Search PubMed⌕ Search

Biomedical subjects

C Cox

Publications and source records attributed to C Cox.

At least 55 records · Page 3Linked to original sources
PubMed2000

Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia.

We used flow cytometry to quantify minimal residual disease (MRD) in 56 patients with acute myeloid leukemia (AML) expressing a leukemia-associated phenotype. Thirty-four patients aged 18 to 60 years were entered into the AML-10 protocol (induction, consolidation, and autologous stem-cell transplantation [ASCT]), whereas 22 patients older than 60 years received the AML-13 protocol (induction, consolidation, and consolidation II). After induction, the level of MRD that was best associated with treatment outcome was 4.5 x 10(-4) residual leukemic cells. However, the outcome in patients with at least 4.5 x 10(-4) cells (n = 26) was not significantly different from that in patients with fewer leukemic cells (n = 30); there were 15 (58%) relapses in the first group and 12 (40%) relapses in the second. After consolidation, the most predictive MRD cutoff value was 3.5 x 10(-4) cells: 22 patients had an MRD level of 3.5 x 10(-4) cells or higher and 17 (77%) of these patients had relapse, compared with 5 of 29 patients (17%) with lower MRD levels (P <.001). An MRD level of 3.5 x 10(-4) cells or higher after consolidation was significantly correlated with poor or intermediate-risk cytogenetic findings, a multidrug resistance 1 (MDR1) phenotype, short duration of overall survival, and short duration of relapse-free survival (P =.014,.031,.00022, and.00014, respectively). In multivariate analysis, this MRD status was significantly associated with a high frequency of relapse (P <.001) and a short duration of overall (P =.025) and relapse-free survival (P =.007). ASCT did not alter the prognostic effect of high MRD levels after consolidation: the relapse rate after transplantation was 70%. Thus, we found that an MRD level of 3.5 x 10(-4) cells or higher at the end of consolidation strongly predicts relapse and is significantly associated with an MDR1 phenotype and intermediate or unfavorable cytogenetic findings. (Blood. 2000;96:3948-3952)

Actuarial Analysis↗
PubMed2000

Synthesis of the functionalized tricyclic core of lactonamycin by oxidative dearomatization.

[reaction: see text] We report in this Letter a synthesis of the densely oxygenated CDEF ring system (27) corresponding to that found in the recently discovered antibiotic lactonamycin. The key steps in the synthesis consist of an intramolecular Wessely oxidative lactonization of acid 18, followed by a hydroxyl-directed epoxidation of enol ether 21.

Anti-Bacterial Agents↗
PubMed2000

Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy.

BACKGROUND: The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration. METHODS: 12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment. FINDINGS: MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal. INTERPRETATION: 5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.

Adrenoleukodystrophy↗
PubMed2000

Incidental discovery of pelvic cholelithiasis on diagnostic laparoscopy.

Laparoscopic cholecystectomy, although a safe technique for removal of the gallbladder, is associated with surgery-related complications. We report a complication caused by this procedure in a young woman, in whom a diagnostic laparoscopy led to the incidental finding of retained gallstones in the pelvis. A 30-year-old woman underwent diagnostic laparoscopy for exclusion of an ectopic pregnancy. She had undergone laparoscopic cholecystectomy 3 years before presentation. Diagnostic laparoscopy ruled out ectopic pregnancy, but yellow nodules were noted in her pelvis. Removal of these nodules was not attempted because of their close proximity to the ureter. A biopsy of these lesions confirmed amorphous material suggestive of gall stones. The finding was documented in the case notes and explained to the patient after the procedure.

Adult↗
PubMed2000

Twenty-seven years studying the human neurotoxicity of methylmercury exposure.

Research at the University of Rochester (U of R) has been focused on mercury for nearly half a century. Initially studies focused on dosimetry, especially the accuracy of measuring exposure, and experimental work with animal models. Clinical studies in human populations started when the U of R mercury group was asked to assist with dosimetry in the Iraq epidemic of 1971-1972. Initial clinical studies described the effects of methylmercury (MeHg) poisoning on adults and children. A dose-response curve for prenatal exposure was determined and it suggested that relatively low exposures might be harmful to the fetus. Since most human exposure to MeHg is dietary from fish consumption, these theoretical dangers had far-reaching implications. After Iraq, the Rochester team pursued exposure from fish consumption in both adults and children. Populations with high fish consumption were identified in Samoa and Peru for studying adults and in Peru and the Seychelles islands for studying children. The possible health threat to the fetus from maternal fish consumption quickly became the focus of research efforts. This paper reviews the Rochester experience in studying human exposure to MeHg from fish consumption.

Adult↗
PubMed2000

Association between methylmercury exposure from fish consumption and child development at five and a half years of age in the Seychelles Child Development Study: an evaluation of nonlinear relationships.

