Panuveitis as a presenting feature of giant cell arteritis.
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Aged↗
Biomedical subjects
M Cole
Publications and source records attributed to M Cole.
A World Wide Web-based health resource. Survey of Missouri school nurses to determine priority health information resources for SchoolhealthLink.
Two hundred ninety-two school nurses in Missouri participated in a mailed survey to aid in the design of SchoolhealthLink, a World Wide Web (WWW)-based information service for Missouri school nurses and children. The nurses identified specific health information resources likely to benefit school nurses and school children and prioritized these resources. The school nurses assigned high priority to 11 types of health information resources: individualized health care plans, emergency care plans, communicable disease control plans, acute illness, injuries, communicable diseases, hotline numbers, medications in schools, immunization protocols and standards, community-based health care resources, and Department of Elementary and Secondary Education regulations that affect school nurse practice. The four most common health problems school nurses identified were asthma, attention deficit disorder, diabetes, and head lice. SchoolhealthLink will provide a one-stop WWW-based resource for school nurses and school children.
Adult↗
Prolonged exposure to intermittent alcohol vapors blunts hypothalamic responsiveness to immune and non-immune signals.
BACKGROUND: We have previously shown that long-term alcohol treatment blunts the ACTH response to alcohol itself, as well as to other stresses, and is accompanied by decreased pituitary responsiveness to vasopressin (VP), but not corticotropin-releasing factor (CRF). The present work aims to determine the relevance of changes in CRF and VP receptors in the pituitary gland and/or peptide stores of CRF neurons in the paraventricular nucleus (PVN) of the hypothalamus, the areas that are most directly involved in ACTH release. METHODS: Intact male rats were exposed to alcohol using a new vapor delivery system which enables individual rat housing in boxes. Alcohol treatment was delivered for 6 hr once daily (0700-1300), after which the rats were returned to their home cages where they had free access to food and water. Control rats were kept in similar boxes, but not exposed to alcohol. Total treatment time was 8 days. All animals were equipped with indwelling jugular cannulae that were used to monitor blood alcohol levels (BALs) as well as ACTH and corticosterone release throughout drug exposure. Due to the presence of a swivel, the animals' movements were not restricted or hindered by the presence of these cannulae. On the morning of day 9, the animals were decapitated under basal conditions or exposed to a neurogenic (mild electrofootshocks) or systemic [i.v. lipopolysaccharide (LPS)] stimulus. PVN neuronal responses, indicated by changes in mRNA concentrations of the immediate early genes (IEGs) c-fos and NGFI-B, and plasma ACTH levels were measured before and during endotoxemia or electrofootshocks. RESULTS: In the absence of alcohol, plasma ACTH and corticosterone remained at basal levels, indicating the absence of environment-induced stress. In rats exposed to alcohol, BALs were consistent and predictable, and we targeted peak values of about 200 mg%. At the end of the drug treatment period, there were no significant differences between CRF and VP receptor mRNA levels in the anterior pituitary of control and alcohol-treated rats. In contrast, alcohol treatment respectively decreased CRF and increased VP stores in the external zone of the median eminence. It also increased NGFI-B and c-fos transcripts in the magnocellular (m) portion of the PVN, but not the parvicellular (p) division of this nucleus under basal conditions (i.e., in the absence of shocks or LPS). After exposure to these stressors, on the other hand, all groups of rats showed significant increases in plasma ACTH levels as well as up-regulation of their PVN neuronal response, as indicated by changes in pPVN IEGs transcripts. However, these hormonal and neuronal responses were significantly blunted in animals pretreated with alcohol. CONCLUSIONS: Collectively, our results suggest that decreased PVN neuronal activation represents an important mechanism of the ability of long-term alcohol treatment to blunt the ACTH response to shocks or endotoxemia. In addition, the new system of alcohol delivery that we developed is practical and reliable, and has the significant advantage that it enables measurement of circulating hormone levels during drug exposure of the animals.
Adrenocorticotropic Hormone↗
Surgery in the nineties.
The population of the United States is aging, and by 2020 it is estimated that 16 per cent of U.S. citizens will be over 65 years of age. Little has been published about the results of surgery in nonagenarians but mortality rates of 45 per cent are reported. Given recent improvements in perioperative care we reviewed the experience with major general surgical operative procedures in nonagenarians. We reviewed the charts of patients greater than or equal to 90 years of age who underwent general surgical procedures at UCLA Medical Center since 1986. No patients were excluded. Thirty-two patients were identified. Most (87.5%) patients had significant premorbid conditions. The most common diagnoses were cancer (12), incarcerated hernia (seven), trauma (three), colonic volvulus (two), and cholecystitis (two). Overall perioperative mortality was 9.4 per cent (3 of 32). Twenty-two surgeries (69%) were performed on an emergency basis, and all three deaths were in this group (13.6%). Overall morbidity rate was 57 per cent. Mean intensive care unit stay was 4.8 days. Most patients were discharged home. Our findings support the perioperative safety of elective general surgery in nonagenarians (0% mortality and 20% morbidity). We also found an acceptable risk (13.6% mortality and 68% morbidity) for emergency procedures despite significant comorbid conditions. Most of the patients had acceptable functional outcomes.
