Biomedical subjects

C Cox

Publications and source records attributed to C Cox.

At least 163 records · Page 9Linked to original sources

PubMed1997

Efficacy of nonfetal human RPE for photoreceptor rescue: a study in dystrophic RCS rats.

This study determines the efficacy of nonfetal human retinal pigment epithelium (RPE) for photoreceptor rescue utilizing the dystrophic RCS rat as an animal model. Eyes from 10- and 49-year-old donors were obtained through the Rochester Eye and Human Parts Bank. The RPE was isolated by enzymatic treatment of the choroid-RPE with 2% dispase for 30 min at 37 degrees C. Mechanically dissociated RPE cells were injected at the superior hemisphere into the subretinal space of dystrophic RCS rats during the fourth postnatal week. Rats receiving vehicle injection served as sham controls. The animals were immunosuppressed with daily cyclosporine injections (10 mg/kg) and sacrificed 30 days posttransplantation for histologic evaluation of the RPE graft and its effect on photoreceptor survival. Transplantation of adult human RPE promoted the survival of photoreceptors in the dystrophic RCS rat. Morphometric analysis of the grafted superior hemisphere demonstrated a threefold increase in photoreceptor cell density (149.2 +/- 50 SD) compared to sham controls (39.7 +/- 31 SD) and the untouched inferior hemisphere (52.8 +/- 28 SD). RPE from the 49-year-old donor was as effective as RPE from the 10-year-old donor in promoting photoreceptor survival. The results of this study in RCS rats suggests that RPE from adult human donors of varied ages is suitable for transplantation and retains the capability to promote survival of photoreceptor cells. This finding opens the possibility of using nonfetal RPE cells in human retinal transplantation.

Aged↗

PubMed1997

Extraordinary conservation of cysteines among homologous Chironomus silk proteins sp185 and sp220.

Aquatic larvae of the midge, Chironomus tentans, synthesize a 185-kDa silk protein (sp185) with the cysteine-containing motif Cys-X-Cys-X-Cys (where X is any residue) every 20-28 residues. We report here the cloning and full-length sequence of cDNAs encoding homologous silk proteins from Chironomus pallidivittatus (sp185) and Chironomus thummi (sp220). Deduced amino acid sequences reveal proteins of nearly identical mass composed of 72 blocks of 20-28 residues, 61% of which can be described by the motif X5-8-Cys-X5-(Trp/Phe/Tyr)-X4-Cys-X-Cys-X-Cys. Spatial arrangement of these residues is preserved more than surrounding sequences. cDNA clones enabled us to map the genes on polytene chromosomes and identify for the first time the homolog of the Camptochironomus Balbiani ring 3 locus in Chironomus thummi. The apparent molecular weight difference between these proteins (185 vs 220 kDa) is not attributable to primary structure and may be due to differential N-linked glycosylation. DNA distances and codon substitutions indicate that the C. tentans and C. pallidivittatus genes are more related to each other than either is to C. thummi; however, substitution rates for the 5'- and 3'-halves of these genes are different. Blockwise sequence comparisons suggest intragenic variation in that some regions evolved slower or faster than the mean and may have been subjected to different selective pressures.

Amino Acid Sequence↗

PubMed1997

Use of 2% propofol to produce diurnal sedation in critically ill patients.

OBJECTIVE: The assessment of propofol to produce diurnal sedation in critically ill patients. DESIGN: Prospective clinical study. SETTING: Intensive Care Unit, University Hospital. PATIENTS AND PARTICIPANTS: Thirty consecutive patients admitted to the Intensive Care Unit older than 18 years who were expected to be sedated for more than 50 h. INTERVENTIONS: The patients were randomised into two groups. All received sedation with a constant background infusion of morphine and a variable infusion rate of propofol, which was altered hourly to maintain the intended sedation score. The first group received constant light sedation (CLS) over 50 h aiming for a Ramsay score of 2-3. The second group received CLS between 0600 h and 2200 h and additional night sedation (ANS) with propofol between 2200 h and 0600 h, aiming for a sedation score of 4-5. MEASUREMENTS AND RESULTS: Patients were studied for 50 h from 1800 h on the first day of admission. Recordings of heart rate, blood pressure, sedation scores and propofol and morphine infusion rates were made hourly. An APACHE II score was recorded for each patient. Sedation scores were analysed by blind visual assessment and cosinor analysis, which is used in chronobiology to examine the correlation of data with a cosine curve. Patients in the ANS group had significantly better rhythmicity of sedation levels using cosinor analysis (r = 26% v 8%) p < 0.01. There was no difference between the CLS and ANS groups with respect to age, sex or APACHE II scores. Nine out of 15 patients in the ANS group achieved diurnal sedation. Three patients in the CLS group showed diurnal rhythmicity of sedation, which can be attributed to natural sleep, and had a median APACHE II score of 12. Five patients in the CLS group and three in the ANS group showed a deep constant sedation pattern. They had high APACHE II scores (median 21.5) and an obtunded conscious level on admission due to severe sepsis. CONCLUSION: Propofol can safely provide diurnal sedation in the critically ill when titrated against the Ramsay score. Sedation levels cannot be manipulated in some severely ill patients.

