Transient ischaemic attacks: mimics and chameleons.

Suspected transient ischaemic attack (TIA) is a common diagnostic challenge for physicians in neurology, stroke, general medicine and primary care. It is essential to identify TIAs promptly because of the very high early risk of ischaemic stroke, requiring urgent investigation and preventive treatment. On the other hand, it is also important to identify TIA 'mimics', to avoid unnecessary and expensive investigations, incorrect diagnostic labelling and inappropriate long-term prevention treatment. Although the pathophysiology of ischaemic stroke and TIA is identical, and both require rapid and accurate diagnosis, the differential diagnosis differs for TIA owing to the transience of symptoms. For TIA the diagnostic challenge is greater, and the 'mimic' rate higher (and more varied), because there is no definitive diagnostic test. TIA heralds a high risk of early ischaemic stroke, and in many cases the stroke can be prevented if the cause is identified, hence the widespread dissemination of guidelines including rapid assessment and risk tools like the ABCD2 score. However, these guidelines do not emphasise the substantial challenges in making the correct diagnosis in patients with transient neurological symptoms. In this article we will mainly consider the common TIA mimics, but also briefly mention the rather less common situations where TIAs can look like something else ('chameleons').

At-Home Administration of Gantenerumab by Care Partners to People with Early Alzheimer's Disease: Feasibility, Safety and Pharmacodynamic Impact.

BACKGROUND: Monoclonal antibodies that target amyloid-beta and remove amyloid plaques can slow cognitive and functional decline in early Alzheimer's disease. Gantenerumab is a subcutaneously administered fully-human anti-amyloid-beta monoclonal antibody with highest affinity for aggregated amyloid-beta. Since the phase 3 GRADUATE trials did not meet the primary endpoint (change from baseline to Week 116 in Clinical Dementia Rating scale - Sum of Boxes), development of gantenerumab in sporadic Alzheimer's disease was stopped and all ongoing trials were terminated early due to sponsor decision. Subcutaneous administration at the clinic or at home by care partner would be an important option for other therapies in this class in order to increase flexibility and reduce overall burden. The insights obtained from the experience with gantenerumab home administration by care partner in the phase 2 GRADUATION trial will serve to guide the ongoing efforts with other anti-amyloid-beta antibodies. OBJECTIVES: To evaluate the pharmacodynamic effects on brain amyloid load of once weekly subcutaneous administration of gantenerumab and the safety and feasibility of home administration by care partners. DESIGN: Phase 2, open-label, single arm study. SETTING: Multicenter trial conducted in 33 sites in 8 countries from November 2020 to March 2023. PARTICIPANTS: Participants aged 50 to 90 with early symptomatic Alzheimer's disease (mild cognitive impairment/mild dementia due to Alzheimer's disease), and evidence of amyloid positron emission tomography positivity. INTERVENTION: Participants could receive up to 255 mg gantenerumab once-weekly, administered subcutaneously at site or at home by healthcare professionals or non-healthcare-professional care partners. MEASUREMENTS: The primary endpoint was the change from baseline to Week 52 and to Week 104 in brain amyloid load as measured by PET centiloid levels. The secondary endpoints were responses to the home administration questionnaire, plasma concentrations and safety. RESULTS: The overall number of participants enrolled was 192, with a mean (standard deviation) amyloid PET load at baseline of 101.80 (29.80) centiloids. At the time of early study termination by sponsor, 149 participants had valid Week 52 amyloid PET data (primary endpoint), and 12 participants had an early termination PET within the pre-defined time range of Week 104. The mean change in amyloid PET from baseline to Week 52 and Week 104 was -26.19 centiloids (range: -75.6-15.8; n=149) and -35.48 centiloids (range: -63.2--7.0; n=12), respectively. Responses to the home administration questionnaire at Week 52 (n=148) indicated that the majority of care partners (88-97%) considered administration of study drug at home easy (30.4%) or very easy (57.4%), and convenient (25.7%) or very convenient (70.9%). Care partners felt confident (31.1%) or very confident (62.2%) and satisfied (29.7%) or very satisfied (64.9%) with giving the injection at home. Responses by care partners at Week 36 (n=72), Week 76 (n=126) and Week 104 (n=29) and participant (patient) assessment of convenience and satisfaction at these time points were similar. There were no new safety findings associated with gantenerumab administered subcutaneously once weekly at 255 mg or safety issues associated with at-home injections by non-healthcare professional care partners. CONCLUSIONS: Once-weekly subcutaneous home administration of the anti-amyloid-beta antibody gantenerumab by non-healthcare-professional care partners to participants with early Alzheimer's disease was feasible, safe, well tolerated, and considered as a convenient option by both the care partners and participants with Alzheimer's disease. Although gantenerumab's development has been stopped due to lack of efficacy, this approach has the potential to reduce the frequency of hospital/outpatient clinic visits required for treatment with other anti-amyloid-ß antibodies and can increase flexibility of drug administration for people living with Alzheimer's disease and their families.

