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Biomedical subjects

John Hunter

Publications and source records attributed to John Hunter.

At least 19 recordsLinked to original sources

Parkinson's disease and driving ability.

OBJECTIVES: To explore the driving problems associated with Parkinson's disease (PD) and to ascertain whether any clinical features or tests predict driver safety. METHODS: The driving ability of 154 individuals with PD referred to a driving assessment centre was determined by a combination of clinical tests, reaction times on a test rig and an in-car driving test. RESULTS: The majority of cases (104, 66%) were able to continue driving although 46 individuals required an automatic transmission and 10 others needed car modifications. Ability to drive was predicted by the severity of physical disease, age, presence of other associated medical conditions, particularly dementia, duration of disease, brake reaction, time on a test rig and score on a driving test (all p<0.001). The level of drug treatment and the length of driving history were not correlated. Discriminant analysis revealed that the most important features in distinguishing safety to drive were severe physical disease (Hoehn and Yahr stage 3), reaction time, moderate disease associated with another medical condition and high score on car testing. CONCLUSIONS: Most individuals with PD are safe to drive, although many benefit from car modifications or from using an automatic transmission. A combination of clinical tests and in-car driving assessment will establish safety to drive, and a number of clinical correlates can be shown to predict the likely outcome and may assist in the decision process. This is the largest series of consecutive patients seen at a driving assessment centre reported to date, and the first to devise a scoring system for on-road driving assessment.

Age Factors↗

Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice.

Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the variable onset and non-visible nature of prostate tumor development limit their use for such applications. We now report the generation of a transgenic reporter mouse that should obviate these limitations by enabling noninvasive in vivo bioluminescence imaging of normal and spontaneously transformed prostate tissue in the mouse. We used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to achieve specific and robust expression of firefly luciferase in the prostate glands of transgenic mice. Ex vivo bioluminescence imaging and in situ hybridization analysis confirmed that luciferase expression was restricted to the epithelium in all four lobes of the prostate. We also show that PSA-Luc mice exhibit decreased but readily detectable levels of in vivo bioluminescence over extended time periods following androgen ablation. These results suggest that this reporter should enable in vivo imaging of both androgen-dependent and androgen-independent prostate tumor models. As proof-of-principle, we show that we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can be successfully used to image tumor response to androgen ablation in transgenic mice and, as a result, that we can rapidly identify individual animals capable of sustaining tumor growth in the absence of androgen.

Androgens↗

Functional holography analysis: simplifying the complexity of dynamical networks.

We present a novel functional holography (FH) analysis devised to study the dynamics of task-performing dynamical networks. The latter term refers to networks composed of dynamical systems or elements, like gene networks or neural networks. The new approach is based on the realization that task-performing networks follow some underlying principles that are reflected in their activity. Therefore, the analysis is designed to decipher the existence of simple causal motives that are expected to be embedded in the observed complex activity of the networks under study. First we evaluate the matrix of similarities (correlations) between the activities of the network's components. We then perform collective normalization of the similarities (or affinity transformation) to construct a matrix of functional correlations. Using dimension reduction algorithms on the affinity matrix, the matrix is projected onto a principal three-dimensional space of the leading eigenvectors computed by the algorithm. To retrieve back information that is lost in the dimension reduction, we connect the nodes by colored lines that represent the level of the similarities to construct a holographic network in the principal space. Next we calculate the activity propagation in the network (temporal ordering) using different methods like temporal center of mass and cross correlations. The causal information is superimposed on the holographic network by coloring the nodes locations according to the temporal ordering of their activities. First, we illustrate the analysis for simple, artificially constructed examples. Then we demonstrate that by applying the FH analysis to modeled and real neural networks as well as recorded brain activity, hidden causal manifolds with simple yet characteristic geometrical and topological features are deciphered in the complex activity. The term "functional holography" is used to indicate that the goal of the analysis is to extract the maximum amount of functional information about the dynamical network as a whole unit.

Algorithms↗

Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial.

