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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 289 records · Page 16Linked to original sources

Rectal necrosis after a phosphate enema.

We describe a patient who developed rectal ulceration after an apparently minor injury caused during the administration of a 130 ml 'disposable' phosphates enema. Treatment included parenteral antibiotics and a colostomy. Minor degrees of injury by rectal procedures are common. Rectal necrosis is a complication of injury during the administration of phosphates enemata which, although rare, deserves greater awareness. Painless rectal bleeding may be the only sign of injury and is an indication for thorough and repeated rectal examinations and early intervention.

Aged↗

The nasal cycle and clinical examination of the nose.

A recent study from this department demonstrated the importance of interobserver variation in examination of the nasal airways. Part of this variation may have been due to the mucosal changes of the nasal cycle. We investigated this suggestion and assessed the correlation between anterior rhinometry, a patient questionnaire and 4 different methods of recording the findings of clinical examination. Applying the Kappa statistic we found there was no significant reduction in interobserver variation despite eliminating nasal cycle influence.

Airway Resistance↗

Regulation of spo0H, an early sporulation gene in bacilli.

The construction of lacZ fusions in frame with the spo0H gene of Bacillus licheniformis enabled us to study the expression of this gene under various growth conditions and in various genetic backgrounds. spo0H was expressed during vegetative growth, but the levels increased during early stationary phase and then decreased several hours later. Expression of the gene was not repressed by glucose, but was induced by decoyinine, an inhibitor of guanine nucleotide biosynthesis, which can induce sporulation. Of those tested, the only spo0 gene required for the expression of spo0H was spo0A, and this requirement was eliminated by the abrB mutation, a partial suppressor of spo0A function. spo0H-lacZ expression was much higher in a strain with a deletion in the spo0H gene.

Bacillus↗

Estimation of tetrahydrobiopterin and other pterins in cerebrospinal fluid using reversed-phase high-performance liquid chromatography with electrochemical and fluorescence detection.

We describe an isocratic, reversed-phase high-performance liquid chromatographic method for the simultaneous measurement of fully oxidised, dihydro- and tetrahydropterins in cerebrospinal fluid. Tetrahydrobiopterin is detected electrochemically using an ESA Coulochem detector in the redox mode. Dihydropterins are detected by fluorescence following post-column electrochemical oxidation, and fully oxidised pterins by their natural fluorescence. Apart from addition of antioxidants, no sample preparation is required. Comparison is made with methods requiring chemical oxidation for detection of tetrahydrobiopterin. Some results on children with neurological disease are presented.

Antioxidants↗

Effects of afternoon injections of O-acetyl-5-methoxytryptophol, melatonin or 5-methoxytryptophol in female Syrian hamsters.

Female Syrian hamsters were maintained in a 14:10 light: dark photoperiod (lights on 6 a.m.) and injected each afternoon between 4 p.m. and 6 p.m. with diluent or with 25 micrograms melatonin, O-acetyl-5-methoxytryptophol (aML) or 5-methoxytryptophol (ML). After 7 or 12 weeks of treatment, only the melatonin-treated hamsters were acyclic. Gross inspection of their ovaries revealed that they were smooth, brown, and devoid of corpora lutea and large follicles. Progesterone levels of the acyclic animals were midway between the high levels observed during estrus and postestrus and the low levels observed on cycle days 2 and 3. Additionally, the melatonin-treated hamsters had significantly reduced uterine weights and pituitary and plasma levels of prolactin. Hamsters treated with aML had significantly lower pituitary prolactin and plasma and pituitary levels of LH only at the 7 week timepoint. ML-treated hamsters had lower pituitary prolactin levels also at 7 weeks. The endocrine changes wrought by injections of aML and ML, however, were insufficient to ultimately affect vaginal cyclicity. In conclusion, it would appear that at the dose used and the time administered melatonin is the more active of the indoles tested in the female hamster, at least in terms of alterations in reproductive physiology.

Animals↗

Biopterin and neurotransmitter amine metabolism in children with acute lymphoblastic leukemia receiving methotrexate therapy.