Characteristics of intracerebral haemorrhage associated with COVID-19: a systematic review and pooled analysis of individual patient and aggregate data.

BACKGROUND AND PURPOSE: There are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19. METHODS: We systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data. RESULTS: We included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53-67) years and 64% (95% CI 54-73.7%) were male; 79% (95% CI 70.0-86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3-76.0%), and of multifocal ICH was 36% (95% CI 26.4-47.0%). 71% (95% CI 61.0-80.4%) of patients were treated with anticoagulation (58% (95% CI 48-67.8%) therapeutic). The median NIHSS was 28 (IQR 15-28); mortality was 54% (95% CI 43.7-64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (n = 63,390) was 0.38% (95% CI 0.22-0.58%). CONCLUSIONS: Our data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials.

The role of sex steroids in controlling pubertal growth.

Longitudinal growth, which is primarily due to chondrocytic activity at the level of the epiphyseal growth plate, is influenced by many hormones and growth factors in an endocrine and paracrine manner. Their influence is even more complex during the accelerated growth period of puberty that accounts for about 20% of final adult height. Although abnormalities of growth during puberty are very common, the underlying mechanisms that govern the beginning and cessation of pubertal growth at the level of the growth plate are poorly understood. Sex steroids play a crucial role in pubertal growth both at the systemic level via the GH/IGF-1 axis and at the local level of the epiphyseal growth plate. In both sexes it is now accepted that oestrogen is the critical hormone in controlling growth plate acceleration and fusion. This paper reviews the mechanisms that influence pubertal growth and the problems that are associated with disorders of gonadal function.

Calcium regulation in neurons: transport processes.

The ionic stoichiometry of the major Ca2+ transport mechanisms in neurons is still a matter for debate. The past year has seen some particularly interesting developments in this field, not least the finding that the neuronal Na(+)-Ca2+ exchange may be able to transport K+.

Behavior and treatment in frontotemporal dementia.

Behavioral syndromes are central to the clinical presentation of frontotemporal dementia. The authors review the behavioral changes seen in frontotemporal dementia and describe pharmacologic interventions for these behavioral syndromes.

Differentiating frontal and temporal variant frontotemporal dementia from Alzheimer's disease.

OBJECTIVE/BACKGROUND: To determine whether difficulty in the early differentiation between frontotemporal dementia (FTD) and AD may arise from a failure to discriminate between the temporal and frontal variants of FTD. METHODS: Neuropsychological profiles of patients with early dementia of Alzheimer type (DAT; n = 10), the temporal variant of FTD (tv-FTD or semantic dementia; n = 5), and the frontal variant of FTD (fv-FTD; n = 10) were compared to each other and normal controls (n = 10). Structural MRI demonstrated temporal lobe atrophy in the tv-FTD patients and frontal lobe atrophy in the fv-FTD group. RESULTS: Subjects with tv-FTD showed severe deficits in semantic memory with preservation of attention and executive function. Subjects with fv-FTD showed the reverse pattern. Attention and executive function impairment separated the fv-FTD patients from the early DAT subjects, who were densely amnesic. CONCLUSION: The double dissociation in performance on semantic memory and attention/executive function clearly separated the temporal and frontal variants of FTD and aids the early differentiation of FTD from AD. The characteristic cognitive profiles reflect the distribution of pathology within each syndrome and support the putative role of the inferolateral temporal neocortex in semantic memory, the medial temporal lobe structures of the hippocampal complex in episodic memory, and the frontal lobes in executive function.

Patterns of brain atrophy in frontotemporal dementia and semantic dementia.

