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Biomedical subjects

J A O'Connor

Publications and source records attributed to J A O'Connor.

At least 19 recordsLinked to original sources
PubMed2006

AMPA receptor subunit and splice variant expression in the DLPFC of schizophrenic subjects and rhesus monkeys chronically administered antipsychotic drugs.

Disturbances in glutamate neurotransmission are thought to be one of the major contributing factors to the pathophysiology of schizophrenia. In the dorsolateral prefrontal cortex (DLPFC), glutamate neurotransmission is largely mediated by AMPA receptors. Data regarding alterations of subunit expression in the brains of patients with schizophrenia remain equivocal. This may be due to differences in technique sensitivity, endogenous control selection for normalization of data, or effect of antipsychotic drug treatment in different cohorts of schizophrenia. This study attempted to address these issues by examining the expression of AMPA receptor subunits and splice variants in the DLPFC of two schizophrenia cohorts using quantitative PCR (qPCR) with normalization to the geometric mean of multiple endogenous controls. In addition, a non-human primate model of chronic antipsychotic drug administration was used to determine the extent to which the transcript expression may be altered by antipsychotic drug treatment in the primate DLPFC. AMPA receptor subunits and flip and/or flop splice variants were not significantly different in the DLPFC of schizophrenia subjects versus controls in either of the two cohorts. However, in rhesus monkeys chronically treated with antipsychotic drugs, clozapine treatment significantly decreased GRIA1 and increased GRIA3 mRNA expression, while both clozapine and haloperidol increased the expression of GRIA2 subunit mRNA. Expression of AMPA receptor splice variants was not significantly altered by antipsychotic drug administration. This is the first study to show that AMPA receptor subunit mRNAs in the primate DLPFC are altered by antipsychotic drug administration. Antipsychotic drug-induced alterations may help explain differences in human post-mortem studies regarding AMPA receptor subunit expression and provide some insight into the mechanism of action of antipsychotic drugs.

Adult↗
PubMed2001

Geriatric falls: injury severity is high and disproportionate to mechanism.

OBJECTIVE: Falls are a well-known source of morbidity and mortality in the elderly. Fall-related injury severity in this group, however, is less clear, particularly as it relates to type of fall. Our purpose is to explore the relationship between mechanism of fall and both pattern and severity of injury in geriatric patients as compared with a younger cohort. METHODS: Our trauma registry was queried for all patients evaluated by the trauma service over a 412-year period (1994-1998). Two cohorts were formed on the basis of age greater than 65 or less than or equal to 65 years and compared as to mechanism, Injury Severity Score (ISS), Abbreviated Injury Scale score, and mortality. RESULTS: Over the study period, 1,512 patients were evaluated, 333 greater than 65 years and 1,179 less than or equal to 65 years of age. Falls were the injury mechanism in 48% of the older group and 7% of the younger group (p < 0.05). Falls in the older group constituted 65% of patients with ISS >15, with 32% of all falls resulting in serious injury (ISS >15). In contrast, falls in the younger group constituted only 11% of ISS >15 patients, with falls causing serious injury only 15% of the time (both p < 0.05). Notably, same-level falls resulted in serious injury 30% of the time in the older group versus 4% in the younger group (p < 0.05), and were responsible for an ISS >15 30-fold more in the older group (31% vs. <1%; p < 0.05). Abbreviated Injury Scale evaluation revealed more frequent head/neck (47% vs. 22%), chest (23% vs. 9%), and pelvic/extremity (27% vs. 15%) injuries in the older group for all falls (all p < 0.05). The mean ISS for same-level falls in the older group was twice that for the younger group (9.28 vs. 4.64, p < 0.05), whereas there was no difference in mean ISS between multilevel and same-level falls within the older group itself (10.12 vs. 9.28, p > 0.05). The fall-related death rate was higher in the older group (7% vs. 4%), with falls seven times more likely to be the cause of death compared with the younger group (55% vs. 7.5%) (both p < 0.05). Same-level falls as a cause of death was 10 times more common in the elderly (25% vs. 2.5%, p < 0.05). CONCLUSION: Falls among the elderly, including same-level falls, are a common source of both high injury severity and mortality, much more so than in younger patients. A different pattern of injury between older and younger fall patients also exists.

