Small cell lung carcinoma presenting with acute disseminated encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease characterised by subcortical high-signal white matter lesions on T2 weighted MRI. It most commonly occurs in children following an acute viral illness. We present a case study in which ADEM was the presenting condition in an adult female with small cell lung carcinoma. We discuss the evidence in the literature suggesting that ADEM may be viewed as a paraneoplastic syndrome.

An algorithm to standardise the investigation of the undiagnosed traumatic painful adult hip: results at one year.

INTRODUCTION: A significant number of adults present to accident and emergency departments with a painful hip following a fall. When plain radiography is non-diagnostic, it has been traditionally difficult to decide on further investigations as rapid access MRI is still unavailable in many NHS hospitals and, therefore, alternative methods of reliable investigation are required. PATIENTS & METHODS: An algorithm was designed for the management of these patients without the availability of MRI investigation. Over a 60-week period, 278 patients were admitted of whom 31 were adult patients with trauma-related hip pain with no fracture on plain radiography. RESULTS: We revealed 42% had fractures of the hip or pelvic girdle. None of the hip fractures deteriorated to a worse prognostic grade during the investigation process and no hip fractures were missed. CONCLUSIONS: This approach towards a challenging diagnostic problem has been successful in identifying all hip fractures, and no fracture has deteriorated to a worse prognostic group.

Bone extracellular matrix induces homeobox proteins independent of androgens: possible mechanism for androgen-independent growth in human prostate cancer cells.

BACKGROUND: Differences in gene expression in prostate cells are believed to be secondary to epithelial-stromal interactions. We theorized that bone matrix may provide a fertile "soil" for prostate cancer by inducing androgen-dependent genes and allowing for androgen-independent growth. METHODS: Human prostate cancer cells (LNCaP) were grown under different conditions and analyzed for differential expression of mRNA. LNCaP cells were grown in the presence of 10 nM dihydrotestosterone (DHT), on extracellular matrix (ECM) derived from bone cells (without exogenous DHT), and on plastic culture dishes without exogenous DHT. A differential display of mRNA produced by LNCaP cells grown in the above conditions was then analyzed. RESULTS: Multiple unique transcripts were present in cells that were grown in the presence of DHT and on bone ECM (without exogenous DHT), but not on plastic culture dishes without exogenous DHT. Nine of these transcripts were then cloned and analyzed. Many (5/9) of these transcripts were found to contain multiple ATTA motifs in their corresponding 3'-untranslated regions. ATTA motifs have been shown to be homeobox protein-binding sites. Homeobox proteins and their target genes are thought to regulate cellular differentiation. Consistent with this, we demonstrated by reverse transcription polymerase chain reaction (PCR) that homeobox genes were differentially expressed in LNCaP cells when the cells were grown in the presence of DHT and on bone ECM (without exogenous DHT), but not on plastic culture dishes without exogenous DHT. Furthermore, we assayed LNCaP/fetal fibroblast chimeric tumors (n = 8) that were grown in male nude mice. Some of these tumors continued to grow in these mice despite treatment with surgical castration. In blinded studies, we were able to determine which tumor samples were androgen independent by their expression of homeobox genes. All samples that were androgen independent (n = 4) expressed the homeobox genes. Finally, gel retardation assay demonstrated that the homeobox proteins were able to bind to our cloned DNA sequences. Furthermore, footprinting analysis showed that the homeobox proteins bound to the ATTA motif in the 3'-region of our target DNA. CONCLUSIONS: Bone ECM, in the absence of DHT, has the ability to regulate androgen-responsive genes. Furthermore, many of these genes contain homeobox binding sites and the expression of homeobox genes may itself be regulated by bone ECM. If so, this may partially explain the clinical observation that bone provides a fertile "soil" for prostate cancer growth and metastasis.

Is the acquisition of a separate view of the sacroiliac joints in the prone position justified in patients with back pain?

