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Biomedical subjects

A Abraham

Publications and source records attributed to A Abraham.

At least 19 recordsLinked to original sources

Are national guidelines for total hip replacement in the UK reflected in practice?

INTRODUCTION: A cross-sectional study was performed to compare the practice of total hip replacement (THR) in the UK against national guidelines. MATERIALS AND METHODS: A postal questionnaire was sent to all fellows of the British Orthopaedic Association. RESULTS: Of the 1587 questionnaires sent out, 966 (60.9%) were returned. Of these, 706 (73.1%) were available for data collection and analysis. CONCLUSIONS: Consensus was observed in several areas including the use of pre-admission clinics and modern cementing techniques. Facilities deemed necessary for THR surgery such as HDU/ITU back-up, ultra-clean air and dedicated orthopaedic wards are almost universally available. However, a lack of consensus is evident in many areas including the process of obtaining written consent, thrombo-embolic prophylaxis, duration of antibiotic prophylaxis, supervision of trainee surgeons and follow-up arrangements. The proliferation in the range of implants, particularly aimed at 'younger' patients, available to surgeons has once again been highlighted.

Arthroplasty, Replacement, Hip↗

A comparative study of fuzzy classification methods on breast cancer data.

In this paper, we examine the performance of four fuzzy rule generation methods on Wisconsin breast cancer data. The first method generates fuzzy if-then rules using the mean and the standard deviation of attribute values with 92.2% correct classification rate. The second approach generates fuzzy if-then rules using the histogram of attributes values with 86.7% correct classification rate. The third procedure generates fuzzy if-then rules with certainty of each attribute into homogeneous fuzzy sets with 99.73% correct classification rate. In the fourth approach, only overlapping areas are partitioned with 62.57% correct classification rate. The first two approaches generate a single fuzzy if-then rule for each class by specifying the membership function of each antecedent fuzzy set using the information about attribute values of training patterns. The other two approaches are based on fuzzy grids with homogeneous fuzzy partitions of each attribute. The performance of each approach is evaluated on breast cancer data sets. Simulation results show that the simple grid approach has a high classification rate of 99.73%.

Algorithms↗

There is more than one kind of myofibroblast: analysis of CD34 expression in benign, in situ, and invasive breast lesions.

AIMS: Smooth muscle actin (SMA) positive myofibroblasts have been implicated in tumour invasion; however, acquisition of SMA is not limited to peritumorous fibroblasts and other changes in fibroblasts may be more specifically related to the malignant environment. CD34 is a sialomucin expressed by normal breast fibroblasts but lost in invasive carcinomas. The aim of this study was to establish the relation between CD34 and SMA expression in breast fibroblasts and to analyse whether loss of CD34 is specific for invasive disease. METHODS: Immunohistochemistry for CD34 and SMA was performed on 135 cases including 10 normal, 10 fibroadenomas, 40 infiltrating ductal carcinomas, 55 cases of ductal carcinoma in situ (DCIS), and 20 radial scar/complex sclerosing lesions. The relation between staining pattern and histopathological features was recorded as positive, negative, or reduced. RESULTS: Fibroblasts around all normal duct-lobule units and those showing epithelial hyperplasia were CD34 positive and mainly SMA negative. In fibroadenomas, fibroblasts retained CD34 but acquired SMA expression. In contrast, fibroblasts around invasive carcinoma were CD34 positive and SMA negative. In DCIS, loss of CD34 was significantly more frequent in high grade tumours than in low or intermediate grade ones (p < 0.001). The acquisition of SMA was seen more frequently than the loss of CD34, particularly in non-high grade DCIS. In all radial scars, fibroblasts were SMA positive but CD34 negative, and a similar pattern was seen in stromal cells in areas of fibrosis following core biopsy. CONCLUSIONS: These results show that SMA positive myofibroblasts exhibit variable expression of CD34, indicating that these markers are not coordinately controlled. Loss of CD34 is strongly related to the malignant phenotype, in both invasive and preinvasive disease, but is not entirely specific because radial scar fibroblasts and fibroblasts in reactive fibrosis exhibit a similar phenotype. The functional relevance of altered CD34 expression is unclear but the very focal changes implicate local signalling mechanisms probably of epithelial origin.