Accidental Falls↗
PubMed2000

Posttransplantation lymphoproliferative disorder: endoscopic findings.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) may manifest a variety of nonspecific symptoms and must be suspected in the patient who undergoes solid organ transplantation. Common sites of occurrence include the gastrointestinal tract, the central nervous system, and lymphoid tissue of the oral pharynx, mediastinum, and mesentery. The large incidence of gastrointestinal involvement provides an opportunity for endoscopic diagnosis. This is the description of a characteristic endoscopic finding in patients who have undergone liver transplantation who are under evaluation for suspected PTLD. METHODS: During a 2-year period, 27 liver transplantations were performed in 24 pediatric patients. Fourteen patients underwent endoscopic evaluation. Indications for endoscopy included abdominal pain, vomiting, hematemesis, irritability, growth failure, anemia, occult blood loss, and suspected PTLD. Biopsy specimens were obtained from any endoscopically detected abnormality and from the duodenum, gastric antrum, esophagus, terminal ileum, cecum, and rectum. Specimens with suspected PTLD were evaluated with Epstein-Barr virus latent membrane stain. RESULTS: Six patients were found to have a characteristic lesion, which was raised, rubbery, and erythematous, with a central ulceration. Lesions were singular or multiple and ranged from 5 to 15 mm in diameter. Microscopic evaluation revealed a monotonous proliferation of lymphocytes. All specimens were positive for Epstein-Barr virus latent membrane protein stain. Stains for cytomegalovirus were negative. Biopsy specimens from the eight patients without identified characteristic lesions were negative for PTLD. CONCLUSIONS: Panendoscopy is a useful tool for the diagnosis and treatment of gastrointestinal PTLD. Endoscopy is easily accomplished, may provide an instantaneous result if the characteristic lesion is identified, and provides tissue for disease classification. Patients with unexplained gastrointestinal signs or symptoms should undergo panendoscopy for suspected PTLD.

Adolescent↗
PubMed2000

Acute and chronic viral hepatitis.

Viral hepatitis is the most common cause of acute and chronic hepatitis. The term viral hepatitis generally refers to infections resulting from one of the hepatotrophic viruses: hepatitis A, B, C, D, and E. The last 10 years have brought many important advances in understanding the epidemiology, pathogenesis, molecular biology, and immunoprophylaxis of infections caused by hepatotrophic viruses. Development of sensitive and specific immunoassays has enabled detection of specific agents. This has allowed for identification of infected patients and monitoring response to therapy. Additionally, serologic markers have allowed for isolation of contaminated blood products and a reduction in the spread of disease. The remaining challenge is the application of this knowledge to the treatment and prevention of viral hepatitis. This article explores the risk factors, epidemiology, microbiology, clinical and laboratory diagnosis, treatment, and prevention of the hepatotrophic viral infections.

Acute Disease↗
PubMed1997

Cost-effective supply use in permanent central venous catheter operations.

A prospective, randomized trial was designed to determine whether a streamlined operating room supply pack was cost-effective in the placement of permanent central venous catheters. Over a 12-month period, 139 consecutive patients were randomized and evaluated. There were no differences found between the mean ages, sex, indication for catheter placement, mean operative time, or surgeon and nurse satisfaction between treatment groups. In addition, 30-day catheter infection rate, 30-day catheter malfunction rate, and 30-day catheter removal rate were similar between groups. Supply costs were $411.32 per patient operation in the control group and only $180.34 per patient operation in the study group, resulting in an average cost-effectiveness ratio of $230.98 per catheter placed. Based on these data, a streamlined operating room supply setup is cost-effective in the operative placement of permanent central venous catheters.

Adult↗
PubMed1990

Complications of gastroesophageal antireflux surgery in neurologically impaired versus neurologically normal children.