Studies to date of the developmental effects of pre- and postnatal methylmercury exposure from fish consumption in the Seychelles Islands, using linear regression models for analysis, have not shown adverse effects on neurodevelopmental test scores. In this study we evaluated whether nonlinear effects of methylmercury exposure were present, using scores on six tests administered to cohort children in the Seychelles Child Development Study at 66 months of age. Prenatal exposure was determined by measuring mercury in a segment of maternal scalp hair representing growth during pregnancy. Postnatal exposure was measured in a segment of the child's hair taken at 66-months of age. Generalized additive models (GAMs), which make no assumptions about the functional form of the relationship between exposure and test score, were used in the analysis. GAMs similar to the original linear regression models were used to reanalyze the six primary developmental endpoints from the 66-month test battery. Small nonlinearities were identified in the relationships between prenatal exposure and the Preschool Language Scale (PLS) Total score and Child Behavior Check List (CBCL) and between postnatal exposure and the McCarthy General Cognitive Index (GCI) test scores. The effects are best described graphically but can be summarized by computing the change in the predicted test score from 0 to either 10 or 15 ppm and then above this point. For the PLS the trend involved a decline of 0.8 points between 0 and 10 ppm followed by an increase (representing improvement) of 1.3 points above 10 ppm. For the CBCL there was an increase of 1 point from 0 to 15 ppm, and then a decline (improvement) of 4 points above 15 ppm. The GCI increased by 1.8 points through 10 ppm and then declined 3.2 points (representing worse performance) above 10 ppm. These results are not entirely consistent. Two of the trends involve what appear to be beneficial effects of prenatal exposure. The one possibly adverse trend involves postnatal exposure. In every case the trend changes direction, so that an effect in one direction is followed by an effect in the opposite direction. Because of the descriptive nature of GAMs it is difficult to provide a precise level of statistical significance for the estimated trends. Certainly above 10 ppm there is less data and trends above this level are estimated less precisely. Overall there was no clear evidence for consistent (across the entire range of exposure levels) adverse effects of exposure on the six developmental outcomes. Further nonlinear modeling of these data may be appropriate, but there is also the risk of fitting complex models without a clear biological rationale.

Animals↗
PubMed2000

Neurodevelopmental outcomes of Seychellois children from the pilot cohort at 108 months following prenatal exposure to methylmercury from a maternal fish diet.

The Seychelles Child Development Study has been unable to confirm any relationship between maternal exposure to MeHg during pregnancy and adverse developmental outcomes. In this report, 87 children from a pilot cohort were evaluated at 9 years of age. Each child was given a battery testing specific cognitive, visual motor, and motor skills using standardized psychometric and neuro-psychological tests. The results indicated no adverse association between maternal MeHg exposure and any developmental outcome measure. For three endpoints (Boston Naming Test and two tests of visual motor coordination), enhanced performance in males was associated with increasing prenatal MeHg exposure. A secondary analysis including both prenatal MeHg and postnatal MeHg exposure was done even though we lacked postnatal hair for about 35% of the cohort. The results of the secondary analysis mirrored the outcomes of the primary analysis regarding prenatal exposure but were less robust. The results of this study are consistent with earlier findings from the 66-month evaluations of the SCDS Main cohort. Since MeHg is neurotoxic, this effect is likely due to other factors associated with consumption of fish.

Adult↗
PubMed2000

Secondary analysis from the Seychelles Child Development Study: the child behavior checklist.

Human exposure to methylmercury (MeHg), a known neurotoxin, is primarily from fish consumption. As part of a large study examining the association between MeHg exposure and child development in a population with high fish consumption we examined school-age behavior using the Achenbach Child Behavior Checklist (CBCL). The CBCL Total T score was a primary endpoint and was reported earlier to show no adverse association with prenatal or postnatal MeHg exposure. In this study we analyzed the T scores of the CBCL subscales to determine if more discrete aspects of measured behavior were associated with exposure. The Seychelles Child Development Study (SCDS) is a prospective, double blind, longitudinal evaluation of over 700 children. The index of prenatal exposure was maternal hair total mercury (T-Hg) in a segment growing during gestation. Postnatal exposure was T-Hg in the child's hair taken at 66 months of age. The child's primary caregiver completed the CBCL during the 66-month evaluation. No association between prenatal or postnatal MeHg exposure and the CBCL subscales was found. In Seychellois children exposed to MeHg from consumption of ocean fish we found no association between either prenatal or postnatal MeHg exposure and behavior as measured by the CBCL subscales.

Adult↗
PubMed2000

Association between prenatal exposure to methylmercury and cognitive functioning in Seychellois children: a reanalysis of the McCarthy Scales of Children's Ability from the main cohort study.

