Precocious puberty: a parent's perspective.
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Biomedical subjects
Publications and source records attributed to E O'Sullivan.
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A retrospective audit was carried out to investigate triptan usage over a period of one year among 360 adult patients with migraine in nine GP practices in the UK and the Republic of Ireland. Data from patient records were analysed, in conjunction with replies to a questionnaire about patients' perceptions of their migraine and its treatment. The majority of patients included in the audit were women (83%), and most patients (81%) were aged between 35 and 64 years. Most patients in the audit population (60%) were in the lowest band of triptan usage (1-36 tablets prescribed over 12 months); 7% had moderate usage (37-53 tablets). A minority of patients appeared to be taking triptans in higher quantities: about 15% of patients had been prescribed 54-94 triptan tablets over a year, 9% had received prescriptions for 95-149 tablets and 7% had received prescriptions for 150 or more tablets. These results indicated that some migraine patients were using triptans at higher than expected rates, and suggested that some patients might have been using their prescribed triptans inappropriately to treat a headache that they incorrectly perceived as migraine (e.g. chronic daily headache). Analyses were carried out to identify predictors of high usage. Predictors identified included the use of several other (non-triptan) medications to treat conditions other than migraine, one triptan dose being reported as sufficient to treat an attack, patient's perception of all headaches as migraine and lack of concern about taking too much medication. Patients identified as using triptans at a higher than expected rate can be called in for review of migraine diagnosis, identification of possible causes of any increased frequency of attacks, and investigation of suspected non-migrainous headaches, such as chronic daily headache and medication-induced headaches. For GPs, such actions would help achieve and maintain a high standard of care for their migraine patients, thus helping to contribute towards meeting the demands of the clinical governance agenda. Audit of triptan usage may also offer financial benefits for the practice, since helping patients to avoid the inappropriate use of triptans could lead to reductions in the overall costs of triptan prescribing within the practice. The high usage predictors could be developed into a checklist of potential indicators for GPs to identify patients who may become high users if prescribed triptans and who might require closer monitoring. We recommend that patients identified as having a potential for high usage should be routinely reviewed, every 3-6 months, to ensure that they are using triptans appropriately to treat migraine. Although triptans are generally safe and well tolerated, unnecessary use of any medication should be avoided.
Cells of Lactococcus lactis MG1363 growing in batch culture in TYG (tryptone, yeast extract, glucose) medium at constant pH 7.0 became gradually more acid sensitive shortly after inoculation until a point of maximum sensitivity was reached in early log-phase. The acid tolerance then gradually increased in the mid- and late-log phase until maximum tolerance was reached at the onset of stationary phase. This pattern has been termed the growth-phase acid tolerance. The variation in acid tolerance seen in pH 7.0 grown cells of L. lactis MG1363 did not result from changes in internal pH or membrane H+ ATPase activity levels. Neither the amount of glucose present during mid-log phase nor the amount of lactate produced by the cells correlated with the pattern of the log-phase acid tolerance. Cells grown in partially spent TYG medium showed a reduced growth rate and increased acid tolerance compared to cells grown in fresh TYG medium. Supplementing the spent medium with tryptone or yeast extract or both restored the growth rate and cells became more sensitive to acid. Fractionation of tryptone yielded a fraction which stimulated the growth of MG1363 in partially spent medium and delayed the acquisition of acid tolerance. The active compound(s) has a putative molecular weight of about 1 kDa and was partially degraded by papain and trypsin.
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Spray drying of skim milk was evaluated as a means of preserving Lactobacillus paracasei NFBC 338 and Lactobacillus salivarius UCC 118, which are human-derived strains with probiotic potential. Our initial experiments revealed that NFBC 338 is considerably more heat resistant in 20% (wt/vol) skim milk than UCC 118 is; the comparable decimal reduction times were 11.1 and 1.1 min, respectively, at 59 degrees C. An air outlet temperature of 80 to 85 degrees C was optimal for spray drying; these conditions resulted in powders with moisture contents of 4.1 to 4.2% and viable counts of 3.2 x 10(9) CFU/g for NFBC 338 and 5.2 x 10(7) CFU/g for UCC 118. Thus, L. paracasei NFBC 338 survived better than L. salivarius UCC 118 during spray drying; similar results were obtained when we used confocal scanning laser microscopy and LIVE/DEAD BacLight viability staining. In addition, confocal scanning laser microscopy revealed that the probiotic lactobacilli were located primarily in the powder particles. Although both spray-dried cultures appeared to be stressed, as shown by increased sensitivity to NaCl, bacteriocin production by UCC 118 was not affected by the process, nor was the activity of the bacteriocin peptide. The level of survival of NFBC 338 remained constant at approximately 1 x 10(9) CFU/g during 2 months of powder storage at 4 degrees C, while a decline in the level of survival of approximately 1 log (from 7.2 x 10(7) to 9.5 x 10(6) CFU/g) was observed for UCC 118 stored under the same conditions. However, survival of both Lactobacillus strains during powder storage was inversely related to the storage temperature. Our data demonstrate that spray drying may be a cost-effective way to produce large quantities of some probiotic cultures.