OBJECTIVE: Laparoscopic paraesophageal hernia repair (LPEHR) is associated with a high recurrence rate. Repair with synthetic mesh lowers recurrence but can cause dysphagia and visceral erosions. This trial was designed to study the value of a biologic prosthesis, small intestinal submucosa (SIS), in LPEHR. METHODS: Patients undergoing LPEHR (n = 108) at 4 institutions were randomized to primary repair -1 degrees (n = 57) or primary repair buttressed with SIS (n = 51) using a standardized technique. The primary outcome measure was evidence of recurrent hernia (> or =2 cm) on UGI, read by a study radiologist blinded to the randomization status, 6 months after operation. RESULTS: At 6 months, 99 (93%) patients completed clinical symptomatic follow-up and 95 (90%) patients had an UGI. The groups had similar clinical presentations (symptom profile, quality of life, type and size of hernia, esophageal length, and BMI). Operative times (SIS 202 minutes vs. 1 degrees 183 minutes, P = 0.15) and perioperative complications did not differ. There were no operations for recurrent hernia nor mesh-related complications. At 6 months, 4 patients (9%) developed a recurrent hernia >2 cm in the SIS group and 12 patients (24%) in the 1 degrees group (P = 0.04). Both groups experienced a significant reduction in all measured symptoms (heartburn, regurgitation, dysphagia, chest pain, early satiety, and postprandial pain) and improved QOL (SF-36) after operation. There was no difference between groups in either pre or postoperative symptom severity. Patients with a recurrent hernia had more chest pain (2.7 vs. 1.0, P = 0.03) and early satiety (2.8 vs. 1.3, P = 0.02) and worse physical functioning (63 vs. 72, P = 0.03 per SF-36). CONCLUSIONS: Adding a biologic prosthesis during LPEHR reduces the likelihood of recurrence at 6 months, without mesh-related complications or side effects.

Aged↗

Predicting those who will walk after rehabilitation in a specialist stroke unit.

OBJECTIVE: To establish whether the ability to use a wheelchair shortly after a stroke or continence are related to the likelihood of walking by time of discharge. DESIGN AND SUBJECTS: An observational study in patients admitted to a stroke rehabilitation unit for under-65s over a three-year period. METHODS: Functional Independence Measure (FIM) subscores for walking were examined on all patients at time of admission and discharge. Walking was defined by an FIM > or = 5 in that section. Comparisons were then made between those who could self-propel a wheelchair within a week of admission with those who could not. Continence (defined by an FIM subscore of > or = 6 in that category) was also correlated to walking at discharge. MAIN OUTCOME MEASURE: Walking at time of discharge defined by an FIM > or = 5 in that section. RESULTS: From 393 admissions, 135 were excluded because they could already walk (FIM subscore > or = 5 in that particular section) and three died during their admission. Out of the remaining 255 patients, 108 could self-propel on admission and 147 could not. While 105 (97%) of the self-propellors could walk by time of discharge, only 91 (62%) of the non-propellors could do so (chi2 = 42.237, df = 1, P < 0.001, odds ratio (OR) 21.54 (6.52-71.51)). Although continence also predicted improved likelihood of walking, this was at a lower level of significance and correspondingly lower odds ratio (chi2=5.894, df = 1, P= 0.015, OR 1.94 (1.13-3.32)). CONCLUSIONS: The ability to self-propel a wheelchair shortly after a stroke is a significant predictor of eventually being able to walk. Our data suggest that it is even more significant than continence, which is the most consistent predictor previously found.

Humans↗

Extracranial meningioma presenting as a neck mass in a patient with underlying ankylosing spondylitis.

Extracranial meningiomas are rare. They account for only 2% of meningiomas compared to the much more common intracranial site. We describe a rare case of extracranial meningioma presenting as a neck lump in a patient with preexisting neck disease due to ankylosing spondylitis. Extracranial meningioma should be considered in the differential diagnosis of atypical neck lumps. Investigations including magnetic resonance imaging and histopathology are discussed, as well as the results of a literature review on extracranial meningiomas.

Diagnosis, Differential↗

The interrater variation of ED abdominal examination findings in patients with acute abdominal pain.

OBJECTIVE: The physical examination of the abdomen is crucial to emergency department (ED) management of patients with abdominal pain. We sought to determine the interrater variation between attending and resident physicians in detecting abdominal exam findings. METHODS: Research enrollers surveyed attending and resident physicians on abdominal exam findings in the ED in patients with abdominal pain. Strength of agreement was calculated using the kappa statistic. RESULTS: A convenience sample of 122 surveys was completed. Calculated kappa results are in parentheses. There was almost perfect agreement on the presence of masses and substantial agreement on the need for imaging studies. There was moderate agreement on guarding, distension, tenderness, and need for laboratory tests and surgical consultation. For 88 (72%) patients with tenderness, substantial agreement was calculated for epigastric tenderness, moderate agreement on right upper quadrant, supraumbilical, suprapubic, left lower quadrant, right lower quadrant tenderness, and fair agreement on left upper quadrant tenderness. Sixty-one (50%) patients received pain medicine in the ED. Among those, there was fair agreement on a presence of a surgical abdomen. Upper level resident physicians noted a higher level of agreement with the attending physician for tenderness than junior resident physicians. CONCLUSIONS: There was moderate agreement between resident and attending physicians for most of the findings in patients with abdominal pain. Recognition that selected findings are more variable than others should encourage careful confirmation of resident physicians' assessments in teaching settings.

