PDNS, PMWS and porcine circovirus type 2 in Scotland. Porcine dermatitis and nephropathy syndrome. Post-weaning multisystemic wasting syndrome.
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Animals↗
Biomedical subjects
B Smith
Publications and source records attributed to B Smith.
Biochemical characterization of the catalytic domain of human matrix metalloproteinase 19. Evidence for a role as a potent basement membrane degrading enzyme.
We have recently cloned MMP-19, a novel matrix metalloproteinase, which, due to unique structural features, was proposed to represent the first member of a new MMP subfamily (Pendás, A. M., Knäuper, V. , Puente, X. S., Llano, E., Mattei, M. G., Apte, S., Murphy, G., and López-Otin, C. (1997) J. Biol. Chem. 272, 4281-4286). A recombinant COOH-terminal deletion mutant of MMP-19 (proDelta(260-508)MMP-19), comprising the propeptide and the catalytic domain, was expressed in Escherichia coli, refolded, and purified. Interestingly, we found that proDelta(260-508)MMP-19 has the tendency to autoactivate, whereby the Lys(97)-Tyr(98) peptide bond is hydrolyzed, resulting in free catalytic domain. Mutation of two residues (Glu(88) --> Pro and Pro(90) --> Val) within the propeptide latency motif did not prevent autoactivation but the autolysis rate was somewhat reduced. Analysis of the substrate specificity revealed that the catalytic domain of MMP-19 was able to hydrolyze the general MMP substrate Mca-Pro-Leu-Gly-Dpa-Ala-Arg-NH(2) and, with higher efficiency, the stromelysin substrate Mca-Pro-Leu-Ala-Nva-Dpa-Ala-Arg-NH(2). Kinetic analysis of the interactions of the catalytic domain of MMP-19 with the natural MMP inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), showed strong inhibition using TIMP-2, TIMP-3, and TIMP-4, while TIMP-1 was less efficient. We also demonstrated that synthetic hydroxamic acid-based compounds efficiently inhibited the enzyme. The catalytic domain of MMP-19 was able to hydrolyze the basement membrane components type IV collagen, laminin, and nidogen, as well as the large tenascin-C isoform, fibronectin, and type I gelatin in vitro, suggesting that MMP-19 is a potent proteinase capable of hydrolyzing a broad range of extracellular matrix components. Neither the catalytic domain nor the full-length MMP-19 was able to degrade triple-helical collagen. Finally, and in contrast to studies with other MMPs, MMP-19 catalytic domain was not able to activate any of the latent MMPs tested in vitro.
Amino Acid Sequence↗
An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults.
Pertussis is increasingly being recognized as an important cause of cough illness in adolescents and adults. To evaluate the safety and immunogenicity of an adult formulation of a five-component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine combined with diphtheria and tetanus toxoids, we randomly allocated 749 healthy adolescents and adults from 12-54 years of age recruited from five Canadian communities to receive either tetanus-diphtheria vaccine (Td), acellular pertussis vaccine (aP) or combined diphtheria-tetanus-acellular pertussis vaccine (TdaP). Subjects and personnel were unaware of the vaccine allocation. Antibody levels were measured before and one month postimmunization; adverse events were collected at 24 and 72 h and 8 to 10 days. Adverse events were reported in similar frequency amongst the three vaccine groups. Moderate pain at the injection site was reported less frequently in the aP group than the TdaP group (10.7% compared to 19.4%; relative risk 0.6, 95% confidence interval 0.3-0.9). Chills were reported less frequently after Td (5.3%) than after TdaP (12.5%; relative risk 0.4, 95% confidence interval 0.2-0.9). There were no statistically significant differences between recipients of Td and TdaP in tetanus and diphtheria antitoxin levels achieved. Antibody response against Bordetella pertussis antigens was vigorous in all groups although recipients of aP alone had higher levels of antibody levels against pertussis toxoid, fimbriae, and agglutinins and lower antibody levels against pertactin than did TdaP recipients. We conclude that this adult formulation 5-component acellular pertussis vaccine is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.
