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Biomedical subjects

G Carlson

Publications and source records attributed to G Carlson.

At least 19 recordsLinked to original sources
PubMed2006

Chromogenic in situ hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma.

OBJECTIVE: To determine whether loss of melastatin (MLSN) is a universal phenomenon in American Joint Committee on Cancer (AJCC) stage I and II melanoma patients who experienced recurrence. MATERIAL AND METHODS: Paraffin blocks of primary melanomas (PMs) were retrieved from 30 patients who had a negative sentinel lymph node biopsy and developed recurrent melanoma (AJCC stage I and II). Chromogenic in situ hybridization (CISH) methods were utilized to evaluate the expression of MLSN mRNA. These results were correlated with clinicopathologic data. RESULTS: Variable, heterogeneous expression of MLSN mRNA was identified in normal, in situ and invasive melanocytes within and between cases. For the invasive PM component, 24 (80%) had focal, regional or complete loss of MLSN mRNA. The remaining 20% had either regional or total partial downregulation of MLSN mRNA. Intact MLSN mRNA expression was present regionally in 14/30 (47%), with mean relative tumor area of 38%, range 5-85%. Increasing loss of MLSN mRNA significantly correlated with increasing tumor depth and microsatellites (r = 0.1/0.4, p = 0.04). However, thin, AJCC T stage 1a PM had higher relative mean loss than intermediate AJCC T stage 2a/2b/3a thickness PM (65% vs. 34%/48%/25%). Increasing loss of MLSN mRNA significantly impacted on disease free survival (DFS) by multivariate analysis (58 vs. 0% 2 years DFS, < or = 75 vs. > 75% mRNA loss, p = 0.02). Decreased overall survival significantly correlated with increasing age and vascular invasion on multivariate analysis. CONCLUSION: Extensive loss of MLSN in PM correlated with aggressive metastatic melanoma. Ancillary testing for MLSN mRNA expression by CISH could offer a means to more accurately identify AJCC stage I and II patients at risk for metastatic disease, who could benefit from adjuvant therapy.

Adult↗
PubMed2004

Differential regulation of caspase-3 by pharmacological and developmental stimuli as demonstrated using humanised caspase-3 mice.

Caspase-3 is a potential therapeutic target for a number of degenerative diseases. However the development of specific caspase-3 inhibitors has been hampered by inter-species differences and the high degree of homology shared by different caspases. To circumvent these issues, we have produced and characterised a humanised caspase-3 mouse line (possessing one copy of the human gene with both copies of the murine gene disrupted) by crossing human caspase-3 transgenic mice with nullizygous caspase-3 knock-out mice. Humanised mice appeared normal and survived to adulthood. Analysis of the human gene revealed that human pro-caspase-3 was expressed in the same tissues as its murine counterpart. However humanised mice retained the hypercellularity of frontal cortex seen in their knock-out parental line and there was no biochemical evidence of human protein processing during naturally occurring neuronal death taking place during brain development. In contrast, the human protein was cleaved by the mouse machinery following anti-Fas treatment of adult mice. These data suggest that there is a fundamental difference between the activation pathways leading to caspase-3 cleavage during naturally occurring cell death in development/embryogenesis and following an apoptotic stimulus in the adult.

Animals↗
PubMed2004

Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia.

Caspase 3 activation has been implicated in cell death following a number of neurodegenerative insults. To determine whether caspase genes can affect the susceptibility of cells to neurodegeneration, a transgenic mouse line was created, expressing human caspase 3 under control of its own promoter. The human gene was regulated by the murine homeostatic machinery and human procaspase 3 was expressed in the same tissues as mouse caspase 3. These novel transgenic mice appeared phenotypically and developmentally normal and survived in excess of 2 years. Behavioural assessment using the 5-choice serial reaction time task found no differences from wild-type littermates. Caspase activity was found to be tightly regulated under physiological conditions, however, significantly larger lesions were obtained when transgenic mice were subjected to focal cerebral ischaemia/reperfusion injury compared to wild-type littermates. These data demonstrate that mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults.

Animals↗
PubMed2003

Classifying client goals in community-based ABI rehabilitation: a taxonomy for profiling service delivery and conceptualizing outcomes.