Abdominal Pain↗

Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy.

The effects of probiotic supplementation on the intestinal re-growth microbiota following antibiotic therapy were studied in a double-blind placebo-controlled study. In the placebo group, numbers of facultative anaerobes and enterobacteria increased significantly, and at day 35 the numbers were significantly higher in the placebo group than in the active group; in the active group, the numbers of bacteroides increased significantly. Although the numbers of enterococci in both groups did not change, in the placebo group the number of patients harbouring antibiotic-resistant enterococci post therapy increased significantly. There was no change in the incidence rate of antibiotic resistance among the patients in the probiotic group.

Anti-Bacterial Agents↗

General mental ability in the world of work: occupational attainment and job performance.

The psychological construct of general mental ability (GMA), introduced by C. Spearman (1904) nearly 100 years ago, has enjoyed a resurgence of interest and attention in recent decades. This article presents the research evidence that GMA predicts both occupational level attained and performance within one's chosen occupation and does so better than any other ability, trait, or disposition and better than job experience. The sizes of these relationships with GMA are also larger than most found in psychological research. Evidence is presented that weighted combinations of specific aptitudes tailored to individual jobs do not predict job performance better than GMA alone, disconfirming specific aptitude theory. A theory of job performance is described that explicates the central role of GMA in the world of work. These findings support Spearman's proposition that GMA is of critical importance in human affairs.

Achievement↗

A critical review of the diagnosis and management of Barrett's esophagus: the AGA Chicago Workshop.

BACKGROUND & AIMS: The diagnosis and management of Barrett's esophagus (BE) are controversial. We conducted a critical review of the literature in BE to provide guidance on clinically relevant issues. METHODS: A multidisciplinary group of 18 participants evaluated the strength and the grade of evidence for 42 statements pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each member anonymously voted to accept or reject statements based on the strength of evidence and his own expert opinion. RESULTS: There was strong consensus on most statements for acceptance or rejection. Members rejected statements that screening for BE has been shown to improve mortality from adenocarcinoma or to be cost-effective. Contrary to published clinical guidelines, they did not feel that screening should be recommended for adults over age 50, regardless of age or duration of heartburn. Members were divided on whether surveillance prolongs survival, although the majority agreed that it detects curable neoplasia and can be cost-effective in selected patients. The majority did not feel that acid-reduction therapy reduces the risk of esophageal adenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associated with a cancer risk reduction and are of promising (but unproven) value. Participants rejected the notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE but agreed that this may be an appropriate strategy in a subgroup of patients with high-grade dysplasia. CONCLUSIONS: Based on this review of BE, the opinions of workshop members on issues pertaining to screening and surveillance are at variance with published clinical guidelines.

Adenocarcinoma↗

Detection of activity centers in cellular pathways using transcript profiling.

We present a new computational method for identifying regulated pathway components in transcript profiling (TP) experiments by evaluating transcriptional activity in the context of known biological pathways. We construct a graph representing thousands of protein functional relationships by integrating knowledge from public databases and review articles. We use the notion of distance in a graph to define pathway neighborhoods. The pathways perturbed in an experiment are then identified as the subgraph induced by the genes, referred to as activity centers, having significant density of transcriptional activity in their functional neighborhoods. We illustrate the predictive power of this approach by performing and analyzing an experiment of TP53 overexpression in NCI-H125 cells. The detected activity centers are in agreement with the known TP53 activation effects and our independent experimental results. We also apply the method to a serum starvation experiment using HEY cells and investigate the predicted activity of the transcription factor MYC. Finally, we discuss interesting properties of the activity center approach and its possible applications beyond the comparison of two experiments.

Algorithms↗

Preventing falls and stump injuries in lower limb amputees during inpatient rehabilitation: completion of the audit cycle.