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The effect of increasing delay on the metrics of remembered saccades was studied in 10 subjects with mild Parkinson's disease, none of whom was receiving treatment with L-dopa, and nine age-matched control subjects. Delays of 1 msec, 250 msec, 1000 msec, 2500 msec, and 5000 msec were used, and reflexive saccades used as a control condition. Results were analyzed for the gain of the primary saccade and the accuracy of the final eye position (FEP gain). Reflexive saccades were normal in subjects with Parkinson's disease, but remembered saccades showed marked hypometria of primary saccade gain at all delays. FEP gain was unimpaired in Parkinson's disease, and primary saccade gain and FEP gain did not vary as a function of delay. Hypometria of primary saccades is compatible with dysfunction in striato-collicular inhibitory pathways in Parkinson's disease, arising as a functional consequence of dopamine deficiency in the basal ganglia. Maintenance of an accurate FEP gain suggests no deficit in oculomotor spatial working memory in Parkinson's disease, at least at delays of up to 5 sec.
The term 'dedicated airway' was first used in connection with nasal fibreoptic intubations using the cuffed nasopharyngeal airway. Since that time, the concept has developed and the term has been extended to include fibreoptic intubation techniques involving both the laryngeal mask airway and cuffed oropharyngeal airway. 'Dedicated airway' can now be defined as: 'An upper airway device dedicated to the maintenance of airway patency while other major airway interventions are anticipated or are in progress. The device should be compatible with spontaneous and controlled ventilation. 'Dedicated airway techniques allow planned fibreoptic intubations in difficult cases and provide an emergency airway option in an unexpected difficult intubation when the alternative may be to wake the patient. As well as promoting safe conditions for training fibreoptic intubation in general, there is the particular advantage of being able to train using these techniques in patients known to be difficult to intubate. The authors' evolved clinical experiences in promoting the concept and the relevant literature are reviewed.
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The acid tolerance response (ATR) of chemostat cultures of Lactococcus lactis subsp. cremoris NCDO 712 was dependent on the dilution rate and on the extracellular pH (pHo). A decrease in either the dilution rate or the pHo led to a decrease in the cytoplasmic pH (pHi) of the cells, and similar levels of acid tolerance were observed at any specific pHi irrespective of whether the pHi resulted from manipulation of the growth rate, manipulation of the pHo, or both. Acid tolerance was also induced by sudden additions of acid to chemostat cultures growing at a pHo of 7.0, and this induction was completely inhibited by chloramphenicol. The end products of glucose fermentation depended on the growth rate and the environmental pHo of the cultures, but neither the spectrum of end products nor the total rate of acid production correlated with a specific pHi. The rate of ATP formation was not correlated with pHi, but a good correlation between the cellular level of H+-ATPase and pHi was observed. Moreover, an inverse correlation between the cytoplasmic levels of ATP and pHi was established. Each pHi below 6. 6 was characterized by unique levels of ATR, H+-ATPase, and ATP. High levels of H+-ATPase also coincided with high levels of acid tolerance of cells in batch cultures induced with sublethal levels of acid. We concluded that H+-ATPase is one of the ATR proteins induced by acid pHi through growth at an acid pHo or a slow growth rate.
A cuffed oropharyngeal airway has recently been introduced which has larger internal dimensions than a comparable Guedel airway. This allows a ventilation/exchange bougie, the Aintree Intubation Catheter, mounted on a fibreoptic laryngoscope to pass through it. Its 15-mm connector and pharyngeal cuff suggested the possibility of using a Rüsch sealed-port angle piece to allow ventilation through the oropharyngeal airway during fibreoptic laryngoscopy. This study investigated using this equipment to intubate the trachea through the cuffed oropharyngeal airway in paralysed patients, whilst maintaining ventilation manually with a Bain system. In 20 patients, airway control was satisfactory throughout and tracheal intubation was accomplished without complications. The cuffed oropharyngeal airway was easy to manipulate to improve a suboptimal fibreoptic view of the larynx. This may give it an advantage over the laryngeal mask airway when used as a ventilation/intubation conduit.
A rapid detection method for the six established genotypes of rabies and rabies-related viral RNA using RT-PCR-ELISA is described. The detection of digoxigenin-labelled amplified products is performed by solution hybridization to two specific, biotin-labelled, capture probes, which are complementary to the inner region of the amplification products. The capture probe and amplified product hybrid are then immobilised on a streptavidin-coated microtitre plate, bound products are detected by an anti-DIG Fab fragment conjugated to peroxidase, and colorimetric reaction automatically measured. This method was up to 100-fold more sensitive than Southern blot hybridization, detecting 0.00002 TCID50/ml of a genotype 1, classical rabies virus strain. The complete detection methodology from RT-PCR to PCR-ELISA detection could be completed within 10 h. Using this procedure, we were 100% successful in detecting 60 isolates from a representative selection of the six established genotypes from all over the world. This test is a useful additional tool for the detection of the rabies and rabies-related viruses, which is easy to perform, rapid and highly sensitive.
