Design of Case-controls Studies with Unscreened Controls

Traditionally in genetic case‐control studies controls have been screened to exclude subjects with a personal history of illness. This control group has the advantage of optimal power to detect loci involved in illness, but requires more work and may incur substantial cost in recruitment. An alternative approach to screening is to use unscreened controls sampled from the general population. Such controls are generally plentiful and inexpensive, but in general there is a risk that some may have the same disease as the cases, which will reduce power to detect associations. We have quantified the extent of this power loss, and produced mathematical formulae for the number of unscreened controls necessary to achieve the same power as a fixed sample of screened controls. The effect of using unscreened controls will also depend on the ratio of the number of screened controls to cases specified in the original study design, and this is also investigated. We have also investigated the cost‐benefits of the screened and unscreened approaches, according to variation in the relative costs of sampling screened and unscreened controls, together with genotyping costs. We have, thus, identified the range of situations in which using unscreened controls is a cost‐effective alternative to the screened control method and could be considered when designing a study. In many of the typical, real‐world situations in complex genetics, the use of unscreened controls is potentially cost‐effective and can, in general, be considered for disorders with population prevalence K_p < 0.2. With the steady reduction in genotyping costs and the availability of common sets of “population controls” this design is likely to become increasingly cost effective.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Development of a new wound dressing with antimicrobial delivery capability

A bilaminar wound dressing composed of an outer membrane and an inner three-dimensional matrix of a fabric or a sponge may be considered to constitute an ideal structure that promotes wound healing: the outer membrane prevents body fluid loss, controls water evaporation, and protects the wound surface from bacterial invasion, and the inner matrix encourages adherence by tissue growth into the matrix. Using this concept, we developed a biosynthetic wound dressing with a drug delivery capability. This medicated wound dressing is composed of a spongy sheet of a chitosane derivative and collagen mixture that is laminated to an antimicrobial-impregnated polyurethane membrane. In this study, a gentamycin sulfate-impregnated wound dressing was prepared and evaluated. The antimicrobial efficacy of this wound dressing was examined on an agar plate seeded with Pseudomonas aeruginosa. Also, the cytotoxicity of an antimicrobial released from this wound dressing was examined in an in vitro system with cultured skin substitutes. Both in vitro tests have shown that this wound dressing is capable of suppressing bacterial growth and minimizing cellular damage. In addition, in the treatment of wounds inflicted on rats and rabbits, this wound dressing was shown to be efficacious in covering full-thickness and split-thickness skin defects. Finally, the efficacy of this wound dressing was evaluated in a nonrandomized open-label study of 31 clinical cases. In 31 cases treated with this wound dressing, good or excellent wound healing was achieved.     

Use of a Strecker oesophageal stent in the treatment of benign oesophageal stricture

The use of self-expanding prostheses in the management of malignant oesophageal strictures has become well established. The majority of benign peptic oesophageal strictures can be successfully managed using endoscopic or fluoroscopically guided balloon oesophageal dilatation combined with long-term drug therapy, particularly using proton pumper inhibitors. Although endoscopic oesophageal dilatation can be performed on an outpatient basis, it requires repeated hospital visits. There is a small risk of oesophageal perforation whilst cardio-respiratory complications may be encountered during the use of intravenous sedation in an elderly population. The use of a self-expanding Strecker stent in a 98 year old woman with a benign oesophageal stricture is described.     

Novel C3 nephritic factor activity in the glomerulonephritis of staphylococcal endocarditis

A case of glomerulonephritis complicating staphylococcal endocarditis is presented. Hypocomplementaemia and a C3-activating factor in the serum suggested that the patient might have mesangiocapillary glomerulonephritis in association with C3-nephritic factor. Renal biopsy showed that this was not so and further examination of the serum factor showed that it differed from classical C3-nephritic factor because it was not an immunoglobulin. It is postulated that complement activation and glomerulonephritis in staphylococcal endocarditis may be the direct result of a bacterial product. A substance in the serum which activates C3 should be confirmed to be an immunoglobulin before the presence of classical C3-nephritic factor is assumed.     

Asbestos-related focal lung masses: manifestations on conventional and high-resolution CT scans

In 260 asbestos-exposed individuals evaluated by means of computed tomography (CT), 43 unsuspected pulmonary masses were found in 27 individuals. The masses included fissural pleural plaques (n = 10), dense fibrotic bands (n = 3), round atelectasis (n = 11), carcinomas (n = 3), and other presumed benign masses (n = 16). The most helpful features in the diagnosis of rounded atelectasis with CT were (a) contiguity to areas of diffuse pleural thickening, (b) a lentiform or wedge-shaped outline, (c) evidence of volume loss in the adjacent lung, and (d) a characteristic "comet tail" of vessels and bronchi sweeping into the margins of the mass. Less advanced areas of focal atelectasis had fewer classic features. Intrafissural pleural plaques were readily identified with high-resolution CT. In asbestos-related masses, the demonstration of stability over time is necessary. Careful interpretation of CT and high-resolution CT features and close surveillance can obviate the need for biopsy in the majority of instances.