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Biomedical subjects

J Gibbs

Publications and source records attributed to J Gibbs.

At least 19 recordsLinked to original sources
PubMed2006

Proximal anterior cruciate ligament avulsion fracture in a skeletally immature athlete: a case report and method of physeal sparing repair.

Traumatic rupture of the anterior cruciate ligament (ACL) in adulthood is relatively common and surgical reconstruction is frequently required to allow return to high-level activities. There is growing evidence to suggest that ACL rupture in children is more common than previously thought and a poor outcome is associated with conservative management. The site of rupture in childhood is predominantly tibial avulsion, but mid-substance tears have also been reported. We report a case of a proximal ACL avulsion in an 11-year-old athlete and discuss a method of extra-physeal repair. There are very few previous reports of proximal avulsion fractures in skeletally immature patients.

Anterior Cruciate Ligament↗
PubMed2005

Assessing psychological well-being: a holistic investigation of NHS employees.

A substantial body of research has investigated the effects of work on the psychological well-being of employees. However, there has been little assessment of the ways in which workplace factors (such as job demands, working conditions, inter-personal relations and workplace change) interact with personal factors (such as work-life balance, family circumstances, key personality traits or demographic characteristics) to affect psychological health. This article reports findings from a study which aimed to construct and test a comprehensive model of the influences on employee well-being within the UK National Health Service (NHS). The results show that psychological well-being is influenced by a complex array of personal, environmental and work factors. A key finding is that there are clear associations between workplace change and well-being and between work-life (im)balance and well-being. These effects appear to be independent of one another and therefore require separate attention from managers and employers.

Data Collection↗
PubMed2005

Primary adenocarcinoma of cervical esophagus.

Most upper esophageal malignancies are squamous cell carcinomas, rarely adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas from heterotopic gastric mucosa without evidence of Barrett's especially in the cervical part of the esophagus. We report a case of adenocarcinoma of the polypoid type in the upper esophagus (cervical esophagus) arising from ectopic gastric mucosa, in a 60 year-old man who presented with progressive dysphagia. Accurate diagnosis by esophagogram revealed a large mass in the cervical esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet, esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the incisors with a biopsy confirming moderately differentiated adenocarcinoma with no evidence of Barrett's esophagus. Through a left cervical approach and resection of medial third of clavicle, the tumor was removed by partial esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation with no evidence of recurrence or metastasis in six years of follow up. It seems this tumor has a much better prognosis than adenocarcinomas arising from Barrett's. To our knowledge only 19 cases have been reported in literature so far.

Adenocarcinoma↗
PubMed2004

Neuropeptide Y inhibits capsaicin-sensitive nociceptors via a Y1-receptor-mediated mechanism.

Neuropeptide Y (NPY) is expressed in certain primary afferent fibers, is up-regulated in response to tissue injury and is capable of inhibiting nociceptive behavior at the spinal level. However, the spinal mechanism(s) for NPY-evoked antinociception is unknown. In this study, we evaluated the hypothesis that agonists at the NPY Y1 receptor subtype (Y1-R) inhibit exocytosis from the capsaicin-sensitive class of nociceptors. Using in vitro superfusion of rat dorsal spinal cord slices, pre-treatment with the Y1-R agonist [Leu(31)Pro(34)]NPY significantly inhibited capsaicin-evoked release of immunoreactive calcitonin gene-related peptide with an EC(50) value of 10.6 nM. This inhibitory effect was concentration dependent, significantly attenuated by pre-treatment with the Y1 receptor antagonist BIBP3226 and reproduced by synthetic NPY. Examination of adult rat dorsal root ganglia using double immunofluorescent labeling revealed frequent co-localization of Y1 receptor immunoreactivity in vanilloid receptor type 1-immunoreactive neurons, indicating that Y1 agonists may directly modulate the capsaicin-sensitive class of nociceptors. Collectively, these results indicate that NPY is capable of inhibiting capsaicin-sensitive neurons via a Y1 receptor mechanism, suggesting the mechanisms for spinal NPY-induced antinociception is due, at least in part, to inhibition of central terminals of capsaicin-sensitive nociceptors.

Analgesics↗
PubMed2003

Epilepsy in mainstream and special educational primary school settings.

This population based study compared the prevalence, nature and management of epilepsy between primary school children in mainstream education and those attending a special educational placement (children with special needs). The overall prevalence of epilepsy was 4.3/1000, but was 30 times higher in children with special needs, many of whom also had severe physical disabilities. Seizure types and the proportion of subjects with multiple seizures were similar in mainstream children and those with special needs. Epilepsy syndromes were identified in 74% of children. Although seizures were better controlled in children at mainstream school, 44% of these children did not have well controlled seizures. Children with epilepsy are an educationally vulnerable group and both education and health staff need to be aware of the additional support that many of these children require in all types of primary educational settings.