Adolescent↗
Raman spectroscopic method for identification of clinically relevant microorganisms growing on solid culture medium.
Routine clinical microbiological identification of pathogenic microorganisms is largely based on nutritional and biochemical tests. In the case of severely ill patients, the unavoidable time delay associated with such identification procedures can be fatal. We present a novel identification method based on confocal Raman microspectroscopy. With this approach it is possible to obtain Raman spectra directly from microbial microcolonies on the solid culture medium, which have developed after only 6 h of culturing for the most commonly encountered organisms. Due to the limited thickness of microcolonies, some of the underlying culture medium is sampled together with the bacteria. Spectra measured at different depths in a microcolony contain different amounts of the medium signal. A mathematical routine, involving vector algebra, is described for the nonsubjective correction of spectra for variable signal contributions of the medium. To illustrate the possibilities of our approach for the identification of microorganisms, Raman spectra were collected from 6-h microcolonies of five bacterial strains on solid culture medium. The classification results show that confocal Raman microspectroscopy has great potential as a powerful new tool in clinical diagnostic microbiology.
Bacteriological Techniques↗
Rational treatment of empyema in children.
HYPOTHESIS: Efficacious and cost-effective treatment of pediatric empyema can be accomplished following a protocol based on its radiographic appearance. Therapeutic modalities include thoracostomy tube drainage (TTD) with or without fibrinolytic therapy (FT) and video-assisted thoracoscopic debridement (VATD). DESIGN: Retrospective case series. SETTING: Tertiary referral center. RESULTS: From 1995 through 1999, 31 children were treated ranging in age from 11 months to 18 years (mean age, 5.1 years). Twenty-seven (87.1%) underwent TTD; of these, 22 (81.5%) received FT with urokinase. The TTD failed in 4 children (14.8%) who required salvage VATD. Primary VATD was performed in another 4 children (12.9%). The mean length of stay was 14.6 days (TTD, 14.1 days; salvage VATD, 20. 0 days; primary VATD, 11.5 days), ranging from 8.0 to 30.0 days. Complications included readmission for fever (2 patients [6.5%]) and gastrointestinal bleeding (1 patient [3.2%]). There were no anaphylactic reactions or bleeding episodes due to urokinase. Two patients (7.4%) treated with TTD and FT developed an air leak that resolved spontaneously. The mean hospital charges were $78,832 (TTD with or without FT, $75,450; salvage VATD, $107,476; primary VATD, $69,634). The procedural charges were highest for salvage VATD. CONCLUSIONS: Most cases of pediatric empyema can be treated by TTD with or without FT. This therapy is safe and effective for children with nascent disease. Primary VATD is preferred in children with advanced disease. Cost-effectiveness could be further improved through better prediction of those patients likely to fail TTD and require salvage VATD. An algorithmic approach based on findings from computed tomography or (better) ultrasonography of the chest may be the best way to make this distinction and rationalize care.
Adolescent↗
Home care by outreach nursing for chronic obstructive pulmonary disease.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and deterioration in health. It is associated with significant morbidity, mortality and costs to health care systems. Care strategies, such as outreach nursing in the community, may reduce this burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for patients with COPD in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and hospital service utilisation. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTS were contacted for other published and unpublished studies. SELECTION CRITERIA: Only randomised control trials of patients with COPD were included. The intervention was an outreach nurse visiting patients in their homes, providing support, education, monitoring patient status and providing liaison with physicians. Interventions that used nurse practitioners who provided therapeutic intervention were also included. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. MAIN RESULTS: Four studies were found. Three assessed mortality following twelve months of care (n=96, 152 and 301), and one after seven months(n=75). Meta-analysis demonstrated that mortality was not significantly reduced by the intervention, Peto Odds Ratio 0.72; 95 % confidence interval 0.43, 1.21. Post hoc subgroup analysis suggested that mortality was reduced by the outreach nursing programme in patients with less severe disease. Significant improvements in health related quality of life were reported in one study in moderate COPD, but not in a study in patients with severe disease. No changes in lung function or exercise performance were found in the studies where data were available. Hospital admissions were reported in only one study in patients with severe disease and no benefit was observed. REVIEWER'S CONCLUSIONS: Patients with moderate COPD may have mortality and health related quality of life gains from a nursing outreach programme, but there are no data about reductions in hospital utilisation. Patients with severe COPD do not appear to have benefit from such programmes and one large study found no reduction in hospital admissions in such patients.