Aged↗
Ascorbic acid is a potent inhibitor of various forms of T cell apoptosis.
This study was designed to examine the effect of ascorbic acid (vitamin C) on various death pathways of mouse T cells. Unlike humans, mice produce their own ascorbic acid and our study tested the effect of additional ascorbic acid on murine T cells. Our data show that three T cell death pathways (growth factor withdrawal-, spontaneous-, and steroid-induced death) were inhibited when T cells were incubated with ascorbic acid. The data show that both activated and resting T cells were responsive to ascorbic acid since both populations were resistant to death stimuli when treated with ascorbic acid. Additionally, effector T cells were more likely to enter S phase if treated with ascorbic acid. Our data implicate ascorbic acid as a potent inhibitor of various forms of T cell death and suggest that vitamin C may function as an immune booster through this mechanism.
Animals↗
Clinical problem-solving: diagnosis of tuberculous meningitis.
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Aged↗
B-cell leukemia protein-2 and peptide YY chemotherapy resistance in colon cancer.
BACKGROUND: Inhibition of apoptosis may allow cells with drug-induced damage to escape programmed cell death. The bcl-2 protein inhibits apoptosis and bcl-2 overexpression has been associated with drug resistance. It is our hypothesis that higher levels of bcl-2 expression will be seen in colon cancer cells resistant to PYY treatment. METHODS: Caco2 and HCT116 colon cancer cells were treated with 2 microM PYY for 24 hours. Protein was extracted from cells surviving PYY treatment; bcl-2 expression was measured by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting. RESULTS: Caco2 and HCT116 cells surviving PYY treatment demonstrated increased bcl-2 from 20.54+/-2.7 to 28.63+/-2.20 units/mL (P <0.05) and 21.98+/-1.28 to 29.32*+/-2.26 units/mL, respectively. CONCLUSIONS: Increased expression of bcl-2 is seen in a population of colon cancer cells resistant to PYY. Hence, bcl-2 may protect neoplastic cells from apoptosis; its levels may be useful in predicting chemotherapy response and in selecting appropriate drug regimens.
Apoptosis↗
Cyclophosphamide metabolism in children with Fanconi's anaemia.
Although patients with Fanconi's anaemia (FA) exhibit a heightened sensitivity to DNA cross-linking agents, modified doses of CY continue to be used in their conditioning prior to BMT. We measured the pharmacokinetics and metabolism of CY in six children with FA using an established high performance thin layer chromatography technique. CY doses ranged between 5 and 20 mg/kg (median 10 mg/kg). The median CY clearance was 0.6 l/h/m2 (range 0.4-1.1 l/h/m2), t1/2 was 8.1 h (range 6.7-9.5 h) and volume of distribution was 0.19 l/kg (range 0.16-0.34 l/kg), respectively. These results contrast with those previously reported from a comparable group of non-FA children in whom the median CY clearance was 3.2 l/h/m2 (range 2-5 l/h/m2) (P = 0.035), t1/2 was 2.4 h (range 2-3.8 h) (P = 0.035) and volume of distribution 0.5 l/kg (range 0.26-0.95 l/kg) (NS). Unlike the control group in whom the presence of inactive metabolites of CY was common, metabolites could not be found in any FA patient. The enhanced sensitivity of children with FA to CY may in part result from altered drug metabolism.
Bone Marrow Transplantation↗
T and Tk antigen activation in necrotising enterocolitis: manifestations, severity of illness, and effectiveness of testing.
AIMS: To determine if T or Tk antigen activation is associated with different and more severe manifestations of illness in infants with necrotising enterocolitis (NEC); and if a policy of testing infants with suspected sepsis or NEC for T and Tk antigen activation is effective. METHODS: A case-control study of infants with confirmed NEC, born after the introduction of screening, was undertaken:17 activated infants were compared with 28 non-activated controls, matched for gestation and weight. A historical control study compared the outcome of infants before and after the introduction of testing. RESULTS: Of 201 infants with confirmed NEC, 27 were T or Tk antigen activated-10 (9%) before and 17 (19%) after the introduction of testing. T or Tk antigen activated infants had a significantly higher mortality (35% vs 7%); more frequent (71% vs 21%) and severe haemolysis, hyperkalaemia, renal impairment, acidosis; and they received more colloid for resuscitation. While only known activated infants in both time periods were managed with the use of low titre T antibody blood products, there was a significant increase in mortality (odds ratios 2.6; 95% CI 1.2, 5.6) and incidence of surgery (OR 2.7; 1.5, 4.9) after the introduction of testing. The increased mortality (OR 2.6; 0.8, 5.2) and incidence of surgery (OR 1.8; 0.9, 3.7) were no longer significant after adjustment for several perinatal risk factors. CONCLUSIONS: In a retrospective case-control study, routine testing of at risk infants increased the detection rate of T and Tk antigen activation. The use of low titre T plasma products in these patients did not reduce mortality compared with historical controls. A randomised controlled trial of testing in at risk infants, or of the use of low titre T plasma products in babies with NEC and T activation, is warranted.
