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Biomedical subjects

C Cox

Publications and source records attributed to C Cox.

At least 217 records · Page 12Linked to original sources

Computer database for melanoma registry. A clinical management and research tool to monitor outcomes and ensure continuous quality improvement.

The need for an efficient method of handling data is more apparent today in medical practice than at any time in the past. This PC-based database helps with the daily collection, filing, storage, and abstraction of data for clinical management and research. The program also provides a mechanism for continuous quality assessment to monitor clinical standards of care and make interventions to improve the care of the melanoma patient.

Databases, Factual↗

Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge.

We examined the role of common genetic variation in determining the consistency and magnitude of change in plasma total cholesterol (TC) levels in response to two separate changes from a high-saturated (SFA) to a low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of free-living healthy men and women. Consistent responders were defined as those whose mean difference in the change in TC was within one SD of the mean for all participants, and the remainder were defined as variable responders. DNA was obtained from 55 individuals and genotype determined at the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T) and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent responders, the apoBSP24 allele was significantly more common than in the 17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). No other polymorphism showed a significant frequency difference between groups. In the group as a whole, the correlation between the change in TC level in response to the first and second dietary change was 0.28 (p = 0.05), but those with one or more apoB SP24 alleles and those with the apoCIII genotype CC had a significantly higher correlation than those with other genotypes (0.46 (p = 0.05) vs. 0.12 (NS) and 0.31 (p = 0.05) vs. 0.02 (NS), respectively). In the group as a whole, mean response left TC 10% higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII genotypes affected the magnitude of this response. However, individuals with the LPL HindIII genotype H+ H+ had a significantly smaller change in mean TC in response to diet than those with one or more H- allele (9.3% vs. 14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects the consistency of response to change in dietary fat content, while variation at the LPL gene locus affects magnitude of response.

Apolipoproteins B↗

Autonomic control of heart rate after brain injury in children.

OBJECTIVES: To study sequential changes in heart rate, respiratory rate, blood pressure, heart rate power spectra, and plasma catecholamine concentrations in patients with acute brain injury and correlate these variables with the severity of neurologic dysfunction and patient outcome. DESIGN: Prospective, clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Thirty-seven pediatric patients with acute brain injury caused by trauma, anoxia/ischemia, hemorrhage, or infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found significant associations between low-frequency (0.01 to 0.15 Hz) heart rate power and severity of neurologic dysfunction (as assessed by the admission Glasgow Coma Scale) (p < .001) and patient outcome (as assessed by the Glasgow Outcome Scale) (p = .05). The admission (p = .05) and maximum (p < .001) values for low-frequency heart rate power and the minimum value for high-frequency (0.15 to 0.50 Hz) heart rate power obtained during hospitalization (p = .001) predicted an increased likelihood of survival. Ten brain-dead patients had significantly decreased low-frequency heart rate power (p = .008) and plasma norepinephrine (p = .015), epinephrine (p = .03), and dopamine (p = .04) concentrations when compared with six non-brain-dead patients with a Glasgow Coma Scale score of 3. CONCLUSIONS: Our results imply that autonomic nervous system control of heart rate is disrupted in proportion to the degree of neurologic insult in children after acute brain injury. Thus, heart rate power spectral analysis and plasma catecholamine concentrations may prove to be useful adjuncts in determining severity of neurologic injury and prognosis for recovery in children suffering from brain injury. In addition, these techniques may aid in the determination of brain death.

Adolescent↗

Association of pre mortem diagnosis and autopsy findings in pediatric intensive care unit versus emergency department versus ward patients.

OBJECTIVE: As part of the overall quality assurance program for the Department of Pediatrics, we determined whether there were differences in the rates of unexpected autopsy findings between pediatric intensive care unit (ICU), emergency department, and ward patients. DESIGN: Prospective, descriptive study. SETTING: Tertiary care children's hospital. PATIENTS: Pediatric deaths (n = 212). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Autopsies were obtained more frequently in emergency department patients (27/29 [93%]) compared with pediatric ICU (88/121 [73%] and ward (42/62 [68%]) patients (p = .03). The medical examiner's cases were more frequently from emergency department patients (22/27 [81%]) compared with pediatric ICU (39/88 [44%]) or ward (11/42 [26%]) patients (p < .001). We found unexpected autopsy findings in 19 (12%) of 157 patients. There were no unexpected findings from the medical examiner's cases. The most common unexpected findings were unidentified infections (n = 7 [three fungal, three viral, and one nonspecific]) and unrecognized cardiac malformations (n = 4). Unexpected findings occurred more frequently in pediatric ICU patients (16/88 [18%]) vs. emergency department (2/27 [7%]) or ward (1/42 [2%]) patients (p = .03). The occurrence rates of major unexpected findings (Class I and II) in pediatric ICU (7/79 [9%]), emergency department (2/27 [7%]), and ward (1/42 [2%]) patients were similar (p = .4). There were two Goldman's Class I unexpected findings in the pediatric ICU and emergency department patients, and one Goldman's Class I unexpected finding in the ward patients. CONCLUSIONS: Autopsies were performed more frequently in emergency department patients. Class I through IV unexpected findings occurred more frequently in pediatric ICU patients compared with emergency department or ward patients. Autopsy examinations are an especially valuable diagnostic tool for pediatric ICU patients and physicians.