OBJECTIVE: To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD). METHODS: Twenty patients with FTLD were classified as having FTD (N = 8) or SemD (N = 12) based on current clinical criteria. Both groups showed a similar spectrum of behavioral abnormalities, as indicated by the neuropsychiatric inventory. T1-weighted MRI was obtained for each patient and 20 control subjects. The regions of focal gray matter tissue loss associated with both FTD and SemD, as well as those differing between the two groups were examined using voxel-based morphometry. RESULTS: Regions of significant atrophy seen in both groups were located in the ventromedial frontal cortex, the posterior orbital frontal regions bilaterally, the insula bilaterally, and the left anterior cingulate cortex. The FTD, but not the SemD, group showed atrophy in the right dorsolateral frontal cortex and the left premotor cortex. The SemD, but not the FTD, group showed tissue loss in the anterior temporal cortex and the amygdala/anterior hippocampal region bilaterally. CONCLUSIONS: Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups. The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD may underlie some the behavioral symptoms seen in the two disorders.

The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer's disease: relationship to episodic and semantic memory impairment.

The development of cholinergic therapies for Alzheimer's disease (AD) has highlighted the importance of understanding the role of attentional deficits and the relationship between attention and memory in the earliest stages of the disease. Variability in the tasks used to examine aspects of attention, and in the disease severity, between studies makes it difficult to determine which aspects of attention are affected earliest in AD, and how attentional impairment is related to other cognitive modules. We tested 27 patients in the early stages of the disease on the basis of the MMSE (minimal 24-30 corresponding to minimal cognitive impairment, very mild or possible AD in other classifications; and mild 18-23) on a battery of attentional tests aimed to assess sustained, divided, and selective attention, plus tests of episodic memory, semantic memory, visuoperceptual and visuospatial function, and verbal short-term memory. Although the mildly demented group were impaired on all attentional tests, the minimally impaired group showed a preserved ability to sustain attention, and to divide attention based on a dual-task paradigm. The minimally demented group had particular problems with response inhibition and speed of attentional switching. Examination of the relationship between attention and other cognitive domains showed impaired episodic memory in all patients. Deficits in attention were more prevalent than deficits in semantic memory suggesting that they occur at an earlier stage and the two were partially independent. Impairment in visuoperceptual and visuospatial functions and verbal short-term memory were the least common. Although attention is impaired early in AD, 40% of our patients showed deficits in episodic memory alone, confirming that amnesia may be the only cognitive deficit in the earliest stages of sporadic AD.

Elevated nicotine levels in patients undergoing hemodialysis. A role in cardiovascular mortality and morbidity?

The incidence of cardiovascular disease in patients with end-stage renal disease undergoing long-term maintenance hemodialysis is excessively high. The reason for this excess morbidity and mortality has remained unclear. Cigarette smoking is one factor that has been associated with increased cardiovascular risk. To learn more about the effects of tobacco smoking in these patients, nicotine levels were assayed in the serum of 10 patients with end-stage renal disease undergoing maintenance hemodialysis. Specimens were obtained before and after smoking one cigarette and following dialysis or an equivalent period in control subjects. Serum nicotine levels (+/-SEM) in control subjects measured 19.0 +/- 7.2 ng/ml initially, 36.1 +/- 8.2 ng/ml after smoking, and 9.3 +/- 3.5 ng/ml after a period of 4.35 hours. These compare with respective values of 76.6 +/- 16.8 ng/ml (p less than 0.004), 132.9 +/- 19.7 ng/ml (p less than 0.001), and 51.9 +/- 10.5 ng/ml (p less than 0.001) in patients undergoing hemodialysis. These data demonstrate markedly higher nicotine levels in hemodialysis patients compared with control subjects, which may have serious implications regarding morbidity and mortality.

Radiation dose from breastfeeding following administration of thallium-201.