Community-Institutional Relations↗
Long-acting beta2-agonists for chronic obstructive pulmonary disease.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation which is only partially reversible. Long acting beta2-agonists, effective in the management of asthma,are also recommended for COPD management so it is important to establish whether these drugs are effective in reducing COPD symptoms in view of the potential side effect and cost burden. OBJECTIVES: To determine the effectiveness of long acting beta2-adrenoceptor agonists in improving lung function and quality of life and reducing dyspnoea in patients with COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. In addition, unpublished studies were also obtained from the pharmaceutical companies that manufacture long acting beta2- adrenoceptor agonists. SELECTION CRITERIA: All randomised controlled trials over four weeks in duration comparing treatment with long-acting beta2-adrenoceptor agonists (salmeterol and formoterol) with placebo in patients with stable non-reversible COPD. Outcome measures included forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), symptom scores, six minute walk distance, quality of life scores, Borg scores for dyspnoea and rescue bronchodilator use. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data were required, authors of studies were contacted. MAIN RESULTS: Thirty three abstracts were identified as potentially relevant. Of these, four randomised controlled trials (RCTs) were included in this review. Two were parallel group studies of 16 week duration and two were cross-over studies with four week treatment arms. All four RCTs assessed the efficacy of salmeterol in COPD. In a 16 week study of salmeterol 50 mcg and 100 mcg twice daily treatment, a significant increase in FEV1 was seen in both treatment groups. The weighted mean difference (WMD) for the increase in FEV1 for the 50 mcg group was 0.10 litre (95% CI: 0.05;0. 15) and in the 100 mcg group the WMD was 0.12 litre (95% CI: 0.06; 0. 17 ). In the two cross-over studies of four weeks treatment, salmeterol 50 mcg twice daily treatment did not show significant increases in FEV1 (WMD = 0.04 litre, 95% CI: -0.06; 0.15). Similarly, morning and night time PEFR was not significantly improved with salmeterol treatment. In a 16 week study, disease-specific quality of life, measured using the St. George's Respiratory Questionnaire (SGRQ), showed a significant improvement after 50 mcg twice daily, but not after 100 mcg twice daily. This improvement exceeded the threshold for a clinically significant change with this questionnaire. General health status, as measured by the Medical Outcomes Short Form 36, did not improve in any of the eight components with either salmeterol dose. No significant difference was demonstrated in the mean change from baseline in the six minute walk distance (WMD = 1.9 metres, 95% CI: -15.4;19.3). Breathlessness was reduced in one study in patients receiving salmeterol 50 mcg twice daily group. Significantly more patients in this group had Borg scores for breathlessness less than three (a score of three indicating moderate dyspnoea) compared to the placebo treated group (Peto Odds Ratio = 0.60, 95% CI: 0.40; 0.88). Neither dose of salmeterol influenced the incidence of COPD exacerbations, (50 mcg: Peto Odds Ratio = 0.74, 95% CI: 0.47, 1.15) and (100 mcg: Peto Odds Ratio = 0.98, 95% CI: 0.64, 1.52). REVIEWER'S CONCLUSIONS: Treatment of patients with COPD with long acting beta2-agonists produces only small increases in FEV1. In one study, a dose of salmeterol 50 mcg twice daily produced a reduction in breathlessness and a clinically significant improvement in quality of life. (ABSTRACT TRUNCATED)
Adrenergic beta-Agonists↗
Quantitative description of the workload associated with airway management procedures.