To test the hypothesis that some of the neurologic sequelae of treatment for acute lymphoblastic leukemia (ALL) might be related to abnormalities in biopterin metabolism associated with methotrexate (MTX) therapy, total biopterin levels in cerebrospinal fluid (CSF) and plasma, and homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) were measured in a cross-sectional study of 80 children with ALL. For comparison, biopterins were also measured in a group of children of similar age undergoing investigation for neurologic disease. In children with ALL studied before therapy, no significant difference was found between the means of plasma biopterin or CSF biopterin concentrations and the means in the control group. In children receiving MTX, plasma biopterin values were higher in the group given maintenance therapy than in children observed before treatment. CSF levels were significantly increased only in those patients who had completed 2 years of maintenance therapy. CSF concentrations of HVA and 5HIAA in patients with ALL who had received no treatment (median values 52 and 18 ng/ml, respectively) showed a wide scatter and were inversely related to age. In patients receiving MTX, concentrations of these metabolites were higher than in the untreated group, again reaching a peak in patients just completing 2 years of treatment (median HVA 110 ng/ml, 5HIAA 34 ng/ml). These results provide no support for the idea that neurotransmitter amine deficiency occurs in children with ALL receiving MTX, and indicate, rather, that amine and biopterin synthesis increases in such patients.

Adolescent↗

Low velocity hand-gun injuries of the maxillofacial region.

In contrast to the number of reports in the literature describing high velocity injuries of the maxillo-facial region, there are relatively few which deal with civilian type gunshot injuries. The purpose of this study was to undertake a retrospective analysis of 40 cases of low-velocity hand-gun injuries of the maxillo-facial region. The majority of cases were due to assault followed by accidental shootings and failed suicide attempts. Injuries ranged from mild soft tissue damage without fractures to severe, comminuted fractures of the facial bones. In some cases, soft tissue damage was severe. Rarely were injuries life threatening. Entrance wounds were characteristically small and well circumscribed. In 60 per cent of cases the bullet did not exist and was retained within the tissues. The floor of the mouth and tongue were the soft tissues most commonly injured. Other structures injured were major blood vessels, nerves and the eye. Mandibular fractures occurred in 58 per cent of cases, followed in frequency by maxillary complex fractures. Twenty per cent of fractures simultaneously involved bones of the upper, middle and lower-thirds of the facial skeleton. The above injuries are discussed and a classification of low-velocity hand-gun injuries of the maxillo-facial region is proposed.

Adolescent↗

Subdivision of daughter strains of bacille Calmette-Guérin (BCG) according to secreted protein patterns.

In order to identify proteins secreted by live organisms, daughter strains of the Bacillus Calmette-Guérin (BCG) were grown for 4-7 d in a defined medium containing [35S]methionine. Secreted components were then separated by polyacrylamide gel electrophoresis under both denaturing and non-denaturing conditions, and analysed by autoradiography and in an Ambis beta-scanner. The results indicate that BCG daughter strains can be subdivided into two groups according to their secretion of a 46 kDa protein dimer consisting of two similar 23 kDa subunits. High-producer strains (Japanese, Brazilian and Russian) secrete very large quantities of this material, which constitutes approximately 23% of all secreted protein. These findings correlate with earlier studies in which degradation products of the protein dimer may have been identified, and with the data from patterns of cell wall lipids.

Bacterial Proteins↗

A study on carbamazepine levels, including estimation of 10-11 epoxy-carbamazepine and levels in free plasma and saliva.

Blood and saliva were collected from 48 children, aged three to 17 years, before a morning dose of carbamazepine and then at three, six and eight hours afterward. There was no significant difference in the ratio of 10-11 epoxy-carbamazepine to total carbamazepine for children on carbamazepine alone (0.18) and those on an additional anticonvulsant (0.19). 11 children were studied on their first day of therapy. Though four of them achieved levels of total carbamazepine which would have given a readily measurable 10-11 epoxide on the above ratio, 10 of the 11 consistently had levels less than 4 mumol/l. This may be of help in detecting non-compliance. For 16 children free carbamazepine also was estimated and there was an over-all correlation coefficient of 0.85 between saliva and free-drug levels. The proportion of free to total carbamazepine varied between 19 and 54 per cent. There was a significantly higher proportion of free drug at the pre-dose sampling time than at other times. Protein binding of carbamazepine therefore is very variable and saliva estimations can contribute usefully to the monitoring of drug levels.