APACHE↗

PubMed1997

Ruminative thinking in older inpatients with major depression.

Ruminative thinking, the tendency to dwell on particular ideas or themes, can be a prominent part of the phenomenology of major depression, but it rarely has been the focus of empirical research. We attempted to replicate (in adult psychiatric inpatients age > or = 50 years with DSM-III-R major depression) the previously published finding that ruminative thinking was associated with melancholia and with psychosis. In our sample, these associations were not present. In addition, we explored the relationships of ruminative thinking to specific areas of thought content (e.g., suicidal ideation, somatic worry), cognitive function and overall functional status; ruminative thinking was not associated with suicidal ideation, but was associated with greater somatic worry and with poorer functional status, although these associations were not independent of overall depressive severity. A substantial proportion of subjects were unable to complete the cognitive measures; ruminative thinking was independently associated with inability to complete these tasks. We conclude that ruminative thinking is a meaningful and common clinical phenomenon among severely depressed older inpatients. Further investigations in inpatients and other populations examining its relationships to other phenomenology, to course and outcome, and to putative underlying mechanisms of depression are warranted.

Adult↗

PubMed1997

A dilemma in analysis: issues in the serial measurement of quality of life in patients with advanced lung cancer.

Despite the availability of several instruments to evaluate quality of life (QL) over time in patients with lung cancer, barriers in measurement remain. This methodological study used LCSS data (Lung Cancer Symptom Scale, a disease- and site-specific QL measure) to examine analysis methods to quantify QL where data needed for serial evaluation may be missing. Data from two large randomized trials, conducted at 30 centers, of a new combination chemotherapy regimen incorporating a new agent for patients (n = 673) with Stage III and IV non-small cell lung cancer were obtained for this study. QL had been prospectively measured at baseline, day 29, and every six weeks thereafter using the LCSS. For the slope analysis (SA) and area under the curve (AUC) analyses, an adjustment score of zero was used to indicate QL on the day of death (mortality adjustment) and each subsequent day until the end of the assessment period. Significant differences in QL, symptom scores and known prognostic factors at baseline were found in the attrition group. SA and AUC analysis allowed inclusion of 581 patients, giving an adequacy rate of 86%. By using a mortality adjustment, an additional 45 patients were included, increasing the inclusion rate to 93%. With the use of the mortality adjustment, QL was shown to decline over the interval, as opposed to rise if the adjustment had not been performed. The conclusions of the study were: (1) analysis for serial data using SA and AUC provides useful, but differing information; (2) when attrition (caused by death) is a factor, a mortality adjustment presented a more accurate assessment of QL as an endpoint; (3) more frequent evaluations of QL will capture rapid changes in patient status and reduce the attrition bias; (4) all patients should be followed until they die; and (5) QL should be given full consideration as a primary endpoint separate from survival.

Aged↗

PubMed1997

Transvaginal ultrasound in patients with low beta-human chorionic gonadotropin values: how often is the study diagnostic?

STUDY OBJECTIVE: To determine how often pelvic ultrasonography diagnoses or excludes ectopic pregnancy (EP) in patients who present with abdominal pain or vaginal bleeding and a beta-human chorionic gonadotropin (beta-hCG) level lower than 1,000 mIU/mL. METHODS: This was a retrospective chart review of all patients who presented to the ED of an urban teaching hospital from August 1991 through July 1995 with lower abdominal pain or bleeding, a positive beta-hCG assay, and a quantitative beta-hCG value lower than 1,000 mIU/mL in whom pelvic transvaginal ultrasound was performed within 24 hours of the ED visit. Ultrasound procedures were performed in the radiology department by ultrasound technicians under the direct supervision of an attending radiologist or resident in radiology. Patients were excluded if they had recently delivered or undergone dilatation and curettage, had had a previous ultrasound examination during this pregnancy, had decreasing beta-hCG values, or were lost to follow-up before a definitive diagnosis was made. RESULTS: : A total of 111 patients met the inclusion criteria; 19 patients (17%; 95% confidence interval [CI], 10% to 24%) had diagnostic ultrasound findings. Of these, 10 findings were diagnostic of intrauterine pregnancy and 9 for EP. The beta-hCG values for the patients with diagnostic examinations ranged from 47 to 995 mIU/mL. Twenty-three study patients ultimately received a diagnosis of EP; of these, 9 (39%; CI, 19% to 59%) had a diagnostic initial ultrasound study. Five of the nine had beta-hCG values lower than 500 mIU/mL. CONCLUSION: Approximately one third of women with EP who present with beta-hCG values lower than 1,000 mIU/mL were identified with an urgent transvaginal ultrasound examination performed by trained ultrasound technicians. Clinicians should consider the use of pelvic ultrasound in patients with suspected EP, regardless of their beta-hCG values, particularly at institutions where ultrasound is readily available.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed1997

Hemolysis in vivo from exposure to pulsed ultrasound.