Autopsy↗

Persistent Epstein-Barr virus infection in the common marmoset (Callithrix jacchus).

Epstein-Barr virus (EBV) infection of the common marmoset causes long-term infection, with production of antibodies to virus-induced antigens, without clinical illness. Attempts to show the presence of EBV DNA in saliva of infected animals by PCR were initially unsuccessful, although slot-blot hybridization analysis demonstrated that viral DNA was present. Further investigations showed that most samples of pilocarpine-induced saliva, and 33% of the samples of whole mouth fluids (WMF) tested, were inhibitory to PCR. Similar results were found using human WMF. A method of assessing samples of marmoset WMF for the presence of EBV, by PCR using an EBV BamHI W probe, and removing inhibition with Chelex 100, is described. A total of 202 samples from 21 EBV infected, and seven non-infected animals was tested. Five seropositive animals shed virus on every occasion, and 15 intermittently. Two marmosets, infected as neonates, showed progressively increasing humoral responses to viral antigens, and shed virus on every occasion tested over 3 years. When mated with uninfected animals, the latter seroconverted 4 and 6 weeks later, respectively, and later shed virus into their WMF. The naturally infected animals were paired with naive marmosets, and were able to pass on infection. These results establish that long-term, permissive EBV infection occurs in the common marmoset, and demonstrate again the similarities in the response to EBV between marmoset and man.

Animals↗

Sperm concentrations and quality in beta-thalassaemia major.

We report semen analyses in eight patients with beta-thalassaemia major, with poor results in all but the youngest. The causation is multi-factorial, with iron deposition in the pituitary gland resulting from life-long dependence on blood transfusions being a major factor. We speculate on other contributing causes, but further research is required to elucidate these. Improving haematological care means that these men are increasingly surviving to adult life. Relevant techniques to enable them to achieve their desire for fatherhood are considered.

Adolescent↗

Cross-discipline disparities in perceptions of mental disorders in a long-term care facility.

OBJECTIVES: This study compared prevalence rates of mental disorders in a single long-term care facility as perceived by three professional disciplines and compared professionals' perceptions with two standardized measures of psychopathology. DESIGN: Comparison of (1) prospective standardized psychiatric evaluations performed by psychiatrists, (2) chart reviews of mental disorders as documented by primary care physicians, and (3) interviews of nurses. SETTING: The residential health care facility at Monroe Community Hospital in Rochester, New York. PARTICIPANTS: A 20% random sample of adult residents, stratified by ward (n = 80). MEASUREMENTS: Prevalence rates of psychopathology as determined by each data collection method: psychiatric diagnoses as determined by psychiatrists and primary care physicians, the Brief Psychiatric Rating Scale, and the Psychogeriatric Dependency Rating Scale. RESULTS: Prevalence rates of psychopathology ranged from 60 to 91% across discipline-specific data collection methods. Using psychiatrists' diagnoses as the benchmark, primary care physicians and nurses underestimated the prevalence of mental disorders, particularly organic mental disorders. All disciplines agreed on the presence of personality and developmental disorders. The Brief Psychiatric Rating Scale and Psychogeriatric Dependency Rating Scale validated perceptions of psychopathology by psychiatrists and nurses, but not by primary care physicians' chart diagnoses. CONCLUSION: Disparities in perceptions of mental disorders across disciplines pose a threat to patient care and suggest a need for more reliable incorporation of mental health expertise in the long-term care setting.

Aged↗

Relationships of age and axis I diagnoses in victims of completed suicide: a psychological autopsy study.