PURPOSE: To develop, confirm and trial a framework for analysing the content of goals set within community-based rehabilitation. This framework (taxonomy) is proposed as a tool to assist in service evaluation and outcome exploration. METHOD: Qualitative thematic analysis and categorization of 1765 rehabilitation goal statements in a four phase process of synthesis, refinement, verification and application. RESULTS: A taxonomy of goal content was developed comprising 21 categories within five domains, utilizing 125 descriptors. The taxonomy demonstrated good inter-rater consistency and was able to discriminate between similar but related data sets comprising goal statements. CONCLUSION: Structured analysis of the content of goal setting (particularly in community rehabilitation) utilizing a framework such as the proposed taxonomy has considerable potential as a 'window' into service delivery to broaden the parameters of existing service evaluation and to more clearly link outcome exploration to intervention.

Activities of Daily Living↗
PubMed2001

Ukrainian application of the Children's Somatization Inventory: psychometric properties and associations with internalizing symptoms.

This paper examines the psychometric properties of the Children's Somatization Inventory (CSI) in 600 10-12-year old children in Kyiv, Ukraine, replicating and extending the original findings from a sample in Nashville, Tennessee (J. Garber et al. 1991). The Kyiv children had significantly lower CSI total scores and reported significantly fewer symptoms than the American children. The Kyiv mothers, however, reported significantly more somatization symptoms in their children than did the American mothers. A factor analysis of the children's data yielded four similar factors encompassing pseudoneurologic, cardiovascular, gastrointestinal, and pain/weakness symptoms. Consistent with the findings from the Nashville study, the CSI was significantly related to the children's self-reports of health and depressive and anxiety symptoms and to maternal reports of child depression and anxiety symptoms. In addition, although more children with the highest CSI scores (25+) reported various illness experiences than those with 0-1 symptoms, no differences were found in the school absentee records. Thus, the results were congruent with the findings of the Nashville study, indicating that the CSI reliably measured somatization in this Ukrainian sample.

Anxiety↗
PubMed2001

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.

Aged↗
PubMed2001

The value of point-of-care testing when instituting an insulin drip protocol.

The critically ill patient's response to stress is to increase production of glucose; his can lead to hyperglycemia as insulin releasing factors become overloaded. Although parenteral insulin can aid in preventing complications of hyperglycemia by maintaining a euglycemic state, care must be taken to prevent hypoglycemia. The safest way to prevent large fluctuations in blood glucose levels is frequent monitoring of blood glucose levels via bedside glucose testing. As blood glucose levels fluctuate, the critical care nurse may titrate an insulin drip without specific orders for how much to increase or decrease the amount of insulin infusing. By developing a protocol, including a formula to calculate the amount of insulin to infuse, based on blood glucose levels, the critical care nurse can safely, competently, and accurately maintain blood glucose levels under 250 mg/dL.

Blood Glucose↗
PubMed2000

Children's well-being 11 years after the Chornobyl catastrophe.

BACKGROUND: The psychological effects of technological disasters have rarely been studied in children. This study assessed the aftermath of the 1986 Chornobyl disaster in children evacuated to Kyiv from the contaminated zone surrounding the nuclear power facility. METHODS: In 1997, we evaluated three hundred 10- to 12-year-old children in Kyiv who were in utero or infants at the time of the disaster and who had resided near Chornobyl (evacuees) and 300 sex-matched homeroom classmates who had never lived in a radiation-contaminated area. Response rates were 92% (evacuees) and 85% (classmates). Data were obtained from children, mothers, and teachers using standard measures of well-being and risk factors for childhood psychopathology. The children also received physical examinations and basic blood tests. RESULTS: The evacuees and classmates perceived their mental health similarly except for Chornobyl-related anxiety symptoms and perceived scholastic competence. No differences were found on the Iowa Conners' Teacher Rating Scale. Although the physical examination and blood test results were normal, the evacuee mothers rated their children's well-being as significantly worse, especially with respect to somatic symptoms on the Children's Somatization Inventory and Child Behavior Checklist. The most important risk factors for these ratings were maternal somatization and Chornobyl-related stress. CONCLUSIONS: Given the multiple stressful experiences to which evacuee families were exposed, the small differences in the children's self-reports suggest that there are protective factors in the lives of these children. The trauma experienced by the mothers was reflected in their perceptions of their children's well-being, particularly somatic symptoms, but was not transmitted to the children themselves.

Adolescent↗
PubMed2000

Congruence of diagnoses 2 years after a first-admission diagnosis of psychosis.