Actins↗

Sensorineural hearing loss following acute bacterial meningitis in non-neonates.

OBJECTIVE: Sensorineural hearing loss (SNHL) is an important sequelae of acute bacterial meningitis (ABM) in children. This study was undertaken to determine the incidence of SNHL following meningitis in non-neonates and its correlation with various factors. METHODS: Children between the ages of 1 month and 12 years with ABM admitted in a teaching hospital over a period of 18 months were enrolled. Detailed history was taken, clinical examination performed and cerebrospinal fluid analyzed at commencement of therapy, 48 hours later and at the end of treatment. On discharge brainstem evoked response audiometry (BERA) was recorded. Data were analyzed using appropriate statistical tests. RESULTS: Out of 32 children enrolled, 9 (28.1%) developed SNHL, bilateral in 21.9% and unilateral in 6.2%. Among hearing impaired subjects, 11.2% had mild while 44.4% each had moderate and profound hearing loss. Age, presence of vomiting, altered sensorium seizures and aminoglycoside usage were not significantly different in those with and without SNHL, but the total duration of fever was (p<0.05). There was significantly higher protein content and neutrophils in the second CSF sample of those with SNHL. CONCLUSION: There is a greater than 50% probability of the child developing SNHL if neutrophil percentage in the second CSF is 80% or more. Since the overall risk of SNHL is significant in children with meningitis, it is recommended that BERA be recorded in all, so that early intervention may be possible.

Child↗

Prognostic significance of intratumoural microvessel density (IMD) in resected pancreatic and ampullary cancers to standard histopathological variables and survival.

AIM: Angiogenesis is required for tumour growth. Its evaluation, by intratumoural microvessel density (IMD), has prognostic significance in many solid tumours. There is controversy regarding its use in pancreatic cancer and little is known about its role in ampullary tumours. The aim is to study IMD as a prognostic marker in resected ductal adenocarcinomas of head of pancreas and cancers of the ampullary region. METHODS: Forty-seven patients (23 pancreatic and 24 ampullary, mean age 62.0 years) surviving a potentially curative (R0/R1) resection were analysed. Paraffin-embedded sections of these tumours were immunohistochemically stained for CD-34 and IMD was determined (magnification x200). This was correlated with histopathological data and survival using Cox's multivariate analysis. RESULTS: Mean survival for the pancreatic cancer group was 18.4 months (SE=2.7) and 81.2 months (SE=9.9) for the ampullary cancer group. In the pancreatic cancer group, IMD was found to have independent prognostic significance to survival on multivariate analysis (P=0.002, Hazard Ratio (HR) 13.60) along with microscopic resection margin involvement (P=0.003, HR 15.18). For ampullary cancers, IMD was higher in those with lymph node metastasis (P=0.02, Mann-Whitney U -test). CONCLUSION: IMD in resected pancreatic cancers correlates with survival.

Adenocarcinoma↗

Refractures in patients at least forty-five years old. a prospective analysis of twenty-two thousand and sixty patients.