Bartter's syndrome is a rare autosomal recessive disorder characterized by hypokalemia, hyperaldosteronism, sodium wasting, normal blood pressure, hypochloremic alkalosis, and hyperplasia of the juxtaglomerular apparatus. We present a 21-year-old African-American nulliparous patient who was referred to our clinic at 9 weeks' gestation with a history of Bartter's syndrome. Her antenatal course was complicated by muscle cramps, which required increasing potassium supplementation. She developed hypomagnesemia in the third trimester of pregnancy, which necessitated magnesium therapy. She delivered an unaffected infant at term. Bartter's syndrome, although extremely rare in pregnancy, requires prompt recognition and careful management, as it may have significant maternal and neonatal implications.
This study demonstrates that exposure of log-phase Lactococcus lactis subsp. cremoris 712 cells to mildly acid conditions induces resistance to normally lethal intensities of environmental stresses such as acid, heat, NaCl, H2O2, and ethanol. The intracellular pH (pHi) played a major role in the induction of this multistress resistance response. The pHi was dependent on the extracellular pH (pHo) and on the specific acid used to reduce the pHo. When resuspended in fresh medium, cells were able to maintain a pH gradient even at pHo values that resulted in cell death. Induction of an acid tolerance response (ATR) coincided with an increase in the ability of cells to resist change to an unfavorable pHi; nevertheless, a more favorable pHi was not the sole reason for the increased survival at acid pHo. Cells with an induced ATR survived exposure to a lethal pHo much better than did uninduced cells with a pHi identical to that of the induced cells. Survival following lethal acid shock was dependent on the pHi during induction of the ATR, and the highest survival was observed following induction at a pHi of 5.9, which was the lowest pHi at which growth occurred. Increased acid tolerance and the ability to maintain a higher pHi during lethal acid stress were not acquired if protein synthesis was inhibited by chloramphenicol during adaptation.
A heminested reverse transcriptase PCR (hnRT-PCR) protocol which is rapid and sensitive for the detection of rabies virus and rabies-related viruses is described. Sixty isolates from six of the seven genotypes of rabies and rabies-related viruses were screened successfully by hnRT-PCR and Southern blot hybridization. Of the 60 isolates, 93% (56 of 60) were positive by external PCR, while all isolates were detected by heminested PCR and Southern blot hybridization. We also report on a comparison of the sensitivity of the standard fluorescent-antibody test (FAT) for rabies antigen and that of hnRT-PCR for rabies viral RNA with degraded tissue infected with a genotype 1 virus. Results indicated that FAT failed to detect viral antigen in brain tissue that was incubated at 37 degrees C for greater than 72 h, while hnRT-PCR detected viral RNA in brain tissue that was incubated at 37 degrees C for 360 h.
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The ventilation-exchange bougie is a new airway device which can be mounted on a fibreoptic laryngoscope for passage through the larynx into the trachea via a laryngeal mask airway. Subsequent removal of the fibreoptic laryngoscope and laryngeal mask airway allows a tracheal tube to be railroaded into position over the ventilation-exchange bougie. This study described the use of this technique for elective tracheal intubation in two groups of 12 subjects in whom difficulty with intubation was not expected. All the subjects were successfully intubated by one of two anaesthetists, one experienced and the other inexperienced with fibreoptic intubation techniques. Neither had had prior experience with the ventilation-exchange bougie. Because ventilation was maintained throughout the procedure, intubation did not need to be hurried. Cusum analysis confirmed the impression of a learning curve and the technique could be considered learnt after four and six intubations for the experienced and inexperienced fibreoptic laryngoscopists respectively. No difficulty was found either in intubating the larynx with the fibreoptic laryngoscope and ventilation-exchange bougie or when railroading the tracheal tube over the ventilation-exchange bougie. It is suggested that this new device could have an important role in teaching fibreoptic techniques, management of the difficult airway and failed intubations.
Saccadic eye movements, fixation, and smooth pursuit were recorded in 17 subjects with amyotrophic lateral sclerosis (ALS) and 11 age-matched controls using a magnetic scleral search coil. Reflexive, remembered and antisaccades, and smooth pursuit at four target velocities were studied. Subjects with ALS showed significantly elevated error rates (distractibility) and latency in the antisaccade and remembered saccade paradigms but no abnormality of reflexive saccades. The frequency of small saccades that intruded on steady fixation (square-wave jerks) was also increased in ALS subjects. Peak velocity gain of smooth pursuit and performance on the Wisconsin Card Sort Test did not differ significantly between the two groups. These findings are consistent with prefrontal dysfunction in ALS and provide an independent source of support for the thesis that the pathology of this condition invades frontal cortex.