OBJECTIVE: Psychiatric illness is a potent risk factor for suicide, rates of which differ markedly with age. The purpose of this study was to examine whether the psychiatric diagnoses of suicide victims vary predictably with age. METHOD: DSM-III-R axis I diagnoses of 141 persons aged 21 to 92 years who had completed suicide were established by the psychological autopsy method. Multiple logistic regression analyses were used to determine whether age, gender, or their interaction predicted the presence of specific disorders. RESULTS: One or more axis I conditions were diagnosable in 90.1% of the suicide victims. Substance use disorders were most frequent, followed by mood disorders and primary psychotic illness. Younger age at death was a significant predictor of substance abuse or dependence and primary psychoses, while older age predicted major mood disorders. Comorbidity of substance use and mood disorders was common. Among victims with substance abuse or dependence, older age at death predicted major depression; among victims with mood disorders, younger age at death predicted comorbid substance abuse or dependence. CONCLUSIONS: The distribution of psychiatric illnesses in suicide victims differs across the life course. Age-related patterns of addictive and psychotic disorders echo their prevalence in the general population. In contrast, the relationship between age and mood disorders among suicide victims is distinctly different from that of the general population. These findings suggest that risk for suicide increases with age in individuals with major affective illness. Depressed elderly men are particular targets for suicide prevention strategies.

Adult↗

Outcomes of hospitalization: factors influencing the discharges of African American and white dementia patients.

Data collected through interviews with caregivers of dementia patients compares the hospital dispositions, home or nursing home of 99 African American and 80 white dementia patients. The majority of each group are discharged home, although the influence of factors associated with these outcomes varies. Discharge home for the African Americans is strongly affected by the availability of an alternative caregiver while for the white patients, this availability as well as formal support services increase the probability of discharge home. Although African American patients were more impaired than the white patients, the original plan of the caregivers was to take the patients home while the white caregivers were originally undecided. For both groups, greater cognitive impairment increases the likelihood of institutional placement. African Americans, although satisfied with the final plan, are more likely to be dissatisfied with their involvement in the planning process.

Black or African American↗

Strain among caregivers: comparing the experiences of African American and Hispanic caregivers of Alzheimer's relatives.

This study of the experiences of seventy-six Black and eighty-six Hispanic caregivers of Alzheimer's relatives sought to determine the factors characterizing the caregiving process and its outcomes, particularly personal and role strain, in each group. The findings reveal that Hispanics are more vulnerable to each type of strain and this may be partially attributed to their caring for more impaired relatives, their younger ages, and comparative lack of expressive supportive relationships. The mediating role played by culture and informal supports in the caregiving process is highlighted by the results as well as the need for the development of sensitive and appropriate interventions and supports.

Adaptation, Psychological↗

Age and the Risk of Breast Cancer Recurrence.

BACKGROUND: Various parameters assist in the definition of prognosis and in the choice of therapy for breast cancer. This study evaluates the effects of prognostic factors on disease outcome in elderly women. METHODS: A retrospective cohort analysis was performed on 1,267 consecutive patients with locoregional breast cancer, including 374 patients 65 years of age or older, who were referred to a university cancer center over an eight-year period. Information on prognostic factors, disease outcome, and survival was analyzed. RESULTS: Women 65 years of age or older were more likely to have early-stage cancers, lower histologic grade, higher hormone receptor levels, and lower S-phase fractions. They experienced a longer time to disease recurrence and overall longer survival than their younger counterparts. CONCLUSIONS: Advancing age should not be considered an unfavorable risk factor for breast cancer. Prognosis and treatment should be based on disease stage and histologic and biologic parameters rather than patient age.

Journal Article↗

Developmental neurotoxicity of methanol exposure by inhalation in rats.

The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concerns about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult rats following perinatal exposure to methanol vapor. Four cohorts of pregnant Long-Evans hooded rats, each cohort consisting of an exposure and a control group, were exposed to 0 parts per million (ppm) (control) or 4,500 ppm methanol vapor for six hours daily beginning on gestation day (GD) 6 with dams and pups then being exposed postnatal day (PND) 21. Exposures took place in 2-m3 Rochester-type inhalation chambers while the animals remained in their plastic breeder cages. Prenatal and postnatal blood methanol concentrations were determined by gas chromatography. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 micrograms/mL throughout gestation and lactation. Average blood methanol concentrations of the pups were about twice those of the dams. Because such results appeared consistently across the other cohorts, we decided to obtain additional data with Cohort 4. Once it had undergone the standard exposure protocol, we selected sets of extra pups from those that had not been assigned previously to the adult phase of behavioral testing. Each set was exposed once, at ages that extended out to PND 52, for one additional six-hour session of exposure to 4,500 ppm methanol. The blood methanol concentrations of these pups declined until about PND 48, at which time they approximated those of the dams. These findings might be accounted for by a process of metabolic maturation in the pups that remains to be identified.