Antigens, Tumor-Associated, Carbohydrate↗
When the left brain is not right the right brain may be left: report of personal experience of occipital hemianopia.
OBJECTIVES: To make a personal report of a hemianopia due to an occipital infarct, sustained by a professor of neurology. METHODS: Verbatim observation of neurological phenomena recorded during the acute illness. RESULTS: Hemianopia, visual hallucinations, and non-occipital deficits without extraoccipital lesions on MRI, are described and discussed. CONCLUSIONS: Hemianopia, due to an occipital infarct, without alexia, is not a disability which precludes a normal professional career. Neurorehabilitation has not been necessary.
Aortic Valve↗
Molar And Molecular Control In Variable-interval And Variable-ratio Schedules.
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Journal Article↗
The effect of fluconazole on cyclophosphamide metabolism in children.
Fluconazole is increasingly used in children receiving chemotherapy. Many of these patients are being treated with cyclophosphamide, which must undergo hepatic metabolism to produce active alkylating species. As a consequence of the cytochrome P-450 inhibitory properties of fluconazole, a potential interaction exists between these two agents that could influence the therapeutic effect of cyclophosphamide. To investigate this interaction, a retrospective case series of patients was chosen from a population of children with a previously established profile of cyclophosphamide metabolism. Twenty-two children who were not receiving other therapy known to influence drug metabolism were selected and analyzed in terms of fluconazole treatment; of these, nine were receiving fluconazole and thirteen were identified as controls. Study design was not randomized. The plasma clearance of cyclophosphamide was lower in patients receiving fluconazole [mean(SD) 2.4(0.71) versus 4.2(1.2) l/h/m2, p =.001]. In vitro studies were performed to characterize the interaction between fluconazole and cyclophosphamide in six human liver microsomes. The concentration of fluconazole required to reduce the production of 4-hydroxycyclophosphamide to 50% of control values (IC50) varied between 9 and 80 microM (median 38 microM). Further studies of the effect of fluconazole on 4-hydroxycyclophosphamide production in vivo are warranted to determine whether this interaction reduces the therapeutic effect of cyclophosphamide in clinical practice.
Adolescent↗
c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets.
We report here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion of c-myc. Two noteworthy exceptions are the gene cad, which has reduced log phase expression and serum induction in c-myc null cells, and the growth arrest gene gadd45, which is derepressed by c-myc knockout. Thus, cad and gadd45 are the only proposed targets of c-Myc that may contribute to the dramatic slow growth phenotype of c-myc null cells. Our results demonstrate that a loss-of-function approach is critical for the evaluation of potential c-Myc target genes.
Animals↗
Neonatal alcohol exposure reduces NMDA induced Ca2+ signaling in developing cerebellar granule neurons.
Glutamatergic neurotransmission through NMDA receptors is critical for both neurogenesis and mature function of the central nervous system (CNS), and is thought to be one target for developmentally-induced damage by alcohol to brain function. In the current study we examined Ca2+ signaling linked to NMDA receptor activation as a potential site for alcohol's detrimental effects on the developing nervous system. We compared Ca2+ signals to NMDA in granule neurons cultured from cerebella of rat neonates exposed to alcohol (ethanol) during development with responses to NMDA recorded in separated control groups. Alcohol exposure was by the vapor chamber method on postnatal days 4-7. An intermittent exposure paradigm was used where the pups were exposed to alcohol vapor for 2. 5 h/day to produce peak BALs of approximately 320 mg%. Control pups were placed in an alcohol-free chamber for a similar time period or remained with their mother. After culture under alcohol-free conditions for up to 9 days, Ca2+ signaling in response to NMDA was measured using fura-2 Ca2+ imaging. Results show that the peak amplitude of the Ca2+ signal to NMDA was significantly smaller in cultured granule neurons obtained from alcohol-treated pups compared to granule neurons from control pups. In contrast, the Ca2+ signal to K+ depolarization was not depressed by the alcohol treatment. Resting Ca2+ levels were also altered by the alcohol treatment. These results show that intermittent alcohol exposure during development in vivo can induce long-term changes in CNS neurons that affect the Ca2+ signaling pathway linked to NMDA receptors and resting Ca2+ levels. Such changes could play an important role in the CNS dysfunction associated with alcohol exposure during CNS development.
