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Biomedical subjects

J Gallagher

Publications and source records attributed to J Gallagher.

At least 19 recordsLinked to original sources

Sucrose and the integration of metabolism in vascular plants.

We consider the hypothesis that sucrose is a signal as well as a substrate. We suggest that the significance of sugar sensing in plants is the integration of whole-plant carbon flux so that the capacity of sources to produce sucrose matches the capacity of sinks to consume it. We pay particular attention to difficulties with this hypothesis and the areas where further or better evidence is needed. We conclude that there is strong correlative evidence for a link between sucrose metabolism and the level of expression of key genes, but that a number of different mechanisms may be involved.

Journal Article↗

Intensive care unit syndrome: a dangerous misnomer.

The terms intensive care unit (ICU) syndrome and ICU psychosis have been used interchangeably to describe a cluster of psychiatric symptoms that are unique to the ICU environment. It is often postulated that aspects of the ICU, such as sleep deprivation and sensory overload or monotony, are causes of the syndrome. This article reviews the empirical support for these propositions. We conclude that ICU syndrome does not differ from delirium and that ICU syndrome is caused exclusively by organic stressors on the central nervous system. We argue further that the term ICU syndrome is dangerous because it impedes standardized communication and research and may reduce the vigilance necessary to promptly investigate and reverse the medical cause of the delirium. Directions for future research are suggested.

Cognition Disorders↗

Does chronic occupational exposure to volatile anesthetic agents influence the rate of neutrophil apoptosis?

PURPOSE: The purpose of this preliminary investigation was to determine whether the rate of neutrophil apoptosis in health care workers is influenced by exposure to volatile anesthetic agents. METHODS: Percentage neutrophil apoptosis (Annexin-V FITC assay) was measured in health care workers (n = 20) and unexposed volunteers (n = 10). For the health care workers, time weighted personal exposure monitoring to N2O, sevoflurane and isoflurane was carried out. RESULTS: The sevoflurane and isoflurane concentrations to which health care workers were exposed were less than recommended levels in all 20 cases. Percent apoptosis was less at 24 (but not at one and 12) hr culture in health care workers [50.5 (9.7)%; P = 0.008] than in unexposed volunteers [57.3 (5.1)%]. CONCLUSION: Inhibition of neutrophil apoptosis at 24 hr culture was demonstrated in health care workers chronically exposed to volatile anesthetic agents. Exposure was well below recommended levels in the both scavenged and unscavenged work areas in which the study was carried out. Further study is required to assess the effect of greater degrees of chronic exposure to volatile anesthetic agents on neutrophil apoptosis.

Adult↗

Tuberculosis in badgers; a review of the disease and its significance for other animals.

This review examines the current state of knowledge of aspects of tuberculosis in the badger. The gross pathology and pathogenesis are elaborated as well as the immune mechanism, diagnosis of infection and excretion and viability of infected products. The epidemiology in badgers is considered, as is the significance of infection in this species for other wildlife species as well as domestic animals sharing the same habitat. Trials of the effects of the removal of badgers on the occurrence of tuberculosis in cattle are summarised. It is concluded that badgers are well adapted as the primary host of bovine tuberculosis in parts of Britain and much of Ireland.

Animals↗

Measuring disability, need and outcome in Australian community mental health services.

OBJECTIVE: This study trialled routine measurement of disability, need and outcome in mental health services within Sydney. METHOD: Fifteen community mental health clinicians with a combined caseload of 283 patients participated in the study. The Health of the Nation Outcome Scales (HoNOS) was used to assess disability and outcome and the patient and staff versions of the Camberwell Assessment of Need (CAN) were used to assess need. RESULTS: The HoNOS and CAN appear to be promising contenders for routine use. Patients receiving assertive case management were rated as having higher levels of disability and need than patients receiving standard case management. Significant change in outcome was demonstrated with the HoNOS. CONCLUSIONS: To ensure the continued measurement of consumer outcome, issues such as staff education, training, and the development of computerised information systems should be addressed.

Adult↗

The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

PURPOSE: Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. MATERIALS AND METHODS: Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. RESULTS: On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Anti-Bacterial Agents↗

Sexuality and cancer: conversation comfort zone.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Psychosocial issues profoundly affect patients with cancer. Of the many complexities that make up the psychosocial dynamic, perhaps the medical profession is most uncomfortable with sexuality. Many elements of sexual behavior remain high-profile taboos. A number of diseases and treatments significantly affect sexual function. Male and female sexuality were discussed in two separate rounds with an emphasis on how to begin a dialogue about sexuality without jeopardizing other aspects of the relationship with patients. Three cases were presented. A patient with prostate cancer considering treatment options for early-stage disease and two patients with gynecologic malignancies; one with a colostomy following cytoreductive surgery for ovarian cancer and the other with a failed vaginal reconstruction for recurrent squamous cell carcinoma of the vagina. Staff discussed the wide diversity of response to sexual dysfunction and the difficulties that patients face. A sensitive and informed approach to discussing sexuality can provide effective support. The elements of successful dialogue are presented in the PLISSIT model.