BACKGROUND: Diagnostic changes may reflect evolution of an illness, emergence of newly disclosed information, or unreliability of assessment. This study evaluates the stability of research diagnoses in a heterogeneous first-admission sample with psychosis. METHODS: A group of 547 subjects initially diagnosed with a psychosis were reassessed 6 and 24 months after enrollment. The DSM-IV consensus diagnoses were formulated by psychiatrists blind to previous research diagnoses. The analysis focuses on agreement over time and the effects of demographic, family history, and clinical variables on the shift from a nonschizophrenia diagnosis to schizophrenia. RESULTS: Seventy-two percent of 6- and 24-month diagnoses were congruent. The most temporally consistent 6-month categories were schizophrenia (92%), bipolar disorder (83%), and major depression (74%); the least stable were psychosis not otherwise specified (44%), schizoaffective disorder (36%), and brief psychosis (27%). The most frequent shift in diagnosis at 24 months was to schizophrenia spectrum (n=45). These 45 subjects had a similar illness course after 6 months as the 171 subjects in this category at both assessments, but their prior clinical functioning was better. Risk factors predicting change to a schizophrenia spectrum diagnosis include facility variables (schizophrenia diagnosis, longer stays, and given antipsychotic medication on hospital discharge); prehospital features (psychotic > or =3 months before admission, poorer adolescent adjustment, lifetime substance disorder); and negative symptoms. CONCLUSIONS: Changes in diagnosis, particularly to schizophrenia, are mostly attributable to the evolution of the illness. Rigid adherence to DSM-IV requirements may have led to underdiagnosis of schizophrenia. The findings support the need for a longitudinally based diagnostic process in incidence samples.

Adolescent↗
PubMed2000

Deletion of Dad1 in mice induces an apoptosis-associated embryonic death.

Dad1 is a putative anti-apoptosis gene identified in several distantly related organisms. Expression of Dad1 in transfected cells inhibits apoptosis in vitro. To determine whether Dad1 has a similar function in vivo, we used gene targeting to delete Dad1. Heterozygous adult mice (+/-) show no obvious phenotype or abnormalities, but genotype analysis of over 100 offspring from heterozygous matings detected no weanling, homozygous Dad1 null (-/-) mice. Subsequent analysis of embryos from heterozygous matings detected Dad1 null (-/-) embryos at E3.5 but no later, suggesting Dad1 is required for development beyond the late blastocyst stage. Increased levels of apoptosis were observed in cultured embryos lacking a functional copy of the gene, consistent with an anti-apoptotic role for Dad1.

Animals↗
PubMed2000

School and neuropsychological performance of evacuated children in Kyiv 11 years after the Chornobyl disaster.

This paper examines the cognitive and neuropsychological functioning of children who were in utero to age 15 months at the time of the Chornobyl disaster and were evacuated to Kyiv from the 30-kilometer zone surrounding the plant. Specifically, we compared 300 evacuee children at ages 10-12 with 300 non-evacuee Kyiv classmates on objective and subjective measures of attention, memory, and school performance. The evacuee children were not significantly different from their classmates on the objective measures (grades; Symbolic Relations subtest of the Detroit Test; forms 1 and 2 of the Visual Search and Attention Test; Benton Form A; Trails A; Underline the Words Test) or on most of the subjective measures (the attention subscale of the Child Behavior Checklist completed by mothers; the attention items of the Iowa Conners Teacher's Rating Scale; mother and child perceptions of school performance). The one exception was that 31.3% of evacuee mothers compared to 7.4% of classmate mothers indicated that their child had a memory problem. However, this subjective measure of memory problems was not significantly related to neuropsychological or school performance. No significant differences were found in comparisons of evacuees and classmates who were in utero at the time of the explosion, children from Pripyat vs. other villages in the 30-kilometer zone, and children manifesting greater generalized anxiety. For both groups, children with greater Chornobyl-focused anxiety performed significantly worse than children with less Chornobyl-focused anxiety on measures of attention. The results thus fail to confirm two previous reports that relatively more children from areas contaminated by radiation had cognitive deficits compared to controls. Possible reasons for the differences in findings among the studies are discussed.

Achievement↗
PubMed1999

Aberrant presenilin-1 expression downregulates LDL receptor-related protein (LRP): is LRP central to Alzheimer's disease pathogenesis?