BACKGROUND: Individuals who sustain a low-energy fracture are at increased risk of sustaining a subsequent low-energy fracture. The incidence of these refractures may be reduced by secondary preventative measures, although justifying such interventions and evaluating their impact is difficult without substantive evidence of the severity of the refracture risk. The aim of this study was to quantify the risk of sustaining another fracture following a low-energy fracture compared with the risk in an age and sex-matched reference population. METHODS: During the twelve-year period between January 1988 and December 1999, all inpatient and outpatient fracture-treatment events were prospectively audited in a trauma unit that is the sole source of fracture treatment for a well-defined local catchment population. During this time, 22,060 patients at least forty-five years of age who had sustained a total of 22,494 low-energy fractures of the hip, wrist, proximal part of the humerus, or ankle were identified. All refracture events were linked to the index fracture in the database during the twelve-year period. The incidence of refracture in the cohort of patients who had sustained a previous fracture was divided by the "background" incidence of index fractures within the same local population to obtain the relative risk of refracture. Person-years at-risk methodology was used to control for the effect of the expected increase in mortality with advancing age. RESULTS: Within the cohort, 2913 patients (13.2%) subsequently sustained a total of 3024 refractures during the twelve-year period. Patients with a previous low-energy fracture had a relative risk of 3.89 of sustaining a subsequent low-energy fracture. The relative risk was significantly increased for both sexes, but it was greater for men (relative risk = 5.55) than it was for women (relative risk = 2.94). The relative risk was 5.23 in the youngest age cohort (patients between forty-five and forty-nine years of age), and it decreased with increasing age to 1.20 in the oldest cohort (patients at least eighty-five years of age). CONCLUSIONS: Individuals who sustain a low-energy fracture between the ages of forty-five and eighty-four years have an increased relative risk of sustaining another low-energy fracture. This increased risk was greater when the index fracture occurred earlier in life; the risk decreased with advancing age. Secondary preventative measures designed to reduce the risk of refracture following a low-energy fracture are likely to have a greater impact on younger individuals.

Age Factors↗

CSF beta-1 Globulin--a potential marker in differentiating multiple sclerosis and acute disseminated encephalomyelitis: a preliminary study.

The exact diagnosis of demyelinating diseases is an enigma even in the best neurological centres. In the present study, the potential role of differential CSF proteins has been critically evaluated in differentiating multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). Cellulose acetate electrophoresis was carried out on CSF and serum samples of 14 MS patients, 23 ADEM patients and 30 controls. There was no statistically significant difference between serum electrophoresis of controls and MS patients. However, in case of CSF electrophoresis there was a statistically significant decrease in beta-1 fraction in 92.2% of MS patients (p=0.01). A comparison between serum electrophoresis of controls and ADEM patients indicated a statistically significant decrease in serum albumin in 87% patients and an increase of alpha-2 globulin in 73.9%. There was no statistically significant difference between CSF electrophoresis of controls and ADEM patients except for the prealbumin fraction which was raised in 60.9% of patients. No statistically significant difference was seen between the serum electrophoresis of ADEM and MS patients. However, on comparing CSF electrophoresis, it was seen that beta-1 fraction was significantly higher in ADEM patients (p<0.05). The predictive value of beta-1 fraction in differentiating MS and ADEM was then evaluated. The negative predictive value was 100% indicating that all samples with a beta-1 fraction of>6.5% cannot be diagnosed as MS. The significant decrease in beta-1 fraction in MS patients may prove to be an early indicator in differentiating between MS and ADEM patients.

Biomarkers↗

Assessment of faecal occult blood loss by qualitative and quantitative methods.

BACKGROUND: Various methods exist for the assessment of faecal occult blood loss in a patient with suspected gastrointestinal blood loss. METHODS: The present study examined the effectiveness and financial implications of a qualitative guaiac-based method (Haemoccult) of faecal occult blood detection and a quantitative measure of haeme-derived porphyrins (Hemoquant) in 184 patients who underwent assessment of faecal blood loss by both methods over a three year period during assessment of iron deficiency anaemia. MAIN FINDINGS: At least one Haemoccult test was positive in 72.2% of patients while Hemoquant was suggestive of significant blood loss (> 2mg haemoglobin/g faeces) in 29.9%. Patients underwent a total of 324 further endoscopic or radiological investigations of which 76.5% demonstrated no abnormality. A diagnosis was reached in 60 patients (32.6%). A significant potential source of gastrointestinal bleeding was found in 48 patients (26.1%). Hemoquant achieved a sensitivity of 62.5% and a specificity of 81.6% while with Haemoccult it was 85.4% and 32.4%, respectively. Hemoquant was normal in 18 patients with significant gastrointestinal conditions including peptic ulcers and colonic polyps. While Haemoccult only missed 7 lesions, two of these were colonic cancers. The quantitative nature of the Hemoquant test gave little clue as to diagnosis. CONCLUSION: Neither of the tests examined was ideal but Hemoquant had an overall better performance and further investigation of patients with evidence of blood loss from this test should be mandatory.