Adult↗

Breakfast cereal and caffeinated coffee: effects on working memory, attention, mood, and cardiovascular function.

This study examined the effects of breakfast cereal and caffeinated coffee on working memory, attention, mood, and cardiovascular function. One hundred and forty-four volunteers (72 male, 72 female, mean age 21 years) were assigned to one of the groups formed by combining breakfast (cereal versus no breakfast) and caffeine (caffeinated versus decaffeinated coffee) conditions. The volunteers completed a baseline session between 0800 and 0845 h. The breakfast/caffeine administration took place between 0845 and 0915 h. They then completed another test session (starting at 0945) and had a coffee break at 1045, followed by a final session starting at 1145. The results showed that those who consumed breakfast cereal had a more positive mood at the start of the test sessions, performed better on a spatial memory task, and felt calmer at the end of the test session than those in the no breakfast condition. Ingestion of caffeine had no effect on initial mood or working memory, but it did improve encoding of new information and counteracted the fatigue that developed over the test session. Caffeine increased blood pressure and pulse rate, whereas breakfast cereal consumption only had an effect on pulse. Overall, these results confirm previous findings on the effects of breakfast and caffeine, and demonstrate distinct profiles for two common examples of early-morning food and drink, breakfast cereal and caffeinated coffee.

Adult↗

Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis.

OBJECTIVE: Proteoglycan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA), both in terms of its pathology and its genetics. PGIA can only be induced in susceptible murine strains and their F2 progeny. As with RA, the genetics are complex, containing both major histocompatibility complex (MHC)-related and non-MHC-related components. Our goal was to identify the underlying non-MHC-related loci that confer PGIA susceptibility. METHODS: We used 106 polymorphic markers to perform simple sequence-length polymorphism analysis on F2 hybrids of susceptible (BALB/c) and nonsusceptible (DBA/2) strains of mice. Because both strains of mice share the H2d haplotype, this cross permits identification and analysis of non-MHC-related genes. RESULTS: We identified a total of 12 separate quantitative trait loci (QTL) associated with PGIA, which we have named Pgia1 through Pgia12. QTLs associated with the inflammatory symptoms of PGIA were linked to chromosomes 7, 9, 15 (2 separate loci), 16, and 19. QTLs associated with autoantibody production were identified on chromosomes 1, 2, 7, 8, 10, 11, 16, and 18. QTLs on chromosomes 7 and 16 showed linkage to both inflammation and autoantibody production, suggesting a shared regulatory component in arthritis induction. The first inflammation QTL on chromosome 15 and the autoantibody QTL on chromosome 7 originate from the DBA/2 background, which indicates that as in RA, susceptibility genes can originate from heterogeneous backgrounds. CONCLUSION: These data demonstrate the complexity of PGIA, where QTLs may be involved in multiple traits or even originate from a genetic background previously determined to be resistant.

Animals↗

A Phase I study of continuous infusion doxorubicin and paclitaxel chemotherapy with granulocyte colony-stimulating factor for relapsed epithelial ovarian cancer.

A Phase I study of paclitaxel and doxorubicin administered as concurrent 96-h continuous i.v. infusion was performed to determine the maximum tolerated dose (MTD), principal toxicities, and pharmacokinetics of this combination in women with relapsed epithelial ovarian cancer. The paclitaxel dose was fixed at 100 mg/m2 (25 mg/m2/day for 4 days). The dose of doxorubicin was escalated from 30 mg/m2 (7.5 mg/m2/day for 4 days) in increments of 10 mg/m2 until dose-limiting toxicity was observed. All patients received granulocyte colony-stimulating factor 5 microg/kg/day prophylactically. Apparent steady-state plasma levels of both drugs were determined in the final cohort of patients treated at the MTD. A total of 17 patients received 52 cycles of therapy. The median age was 58 years, and all patients had previously received one to five different regimens (median, 2) of chemotherapy, including both platinum and paclitaxel. The treatment was tolerated well, with grade 1-2 nausea being the most frequent side effect (73% of cycles). Anemia, neutropenia, thrombocytopenia, and mucositis became dose limiting at the fourth dose level, defining the MTD of doxorubicin in this regimen as 50 mg/m2. There were four partial responses and one complete response in 15 evaluable patients. Apparent steady-state plasma concentrations (mean +/- SD) of paclitaxel and doxorubicin in the three patients treated at the MTD were 33.9 +/- 12.5 nM and 15.7 +/- 1.3 nM, respectively. Paclitaxel and doxorubicin by continuous infusion is a well-tolerated and active chemotherapy regimen for recurrent ovarian cancer.

Adult↗

Hemolytic uremic syndrome: defining the need for long-term follow-up.