Low density lipoprotein receptor-related protein (LRP) polymorphisms have recently been associated with an increased susceptibility of Alzheimer's disease (AD). Furthermore, LRP has been linked to molecules that confer susceptibility to AD (apolipoprotein E, alpha-2-macroglobulin, amyloid precursor protein), previously with the exception of the presenilins. Here we report that aberrant presenilin-1 expression in vivo and in vitro downregulates LRP. Specifically, transgenic mice overexpressing the M146L or L286V presenilin-1 mutation show decreased levels of LRP expression in neuronal populations where presenilin-1 and LRP are closely colocalized or coexpressed. Moreover, cell lines transfected with presenilin-1 also expressed decreased levels of LRP. These findings suggest that LRP may be central to AD pathogenesis since all proteins genetically associated with AD can now be linked via a single pathway to LRP.

Alzheimer Disease↗
PubMed1999

Neuromuscular blockade administration to end suffering: an ethical dilemma.

Critical care nurses face ethical issues every day in relation to end-of-life decisions. This article presents a case study involving the administration of a neuromuscular blocking agent prior to removing a patient from the respirator. The decision to use a paralyzing agent caused an ethical conflict between the nurse and physician. The article discusses ethical principles in relation to end-of-life decisions from the nurse, physician, and family's perspective. Whatever the belief, critical care nurses must consider the belief's of the patient and family while trying to maintain their own convictions.

Aged↗
PubMed1999

Cross-sectional study of gastric ulcers of the squamous mucosa in thoroughbred racehorses.

Although gastric ulcers have been identified relatively frequently in racing Thoroughbreds, there have been no large scale studies to determine their effect on health and performance. Two hundred and two Thoroughbred horses in active race training were selected by the attending veterinarians for gastro-endoscopic examination. Images of the stomach mucosa were stored in a digitised format for subsequent evaluation. The number of ulcers and a score of severity were determined. Gastric ulceration of the squamous mucosa was identified in 82% of horses. Seventy-three (39%) horses displayed clinical signs consistent with gastric ulceration. Increasing Furr and Murray Score was associated with poor hair coat (P = 0.03), colic (P = 0.03), and increasing serum creatinine concentration (P = 0.029). There were no associations between haematology and serum biochemistry values (other than serum alkaline phosphatase concentration and serum creatinine concentration) and gastric ulceration. Our study confirmed the relatively high incidence of gastric ulceration in Thoroughbred horses involved in active race training. Gastric ulceration is a potential, but rare, cause of overt colic, but may produce more subtle detrimental effects on a horse's condition. It is concluded that the diagnosis of gastric ulceration should be based on an endoscopic examination of the stomach, although future studies are required to elucidate further the aetiology and clinical significance of gastric ulceration.

Animals↗
PubMed1998

Pharmacokinetic interaction between ritonavir and clarithromycin.

BACKGROUND: Because ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, and clarithromycin, a macrolide antibiotic used in the treatment of disseminated infection caused by Mycobacterium avium complex, are likely to be administered concurrently for treatment of patients with HIV and acquired immunodeficiency syndrome (AIDS), the drug interaction potential of these 2 agents was evaluated. Both clarithromycin and ritonavir are metabolized to a significant extent through cytochrome P450-mediated biotransformation and are potential inhibitors of these enzymes. OBJECTIVE: To evaluate the pharmacokinetic effects of concomitant administration of multiple doses of ritonavir and clarithromycin. METHODS: This was an open-label, randomized, 3-period crossover study. Ritonavir alone (200 mg every 8 hours), clarithromycin alone (500 mg every 12 hours), and ritonavir and clarithromycin in combination were administered to 22 healthy volunteers. Blood samples were collected on day 4 for determination of ritonavir, clarithromycin, and its metabolite 14-(R)-hydroxyclarithromycin. RESULTS: Ritonavir practically completely inhibited the formation of 14-(R)-hydroxyclarithromycin. The mean area under the plasma concentration-time curve (AUC) for clarithromycin increased by 77% with concomitant ritonavir, and the harmonic mean terminal half-life increased from 5 hours to 14 hours. Statistically significant increases in peak plasma concentration (31%) and minimum plasma concentration (182%) were also observed. The effect of concomitant clarithromycin administration on ritonavir pharmacokinetics was statistically significant but small, with a 12.5% increase in mean AUC and a 15.3% increase in peak plasma concentration. The terminal half-life increased from 3.47 to 3.87 hours with concomitant clarithromycin. CONCLUSIONS: No adjustment of the ritonavir dose is necessary when administered with clarithromycin. In addition, no changes in clarithromycin dose are warranted in patients with normal renal function.

AIDS-Related Opportunistic Infections↗