UNLABELLED: Radiation exposure to a breast feeding infant was estimated when the mother underwent a nuclear medicine procedure using 201Tl. METHODS: A lactating mother was administered 111 MBq of 201Tl for a brain scan. Breast milk samples were collected over a period of three days, and the rate of 201Tl secretion was determined. The infant was not breast fed during that time. Based on our data, we determined the time-activity function for radioactivity in the breast milk. From these data, and assuming an intake of 1000 ml/day, we calculated the fraction of administered activity that might be taken in by the infant. We also calculated the intake assuming breastfeeding delays of 2, 24, 48, 72, 96 and 500 hr. RESULTS: We calculated the radiation dose to various organs and the effective dose to an infant and a 1-yr-old for breastfeeding delays of 2 to 500 hr. The effective dose to a 1-yr-old from an administration of 111 MBq of 201Tl to the mother ranged from 0.90 mSv to 0.00072 mSv, and the effective dose to a newborn ranged from 1.6 mSv to 0.0013 mSv depending on delay time. CONCLUSION: Our estimates of radiation exposure to an infant from breastfeeding indicate that in this case, a 1-yr-old would have received less than the NCRP's proposed limit on annual effective dose to members of the general public of 1 mSv with a 48-hr delay and no restrictions on holding the child. A newborn would have received less than the proposed infrequent exposure limit of 5 mSv without any delay or restrictions in breastfeeding.

Effects of positive end-expiratory pressure on oscillated flow rate during high-frequency chest compression.

OBJECTIVE: To investigate the effects of positive end-expiratory pressure (PEEP) on end-expiratory lung volume (EELV) and mean oscillated flow rate (VOSC) during high-frequency chest compression (HFCC) in normal subjects and patients with severe COPD. DESIGN: Comparative study. SETTING: Pulmonary function and lung mechanics laboratory, University of Alberta Hospitals. PARTICIPANTS: Six normal subjects (five male; one female) and six patients with clinically stable COPD (five male; one female) with hypercapnia. INTERVENTIONS: A pneumatic vest system was operated at 10 Hz with a mean chest wall pressure of 16 cm H2O to provide the HFCC. A closed-circuit spirometer system permitted measurement of HFCC- and PEEP-induced changes in EELV that were expressed as per cent baseline functional residual capacity (FRC). An isothermic chamber connected near the mouthpiece permitted measurement of VOSC. RESULTS: For the normal subjects, HFCC caused a significant decrease in EELV to 82.0% of FRC (p < or = 0.01) and the addition of 4.8+/-0.5 cm H2O of PEEP during HFCC increased EELV to 97.5% FRC. In the COPD patients, HFCC decreased EELV to 92.3% of FRC (p < or = 0.01), and the addition of 3.7+/-1.0 cm H2O of PEEP increased EELV to 98.4% FRC. For the normal subjects, increasing EELV to near FRC caused VOSC during expiration to increase 14.6% (p < or = 0.01), but there was no significant effect on VOSC during inspiration (5.1% increase). In the COPD patients, PEEP increased VOSC during both inspiration (30.5%) and expiration (57.0%) (both, p < or = 0.01). CONCLUSIONS: Addition of a modest amount of PEEP during HFCC prevents the decrease in EELV and increases VOSC during both phases of spontaneous breathing in COPD patients. This higher VOSC during HFCC+PEEP may improve the effectiveness of HFCC in clearing mucus from the lungs of patients with airway disease.

Regional impairment of mucociliary clearance in chronic obstructive pulmonary disease.

Asthmatic subjects with tidal expiratory flow limitation have mucociliary clearance (MC) impairment in central airways. Because tidal flow limitation develops in COPD, it is possible that regional MC in these patients also may be affected. We tested this hypothesis by measuring MC in the presence or absence of flow limitations. Patients with COPD and chronic flow limitation were compared with non-flow-limited normal volunteers. Deposition was normalized for regional lung volume and expressed as the specific central to peripheral (sC/P) ratio. In COPD subjects, clearance from the whole lung and central airways was significantly different from that of normal subjects after 20 min of observation. In the peripheral airways, there were no significant differences between COPD and normal subjects. An alternative analysis of regional MC indicated patients retained particles in central airways while normal subjects, with intact MC, emptied central airways. Thus, COPD subjects with tidal expiratory flow limitation have impaired MC in their central airways.

Targeting HDL-mediated cellular cholesterol efflux for the treatment and prevention of atherosclerosis.