STUDY OBJECTIVES: To measure the workload associated with specific airway management tasks. SETTING AND INTERVENTION: Written survey instrument. PATIENTS: 166 Stanford University and 75 University of California, San Diego, anesthesia providers. MEASUREMENTS AND MAIN RESULTS: Subjects were asked to use a seven-point Likert-type scale to rate the level of perceived workload associated with different airway management tasks with respect to the physical effort, mental effort, and psychological stress they require to perform in the typical clinical setting. The 126 subjects completing questionnaires (overall 52% response rate) consisted of 43% faculty, 26% residents, 23% community practitioners, and 8% certified registered nurse-anesthetists (CRNAs). Faculty physicians generally scored lower workload measures than residents, whereas community practitioners had the highest workload scores. Overall, workload ratings were lowest for laryngeal mask airway (LMA) insertion and highest for awake fiberoptic intubation. Airway procedures performed on sleeping patients received lower workload ratings than comparable procedures performed on awake patients. Direct visualization procedures received lower workload ratings than fiberoptically guided procedures. CONCLUSIONS: These kinds of data may permit more objective consideration of the nonmonetary costs of technical anesthesia procedures. The potential clinical benefits of the use of more complex airway management techniques may be partially offset by the impact of increased workload on other clinical demands.
Adult↗
Transient hemifacial sensory loss with xerophthalmia following temporal lobectomy.
OBJECTIVE AND IMPORTANCE: The occurrence of a unilateral sensory loss in the second trigeminal distribution and the inability to tear following an ipsilateral temporal lobectomy has not been noted despite a number of reports of cranial nerve compromise under similar situations. CLINICAL PRESENTATION: A 48-year-old woman experienced complex partial seizures over three years attributable to the presence of cavernous malformations of the right temporal lobe. INTERVENTION: An anterior temporal extrahippocampal resection was performed. The surgery was marked by the need for electrocoagulation of the dural base of the temporal lobe where numerous bleeding points were encountered. Postoperatively, the patient experienced an ipsilateral maxillary division sensory loss, absence of tearing, and diminished nasal congestion for an eight-month period until resolution. CONCLUSION: Injury of the fibers of the maxillary division of the trigeminal nerve and the adjacent greater superficial petrosal nerve appears to be the cause. No prior account of such an occurrence has been published.
Electrocoagulation↗
Caspase-dependent and independent cell death in rat hepatoma 5123tc cells.
The objective of this study was to establish whether apoptosis in 5123tc rat hepatoma cells required the caspase-3 dependent pathway. Apoptosis was induced by either growth factor deprivation or treatment with a topoisomerase II inhibitor, VM26, in the absence or presence of caspase inhibitors (DEVD-fmk, z-VAD-fmk and BAF). The results indicated that, although these inhibitors at 10 microM concentration completely blocked caspase-3 activity, they had no effect on either the rate of cell death or on any other apoptotic features, e.g., chromatin condensation, DNA fragmentation, protein cleavage, suggesting that caspase-3 was not required to mediate nuclear destruction in these hepatoma cells. At higher concentrations, up to 100 microM, z-VAD-fmk and BAF, but not DEVD-fmk, did block apoptosis, however, they also caused cell swelling and membrane permeabilization, which are the hallmarks of necrotic cell death. Clearly, high concentrations of these inhibitors must have interfered non-specifically with other metabolic pathways, e.g., z-VAD-fmk at a high concentration blocked protein phosphorylation, and caused cell death by a different mechanism.
Amino Acid Chloromethyl Ketones↗
Multiple respiratory symptoms predict quality of life in chronic lung disease: a population-based study of Australian adults.