Animals↗

Transplantation of human fetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina.

PURPOSE: The Royal College of Surgeons (RCS) rat suffers from a well-characterized, early-onset, and relentless form of photoreceptor cell degeneration. It has been shown that allografts of retinal pigment epithelial cells from normal perinatal rats have rescue effects in this condition. In preparation for human application, the authors determined whether human fetal retinal pigment epithelium (RPE) grafts have a photoreceptor rescue effect in RCS dystrophic rat retinas. METHODS: Sheets of RPE from human fetal eyes (10 to 16 weeks gestational age) were isolated according to the authors' recently described method. Fragments of the RPE sheets were transplanted to the subretinal space within the superior hemisphere. Transplants were performed within the superior equatorial region of five dystrophic RCS rats, one eye per animal. A similar volume of vehicle was injected into the subretinal space of five age-matched control rats, again one eye per rat. All rats were immunosuppressed with daily injections of cyclosporine. Using light microscopy, photoreceptor cell nuclear profiles of superior equatorial (SE) and inferior equatorial (IE) regions of transplanted and sham-injected control animals were counted. RESULTS: Four weeks after transplantation, a dramatic rescue effect was observed. Microscopically, presumptive donor RPE cells were seen as single pigmented cells and as cell clusters in the subretinal space. An outer nuclear layer three to four profiles thick was present in the area of the RPE transplant but was nearly absent in the rest of the retina, as well as in the retinas of control rats. The number of photoreceptor nuclear profiles per 100 microns was 34.7 +/- 2.2 (mean +/- SEM) in the SE region of transplanted rats and 3.5 +/- 1.4 in the same region of sham-injected rats. There were 3.0 +/- 1.0 photoreceptor nuclear profiles in the IE region of transplanted rats and 3.5 +/- 1.2 in the IE region of sham-injected eyes. No evidence of graft rejection was seen. CONCLUSIONS: This study provides the first indication that transplanted human fetal RPE cells are able to rescue photoreceptor cells in a model of hereditary retinal degeneration.

Animals↗

Medical-legal pitfalls for the breast surgeon: incomplete mammographic localization of suspicious lesions and the correlation between palpable and mammographic abnormalities.

In approximately 5 per cent of mammographically detected lesions, the mammographic abnormality is present in only one view, either craniocaudal or mediolateral. In such a scenario, the physician has been left with the option of closely following the lesion, hoping it will eventually become apparent in two views, or guessing the approximate location of the lesion for subsequent open biopsy. However, with today's advances in technology, CT scan and its production of a three-dimensional image can compensate for mammography's two-dimensional limitation. With diminished need for identification on two mammographic views, localization in these instances falls more within the realm of possibility. This paper highlights Moffitt Cancer Center's experience with CT-directed breast biopsy as an alternative to close follow-up or blind-biopsy. In addition, because palpable breast abnormalities may not be the same as mammographic abnormalities, the report details the accuracy of CT-directed biopsy in allowing the surgeon to perform precise open biopsy, thus avoiding medical-legal exposure.

Biopsy↗

Comparison of two warfarin regimens in the prevention of venous thrombosis following total knee replacement.

A prospective, randomized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement. Adult patients scheduled for primary or revision total knee replacement were randomly assigned to receive either a "two-step" warfarin regimen beginning 10-14 days pre-operatively or, alternatively, to begin warfarin the night before surgery. Post-operatively, the dose was adjusted in both groups to achieve a target International Normalized Ratio (INR) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. The occurrence of deep vein thrombosis was nearly the same in the two treatment groups, 39% in patients randomized to the two-step regimen as compared to 38% in those beginning the night before surgery. The occurrence of proximal vein thrombosis was also similar, 5% versus 7% (p = NS). Patients in the two-step group received 1.33 +/- 1.26 transfusions compared to 0.95 +/- 1.22 in the night before group (p < 0.05) and also had a lower nadir post-operative hematocrit of 26.7 +/- 3.1 as compared to 28.5 +/- 3.2 (p < 0.0001). Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group. Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis. We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10-14 days pre-operatively. Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications.

Adult↗

Human performance during exposure to toluene.

