndrome may be heterogeneous or more variable than previously known.


Subject(s)
Abnormalities, Multiple/pathology , Dwarfism/pathology , Fingers/abnormalities , Ribs/abnormalities , Toes/abnormalities , Abnormalities, Multiple/diagnostic imaging , Humans , Infant, Newborn , Male , Radiography , Syndrome
17.
Br J Obstet Gynaecol ; 88(6): 663-8, 1981 Jun.
Article in English | MEDLINE | ID: mdl-6788068

ABSTRACT

This study comprises 336 consecutive patients of whom 283 were candidates for conservative therapy involving either cryosurgery or the carbon dioxide laser for the management of cervical intraepithelial neoplasia (CIN). A total of 152 patients were treated first in the series with cryosurgery followed by 131 patients in the laser group. Distribution of disease classification within CIN groups was similar. The overall persistent disease after one treatment was higher in the cryo group (14.5 per cent) as compared to the laser group (3.1 per cent). Of particular significance is the high percentage of failures in the cryo treated group (25.0 per cent) with CIN III disease as compared to the CIN III laser treated group (7.7 per cent). The high persistent disease rate observed in the CIN III lesions treated by cryosurgery suggests that this modality be employed with caution in this disease classification.


Subject(s)
Cryosurgery , Laser Therapy , Uterine Cervical Neoplasms/surgery , Carbon Dioxide , Cervix Uteri/surgery , Female , Humans
18.
Can Med Assoc J ; 122(8): 901-5, 1980 Apr 19.
Article in English | MEDLINE | ID: mdl-7370874

ABSTRACT

Two cases are presented in which the effects of blunt trauma to a pregnant woman's abdomen were apparently minor but resulted in fetal death. Blunt trauma may result in serious injury to the fetus or the placenta. Three-point restraint systems should be worn by pregnant women travelling in automobiles to minimize the risks to mother and fetus. Awareness of the potential for injury in these circumstances is essential to reduce the risks to the fetus.


Subject(s)
Abdominal Injuries/etiology , Fetal Death/etiology , Wounds, Nonpenetrating/complications , Abdominal Injuries/therapy , Accidents, Traffic , Adult , Female , Fetal Death/diagnosis , Fetal Heart/physiopathology , Heart Rate , Humans , Pregnancy , Seat Belts , Wounds, Nonpenetrating/therapy
20.
Trans Ophthalmol Soc U K (1962) ; 97(1): 206-9, 1977 Apr.
Article in English | MEDLINE | ID: mdl-339415

ABSTRACT

This paper presents a clinical assessment of the Ocusert pilocarpine therapeutic system in 22 patients. Severe patients were 'wearing failures' and one was a 'therapeutic failure'. In the remaining patients intraocular pressure were controlled satisfactorily by a small daily dose of pilocarpine and there was relief from the burden of regular drop administration and the transient myopia which follows each instillation. This study confirms a place for the 'Ocusert' system in the management of some patients with chronic glaucoma.


Subject(s)
Glaucoma/drug therapy , Pilocarpine/administration & dosage , Adult , Aged , Chronic Disease , Clinical Trials as Topic , Delayed-Action Preparations , Female , Humans , Male , Middle Aged , Myopia/chemically induced , Pilocarpine/adverse effects , Pilocarpine/therapeutic use , Visual Acuity
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