Methylmercury (MeHg) is a neurotoxicant whose high-dose effects first became known following a number of poisoning outbreaks that occurred worldwide. The primary human exposure is low dosage from fish consumption. Studies of fish-eating populations have not found a consistent pattern of association between exposures and outcomes. Therefore, examining specific areas of cognitive functioning has been suggested as an important approach to determine whether more subtle effects of MeHg exposure are present. In the Seychelles longitudinal study of prenatal and postnatal MeHg exposure from fish consumption and development, the McCarthy Scales of Children's Abilities (MSCA) were administered to children at age 66 months. No association between MeHg exposure and performance on the MSCA General Cognitive Index was identified. We analyzed these data further to determine whether associations were present on specific subscales of the MSCA. The standard MSCA subscales were analyzed. Then, more specific subscales of the MSCA were defined and analyzed utilizing a neuropsychological approach. The subscales were recombined to approximate the domains of cognitive functioning evaluated in the Faroes and New Zealand studies. Analyses of both the standard and the recombined MSCA subscales showed no adverse associations with MeHg exposure and neuropsychological endpoints. A positive association between postnatal MeHg exposure and performance on the MSCA Memory subscale was found. These findings are consistent with previous reports from the Seychelles study in that no adverse effects of MeHg exposure from fish consumption can be detected in this cohort.

Animals↗
PubMed2000

Synthetic catalysis of amide isomerization.

Rotation about the C-N bond in amides can be catalyzed by Bronsted and Lewis acids, as well as nucleophiles and bases. Catalysis of amide isomerization occurs in biological systems via "rotamase" enzymes; however, the mechanisms by which these proteins operate are not completely understood. We outline investigations that provide experimental support for mechanisms believed to be feasible for the catalysis of amide isomerization and present practical applications that have resulted from this work.

Amides↗
PubMed2000

Sustained ex vivo and in vivo transfer of a reporter gene using polyoma virus pseudocapsids.

Properties of a virus-like artificial gene delivery vehicle, synthesised from recombinant major coat protein of mouse polyoma virus, have been explored. The protein, VP1, self assembles into protein spheres, or 'pseudocapsids, which can bind and transfer DNA into cells in vitro and in vivo. Here, the ability of pseudocapsids to carry DNA into a complex cell system (ex vivo organ cultures of rabbit cornea) or whole animals (mice) has been assessed. Evidence from histochemical and PCR experiments indicate that pseudocapsids stimulate uptake and stable maintenance of marker DNA in nondividing corneal cells as efficiently as a recombinant adenovirus. In athymic and immunocompetent mice, gene transmission occurs with no apparent adverse effects on the animals. In the presence of pseudocapsids, the marker gene was transferred to a range of organs, including the brains of animals, following peripheral or intranasal administration. In immunocompetent mice, significant long-term transcriptional expression (at least 22 weeks) was observed with pseudocapsids, a period significantly longer than observed with DNA alone (several weeks only), again with no obvious adverse effects. This study demonstrates that pseudocapsids from the murine virus, polyoma, constitute a novel transfer agent for long-term gene therapeutic applications in tissues or whole animals.

Animals↗
PubMed2000

Gynaecological and obstetrical morbidity in women with type I von Willebrand disease: results of a patient survey.

Type 1 von Willebrand disease (vWD) is generally regarded clinically as 'mild' and the obstetrical-gynaecological features have not been fully described. We administered a patient questionnaire and provider survey of the medical and quality of life aspects of childbirth and menstruation to 99 type 1 vWD patients and compared the patients presently menstruating (n=81) to a cohort of 150 menstruating females in the general population. The following measurements had a statistically higher proportion in the vWD group: number of tampons/towels used for a typical menstrual cycle (P=0. 002); percentage reporting that clothes are stained by menses (P = 0. 001); past or present history of anaemia (P = 0.001); childbirth-related bleeding (P=0.001); and childbirth-related bleeding necessitating RBC transfusion (P=0.002). Quality of life assessment of the impact of menses in both of the above cohorts was measured by a Likert scale using seven quality of life parameters. Compared to the control group, the vWD patients had a significantly higher score, with P-values of < 0.0001 for each parameter. Hormonal interventions for menorrhagia in the vWD patients were < or = 50% effective. Menorrhagia resulted in red blood cell transfusions in 6% of patients, dilatation and curettage in 17% and hysterectomy in 13%. Despite the common connotation of type 1 vWD as clinically 'mild', childbirth and the monthly challenge to haemostasis presented by menstruation result in a substantial degree of morbidity in females with type 1 vWD. These results support the rationale for ongoing international efforts to increase awareness of vWD as a cause for menorrhagia and to improve the quality of life in females with known vWD.

Adolescent↗
PubMed2000

Laparoscopic surgical management of ectopic pregnancy: a district general hospital experience.