PURPOSE: The purpose of this research was to examine the effects of inhalation of toluene on respiratory function and neuropsychological performance of humans. METHODS: We exposed six healthy adults to 100 ppm toluene or air (control) for 6 h, in a double-blind, randomized fashion, with exposures separated by at least 14 d and including 30 min of exercise at a level that quadrupled minute ventilation. Blood and exhaled air toluene levels were measured before, during, immediately, and 1 and 2 h post-exposure. Lung function was measured before and immediately after exposure. Three repetitions of two computerized neuropsychological tests were performed, including a brief standard neuropsychological battery (ANAM) and a 1-h complex performance test (SYNWORK). Statistical analysis of the psychological data was conducted as a repeated measures ANOVA. FINDINGS: Following exercise, the mean blood and exhaled air toluene levels averaged 1.5 micrograms and 28 ppm, respectively. Lung function was unchanged post-exposure. On the SYNWORK test, the Composite score obtained over time during toluene exposure was lower than that during room air (F = 29.20, p = 0.005), with the score from the final hour reduced by 10%. On standard neuropsychological tests, latency but not accuracy proved the sensitive measure for five of the seven subtests presented. CONCLUSIONS: Performance of complex tests and response time to simple brief tests can be disrupted by toluene inhalation at 100 ppm. Differences in performance between air and toluene conditions were greatest after exercise, indicating that physical activity may enhance the response to volatile organic solvents.

Adult↗

Subsets of midbrain dopaminergic neurons in monkeys are distinguished by different levels of mRNA for the dopamine transporter: comparison with the mRNA for the D2 receptor, tyrosine hydroxylase and calbindin immunoreactivity.

The midbrain dopamine system can be divided into two groups of cells based on chemical characteristics and connectivity. The dorsal tier neurons, which include the dorsal pars compacta and the ventral tegmental area, are calbindin-positive, and project to the shell of the nucleus accumbens. The ventral tier neurons are calbindin-negative and project to the sensorimotor striatum. This study examined the distribution of the mRNAs for the dopamine transporter molecule (DAT) and the D2 receptor in the midbrain of monkeys by using in situ hybridization. The distribution patterns were compared to that of tyrosine hydroxylase and calbindin immunohistochemistry. The results show that high levels of hybridization for DAT and the D2 receptor mRNA are found in the ventral tier, calbindin-negative neurons and relatively low levels are found in the dorsal, calbindin-positive tier. Within the dorsal tier, the dorsal substantia nigra pars compacta has the least amount of both messages. These results show that in monkeys, the ventral tegmental area and the dorsal pars compacta form a dorsal continuum of dopamine neurons which express lower levels of mRNA for DAT and D2 receptor than the ventral tier. DAT has been shown to be involved in the selective neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Different levels of DAT mRNA and calbindin may explain the differential effects of MPTP neurotoxicity.

Animals↗

Individual variation in plasma cholesterol response to dietary saturated fat.

OBJECTIVE: To determine the extent to which plasma lipid concentrations of individuals are consistently sensitive to changes in saturated fats; to examine whether groups that consistently have large or small responses can be defined; and to identify factors which predict response of lipids to dietary change. DESIGN: A double crossover design in which two diets (S, providing 21% energy from saturated fat, and P, providing 10%) were followed for periods of six weeks in the sequence SPSP or PSPS. SETTING: 67 free living subjects, total cholesterol 5.5-7.9 mmol/l. MAIN OUTCOME MEASURES: Relation of cholesterol responses to repeated dietary changes and of potential predictors and cholesterol response. RESULTS: Similar average changes in cholesterol mask a wide range of individual responses. Response was not related to compliance. In all participants the change in cholesterol observed when the nature of dietary fat was changed on the two crossovers was correlated (r = 0.31, P = 0.01); the degree of correlation between the two sets of responses was greater in the 46 consistent responders than in the 21 variable responders (r = 0.71 v r = 0.21). Mean differences in cholesterol between diet S and diet P during the two crossovers were 1.16 (SD 0.35) mmol/l and 0.95 (0.26) mmol/l for consistent hyperresponders and 0.18 (0.26) mmol/l and 0.18 (0.25) mmol/l for consistent minimal responders. In consistent responders, changes in total cholesterol in response to increasing saturated fats correlated with baseline cholesteryl ester transfer activity (r = 0.32, P = 0.03); total cholesterol (r = 0.37, P = 0.01); triglycerides (r = 0.30, P = 0.04); and apolipoprotein B (r = 0.54, P = 0.01). CONCLUSIONS: There is a degree of consistency in cholesterol response to instructions to change dietary fat which is not explained by dietary compliance, and there are groups of consistent hyperresponders and minimal responders within a population of hypercholesterolaemic individuals. Several factors predicting response have been identified. These results have relevance to dietary approaches aimed at reducing the lipoprotein mediated risk of coronary heart disease.

Adult↗