One hundred consecutive patients in whom radiographs of the sacroiliac joints had been requested concurrently with radiographs of the lumbar spine and/or pelvis were reviewed to ascertain the diagnostic value of the sacroiliac radiograph. In 92 patients, radiographs of the lumbar spine or pelvis provided complete visualization of the sacroiliac joints, 81 of which were judged normal, six abnormal, and five equivocal. Review of the specific sacroiliac radiographs confirmed the six abnormal cases, and resulted in one equivocal case being judged abnormal. In no case did the sacroiliac joint radiograph result in a normal diagnosis being changed to abnormal. Where the sacroiliac joints appear normal on a lumbar spine or pelvic radiograph, there is no diagnostic benefit, and a considerable radiation penalty, from the performance of additional radiographs specific to those joints.

Hereditary spinal osteochondromas in diaphyseal aclasia.

We present cases of cervical cord compression in father and son with diaphyseal aclasia. Both patients were investigated with plain radiography, CT and MRI. We believe this to be the first report of spinal cord compression in first-degree relatives with diaphyseal aclasia.

Aortic valvulitis complicating Wegener's granulomatosis.

In a case of Wegener's granulomatosis aortic valve replacement was performed for worsening congestive cardiac failure secondary to aortic incompetence. Two paravalvular lesions and an isolated intraleaflet deficiency of the non-coronary cusp were identified at operation. Histological changes were consistent with a connective tissue disease.

The selective isolation of novel cDNAs encoded by the regions surrounding the human interleukin 4 and 5 genes.

We have developed modifications to direct cDNA selection that allow the rapid and reproducible isolation of low abundance cDNAs encoded by large genomic clones. Biotinylated, cloned genomic DNAs are hybridized in solution with amplifiable cDNAs. The genomic clones and attached cDNAs are captured on streptavidin coated magnetic beads, the cDNAs are eluted and amplified. We have applied this protocol to a 425kb YAC that contains the human IL4 and IL5 genes. After two cycles of enrichment twenty-four cDNAs were evaluated, all of which were homologous to the YAC. DNA sequencing revealed that nine cDNAs were 100% homologous to the interferon regulatory factor 1 (IRF1) gene. Six clones were 70% homologous to the murine P600 gene, which is coexpressed with IL4 and IL5 in mouse Th2 cells. The nine remaining clones were unique within the sequence databases and were non redundant. All of the selected cDNAs were initially present at very low abundance and were enriched by as much as 100,000-fold in two cycles of enrichment. This modified selection technique should be readily applicable to the isolation of many candidate disease loci as well as the derivation of detailed transcription maps across large genomic regions.

Athletic footwear: unsafe due to perceptual illusions.

Modern athletic footwear provides remarkable plantar comfort when walking, running, or jumping. However, when injurious plantar loads elicit negligible perceived plantar discomfort, a perceptual illusion is created whereby perceived impact is lower than actual impact, which results in inadequate impact-moderating behavior and consequent injury. The objective of this study was to examine how plantar tactile (mechanical) events affect perceived plantar discomfort. Also, we evaluated the feasibility of a footwear safety standard we propose, which requires elimination of the above illusion. Twenty subjects gave numerical estimates of plantar discomfort produced by simulated locomotion (concurrent vertical (0.1-0.7 kg.cm-2) and horizontal (0.1-0.9 kg.cm-2) plantar loads), with the foot supported by either a smooth rigid surface or a rigid surface with 2 mm high rigid irregularities. Vertical or horizontal load alone evoked no discomfort (P greater than 0.05), whereas together, discomfort emanated from loads as low as 0.4 kg.cm-2. Irregularities heightened discomfort by a factor of 1.89. This suggests that the proposed safety standard is feasible, since compliance could be achieved simply by adding surface irregularities to insoles and by other changes that heighten localized plantar loads. However, until this standard is adhered to, it might be more appropriate to classify athletic footwear as "safety hazards" rather than "protective devices".

Accuracy of pedicular screw placement in vivo.