Antireflux surgery was performed in 234 children over a 5-year period; 153 were neurologically impaired (NI) and 81 were neurologically normal (NN). Initial presentation, demographic data, and type of antireflux operation were similar in the two groups. Eighty-six percent of the NI group versus 30% of the NN group had gastrostomy tubes placed. The incidence of late postoperative complications was 26% in the NI group and 12% in the NN group (P less than .01). During the late postoperative period, NI children underwent reoperation four times as frequently as NN children (19% v 5%, respectively; P less than .01). Wrap herniation accounted for 38% of complications and 59% of reoperations in the late postoperative period. Mortality due to aspiration occurred in 9% of the NI group versus 1% of the NN group. Combined failure rate (reoperation plus aspiration-induced deaths) was 28% in NI and 6% in NN (P less than .01). We conclude that neurological status is the major predictor of operative success and that wrap herniation due to crural disruption is the most common cause of operative failure.

Adolescent↗
PubMed1989

Somatomedin-A inhibits glucagon-stimulated hepatic gluconeogenesis.

Somatomedin/insulin-like growth factors have been noted to produce insulin-like actions on the liver that include the ability to inhibit the formation of glucagon-stimulated but not basal c-AMP production. This raises the possibility that these compounds may also be able to inhibit glucagon-stimulated hepatic gluconeogenesis. The purpose of this study was to determine the effects of varying concentrations of somatomedin-A on glucagon-stimulated gluconeogenesis in isolated perfused rat liver. The infusion of glucagon increased the rate of gluconeogenesis from 0.0038 +/- 0.001 to 0.042 +/- 0.007 microM 14C-glucose made from 14C-alanine per min. This action of glucagon was reduced to 22% of its maximum by the coinfusion of 1 microU/ml of SM-A and completely eliminated by the coinfusion of 100 microU/ml of SM-A. Somatomedin alone did not alter the basal rate of gluconeogenesis. The decrease in the release of 14C glucose from livers that had been stimulated by glucagon could not be attributed to increased glycogenolysis. Thus, it appears that the reduction in 14C release represents SM-A mediated reduction in glucagon-stimulated gluconeogenesis.

Alanine↗
PubMed1982

The influence of strain rate on adaptive bone remodelling.

Bending and compressive loads were applied intermittently at 0.5 Hz through implants chronically inserted into the radius and ulna of experimental sheep. The plane of bending was the same as that imposed during locomotion. The principal variables of the artificial strain regime were the peak strains and strain rates, which never exceeded the range attainable during normal locomotion. The bones were loaded artificially for one hour per day for six weeks. Post mortem, the parameters of the bones' remodelling response were assessed by measuring the change in gross geometry and the amount of new bone formation which was marked with fluorescent label given during the experimental period. The strain-related variable, which had the greatest influence on every remodelling parameter investigated, was the ratio between the maximum strain rate of the artificial regime and the maximum strain rate during walking. The variation in this ratio could be shown to account for between 68 and 81% of the variation in the measures of surface bone deposited. The strain parameter which caused the greatest additional increase in the proportion of total variation explained was most commonly the ratio between the proportion of peak strain due to axial loading in the normal and artificial situations. The effect of this axial strain was far less marked than that of strain rate, however, and only increased the percentage of the total variance which could be explained by between 6 and 12%. The direction of bending and axial loading (tension or compression) appeared to have no effect on the course of the remodelling observed. The most effective influence on the amount of intracortical secondary osteal remodelling was also the maximum strain rate ratio. Its effect on this process seemed less marked than that on surface remodelling, however, since it could only explain 43% of the variance in the total number of secondary osteons formed. The addition of other strain-related variables did not significantly increase this proportion.

Animals↗
PubMed1982

Perfused rat hindlimb wound model: lambda-carrageenan induced.

