Prospective 12-month functional and vocational outcomes of hip arthroscopy for femoroacetabular impingement as part of an evidence-based hip pain rehabilitation pathway in an active military population.

BACKGROUND: Femoroacetabular impingement (FAI) is common with an estimated prevalence of 10-15% among young active individuals. The natural history of the disorder is progression to early osteoarthritis. Hip arthroscopy is recommended if conservative treatments fail; however, outcomes are unclear, particularly in highly active populations. AIM: To evaluate the functional and vocational outcome of hip arthroscopy, as part of an evidence-based rehabilitation hip pain pathway, for the treatment of FAI in an active military population. METHODS: All patients in the defence rehabilitation hip pain pathway, with a confirmed diagnosis of FAI who failed conservative treatment, were assessed prior to surgery and at 2, 6 and 12 months postsurgery. Outcome measures included the Visual Analogue Scale (VAS) for hip pain, Non-Arthritic Hip Score (NAHS) for function, and vocational assessments including functional activity assessment (FAA) and Joint Medical Employment Standard for military employability and deployability. RESULTS: 101 patients completed the study (mean age=33 years) (male:female:75:26) (Royal Navy/British Army/Royal Air Force: 13%/48%/39%). Outcomes demonstrated significant improvements with large effect size. Preoperative NAHS mean=62.9 (SD 16.4), 12-month postoperative NAHS mean=78.8 (18.3), mean improvement in NAHS=15.9 (95% CI 12.3 to 19.5, p<0.001). Preoperative VAS pain mean=51.3 (20.9), 12-month postoperative VAS pain=25.6 (24.5). Mean improvement 25.7 (95% CI 19.4 to 31.99, p<0.001). 73% of patients had a deployable medical category at 12 months postoperative. CONCLUSIONS: These data confirm that hip arthroscopy as part of a structured evidence-based multidisciplinary care pathway produces significant and continued symptomatic, functional and vocational improvements over a 12-month period in a military population exposed to high intensity, weight-bearing exercise in uncontrolled and unforgiving environments.

Outcomes of surgery for chronic exertional compartment syndrome in a military population.

AIM: To determine the outcome following fasciectomy for chronic exertional compartment syndrome (CECS) in the UK military, and the association between presurgical intramuscular pressure (IMP) and outcome. METHODS: All patients who underwent fasciectomy for anterior CECS were identified between 2007 and 2010. Presurgery and postsurgery military medical grading for leg function was extracted from the medical records system. The Wilcoxon signed-rank test compared grades before and after surgery. Spearman's rank correlation examined the relationship between IMP and outcome. RESULTS: Presurgery and postsurgery grading was available for 63% of patients. These patients had significantly better leg function after surgery (Z=-3.63, p<0.001). Of these, 49% improved by at least one grade, 36% showed no improvement in grading and 15% had a poorer outcome. There were no significant correlations between IMP and outcome. CONCLUSIONS: A large proportion of patients do not return to full fitness following fasciectomy in the military population. This is in line with a recent study in the US military, but conflicts with most civilian reports. The reasons for these differences are not clear. Furthermore, the lack of a relationship between IMP and outcome questions the role of pressure in this condition. These results suggest that the role of postoperative rehabilitation protocols and other conservative options should be explored.

How the study of Helicobacter infection can contribute to the understanding of carcinoma development.

The inflammatory environment dramatically impacts the formation of cancer at many levels, acting on the stem cell to foster the initiation of cancer all the way through its contribution to metastatic disease. Using Helicobacter-induced gastric cancer as an example, it can be seen that, early on, chronic inflammation exhausts tissue stem cells, forcing the remaining stem cells to work overtime and calling in replacement cells from marrow sources. Marrow-derived stromal cells orchestrate growth and remodelling through secreted factors and cell-cell communication. Once cancer is present, the inflammatory environment is responsible for the continued growth signals to the cancer stem cells and to the stromal cells which become a vital part of the cancer niche as well as the pre-metastatic niche which will effectively lure cancer cells into peripheral organs for distant growth. This understanding of the inflammatory environment and its many effects on cancer throughout its natural history provides intervention targets directed at the unique aspects of cancer behaviour.

In vivo disruption of the fas pathway abrogates gastric growth alterations secondary to Helicobacter infection.