STUDY OBJECTIVES: Previous studies have shown that it is possible to improve the health-related quality of life (HRQoL) of chronic lung disease (CLD) patients without a concurrent change in morbidity. A valid CLD index that discriminates between different levels of CLD severity and is associated with HRQoL status is an important tool for primary care settings. In this study a symptom-based CLD index was assessed for its validity and relationship with HRQoL in a representative Australian population sample. The study also measured the prevalence of self-reported CLD. DESIGN: Representative population survey of adults aged 18 years and over using a multistage, systematic, clustered area sample. SETTING: Metropolitan Adelaide and country centres in South Australia with a population of over 1000 persons. PARTICIPANTS: Three hundred twenty-nine adults with CLD identified through a representative population survey of 3010 South Australians. MEASUREMENTS AND RESULTS: The CLD index and the SF-36 were administered to participants to assess the association between each subscale of the CLD index with each HRQoL scale. The CLD index was also used to assess the prevalence of CLD and the distribution of severity in self-reported CLD in the South Australian population. Each symptom sub-scale of the CLD index was significantly correlated with all scales of the SF-36. The prevalence of CLD as measured by the CLD index was 7.7% (mild), 2.2% (moderate) and 1.0% (severe). CONCLUSIONS: In the Australian context the CLD index is a reliable patient interview instrument that can be used to assess the effects of CLD on general HRQoL, improve assessment, and lead to interventions for physicians and their patients.
Adolescent↗
In-situ evaluation of barrier-cream performance on human skin using laser-induced breakdown spectroscopy.
Laser-induced breakdown spectroscopy (LIBS) was used to evaluate the effect of barrier creams (skin protective creams) on human skin. A Nd: YAG laser at 1,064 nm was used with a pulse energy of 100 mJ. A method was developed to measure the effectiveness of barrier creams against zinc ion absorption from aqueous zinc chloride solution and oil paste zinc oxide, which represent model hydrophilic and lipophilic metal compounds, respectively. Zinc was chosen since it posed no risk to human skin. 3 representative commercial barrier creams advertised as being effective against lipophilic and hydrophilic substances were evaluated by measuring zinc absorbed through the stratum corneum. 4 consecutive skin surface biopsies (SSB) were taken from biceps of the forearms of 6 volunteers at time periods of 0.5 h and 3 h after application of the protective cream. Results were compared with control skin where no barrier cream was used. The zinc atomic emission line at 213.9 nm was selected. Gate delay and gate width time was optimized to obtain the best signal-to-noise ratio (SNR) and precision. This method provided a facile and rapid screening of the effectiveness of skin barrier creams against zinc ion penetration. The barrier creams were shown to provide appreciable protection against the penetration of both ZnCl2 and ZnO into the skin.
Adult↗
Isolation and flow cytometric analysis of T-cell-depleted CD34+ PBPCs.
BACKGROUND: To extend allogeneic HPC transplantation to a greater range of patients, the use of partially matched related donors is under development. Because of the inherently higher degree of histoincompatibility in such transplants, there is increased risk of GVHD as well as of graft failure. Ex vivo depletion of donor-derived T-lymphocytes from PBPCs is one of the most effective methods of preventing GVHD. Thus far, individual centers have used custom-developed procedures to deplete the graft of T cells that are responsible for alloreactivity, often employing relatively impure, nonstandardized reagents such as soybean agglutinin and complement. In addition, with improved methods of T-cell depletion, it has been difficult to accurately assess the number of T cells remaining. Because different centers have used different protocols to assay T cells, it has been difficult to reproduce and validate the results between institutions, and this has limited direct comparison of data between centers. STUDY DESIGN AND METHODS: A standardized approach for T-cell depletion was developed by using a Good Manufacturing Practice-manufactured magnetic cell separator (Isolex 300i, Nexell Therapeutics) and commercially available OKT3 antibody. T-cell depletion was performed on PBPCs from six haploidentical donors. RESULTS: CD34+ cell recovery was 47 percent (range, 31-63%) with a median purity of 94 percent (range, 75-99%) and median T-cell log depletion of 4.72 (range, 3.90-5.83). Because this high degree of depletion makes it challenging to accurately quantitate the remaining T cells, two highly sensitive flow cytometric protocols were developed, each of which accurately detects T cells with a sensitivity of 2 per 10,000 (0.02%). The purified CD34+ cells administered to the patients (dose range, 6.13-13.50 x 10(6)/kg) provided rapid neutrophil and platelet engraftment. CONCLUSION: With the Isolex 300i and a MoAb directed against T cells, a high degree of T-cell depletion is obtained. Sensitive, accurate, and reproducible assays have now been developed for T-cell enumeration in these highly purified cell populations.
