Assessment of deposition of inhaled aerosol in the respiratory tract of man using three-dimensional multimodality imaging and mathematical modeling.

Multimodality medical imaging enables measurement of the three-dimensional spatial distribution of a radiolabeled aerosol within the lung. Using a conceptual spatial morphological model these data may be transformed to provide information on deposition per airway generation. This methodology has been used to study the intrapulmonary deposition patterns of two formulations of a metered dose inhaler and two nebulizers in control subjects. The nebulizer study has also been stimulated using a computer model of deposition. The comparison between derived experimental results and those from computer modeling shows areas of agreement, although there are also areas of discrepancy. The new methodology has considerable potential value in the fields of inhalation therapy and deposition modeling, although more detailed validation is still required.     

Methicillin-resistant Staphylococcus aureus: investigation of a hospital outbreak using a case-control study

A retrospective case-control study of 50 MRSA-positive patients was carried out during an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) at an acute general hospital in London. Controls were randomly selected from MRSA-negative patients admitted during the outbreak period. Risk factors investigated included length of admission prior to screening, number of ward changes, main diagnosis, extent of staff contact, pressure sores, surgical and other invasive procedures and antibiotic treatment. Outcome variables examined were rates of infection (versus colonization) with MRSA and mortality. Patients with MRSA were in hospital longer before microbiological specimens were taken and moved wards more often than controls. In a logistic regression analysis, length of stay in hospital, pressure sores, physiotherapy and surgical procedures were associated with a significantly increased risk of acquiring MRSA. Odds ratios (and 95% confidence intervals) for having acquired MRSA were: 8·3 (1·02−71·43) if a patient had pressure sores; 3·7 (1·10−12·5) if they received physiotherapy; and 3·2 (1·82−10·0) if they underwent surgical procedures. The rate of clinical infection amongst patients with this strain of MRSA was 26% and included life-threatening infections such as septicaemia, underlining the potential virulence of MRSA. Surgery and physiotherapy may have been markers of debility. Physiotherapy was probably a marker of increased rates of contact with all hospital staff, and high standards of hand hygiene should be promoted amongst all staff as the most important factor in controlling an outbreak of MRSA. Good bed management is essential for hospital infection control.     

Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Error analysis by simulation studies in renography deconvolution

The renogram, defined as the time-activity curve obtained from measurements with a gamma detector over the kidneys after a prior injection of a radioactive tracer, can be quantified using the deconvolution method. Essentially all the inherent information in the renogram, the estimated relative renal uptake function and transit time spectrum through the kidney, can be derived from the computed renal retention function. This study shows how statistical and physiological noise and different backgrounds affect the accuracy of the derived parameters. Confidence intervals for the estimated relative renal function and mean transit time (MTT) are presented. The principal source of error in relative renal function was due to extrarenal background. It was found that the error in mean transit time due to statistical noise was proportional to MTT, that the presence of extrarenal background strongly affected the accuracy of the MTT, whereas the vascular background in the renogram was of minor importance. Physiological noise, interpreted as periodic changes in transit times does, strictly speaking, invalidate the deconvolution principle, but it was possible to calculate a valid mean value of the different actual transit times. The transit time spectrum, measured by differentiation of the computed retention function, was found to be of no practical value with use of the unconstrained matrix method. The signal to noise ratio and consequently the need for smoothing can be estimated from the sum of the squared second derivatives of the renogram itself. The plateau levels in the renal retention function provide a more reliable estimate for the relative function ratio than the relative amplitude of a renogram in which extrarenal background only has been subtracted.