Child↗
PubMed2001

A novel influenza A virus mitochondrial protein that induces cell death.

While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8+ T cells, we found an abundant immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared with other influenza gene products in addition to its mode of translation. These include its absence from some animal (particularly swine) influenza virus isolates, variable expression in individual infected cells, rapid proteasome-dependent degradation and mitochondrial localization. Exposure of cells to a synthetic version of PB1-F2 induces apoptosis, and influenza viruses with targeted mutations that interfere with PB1-F2 expression induce less extensive apoptosis in human monocytic cells than those with intact PB1-F2. We propose that PB1-F2 functions to kill host immune cells responding to influenza virus infection.

Amino Acid Sequence↗
PubMed2001

Postoperative and late survival outcomes after major amputation: findings from the Department of Veterans Affairs National Surgical Quality Improvement Program.

BACKGROUND: A surgical risk model is used to analyze postoperative mortality and late survival for older veterans who underwent above- or below-knee amputations in 119 Veterans Affairs (VA) hospitals from 1991 to 1995. METHODS: Preoperative medical conditions and laboratory values abstracted by the VA National Surgical Quality Improvement Program were linked to subsequent hospitalization and survival through 1999. Logistic regression and proportional hazards models were used to develop risk indexes for postoperative mortality and long-term survival. RESULTS: Thirty-day postoperative mortality was 6.3% for 1909 below-knee and 13.3% for 2152 above-knee amputees. Mortality varied greatly between the lowest-highest risk index quartiles (0.8%-18.4% for below-knee amputation and 2.3%-31.1% for above-knee amputation). Surviving patients had 10,827 subsequent VA hospitalizations during a median 32-month follow-up. Survival probabilities for below- and above-knee amputees were 77% and 59% at 1 year, 57% and 39% at 3 years, and 28% and 20% at 7.5 years. The lowest quartile of survival risk had a 61% five-year survival compared with 14% for the highest-risk quartile. CONCLUSION: A generic surgical risk model can be of use in stratifying prognosis after major amputation. The heavy burden of hospital use by these patients suggests the need for better disease management for this high-risk, high-cost patient population.

Adult↗
PubMed2001

Postoperative and amputation-free survival outcomes after femorodistal bypass grafting surgery: findings from the Department of Veterans Affairs National Surgical Quality Improvement Program.

PURPOSE: A noncardiac surgery risk model was used as a means of analyzing variations in postoperative mortality and amputation-free survival for older veterans undergoing femorodistal bypass grafting surgery. METHODS: A prospective cohort study was undertaken in 105 Veterans Affairs (VA) hospitals at the time of index operation from 1991 to 1995. Each patient was linked to subsequent hospitalizations, major amputation surgery, and survival through 1999. Logistic regression and proportional hazards models were used as a means of developing risk indices on the basis of risk factors from the VA National Surgical Quality Improvement Program. A total of 4288 male veterans 40 years or older underwent artificial, vein, or in situ bypass grafting surgery at the femoral to tibial level. The main outcome measures were 30-day postoperative mortality and amputation-free survival. RESULTS: Approximately half of all patients had undergone an earlier revascularization or amputation at any level for vascular disease. The 30-day postoperative mortality rate was 2.1% and varied greatly between mortality risk index quartiles (0.6%-5.2%). In a median 44.3 months of follow-up, surviving patients had 17,694 subsequent VA hospitalizations, 1147 patients (26.7%) underwent subsequent major amputation, and 1913 patients (44.6%) died. The overall survival probability was 88% at 1 year and 63% at 5 years; 1- and 5-year (any sided) limb salvage rates were 87% and 74%, respectively, for patients who underwent a femoropopliteal bypass grafting procedure, compared with 77% and 63%, respectively, for patients who underwent a tibial bypass grafting procedure. When amputation and death were combined as end points, amputation-free survival probability rates at 1, 3, and 7.5 years were 74%, 56%, and 29%, respectively. Patients with the best 20% survival risk scores had observed mean survival probability rates 30% higher than patients in the poorest 20% of survival risk. CONCLUSION: Risk indices derived from the preoperative workup may be of use to clinicians in assessing and communicating risk and prognosis. Risk-adjustment of outcomes is critical for evaluating future disease management initiatives for patients with advanced peripheral arterial disease.

Aged↗
PubMed2001

Validating risk-adjusted surgical outcomes: chart review of process of care.