Adolescent↗

Characterization of a cloned Bacillus subtilis gene that inhibits sporulation in multiple copies.

We have isolated a 1.0-kilobase fragment of the Bacillus subtilis chromosome which, when present in high-copy-number plasmids, caused a sporulation-proficient strain to become phenotypically sporulation deficient. This is referred to as the sporulation inhibition (Sin) phenotype. This DNA fragment, in multicopy, also inhibited the production of extracellular protease activity, which normally appears at the beginning of stationary growth. The origin of the fragment was mapped between the dnaE and spo0A genes on the B. subtilis chromosome, and its complete DNA sequence has been determined. By analysis of various deletions and a spontaneous mutant the Sin function was localized to an open reading frame (ORF) predicted from the DNA sequence. Inactivation of this ORF in the chromosome did not affect the ability of cells to sporulate. However, the late-growth-associated production of proteases and alpha-amylase was elevated in these cells. The predicted amino acid sequence of the protein encoded by this ORF had a DNA-binding domain, typically present in several regulatory proteins. We propose that the sin ORF encodes a regulatory protein that is involved in the transition from vegetative growth to sporulation.

Alkaline Phosphatase↗

Transcriptional regulation of the spo0F gene of Bacillus subtilis.

We have cloned the early sporulation gene spo0F, which encodes an open reading frame of 124 codons. The putative Spo0F protein derived from this open reading frame, which has been shown to share homology with the Spo0A protein as well as several other regulatory proteins from Escherichia coli, Salmonella typhimurium, and Klebsiella pneumoniae, also shares homology with the E. coli EcoRI methyltransferase. We have shown by S1 nuclease mapping of in vivo transcripts that spo0F is regulated from dual promoters: RNA II was transcribed from an upstream promoter, and RNA I was initated 30 base pairs downstream from RNA II. The promoter sequences for RNA II, but not those for RNA I, conformed to the -10 region consensus sequence for sigma 43 promoters. RNA II was found in low amounts in exponentially growing cells but was not observed in stationary-phase cells, and the presence of RNA II was glucose insensitive. RNA I was found in low amounts in exponentially growing cells, increased three- to fivefold at the end of exponential growth, and remained at this higher level for at least 3 h into stationary phase. RNA I was repressed by glucose during exponential growth but not during stationary phase.

Bacillus subtilis↗

Neurological aspects of biopterin metabolism.

Plasma total biopterin concentration was measured by bioassay in 59 infants with hyperphenylalaninaemia and in 50 children with developmental regression and or movement disorder with normal plasma phenylalanine concentrations. In infants with raised phenylalanine concentrations plasma biopterin concentrations were significantly raised in proportion to the phenylalanine values. Five patients had plasma biopterin concentrations at the extremes of the range, and of these two had defective biopterin metabolism. One with low plasma biopterin concentration apparently had a partial defect of biopterin synthesis but died before investigations were complete. One with high plasma biopterin concentration, even when phenylalanine concentrations had fallen to the normal range, had dihydropteridine reductase deficiency. In this patient concentrations of homovanillic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) were severely reduced. In children without hyperphenylalaninaemia plasma biopterin concentrations were normal. Twenty two patients were subjected to lumbar puncture, of whom six with developmental regression without movement disorder had normal CSF biopterin concentrations, and 11 with movement disorder other than torsion dystonia had significantly lower CSF biopterin concentrations. Five patients with torsion dystonia had normal biopterin concentrations.

Adolescent↗

Early treated hypothyroidism: development at 3 years.

Eighty children from the North West and North East Thames Regional Health Authorities who had been identified as having congenital hypothyroidism either by neonatal screening (76 cases) or by clinical symptoms (four) were seen for psychological assessments at 1 (60 cases), 3 (58), and/or 5 (20) years of age. Almost all the children's scores were in the normal range, and comparisons with matched controls suggested that they were doing only slightly less well than normal children in overall development. They were significantly slower, however, on a motor skills task. Moreover, a low initial serum thyroxine and triiodothyronine value, considerable delay in initial bone age, and an absence of thyroid tissue on isotope scan seemed to be associated with a somewhat poorer prognosis.

Child Development↗