BACKGROUND: Diarrhea-associated (D+) hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Progressive renal insufficiency has been documented on prolonged follow-up of selected patients. However, it is uncertain whether all children recovering from varying degrees of HUS require long-term follow-up. PATIENTS AND METHODS: We reviewed the outcome of 114 patients with D+ HUS presenting to a regional pediatric unit between January 1986 and December 1996. Yearly clinical review post illness included measurement of blood pressure and urinalysis for proteinuria with planned GFR assessments by 51Cr EDTA slope clearance at 1 and 5 years. RESULTS: Treatment of the HUS was conservative in 27%, by peritoneal dialysis in 62%, hemodialysis in 4% and both peritoneal and hemodialysis in 7%. Ninety-two patients were assessed at 1 year - of these, 1 remained on chronic peritoneal dialysis, 5 (5%) had moderate to severe chronic renal failure (CRF) (GFR 25 - 50 ml/min/1.73 m2), 20 (22%) had mild CRF (GFR 50-80) and 66 (72%) had normal renal function (> or =80 ml/min/1.73 m2). Forty patients have had GFRs performed at 1 and 5 years. Of the 28 patients with a normal GFR at 1 year, 3 deteriorated into mild CRF at 5 years. One patient has a single kidney and one had significant proteinuria at 1 year, factors which would have led to long-term follow-up. There was a negative correlation between number of days of dialysis and GFR at 1 year with a Pearson's correlation coefficient of -0.453 (p<0.01). CONCLUSION: We conclude that renal function at I year following HUS cannot be predicted with any certainty from the initial illness and should be formally assessed. However, renal function was within normal limits and remained stable between 1 and 5 years following HUS in most children. The results suggest that longer-term follow-up can probably be restricted to those with proteinuria, hypertension, abnormal ultrasound and/or impaired GFR at 1 year.

Child↗

Role of infected, non-diseased badgers in the pathogenesis of tuberculosis in the badger.

The lungs and kidneys of 15 badgers which had no visible lesions of tuberculosis but from which Mycobacterium bovis was isolated from pooled collections of lymph nodes were serially sectioned. Lesions of tuberculosis were detected by histopathology in the the lungs of 13 and in the kidneys of one of them. The lesions were mostly typical early stage granuloma-lesions which were considered to be the primary foci of infection. These lesions suggest an early containment phase of arrested development previously not observed and provide further evidence on which to propose a hypothesis for the pathogenesis of tuberculosis in the badger.

Animals↗

Protease activity of 1,10-phenanthroline-copper(I). Targeted scission of the catalytic site of carbonic anhydrase.

To investigate the mechanism of scission of proteins by the chemical cleaving agent 1,10-phenanthroline-copper, the active sites of human carbonic anydrase I and bovine carbonic anhydrase II have been targeted for cleavage by a tight binding sulfonamide inhibitor tethered to the metal complex. The inhibitor-phenanthroline-copper conjugate binds to the carbonic anhydrases with sub-micromolar Kd's and, upon addition of a reducing agent, causes scission specifically within the active site of the enzymes to yield a discrete set of cleavage fragments. N- and C-terminal sequencing and mass spectrometric analysis of several fragments indicate that the C-terminal cleavage fragments have free amino groups at their N termini, thereby allowing facile location of the cut sites through standard Edman degradation. The N-terminal cleavage fragments do not have a free carboxyl group at their C termini. It is proposed that scission occurs by abstraction of H at Calpha, followed by oxidation at Calpha by the neighboring cupric ion and cleavage of the Calpha-C(O) bond to give an N-terminal fragment containing a C-terminal acyl amide, and an unstable C-terminal fragment containing an N-terminal isocyanate group which undergoes hydrolysis to a free amino terminus. Modeling of the inhibitor-phenanthroline-copper conjugate within the active site of human carbonic anhydrase I shows that the sites of cleavage that have been identified are fully consistent with the available structural data.

Amino Acid Sequence↗

Severe tiger snake envenomation in a wilderness environment.

A 44-year old bushwalker was envenomed in an isolated area late in the afternoon, and a succession of difficulties with his rescue resulted in his not reaching hospital until nearly 24 hours later. This case highlights the problems of prolonged delays before treatment for envenomation, and points to the advantages of physician-staffed emergency helicopter services carrying snake antivenoms into the field.

Adult↗

Chickenpox ARDS in a health care worker following occupational exposure.

A case is described of chickenpox acute respiratory distress syndrome in an ambulance driver after the inter-hospital transfer of a patient known to have chickenpox pneumonia. Following this exposure, he neither avoided patient contact nor received varicella zoster immune globulin. He subsequently required 13 days of ventilatory support before making a full recovery. The case described supports the contention that health care workers should be screened by serology for immunity to chickenpox before patient contact occurs, with subsequent vaccination of those who are non-immune, when the vaccine becomes available.

Adult↗