Adolescent↗

Growth arrest lines and recurrent patellar dislocation: a new sign.

The phenomenon of growth arrest lines has been widely described in the medical literature. They are usually found at the metaphysis of growing long bones and are the result of short periods of partial growth arrest. Recurrent dislocation of the patella is a well-recognised problem, particularly in adolescents. Several radiological features have been reported in association with patellar dislocation or instability. We have reported a hitherto undescribed radiological sign of patellar growth arrest lines on the skyline radiographs of two patients with this condition. The shape of the patella when symptoms were at their worst corresponded remarkably closely to the outline of the subsequent growth arrest line. We postulated that repeated dislocations adversely affect the process of normal maturation of the patella. With the resolution of symptoms, patella ossification resumes, leaving the telltale sign of previous injury in the form of a growth arrest line and an improvement in bone density once the patella has been stabilised and tracks normally.

Adolescent↗

Assessing an educational intervention to improve physician violence screening skills.

OBJECTIVES: Health professionals play an integral role in assessing the risk of violence in their patients. However, there have been few evaluations of violence prevention education programs for health care personnel. The objective of this study was to evaluate the effects of a violence-screening education program on pediatric residents' and medical students' comfort level and skills in the identification and management of violence risks. SETTING: Adolescent clinic of a tertiary care pediatric hospital. PARTICIPANTS: Fifty-six second-year residents and third-year medical students assigned to a 4-week adolescent clinic rotation. DESIGN: Randomized, controlled comparison study conducted over a 1-year period. INTERVENTION: On alternate months, medical students and residents in the intervention group participated in a 3-hour workshop on violence prevention. The workshop included a didactic session with an overview of firearm, media, and sexual violence; a discussion of risk factors for adolescent violence; and training on the approach to the adolescent interview. Participants also discussed violence risks in the community with a panel of teen health educators, engaged in one-on-one role play with the youth educators, and received feedback on their violence screening skills. The control group received the standard ambulatory clinic manual with articles on violence prevention. EVALUATION METHODS: All participants completed prerotation and postrotation questionnaires assessing their self-reported screening practices, as well as perceived importance and confidence in violence screening. Participants also interviewed and examined an adolescent standardized patient (SP) in the clinic. SPs completed evaluations on the content of the residents' and students' screening, their interpersonal skills, and their skill in the identification and management of the violence-related problem. RESULTS: Over 12 months, 30 control and 26 intervention participants were recruited. There were no differences in prerotation questionnaire scores for intervention and control groups in screening practices, perceived importance and confidence in violence screening. Postrotation intervention participants reported more screening compared with controls on violence in school/neighborhood and fighting history. There was also greater perceived importance in asking about access/use of weapons and violence in school/neighborhood. Intervention participants also had improved performance compared with controls on SP evaluations of screening for violence, identification and management of the violence-related scenario, and interpersonal skills. CONCLUSION: A violence prevention education program with teen health educators improved participants' self-reported violence questioning, as well as increased perceived comfort and importance in violence screening. Participants in the program also improved their identification and management of a standardized violence-related scenario presented in an adolescent clinic setting. adolescent violence, physician education, violence risk screening.

Adolescent↗

Technological properties of milks fermented with thermophilic lactic acid bacteria at suboptimal temperature.