Animals↗
Effectiveness of treatments of depression in older ambulatory patients.
OBJECTIVE: To determine the effectiveness of acute-phase pharmacological and psychological treatments of depression in older ambulatory patients by systematically reviewing original research relevant to this topic. METHODS: Searches in MEDLINE and PsycINFO and manual reviews of bibliographies located 233 articles. Of these, 40 (37 different studies) met our 8 inclusion criteria: original research, written in English or French, subjects 55 years and older, diagnosis of depression, outpatient or community setting, prospective controlled study design, acute-phase pharmacological or psychological treatment, and outcome measure of depression. Two independent reviewers assessed the methodological quality of each article using a standard form and a quality score was computed. Quantitative data on levels of depression at the end of treatment were abstracted. Results were grouped by specific treatment comparison (type of treatment and type of control group). For comparisons that used the Hamilton Depression Rating Scale, we computed mean posttreatment differences. Effect sizes were computed from the Hamilton Depression Rating Scale or an alternative scale. RESULTS: In studies that compared active drugs with placebo, the heterocyclic drugs significantly reduced the posttreatment Hamilton Depression Rating Scale score (mean difference, -5.78; 95% confidence interval, -8.31 to -3.25); other drugs had smaller effects. In studies that compared active drugs, there were no significant differences overall between different classes of drugs; selective serotonin reuptake inhibitors appeared to be as effective as heterocyclic drugs. Rational psychological treatments performed significantly better than no treatment (mean posttreatment Hamilton Depression Rating Scale difference, -7.25; 95% confidence interval, -10.10 to -4.40) but not significantly better than that for controls who received similar attention. Adjustment for the study quality score did not affect these results. CONCLUSIONS: Based on comparisons with untreated controls, heterocyclic antidepressants and rational psychological therapies appear to be the most effective treatments for older ambulatory patients with mild to moderate depression. Based on drug-drug comparisons, selective serotonin reuptake inhibitors appear to be as effective as heterocyclic drugs. However, overall, the magnitude of the treatment effects is modest. Limitations in the quantity and quality of appropriate studies suggest a sober approach to treatment in this population.
Acute Disease↗
Increased soluble interleukin 2 receptor levels in schizophrenia.
Immunological mechanisms have been implicated in schizophrenia, but laboratory results have been variable. We evaluated soluble interleukin 2 receptor (sIL2R alpha) levels in sera of Irish patients with schizophrenia. Twenty-seven patients, 12 females and 15 males, with schizophrenia or schizophreniform psychosis, were sampled, along with 32 controls. Diagnosis was made using the Structured Clinical Interview for DSM IIIR. All but one of the patient group were in the first fortnight of an acute hospital admission. Soluble IL2R alpha levels were measured by ELISA. Soluble IL2R alpha levels were significantly higher (two-tailed p = 0.0019) in patients (median = 1010.4 pg/ml, range = 748.7-5673.3 pg/ml) than in controls (median = 792.3 pg/ml, range = 399.6-1479.5 pg/ml). The elevated sIL2R alpha levels in an Irish population with schizophrenia are consistent with other reports and support the implication of immunological mechanisms in this disorder.
Adolescent↗
Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study.
OBJECTIVE: To explore the possible association between intramuscular vitamin K given to neonates and the subsequent development of childhood cancer. DESIGN: Retrospective case-control study on the basis of hospital records. SETTING: The former Northern Health region of England. SUBJECTS: 685 children who were born and lived in the region and who developed cancer before their 15th birthday, and 3442 controls also born between 1960 and 1991 and matched only for date and hospital of birth. The notes of a further 701 index cases were untraceable. MAIN EXPOSURE MEASURE: Administration of intramuscular vitamin K versus no exposure to vitamin K. RESULTS: There was no association between the administration of vitamin K and the development of all childhood cancers (unadjusted odds ratio 0.89; 95% confidence interval 0.69 to 1.15) or for all acute lymphoblastic leukaemia (1.20; 0.75 to 1.92), but there was a raised odds ratio for acute lymphoblastic leukaemia developing 1-6 years after birth (1.79; 1.02 to 3.15). No such association was seen in a separate cohort-based study not dependent on case note retrieval in which the rates of acute lymphoblastic leukaemia in children born in hospital units where all babies received vitamin K were compared with those born in units where less than a third received prophylaxis. CONCLUSIONS: It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal intramuscular vitamin K administration increases the risk of early childhood leukaemia. Any association may have been masked in earlier studies that did not use controls matched for time and locality by other unidentified factors affecting the spatiotemporal variations in incidence of leukaemia.
Adolescent↗