OBJECTIVE: The primary purpose of this study was to validate risk-adjusted surgical outcomes as indicators of the quality of surgical care at US Department of Veterans Affairs (VA) hospitals. The secondary purpose was to validate the risk-adjustment models for screening cases for quality review. DESIGN: We compared quality of care, determined by structured implicit chart review, for patients from hospitals with higher and lower than expected operative mortality and morbidity (hospital-level tests) and between patients with high and low predicted risk of mortality and morbidity who died or developed complications (patient-level tests). SUBJECTS: 739 general, peripheral vascular and orthopedic surgery cases sampled from the 44 VA hospitals participating in the National VA Surgical Risk Study. MAIN OUTCOME MEASURES: A global rating of quality of care based on chart review. RESULTS: Ratings of overall quality of care did not differ significantly between patients from hospitals with higher and lower than expected mortality and morbidity. On some of the secondary measures, patient care was rated higher for hospitals with lower than expected operative mortality. At the patient level of analysis, those who died or developed complications and had a high predicted risk of mortality or morbidity were rated higher on quality of care than those with a low predicted risk of adverse outcome. CONCLUSIONS: The absence of a relationship between most of our measures of process of care and risk-adjusted outcomes may be due to an insensitivity of chart reviews to hospital-level differences in quality of care. Site visits to National VA Surgical Risk Study hospitals with high and low risk-adjusted mortality and morbidity have detected differences on a number of dimensions of quality. The patient-level findings suggest that the risk-adjustment models are useful for screening adverse outcome cases for quality of care review.

Data Interpretation, Statistical↗
PubMed2001

Comparison of surgical outcomes between teaching and nonteaching hospitals in the Department of Veterans Affairs.

OBJECTIVE: To determine whether the investment in postgraduate education and training places patients at risk for worse outcomes and higher costs than if medical and surgical care was delivered in nonteaching settings. SUMMARY BACKGROUND DATA: The Veterans Health Administration (VA) plays a major role in the training of medical students, residents, and fellows. METHODS: The database of the VA National Surgical Quality Improvement Program was analyzed for all major noncardiac operations performed during fiscal years 1997, 1998, and 1999. Teaching status of a hospital was determined on the basis of a background and structure questionnaire that was independently verified by a research fellow. Stepwise logistic regression was used to construct separate models predictive of 30-day mortality and morbidity for each of seven surgical specialties and eight operations. Based on these models, a severity index for each patient was calculated. Hierarchical logistic regression models were then created to examine the relationship between teaching versus nonteaching hospitals and 30-day postoperative mortality and morbidity, after adjusting for patient severity. RESULTS: Teaching hospitals performed 81% of the total surgical workload and 90% of the major surgery workload. In most specialties in teaching hospitals, the residents were the primary surgeons in more than 90% of the operations. Compared with nonteaching hospitals, the patient populations in teaching hospitals had a higher prevalence of risk factors, underwent more complex operations, and had longer operation times. Risk-adjusted mortality rates were not different between the teaching and nonteaching hospitals in the specialties and operations studied. The unadjusted complication rate was higher in teaching hospitals in six of seven specialties and four of eight operations. Risk adjustment did not eliminate completely these differences, probably reflecting the relatively poor predictive validity of some of the risk adjustment models for morbidity. Length of stay after major operations was not consistently different between teaching and nonteaching hospitals. CONCLUSION: Compared with nonteaching hospitals, teaching hospitals in the VA perform the majority of complex and high-risk major procedures, with comparable risk-adjusted 30-day mortality rates. Risk-adjusted 30-day morbidity rates in teaching hospitals are higher in some specialties and operations than in nonteaching hospitals. Although this may reflect the weak predictive validity of some of the risk adjustment models for morbidity, it may also represent suboptimal processes and structures of care that are unique to teaching hospitals. Despite good quality of care in teaching hospitals, as evidenced by the 30-day mortality data, efforts should be made to examine further the structures and processes of surgical care prevailing in these hospitals.

Education, Medical, Graduate↗
PubMed2001

Human cytomegalovirus protein US2 interferes with the expression of human HFE, a nonclassical class I major histocompatibility complex molecule that regulates iron homeostasis.

HFE is a nonclassical class I major histocompatibility complex (MHC) molecule that is mutated in the autosomal recessive iron overload disease hereditary hemochromatosis. There is evidence linking HFE with reduced iron uptake by the transferrin receptor (TfR). Using a panel of HFE and TfR monoclonal antibodies to examine human HFE (hHFE)-expressing cell lines, we demonstrate the expression of stable and fully glycosylated TfR-free and TfR-associated hHFE/beta2m complexes. We show that both the stability and assembly of hHFE complexes can be modified by the human cytomegalovirus (HCMV) viral protein US2, known to interfere with the expression of classical class I MHC molecules. HCMV US2, but not US11, targets HFE molecules for degradation by the proteasome. Whether this interference with the regulation of iron metabolism by a viral protein is a means of potentiating viral replication remains to be determined. The reduced expression of classical class I MHC and HFE complexes provides the virus with an efficient tool for altering cellular metabolism and escaping certain immune responses.

Amino Acid Sequence↗
PubMed2000

Rapid degradation of a large fraction of newly synthesized proteins by proteasomes.