The hallmark of the atherosclerotic lesion is the overaccumulation of cholesterol in arterial wall cells. As no pathway exists for the degradation of cholesterol in peripheral cells, a mechanism is necessary to prevent its accumulation to toxic levels in these cells and to allow its delivery to the liver for excretion in bile. Promoting this reverse cholesterol transport pathway is believed to be the main cardioprotective action of high density lipoprotein (HDL). The rate-limiting step in this pathway is likely the initial removal of cholesterol from peripheral cells by HDL. The pathway HDL utilizes for inducing efflux of excess cellular cholesterol represents an important and as-yet untapped mechanism to employ for the treatment and prevention of atherosclerotic vascular disease. This review summarizes the potential cardioprotective actions of HDL, the mechanisms of HDL-mediated cellular cholesterol efflux, and evidence that the specific pathway of cholesterol removal by HDL may be enhanced and used as a novel target in the therapy of atherosclerosis.

Improved pulmonary distribution of recombinant human Cu/Zn superoxide dismutase, using a modified ultrasonic nebulizer.

Prophylactic, intratracheal instillation of recombinant human Cu/Zn superoxide dismutase (rhSOD) has been shown to lessen lung injury produced by 48 h of hyperoxia and mechanical ventilation in neonatal piglets. However, instillation of small volumes of rhSOD intratracheally would not be expected to result in uniform pulmonary distribution. Aerosolization is a technique that may improve pulmonary distribution of drugs, but is limited by the poor efficiency of most nebulizers. A newly modified ultrasonic nebulizer was tested to assess pulmonary distribution of rhSOD compared to that achieved by intratracheal instillation. rhSOD was dual-labeled with technetium-99m (99mTc) and a fluorescent analog (permitting quantitative and qualitative assessments of pulmonary distribution), and administered to neonatal piglets by intratracheal instillation or by aerosolization. Intratracheal instillation of rhSOD to piglets when supine resulted in nonuniform distribution, with most of the drug being found in the right caudal lobe, and localized in airways. Placing animals in 30 degrees of Trendelenburg and administering half the dose in the left and half in the right lateral decubitus positions improved distribution, but alveolar deposition remained patchy. Aerosolization using a modified ultrasonic nebulizer uniformly delivered 45.8 +/- 3.8% of the rhSOD to the lungs that had been placed in the nebulizer. The rhSOD was still active and present in airways and alveoli in a homogeneous fashion. We conclude that intratracheal instillation of rhSOD in small volumes results in nonuniform pulmonary distribution, while aerosolization enhances rhSOD distribution and alveolar deposition. This has important implications for ongoing clinical trials of rhSOD for the prevention of acute and chronic lung injury in premature neonates.

The viral safety of intravenous immunoglobulin.

Human immunoglobulin for intravenous (IV) use has an established safety record with regard to transmission of hepatitis B virus. The bulk of available evidence also suggests that the human immunodeficiency virus (HIV) is not transmitted by IV immunoglobulin. There has been one report, however, of isolation of HIV from two patients with hypogammaglobulinaemia who had been treated with several immunoglobulin products. Certain IV immunoglobulin products have transmitted non-A, non-B (NANB) hepatitis but careful clinical assessment of recipients of other products suggests that non-infective preparations can be made. Interpretation of available data most likely to be correct is that contamination with NANB is reduced but not eliminated by cold-ethanol fractionation and that the use of further virucidal procedures in the finishing of immunoglobulin products will confer a higher degree of safety.

Ultrasound of the thyroid gland in the newborn: normative data.

OBJECTIVE: To establish reference ranges for thyroid length, breadth, depth, and volume in healthy term Scottish infants. DESIGN: Prospective observational study of 100 (49 male) neonates. Length, breadth, and depth were measured, and the volume of each lobe was calculated using the formula for a prolate ellipsoid (volume = length x breadth x depth x pi/6). RESULTS: All measurements showed gaussian distribution, with no significant differences between the right and the left lobes. Values (mean (SD) range) were: length (cm), 1.94 (0.24) 0.9-2.5; breadth (cm), 0.88 (0.16) 0.5-1.4; depth (cm), 0.96 (0.17) 0.6-2.0; volume (ml), 0.81 (0.24) 0.3-1.7; combined volume (ml), 1.62 (0.41) 0.7-3.3. Although there was no difference in mean volume between right and left lobes, there was considerable variation (-0.8 to + 0.7 ml) between the two lobes in individual babies. CONCLUSIONS: Both lobes should be measured to give a combined volume. Our findings provide a reference against which thyroid hypoplasia or goitre can be evaluated.