Helicobacter infection is associated with gastric cell growth alterations, plausibly predisposing to ulcer disease and gastric adenocarcinoma. Previous investigations from our laboratory have implicated the involvement of the Fas pathway in Helicobacter-induced apoptotic signaling in vitro. In this report we use C57BL/6J00064 mice to examine the direct role of Fas signaling in Helicobacter-mediated growth alterations in vivo. Helicobacter infection up-regulated gastric cell Fas antigen (Fas Ag) mRNA and increased surface receptor expression, along with concomitant altered apoptotic and proliferative response, measured by terminal deoxytransferase-deoxyuridine 5'-triphosphate nick end labeling and 5-bromo-2'-deoxuridine immunohistochemistry, respectively. In addition, histopathological alterations, including parietal cell loss and gastric atrophy, were noted. In contrast, infection in B6. MRL-FAS(lpr), a Fas Ag knockout mouse in the C57BL/6 background, did not result in increased apoptosis, proliferation, or histological alterations, a finding that argues strongly for the role of Fas-signaling pathway in orchestrating diverse growth responses to Helicobacter infection.

Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells.

Differentiation agents use existing cellular systems to induce neoplastic cells to regain a normal phenotype and/or to cause growth arrest and therefore may offer novel chemotherapeutic approaches to treating solid tumors. In this study, we demonstrate in Caco-2 colon cancer cells that the differentiation agent phenylbutyrate (PB) causes a decrease in viable cells, an increase in cell differentiation, and a G1-S-phase block. The mechanism of this last effect is related to a PB-induced increase in p27Kip1, leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Consistent with the decreased CDK2 kinase activity, we also observed a decrease in the phosphorylation state of the retinoblastoma protein after PB treatment. This was associated with increased binding and consequent inactivation of E2F, a transactivator of genes that regulate the G1 to S phase cell cycle transition. These data suggest that the differentiation agent PB inhibits tumor growth by limiting the availability of active E2F, with a subsequent G1-S-phase block. Additional studies should show whether PB is a clinically effective therapeutic agent against colorectal cancer.

A review of a surgical ward round in a large paediatric hospital: does it achieve its aims?

The review which this paper outlines aimed to explore whether the ward round of the surgical team at Birmingham Children's Hospital achieved its objectives and to investigate the attitudes of medical and nursing staff, patients and their parents towards the round. Initial open-ended interviews generated themes from which questionnaires were constructed and administered to 16 members of the surgical team, 30 nurses, 14 patients and 24 parents. The surgical team generally felt that the round plays a valuable role whereas the nursing team expressed dissatisfaction with many aspects of the round. The majority of the surgical and nursing team thought that the round should change from its present form and a number of suggestions were made as to how changes in the round could improve the quality of the teaching experience and promote quality in patient care. Patients tended to express rather neutral feelings towards the round although a significant minority of parents expressed concerns over confidentiality and the level of anxiety felt by children. It is hoped that the results of this review will be used to inform changes in the way the round is carried out. A further review will be initiated in the future to evaluate the efficacy of any such changes.

Low temperature regulation of the Arabidopsis CBF family of AP2 transcriptional activators as an early step in cold-induced COR gene expression.

Cold-induced expression of the Arabidopsis COR (cold-regulated) genes is mediated by a DNA regulatory element termed the CRT (C-repeat)/DRE (dehydration-responsive element). Recently, we identified a transcriptional activator, CBF1, that binds to the CRT/DRE and demonstrated that its overexpression in transgenic Arabidopsis plants at non-acclimating temperatures induces COR gene expression and increases plant freezing tolerance. Here we report that CBF1 belongs to a small family of closely related proteins which includes CBF2 and CBF3. DNA sequencing of an 8.7 kb region of the Arabidopsis genome along with genetic mapping experiments indicated that the three CBF genes are organized in direct repeat on chromosome 4 at 72.8 cM, closely linked to molecular markers PG11 and m600. Like CBF1, both CBF2 and CBF3 activated expression of reporter genes in yeast that contained the CRT/DRE as an upstream activator sequence. The transcript levels for all three CBF genes increased within 15 min of transferring plants to low temperature, followed by accumulation of COR gene transcripts at about 2 h. CBF transcripts also accumulated rapidly in response to mechanical agitation. The promoter regions of the CBF genes do not contain the CRT sequence, CCGAC, and overexpression of CBF1 did not have a detectable effect on CBF3 transcript levels, suggesting that the CBF gene family is not subject to autoregulation. We propose that cold-induced expression of CRT/DRE-containing COR genes involves a low temperature-stimulated signalling cascade in which CBF gene induction is an early event.

A role for apoptosis in the pathogenesis of AIDS-related idiopathic esophageal ulcers.