Adult↗
Transesophageal echocardiographic diagnosis of acute aortic valve insufficiency after mitral valve repair.
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Acute Disease↗
Role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass-associated acidosis.
BACKGROUND: The development of metabolic acidosis during cardiopulmonary bypass (CPB) is well recognized but poorly understood. The authors hypothesized that the delivery of pump prime fluids is primarily responsible for its development. Accordingly, acid-base changes induced by the establishment of CPB were studied using two types of priming fluid (Haemaccel, a polygeline solution, and Ringer's Injection vs. Plasmalyte 148) using quantitative biophysical methods. METHODS: A prospective, double-blind, randomized trial was conducted at a tertiary institution with 22 patients undergoing CPB for coronary artery bypass surgery. Sampling of arterial blood was performed at three time intervals: before CPB (t1), 2 min after initiation of CPB at full flows (t2), and at the end of the case (t3). Measurements of Na+, K+, Mg2+, Cl-, HCO3-, phosphate, Ca2+, albumin, lactate, and arterial blood gases at each collection point were performed. Results were analyzed in a quantitative manner. RESULTS: Immediately on delivery of pump prime fluids, all patients developed a metabolic acidosis (base excess: 0. 95 mEq/l (t1) to -3.65 mEq/l (t2) (P < 0.001) for Haemaccel-Ringer's and 1.17 mEq/l (t1) to -3.20 mEq/l (t2). The decrease in base excess was the same for both primes (-4.60 vs. -4.37; not significant). However, the mechanism of metabolic acidosis was different. With the Haemaccel-Ringer's prime, the metabolic acidosis was hyperchloremic (Delta Cl-, +9.50 mEq/l; confidence interval, 7.00-11.50). With Plasmalyte 148, the acidosis was induced by an increase in unmeasured anions, most probably acetate and gluconate. The resolution of these two processes was different because the excretion of chloride was slower than that of the unmeasured anions (Delta base excess from t1 to t3 = -1.60 for Haemaccel-Ringer's vs. +1.15 for Plasmalyte 148; P = 0.0062). CONCLUSIONS: Cardiopulmonary bypass-induced metabolic acidosis appears to be iatrogenic in nature and derived from the effect of pump prime fluid on acid-base balance. The extent of such acidosis and its duration varies according to the type of pump prime.
Acid-Base Equilibrium↗
A comparison of bolus versus continuous cardiac output in an experimental model of heart failure.