The accuracy of pedicular screw placement was assessed in 40 consecutive patients treated with the AO "Fixateur Interne." Postoperative CT scans were used to measure canal encroachment from the medial border of the pedicle, the angle of insertion and the point of entry. Eighty-one percent of the screws were placed within 2 mm of the medial border of the pedicle and 6% had 4-8 mm of canal encroachment with two patients developing minor neurological complications that spontaneously resolved. Four percent were inserted lateral to the pedicle. The parameters linked to satisfactory screw placement include entry point, angle of insertion and pedicular isthmus widths. Improvement in accuracy was noted in the latter 25% of screw insertions, reflecting the learning curve associated with this technique.

Running-related injury prevention through innate impact-moderating behavior.

The purpose of these experiments was to test the Robbins and Hanna hypothesis, which relates differences in discomfort from localized deformation at certain positions on the plantar surface to protective behavior (intrinsic foot shock absorption). A penetrometer was used to quantify the relations between localized load and pain and between load and depth of deformation. The magnitude of load required to elicit pain varied significantly (P less than 0.005) in relation to position on the plantar surface. With a load of 9 kg and a 10 mm spherical end on the penetrometer, 6% of the sample reported pain at the heelpad, 32% at the distal first digit, and 66% at the first metatarsal-phalangeal joint. This pattern was predicted by the Robbins and Hanna thesis. Two deformation patterns were observed which were best explained by deformation constraint by tight trabecular tethering of the epithelial membrane at the heelpad and distal first digit and unrestricted deformation due to loose trabecular tethering of the epithelial membrane at the first metatarsal-phalangeal joint. These data provide insight into how, when barefoot, the plantar surface resists perforation yet provides protection to local bony structures. These data further support the notion that plantar sensory feedback plays a central role in safe and effective locomotion.

Overload protection: avoidance response to heavy plantar surface loading.

Current footwear which are designed for use in running are examples of intentional biomechanical model integration into device design. The inadequacy of this footwear in protecting against injury is postulated to be due to fixation on inadequate models of locomotory biomechanics that do not provide for feedback control; in particular, an hypothesized plantar surface sensory-mediated feedback control system, which imparts overload protection during locomotion. A heuristic approach was used to identify the hypothesized system. A random series of loads (0 to 164 kg) was applied to the knee flexed at 90 degrees. In this testing system, plantar surface avoidance behavior was the difference between the sum of the leg weight and the load applied to the knee, and the load measured at the plantar surface; this was produced by activation of hip flexors. Significant avoidance behavior was found in all of the subjects (P less than 0.001). On all surfaces tested, including modern athletic footwear (P less than 0.001), its magnitude increased directly in relation to the load applied to the knee (P less than 0.001). There were significant differences in avoidance behavior in relation to the weight-bearing surfaces tested (P less than 0.05). With the identification of a feedback control system which would serve to moderate loading during locomotion, an explanation is provided as to why current athletic footwear do not protect and may be injurious; thus allowing the design of footwear which may be truly protective.

Running-related injury prevention through barefoot adaptations.

A number of reports indicate an extremely low running-related injury frequency in barefoot populations in contrast to reports about shod populations. It is hypothesized that the adaptations which produce shock absorption, an inherent consequence of barefoot activity and a mechanism responsible for the low injury frequency in unshod populations, are related to deflection of the medial longitudinal arch of the foot on loading. It is also hypothesized that the known inability of this arch of the shod foot to deflect without failure (foot rigidity) is responsible for the high injury frequency in shod populations. To evaluate these hypotheses, 17 recreational runners were analyzed to study the adaptive pattern of the medial longitudinal arch of the foot due to increased barefoot weight-bearing activity. Changes occurred in the medial longitudinal arch which allowed deflection of this arch on loading which substantiated the hypotheses. Other evidence suggests that sensory feedback largely from the glabrous epithelium of the foot is the element of barefoot activity which induced these adaptations. The sensory insulation inherent in the modern running shoe appears responsible for the high injury frequency associated with running. The injuries are considered "pseudo-neuropathic" in nature.