Lack of understanding of the mechanism of tissue destruction associated with idiopathic esophageal ulcers (IEUs) poses a diagnostic and therapeutic dilemma for the clinician. The possible role of apoptosis in IEUs, as suggested by endoscopic and histologic observations, was investigated by examination of archival tissues for apoptosis-related DNA fragmentation using in situ nick end labeling (TUNEL). High levels of apoptosis were observed in mucosal cells immediately adjacent to IEUs. Apoptotic cells were virtually absent in normal control tissues, while the edges and bases of lesions and sloughed-off tissues in IEUs in human immunodeficiency virus (HIV)-infected patients showed elevated levels of apoptotic cell death. However, tissue samples from patients with esophageal ulcerations of known etiology showed no apoptosis of mucosal cells. These data support a role for apoptosis in the pathogenesis of IEUs and suggest a mechanism involving HIV-associated bystander killing of uninfected mucosal cells.

Inflammatory fibroid polyp of the esophagus in an HIV-infected individual: case study.

We report an unusual case of a large esophageal inflammatory fibroid polyp in a man infected with the human immunodeficiency virus complaining of dysphagia. Barium studies and computed tomography demonstrated a long, submucosal-appearing, distal esophageal mass which extended into a hiatal hernia. Inflammatory fibroid polyps should be considered in the differential diagnosis of submucosal and polypoid esophageal masses, although distinctive radiographic features are not found.

Frequency-specific auditory brainstem responses. Effective masking levels and relationship to behavioural thresholds in normal hearing adults.

Ipsilateral masking levels and normal thresholds for tone pip auditory brainstem responses (ABRs) were investigated in normal subjects for the purpose of establishing recording parameters and norms for frequency-specific tone pip ABR testing. White noise was found to effectively mask ABRs to tone pips at mean signal-to-noise ratios of between -1 and -5.5 dB [dB peak-equivalent (pe) SPL/dB SPL] depending on the tone pip frequency. ABR thresholds were established for tone pips in the presence of ipsilateral masking with high-pass filtered noise for 50-Hz tone pips and notched noise for tone pips from 1,000 to 4,000 Hz, at a nominal signal-to-noise ratio of -5 dB (i.e. with the noise SPL measured prior to filtering). Thresholds occurred between 28.6 and 36.6 dB pe SPL, equivalent to 4.4-8.8 dB nHL. ABR thresholds for masked and unmasked tone pips did not differ significantly.

Propranolol and thyroxine-induced hypertrophic rabbit hearts: effect on heart size and regional O2 supply/consumption variables.

The purpose of this study was to determine the effect of acute and chronic propranolol on heart size and regional O2 supply/consumption variables in thyroxine (T4)-treated rabbit hearts. New Zealand white rabbits were given 0.5 mg/kg T4 for 3 or 16 days with and without concomitant 2 mg/kg propranolol. Another group was given 16 days of propranolol alone and another 3-day T4 group was given 2 mg/kg propranolol 1 h before the experiment began. Another group served as control. Myocardial blood flows were determined using radioactive microspheres and small arteriolar and venous O2 saturations were determined using microspectrophotometry. Treatment with T4 for 3 or 16 days increased the heart weight/body weight ratio, myocardial blood flow, and regional O2 consumption. 16-day T4 treatment resulted in myocardial flow 195% and O2 consumption 300% above control group values. When propranolol was given chronically along with T4, heart weight/body weight ratios did not increase to the degree seen with 3 or 16 days of T4, alone. Propranolol given acutely in 3-day T4-treated animals, resulted in a reduced O2 consumption and O2 extraction, though not to the extent seen with chronic propranolol treatment of T4-treated animals. Acute propranolol treatment slightly reduced myocardial blood flow in 3-day T4-treated animals, while chronic treatment significantly reduced it. Chronic propranolol treatment in 16-day T4-treated animals resulted in a significant reduction in flow and O2 consumption. Thus, T4 treatment increased O2 consumption, flow, and heart size and these effects could be attenuated using acute and chronic propranolol.

Acoustic reflex amplitude and noise-induced hearing loss.

Acoustic reflex maximum amplitude measurements elicited both contralaterally and ipsilaterally were obtained from subjects with noise-induced hearing loss and compared with those obtained from normal-hearing subjects. The eliciting signal was a pure tone of 1 kHz presented for 1,000 ms. The groups were matched on age, sex, static immittance and ear canal volume. Acoustic reflex amplitudes were clearly reduced in noise-impaired subjects compared with normal-hearing subjects at a frequency where their hearing thresholds were normal.