OBJECTIVE: The majority of studies examining cardiac output measurement have been done in physiologically stable models with low thermal background noise. Research comparing continuous cardiac output (CCO) with bolus thermodilution cardiac output (COTD) measures in human and animal models have reported high correlations, negligible bias, but large limits of agreement. The purpose of this project was to compare CCO with COTD measures in an experimental model of heart failure where the cardiac output values were low and the range was narrow. DESIGN: A one-group experimental design with preintervention control measures and repeated CCO and COTD measures across nine time points. SETTING: Cardiovascular research laboratory. SUBJECTS: Thirty dogs. MEASURES AND MAIN RESULTS: Univariate and multivariate versions of repeated-measures analysis were used to assess the influences of temperature, weight, and stage of the experimental protocol on CCO, COTD, and the differences between them. The two measures CCO and COTD were assessed for agreement by using methods proposed by Bland and Altman. Two hundred and fifty pairs of measurements were obtained during sinus rhythm. The range for COTD measures was 0.5-4.67 L/min and for CCO measures 1.0-5.40 L/min. Of the 250 cardiac outputs estimated by the continuous method, 73.4% of the values were within +/-15% of that estimated by the repetitive, single thermodilution method. The mean bias for the entire protocol was 0.01 (SD = 0.51) with a range of 4.33 L/min. CONCLUSION: Agreement between the two measures may be the function of biological variability, responses to anesthesia, and technique. Bland and Altman evaluation demonstrated low bias and precision and similar levels of agreement when compared with previous studies in an experimental model where the cardiac output was low and the range was narrow.
Animals↗
Adult formulation of a five component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine is safe and immunogenic in adolescents and adults.
BACKGROUND: Pertussis is increasingly recognized as an important cause of cough illness in adolescents and adults. PURPOSE: To evaluate the safety and antibody response to a single dose of an adult formulation of a five component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine (aP) combined with diphtheria and tetanus toxoids (TdaP) and inactivated poliovirus vaccine (TdaP-IPV) in adolescents and adults and to assess the response to a second dose of the acellular pertussis vaccine in a subset of the adults. POPULATION AND SETTING: The study addressed 1207 healthy participants (736 adults and 466 adolescents) recruited in five Canadian communities. STUDY DESIGN: In a randomized, observer-blind, controlled clinical trial, adult participants received Td followed at a separate visit by aP, TdaP followed by IPV or TdaP-IPV; adolescents received Td-IPV followed at a separate visit by aP or TdaP-IPV. A subgroup of adults was given a booster of aP 1 month after TdaP. OUTCOME MEASURES: Antibody titers measured before and 1 month after each immunization; adverse events enumerated at 24 h, 72 h and 8 to 10 days. RESULTS: The aP vaccine given by itself was associated with adverse events less frequently than were Td, Td-IPV, TdaP or TdaP-IPV vaccines, but reaction rates did not differ significantly among the latter products. The antibody response against Bordetella pertussis antigens was vigorous in all groups, although adults given the TdaP-IPV vaccine had lower antibody titers against filamentous hemagglutinin, pertactin, diphtheria and tetanus antibodies than those given TdaP vaccine. Similarly adolescents given TdaP-IPV had lower antibody titers against pertussis toxin, filamentous hemagglutinin, fimbriae and agglutinins than those given Td-IPV and aP alone. A second dose of acellular pertussis vaccine was not associated with increased adverse events in adults but elicited increased antibody titers over that achieved by a single dose only against pertussis toxin. CONCLUSIONS: This adult formulation five component aP vaccine given as TdaP-IPV is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.
Adolescent↗
Effects of vagus nerve stimulation on progressive myoclonus epilepsy of Unverricht-Lundborg type.
PURPOSE: A 34-year-old woman with progressive myoclonus epilepsy of Unverricht-Lundborg type was considered for vagus nerve stimulation (VNS) therapy. METHODS: After demonstration of intractability to multiple antiepileptic regimens and progressive deterioration in cerebellar function, the patient was implanted with a vagus nerve stimulator and followed for 1 year. Neurological status, seizure frequency, and parameter changes were analyzed. RESULTS: VNS therapy resulted in reduction of seizures (more than 90%) and a significant improvement in cerebellar function demonstrated on neurological examination. The patient reported improved quality of life based in part on her ability to perform activities of daily living. CONCLUSIONS: VNS therapy may be considered a treatment option for progressive myoclonus epilepsy. The effects of VNS on seizure control and cerebellar dysfunction may provide clues to the underlying mechanism(s) of action.
Adult↗