MHC class I molecules function to present peptides eight to ten residues long to the immune system. These peptides originate primarily from a cytosolic pool of proteins through the actions of proteasomes, and are transported into the endoplasmic reticulum, where they assemble with nascent class I molecules. Most peptides are generated from proteins that are apparently metabolically stable. To explain this, we previously proposed that peptides arise from proteasomal degradation of defective ribosomal products (DRiPs). DRiPs are polypeptides that never attain native structure owing to errors in translation or post-translational processes necessary for proper protein folding. Here we show, first, that DRiPs constitute upwards of 30% of newly synthesized proteins as determined in a variety of cell types; second, that at least some DRiPs represent ubiquitinated proteins; and last, that ubiquitinated DRiPs are formed from human immunodeficiency virus Gag polyprotein, a long-lived viral protein that serves as a source of antigenic peptides.

Animals↗
PubMed2000

Massive localized lymphedema: additional locations and association with hypothyroidism.

We report the second series of a new entity called "massive localized lymphedema in morbidly obese patients" (MLL), recently described in medical literature. Our 6 cases present additional locations as well as an association with hypothyroidism. Huge masses, of longstanding duration ranging from 9 months to 8 years, afflicted the thigh, popliteal fossa, scrotum, suprapubic and inguinal region, and abdomen of morbidly obese adults. Although clinical impressions were generally of a benign process, including lipoma and recurrent cellulitis, the possibility of a malignant neoplasm could not be eliminated. Poorly defined and non-encapsulated, these skin and subcutaneous lesions were most remarkable for their sheer size, measuring 50.6 cm in mean diameter (range, 38-75 cm) and weighing a mean of 6764.5 g (range, 2,060-12,000 g) The overlying skin exhibited the induration and peau d'orange characteristic of chronic lymphedema. Grossly and histologically, a prominent marbled appearance, rendered by fibrous bands intersecting lobules of adipose tissue, simulated sclerosing well differentiated liposarcoma. However, the absence of atypical stromal cells, atypical adipocytes, and lipoblasts precluded the diagnosis of well differentiated liposarcoma. Instead, reactive features, encompassing lymphatic vascular ectasia, mononuclear cell infiltrates, fibrosis, and edema between the collagen fibers, as well as ischemic changes including infarction and fat necrosis, established the diagnosis of MLL. Although the pathogenesis of MLL may be as simple as obstruction of efferent lymphatic flow by a massive abdominal pannus and/or prior surgery, the presence of hypothyroidism in 2 of our patients suggests an alternative pathogenesis. Recognition of this entity by both clinicians and pathologists should avert a misdiagnosis as a low-grade liposarcoma.

Adipose Tissue↗
PubMed2000

Regulation of alcoholic fermentation in coleoptiles of two rice cultivars differing in tolerance to anoxia.

To investigate regulation of anaerobic carbohydrate catabolism in anoxia-tolerant plant tissue, rate of alcoholic fermentation and maximum catalytic activities of four key enzymes were assessed in coleoptiles of two rice cultivars that differ in tolerance to anoxia. The enzymes were ATP-dependent phosphofructokinase (PFK), pyrophosphate-dependent phosphofructokinase (PFP), pyruvate decarboxylase (PDC), and alcohol dehydrogenase (ADH). During anoxia, rates of coleoptile elongation and ethanol synthesis were faster in the more tolerant variety Calrose than in IR22. Calrose coleoptiles, in contrast to IR22, also showed a sustained Pasteur effect, with the estimated rate of glycolysis during anoxia being 1.4-1.7-fold faster than that of aerobic coleoptiles. In Calrose after 5 d anoxia, maximum catalytic activities of crude enzyme extracts were (in mumol substrate g-1 fresh weight min.-1) 170-240 for ADH, 4-6 for PDC and PFP and 0.4-0.7 for PFK. During anoxia, activity per coleoptile of all four enzymes increased 3-5.5-fold, suggesting that PFK, and PFP, like PDC and ADH, are synthesised in anoxic rice coleoptiles. Enzyme activities, on a fresh weight basis, were lower in IR22 than in Calrose. In vivo activities of PDC and PFK in anoxic coleoptiles from both cultivars were calculated using in vitro activities, estimated substrate levels, cytoplasmic pH, and S0.5 (the substrate level at which 0.5Vmax is reached, without inferring Michaelis-Menten kinetics). Data indicated that potential carbon flux through PFK, rather than through PDC, more closely approximated rates of alcoholic fermentation. That PFK is an important site of regulation was supported further for Calrose coleoptiles by a decrease in the concentration of its substrate pool (F-6-P + G-6-P) following the onset of anoxia. By contrast, in IR22, there was little evidence for control by PFK, consistent with recent evidence that suggests substrate supply limits alcoholic fermentation in this cultivar.

Alcohol Dehydrogenase↗