Rapid and label-free nanomechanical detection of biomarker transcripts in human RNA.

The availability of entire genome sequences has triggered the development of microarrays for clinical diagnostics that measure the expression levels of specific genes. Methods that involve labelling can achieve picomolar detection sensitivity, but they are costly, labour-intensive and time-consuming. Moreover, target amplification or biochemical labelling can influence the original signal. We have improved the biosensitivity of label-free cantilever-array sensors by orders of magnitude to detect mRNA biomarker candidates in total cellular RNA. Differential gene expression of the gene 1-8U, a potential marker for cancer progression or viral infections, has been observed in a complex background. The measurements provide results within minutes at the picomolar level without target amplification, and are sensitive to base mismatches. This qualifies the technology as a rapid method to validate biomarkers that reveal disease risk, disease progression or therapy response. We foresee cantilever arrays being used as a tool to evaluate treatment response efficacy for personalized medical diagnostics.

Mechanics and imaging of single DNA molecules.

We review recent experiments that have revealed mechanical properties of single DNA molecules using advanced manipulation and force sensing techniques(scanning force microscopy (SFM), optical or magnetic tweezers, microneedles). From such measurements, intrinsic relevant parameters (persistence length, stretch modulus) as well as their dependence on external parameters (non-physiological conditions, coating with binding agents or proteins) are obtained on a single-molecule level. In addition, imaging of DNA molecules using SFM is presented.

Cryptococcal spondylitis: solitary infective bone lesions are not always tuberculous.

Tuberculous spondylitis is a well-recognized cause of back pain and vertebral collapse due to infection and with must not be overlooked even if it is not the most likely diagnosis. If a patient, particularly one of Asian origin, were to present with a solitary destructive bone lesion, without evidence of myeloma or other malignancy, a trial of anti-tuberculous chemotherapy would be one therapeutic approach, even if there was no evidence of tuberculosis elsewhere. However, failure to biopsy the bone lesion and undertake the appropriate microbiology could lead to other important diagnoses being missed. This is illustrated by the case which we report below.

Early mobilisation of Colles' fractures. A prospective trial.

The results of a prospective controlled trial of early mobilisation of Colles' fractures in the elderly are presented. Early mobilisation produced less pain and a stronger grip. It did not lead to any greater loss of reduction of the fracture. However, there was no significant improvement in the final range of movement of the wrist. Immobilisation of the wrist for six weeks in plaster is extremely inconvenient for the elderly living alone and the patients greatly appreciated the reduction of this period of time to a minimum.

A comparison of Keller's arthroplasty and distal metatarsal osteotomy in the treatment of adult hallux valgus.

A prospective trial is reported which compares distal osteotomy of the first metatarsal with Keller's arthroplasty in the treatment of adult hallux valgus. A total of 33 patients attended for review at least three years after operation. Symptomatic improvement, as assessed by patient satisfaction, pain relief, cosmetic improvement and restoration of function, was similar in the two groups. Objective measurement showed that the range of movement of the metatarsophalangeal joint was better maintained after osteotomy, as was the relationship of the sesamoid bones to the head of the first metatarsal. Correction of the valgus deformity also was significantly better in the patients who underwent osteotomy and in these patients the first intermetatarsal angle was reduced to within normal limits. There was no evidence that initial degenerative changes or subluxation at the metatarsophalangeal joint compromised a successful result from osteotomy.

Long-term results of lumbar intervertebral disc prolapse.

A series of 40 patients is presented at least ten years following anterior spinal fusion for intervertebral disc prolapse. The proportion of patients who had complete relief or only isolated transient symptoms at the five-year review (67.5%) showed only a very slight fall over the years (65.0%). The union rate was shown to improve with time. There was no clear evidence that anterior spinal fusion led to accelerated degeneration of adjacent intervertebral discs. The significance of posterior extension of the fusion is discussed.