We established an isolated perfused rat hindlimb wound model using intramuscular injections of lambda-carrageenan. Wound and control hindlimbs of 24-h fasting anesthetized (phenobarbital sodium, 5 mg/100 g body wt) rats were perfused for 60 min (10 ml/min) with media containing 10 mM glucose and physiological levels of amino acids. Analysis of perfusate showed a significant increase in glucose clearance and lactate production from the wounded hindlimb but no significant difference in tissue adenine nucleotide levels. Alterations in net amino acid release were measured over a 60-min period; all amino acids were released in greater concentration from wounded hindlimbs. Comparison of amino acid release, normalized for phenylalanine concentration, suggested the following alterations in amino acid metabolism by the wounded tissue: depressed threonine, glycine serine and alanine release, and increased release of the branched chain amino acids (BCAA), leucine, isoleucine, and valine. The increased release and intracellular concentration of BCAA was supported by decreased BCAA transaminase activity in the wounded muscle tissue. This result may explain the decreased alanine release from the wounded hindlimbs.

Adenine Nucleotides↗
PubMed1981

Effects of differential changes in rat hepatic and renal cytochrome P-450 concentrations on hepatotoxicity and nephrotoxicity of chloroform.

Cytochrome P-450 concentrations in rat liver and kidney were differentially altered by pretreatment with phenobarbital (PB), cadmium or fasting. The rats were then challenged with chloroform. The consequent hepatotoxicity was assayed by alanine amino transferase activity (AlaAT); the nephrotoxicity by inhibition of p-aminohippuric acid (PAH) uptake in vitro and both by histopathology. Fasting increased renal and hepatic cytochromes P-450 and chloroform-mediated necrosis in both organs. PB induction increased and cadmium decreased the liver cytochrome P-450 concentrations and the hepatotoxicity mediated by chloroform. PB and cadmium had no effect on renal cytochrome P-450 concentrations or the nephrotoxicity of chloroform. These results strongly suggest that the nephrotoxic metabolite of chloroform is produced within the kidney and the hepatotoxic metabolite in the liver.

Animals↗
PubMed1980

Hypomagnesemia: higher risk using total parenteral nutrition in the treatment of patients with malignancies.

The syndrome of hypomagnesemia in patients receiving total parenteral nutrition (TPN) is well known. To determine particular high-risk groups for the development of this syndrome, 26 consecutive patients on TPN were initially evaluated for serum magnesium (Mg) and followed at regular intervals. Seventeen had a diagnosis of solid tumor or hematologic malignancy (CA); nine had inflammatory bowel disease and/or small bowel fistulae (ID). All met the standard criteria for being malnourished--anergy, low serum albumin, and recent weight loss. During TPN, all patients received an average of 24 mEq of magnesium sulfate per day, and all had satisfactory anabolic response in terms of weight gain and increase in serum albumin. Ten patients had at least one magnesium determination below the lower limits of normal, and four of these developed symptoms of tremor which responded to increased amounts of magnesium in their TPN. Eight of these ten (80%) had a diagnosis of CA, and four of four (100%) of those requiring additional magnesium to alleviate symptoms had CA. None of the patients with ID developed symptomatic hypomagnesemia. We conclude that patients with solid tumor malignancy are more likely to develop hypomagnesemia, possibly because of the increased requirements for magnesium in lymphocytolysis of tumor cells., and they must be carefully monitored to prevent this complication.

Adolescent↗
PubMed1979

Effect of age on axoplasmic transport of cholinesterase in rat sciatic nerves.

Senile muscle atrophy has been attributed to an impaired ability of old nerves to transport trophic factors. To evaluate the effect of age on axoplasmic transport, we measured the accumulation of cholinesterase activity above a ligature around sciatic nerves of young (7--8 months), middle-aged (19--20 months), and old (31--32 months) male rats. Protein content and cholinesterase activity per mm of nerve were higher in middle-aged and old than in young nerves. However, accumulation of cholinesterase activity was significantly lower by middle age and was strikingly reduced by old age. This large reduction in axoplasmic transport appeared to result from factors other than axonal loss. A model in which old nerves have an increased number of temporary focal blockages of particle movement in axoplasmic channels is proposed to explain the decreased transport.

Aging↗