Technetium 99m radiolabeling of aerosolized drug particles from metered dose inhalers.

To assess mechanisms of bronchodilation and effectiveness of metered dose inhalers, it may be useful to determine sites of drug deposition in the lung. To establish suitable test aerosols, two brands of metered dose inhalers containing bronchodilator (Brethaire, Proventil) were radiolabeled with technetium ( 99mTc) and tested to determine if the distribution of radioisotope in the aerosol was representative of the distribution of agonist activity. Cascade impaction was used to determine the particle size distribution of the radioisotope and drug aerosols by assaying each state of the cascade using scintillation and HPLC techniques. Possible influences of the radiolabeling method and delivery techniques on the particle distribution were assessed by analyzing distributions from nonradiolabeled inhalers using HPLC. For these drugs, there was an excellent correlation between the distribution of radioactivity and the drug within the captured aerosol (Brethaire r = 0.994, Proventil r = 0.998, 20 - 200 consecutive puffs). Distributions were close to log-normal and differences in mass median aerodynamic diameter (MMAD) between the radioisotope and agonist activities were not significant (Brethaire, MMAD +/- sigma g, radiolabel vs drug = 4.7 +/- 2.1 mum, vs 4.4 +/- 1.7 mum, and Proventil, 2.5 +/- 2.1 mum, vs 2.4 +/- 2.0 mum. Non-labeled inhalers produced similar drug distributions (Brethaire, 4.2 +/- 1.8 mum, and Proventil 2.0 +/- 1.9 mum). Pausing between actuations resulted in slightly smaller distributions (Brethaire, 3.6 +/- 1.8 mum, Proventil 1.8 +/- 1.8 mum, 20 puffs-60 sec pauses) but the differences were not significant. In addition, to search for multimodal distributions and assess the accuracy of the MMAD measurement via our cascade impactor (Delron), we also measured the distribution of the mass of material within the aerosols using a weight-sensitive cascade (California Measurements). Using the latter device (1 puff), the mass distributions of both aerosols were similar to the values obtained from the puffs with pauses (Brethaire 3.8 +/- 2.3 mum, Proventil 1.4 +/- 2.2 mum). Multi-modal distributions were not found. By all assessments, the distributions were nearly log-normal with drug activity well described by the radiolabel.

Relationship between tracheobronchial particle clearance rates and sites of initial deposition in man.

Mucociliary clearance was compared in three groups of normal subjects; each group inhaled a different type of aerosol (sebecate, iron oxide, and aqueous) labelled with 99Tc, to determine the relationship between deposition pattern and the subsequent total lung clearance. Standardization for deposition was accomplished by measuring a central to peripheral ratio (C/P) of deposited radioactivity in the thorax. Lung particle retention at 30, 60, 90, 120 min, and 24 h was measured, and compared at each time period to the C/P ratio. A linear relationship between the retention of aerosol at each time period and the C/P ratio was seen among all aerosols, e.g., aerosol with high C/P ratios had less retention of aerosol at a given time period than aerosols with more diffuse deposition patterns and lower C/P ratios. Furthermore, the relationship was similar to that of the more traditional measurement of regional deposition, the 24-h percentage retention. Lung particle retention was compared among aerosols, using analysis of covariance to standardize for C/P ratio. The intersubject variability was similar among all three aerosol groups. Thus, mucociliary clearance can be standardized in healthy subjects by using an initial deposition index, the C/P ratio, with similar accuracy to the 24-h percentage retention, as an index of aerosol deposition. The use of the C/P ratio, however, has distinct advantages over the 24-h retention, in that studies can be conveniently shortened, used with short lived isotopes, and be adapted to techniques investigating lung permeability instead of tracheobronchial clearance. An unexpected finding was the more rapid clearance of sebecate particles, compared with iron oxide or aqueous particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Steroid cover in dentistry: recommendations following a review of current policy in UK dental teaching hospitals.

This article reports a project that was undertaken to determine current UK dental hospital policy with regard to the management of patients taking therapeutic doses of corticosteroids receiving dental treatment under local anaesthesia. There is variation in the medical management of this patient group, and whether practice should be standardized by means of a national policy document warrants consideration.