In the present work the synergistic relationship between different strains of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus was studied at optimal (44 degrees C) and suboptimal temperatures (30 degrees C). Acidification, viscosity, whey syneresis, and bacterial concentration of the final product were evaluated on single-strain and mixed cultures after 24 h at 30 degrees C and 6 h at 44 degrees C. Three pairs of strains (LBB + CP2, LBP + CP2, and LBR + CP2) showed synergistic effect, which was reflected by the viscosity and syneresis of the coagulum. These results were more significant when cultures were incubated at 30 degrees C, reaching apparent viscosity values of 19 to 28 mPa x s. On the other hand, lactobacilli cultures enhanced the growth of two streptococci strains (CP2 and CP4). These results were confirmed by cultures of streptococci supplemented with supernatants of culture of lactobacilli. Those supernatants stimulate the viscosity produced by CP2 and CP4 strains and reduce the syneresis of all cultures of streptococci. Neither the increase of viscosity nor reduction of syneresis could be attributed to a decrease of pH.

Animals↗

Effect of ischemia--reperfusion on heat shock protein 70 and 90 gene expression in rat liver: relation to nutritional status.

Heat shock proteins are intracellular proteins associated with a generalized response of cells to stress. The purpose of this study was to assess RNA levels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion. Northern blot analysis of heat shock proteins was performed. Adenosine triphosphate and glutathione were assessed. In baseline conditions, livers of fasted rats showed a twofold increase in mRNA for both heat shock proteins and 38% and 43% reductions in adenosine triphosphate and glutathione, respectively, when compared with organs from fed rats. After ischemia, livers of fasted rats presented a twofold decrease in heat shock protein mRNA, while no changes were observed in livers of fed rats; reduced glutathione and adenosine triphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs, respectively. After 120 min of reperfusion, heat shock protein mRNA rose threefold in fasted livers, while a slight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returned to 65% and 70% of baseline values in fasted livers and 85% and 90% in fed organs, respectively. In conclusion, the nutritional status affects heat shock protein expression determined by reperfusion. The reduced antioxidant status leading to increased oxidative stress could be the mechanism underlying the phenomenon.

Adenosine Triphosphate↗

Peptidomimetic inhibitors of the human cytomegalovirus protease.

The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency of 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P1 were well tolerated by this enzyme, a fact consistent with previous observations. The S2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and alpha-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.

Antiviral Agents↗

Potent HIV protease inhibitors containing a novel (hydroxyethyl)amide isostere.

A series of HIV protease inhibitors containing a novel (hydroxyethyl)amidosuccinoyl core has been synthesized. These peptidomimetic structures inhibit viral protease activity at low nanomolar concentrations (IC50 < 10 nM for HIV-1 protease). The inhibition constant (Ki) for inhibitor 19 was determined to be 7.5 pM against HIV-1 and 1.2 nM against HIV-2 proteases, respectively. Several compounds (19-24) inhibited HIV-1 replication in cell culture assays with 50% effective concentrations (EC50) = 3.7-35 nM. This series of inhibitors was found to exhibit poor bioavailability (< 10%) in the rat, following oral administration. The synthesis and biological properties of these compounds are discussed. In addition, an X-ray structure of one of these inhibitors (23) in complex with HIV-2 protease provides insight into the binding mode of this novel class of HIV protease inhibitors.

Administration, Oral↗

Subcutaneous T-cell lymphoma in a patient with rheumatoid arthritis not treated with cytotoxic agents.

This case report describes an 81-year-old patient with prolonged rheumatoid arthritis (RA), which was complicated by the occurrence of a subcutaneous T-cell lymphoma. During the course of his illness the patient had not been treated with disease-modifying agents (i.e. cytotoxic agents), but only symptomatically with anti-inflammatory drugs. This finding demonstrates a previously undescribed association between RA and a rare from of subcutaneous T-cell lymphoma, which may add more information to the controversial issue of emergence of malignancy in RA.

Aged↗

Protective immune responses to Theileria annulata of relevance to vaccine development.

A series of projects on Theileria annulata funded by the European Union (STD1/STD2/STD3) have provided convincing evidence that macrophage and natural killer (NK) cell-dependent immune mechanisms may directly control the proliferation of different stages of T. annulata in cattle. The evidence for this conclusion and the implications for vaccine development are discussed in the following paper.

Animals↗