OBJECTIVES: To study the factors contributing to falls among recent lower limb amputees, and to reduce the number of falls during inpatient rehabilitation and resulting injuries. DESIGN: Retrospective, followed by prospective, cohort study, then a follow-up study conducted after interventions. SETTING: Twenty-bedded inpatient rehabilitation unit for amputees. SUBJECTS: Lower limb amputees. INTERVENTIONS: Patient education, environmental modifications and application of a bivalve plaster of Paris stump protector to patients who were aged 70 or over, or cognitively impaired. MAIN OUTCOME MEASURES: Numbers of falls and other accidents, and resulting injuries. RESULTS: In phase 1 of the study, a retrospective audit of incident forms that had been completed on lower limb amputees who had an accident during their inpatient rehabilitation, between 1 April 1996 and 31 Ocotber 1998, was carried out. This showed that approximately a third of admissions (32%) were complicated by an accident. Most accidents were falls. In phase 2, a prospective study of 113 patients admitted to the unit was undertaken. Patients who fell were significantly older than those who did not. In phase 3, 62 consecutive patients were studied. There were 37 accidents in total, of which 35 were falls. Compared with the phase 2 study, there was no reduction in the proportion of patients who had a fall or other accident in phase 3, but significantly fewer falls resulted in any injury (p = 0.05). CONCLUSIONS: Although the interventions employed did not reduce the proportion of patients who had falls or other accidents, significantly fewer falls resulted in injuries.

Accidental Falls↗

Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea.

Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group.

Clostridioides difficile↗

Rapid sequence quadruple joint replacement in a rheumatoid Jehovah's Witness.

We report the case of a wheelchair-bound rheumatoid Jehovah's Witness who underwent rapid sequence, staged, simultaneous ipsilateral hip and knee replacements. Using perioperative erythropoietin and postoperative blood salvage, all four joints were reconstructed without homologous blood transfusion. One year following surgery, the patient has achieved an independent functional status, and all four replaced joints remain painless.

Antibiotic Prophylaxis↗

Dietary selenium levels determine epidermal langerhans cell numbers in mice.

Selenium (Se) is a dietary trace element that is essential for effective immunity and protection from oxidative damage induced by ultraviolet radiation (UVR). Langerhans cells (LC) represent the major antigen-presenting cells resident in the epidermis; a proportion migrate from the skin to the draining lymph nodes in response to UVR. Because it is known that Se deficiency impairs immune function, we determined what effect this has on LC numbers. CH3/HeN mice were weaned at 3 wk and placed on diets containing <0.005 ppm of Se (Se deficient) or 0.1 ppm of Se (Se adequate, control mice). After 5 wk on the diet, the epidermal LC numbers in the Se-adequate group were 966 +/- 51 cells/mm2 and LC counts in the epidermis of the Se-deficient mice were 49% lower (p<0.05). Glutathione peroxidase- I (GPx) activity was measured in the epidermis, lymph nodes, and liver. In the epidermis, the activity of GPx in the Se-deficient mice was only 39% (p<0.01) of that seen in epidermis from Se-adequate mice (1.732 U/mg protein). The mice were then irradiated with one dose of 1440 J/m2 of broadband UVB or mock irradiated. After 24 h, the decrease in LC number after UVB was greater in the Se-adequate mice, (40% decrease) compared to the Se-deficient group (10%). Thus, Se deficiency reduces epidermal LC numbers, an effect that might compromise cutaneous immunity.

Adenosine Triphosphatases↗

Stroke awareness and knowledge retention in children: The Brain Child Project.

BACKGROUND AND PURPOSE: Efforts at public education to improve adults' response to stroke symptoms continue to be disappointing, and very little has been developed to improve the knowledge base of children regarding brain attacks. Children may be able to exert a positive influence on adult behavior and to learn positive healthcare habits, which will also influence their own health. METHODS: A total of 561 children enrolled in grades kindergarten through eighth (K-8), participated in The Brain Child Project, which included (1) assessment of their knowledge of stroke awareness (including initiation of the emergency medical system [EMS]) using a multiple-choice questionnaire, (2) attendance at a multimedia educational program designed to increase stroke knowledge, followed by (3) immediate administration of the same questionnaire, and (4) a final administration of the same questionnaire 10 days later to measure retention of acquired learning. RESULTS: The results showed that these children had a limited understanding of stroke, but with a brief educational program, all grades significantly increased their scores on the average from 64% to 82%. The loss of knowledge between the posttest and the retention test was negligible. CONCLUSIONS: The results of this study indicate that through brief education, children show significant improvement in their knowledge of and response to brain attacks. Future efforts in this direction may positively affect stroke prevention, response and outcomes. A national program could be implemented in the school systems much like heart disease programs, with the ultimate goal of greater public awareness and prevention of stroke.

Child↗