This is an audit of laparoscopic management of ectopic pregnancy in a District General Hospital (DGH), using a retrospective casenote review. The study was conducted at New Cross Hospital, Wolverhampton, a large DGH. We recorded the duration of operation, postoperative opiate requirement, length of hospital stay, operative and postoperative complications. Case notes of patients with surgically treated ectopic pregnancies between January 1996 and June 1998 (n=106) were reviewed and grouped into three categories: (1) immediate laparotomy, (2) laparoscopy followed by laparotomy, and (3) laparoscopic management. Comparisons were made between the three groups. The incidence of ectopic pregnancy was 1-91 live births. The mean age of the patients was 29.9 years (range 14-41). Seven (6.6%) patients were haemodynamically unstable and underwent immediate laparotomy, 66 (62%) patients had laparoscopic management while 33 (31%) patients had laparotomy following preliminary laparoscopy. Mean operative time in the laparoscopic management group was 61.9 minutes. The mean +/- 2 SD was 61.9+/-37.4 (range 27-107) with a mean length of hospital stay of 1.9 days (range 1-4), compared with 49.9 minutes (+/-SD 16.5 (range 35-98) and 3.9 days (range 2-8), respectively, in the laparotomy following preliminary laparoscopy group. Only one patient in the laparoscopic management group required opiate analgesia 24 hours postoperatively compared with all the patients in the immediate laparotomy group and seven patients (21%) in laparotomy following the preliminary laparoscopy group. Complications in the laparoscopic management group included wound infection and a persistent ectopic. One patient in the laparotomy group required subtotal hysterectomy for persistent bleeding from cornual ectopic, while complications in the laparotomy following the laparoscopy group consisted of minor wound infection and a case of deep venous thrombosis (DVT). Laparoscopic management of ectopic pregnancy is safe and can be carried out successfully in a DGH setting with clear advantages, including shorter hospital stay and reduced postoperative opiate requirement.

Journal Article↗
PubMed2000

Pulmonary inflammatory response to inhaled ultrafine particles is modified by age, ozone exposure, and bacterial toxin.

Epidemiological studies demonstrate associations between increasing levels of ambient particles and morbidity in the elderly with cardiopulmonary disease. Such findings have been challenged partly because particles may not act alone to cause these effects. We hypothesized that carbonaceous ambient ultrafine particles and ozone can act together to induce greater oxidative stress and inflammation in the lung than when administered alone and that these effects would be amplified in the compromised, aging lung. Two models of a compromised lung were used: endotoxin priming and old-age emphysema (TSK mice). Young (10 wk) and old (22 mo) male F344 rats and male TSK mice (14-17 mo) were exposed to ultrafine carbon particles (count median diameter 25 nm, 110 micrograms/m3) and to ozone (1 ppm) alone and in combination for 6 h. Inhalation of low-dose endotoxin (70 and 7.5 units estimated alveolar deposited dose in rats and mice, respectively) was used to model respiratory-tract infection. Cellular and biochemical lavage parameters and oxidant release from lung lavage cells were assessed 24 h after exposure. Inflammatory cell influx into the alveolar space was observed for both species and age groups: The combination of inhaled ultrafine carbon and ozone after endotoxin priming resulted in the greatest increase in lavage-fluid neutrophils. In general, the unstimulated and stimulated release of reactive oxygen species (ROS) from lavage inflammatory cells correlated well with the neutrophil response. There were significant effects of carbon particles as well as a consistent interaction between carbon and ozone as determined by analysis of variance (ANOVA). However, this interaction was in the opposite direction in young rats versus old rats and old TSK mice: Carbon and ozone interacted such that ROS activity was depressed in young rats, whereas it was enhanced in old rats and old TSK mice, indicating age-dependent functional differences in elicited pulmonary inflammatory cells. These results demonstrate that ultrafine carbonaceous particles inhaled for short periods of time can induce significant pulmonary inflammation and oxidative stress that are modified by age, copollutants, and a compromised respiratory tract.

Administration, Inhalation↗
PubMed2000

Personality traits and suicidal behavior and ideation in depressed inpatients 50 years of age and older.

Completed suicide may be the most preventable lethal complication of depressive disorders in older adults. Identification of risk factors for suicidal behavior has therefore become a major public health priority. Using data collected on 81 depressed patients 50 years of age and older, we report analyses designed to determine the associations between the personality traits that constitute the Five Factor Model of personality and measures of suicidal behavior and ideation. We hypothesized that low Extraversion would be associated with a lifetime history of attempted suicide, and high Neuroticism would be associated with suicidal ideation. Results were generally consistent with the hypotheses. We also observed a relationship between Openness to Experience and suicidal ideation. These findings suggest that longstanding patterns of behaving, thinking, and feeling contribute to suicidal behavior and thoughts in older adults and highlight the need to consider personality traits in crafting and targeting prevention strategies.

Adult↗