Ultrasonically induced hemolysis in vivo when a commercial ultrasound contrast agent, Albunex, was present in the blood. Murine hearts were exposed for 5 min at either 1.15 or 2.35 MHz with a pulse length of 10 microseconds and pulse repetition frequency of 100 Hz. During the exposure period, four boluses of Albunex were injected into a tail vein for a total of approximately 0.1 mL of Albunex. Following exposure, blood was collected by heart puncture and centrifuged, and the plasma was analyzed for hemoglobin concentration. With Albunex present in the blood, the threshold for hemolysis at 1.15 MHz was 3.0 +/- 0.8 MPa (mean +/- SD) peak positive pressure (approximately 1.9 MPa negative pressure, approximately 180 W cm-2 pulse average intensity). For the highest exposure levels (10 MPa peak positive pressure at the surface of the animal), the mean value for hemolysis was approximately 4% at 1.15 MHz and 0.46% at 2.35 MHz, i.e., the threshold at 2.35 MHz is > 10 MPa peak positive pressure. In contrast, hemolysis in control mice receiving saline injections at 10 MPa or sham-exposed (0 MPa) mice receiving Albunex was approximately 0.4%.

Albumins↗

PubMed1997

Thresholds for fetal hemorrhages produced by a piezoelectric lithotripter.

Hemorrhage to fetal tissues occurred when late-term pregnant mice were exposed to lithotripter fields of relatively low amplitude. These hemorrhages were always observed in tissues near developing bone or cartilaginous structures such as the head, limbs and ribs, while soft tissues distant from bone were relatively free of hemorrhage. Thresholds for hemorrhage in the fetus were determined for exposures of pregnant mice on the 18th day of gestation to 200 pulses from a piezoelectric lithotripter. Animals were exposed to axial peak positive pressures of either 0 (sham), 1, 2, 3, 5 or 10 MPa. Thresholds for hemorrhage to the head, limbs, ribs and lung were all < 1 MPa.

Animals↗

PubMed1997

Ultrasonically induced lung hemorrhage in young swine.

Ten-day old swine were used in the final step of a study of the age dependence of the threshold for lung hemorrhage resulting from exposure to diagnostically relevant levels of pulsed ultrasound. A 2.3-MHz focused transducer (pulse length of 10 microseconds, 100-Hz pulse repetition frequency) was incremented vertically at several sites for a distance of 2 or 2.5 cm over the chest of the subject for a total exposure period of 16 or 20 min. The procedure was repeated at a total of four sites per animal. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.3-MPa peak positive pressure in water and the surface of the animal or, at the surface of the lung, 0.8-MPa peak positive pressure, 0.8-MPa fundamental pressure, 0.7-MPa maximum negative pressure and 20 Wcm-2 pulse average intensity. These values are essentially the same as those reported previously for neonatal swine, and neonatal, juvenile and adult mice.

Animals↗

PubMed1997

Age dependence of ultrasonically induced lung hemorrhage in mice.

Thresholds for ultrasonically induced lung hemorrhage were determined in neonatal mice (24-36 h old), juvenile mice (14 d old) and adult mice (8-10 weeks old) to assess whether or not the threshold for lung hemorrhage is dependent upon age. Ultrasonic exposures were at 1.15 MHz with a pulse length of 10 microseconds, pulse repetition frequency of 100 Hz and a total exposure duration of 3 min. The threshold for lung hemorrhage occurred at a peak positive acoustic pressure of approximately 1 MPa for mice in all three age groups. Although the thresholds were similar for neonatal, juvenile and adult mice, the sizes of the suprathreshold hemorrhages were significantly larger in adult mice than in neonatal or juvenile mice.

Aging↗

PubMed1997

Hemolysis of 40% hematocrit, Albunex-supplemented human erythrocytes by pulsed ultrasound: frequency, acoustic pressure and pulse length dependence.

The dependence of hemolysis produced by pulsed ultrasound on ultrasound frequency, acoustic pressure and pulse length was explored. Human erythrocytes (40% hematocrit; in Albunex-supplemented autologous plasma) were exposed (60 s) to 20 or 200 microns pulses of ultrasound at frequencies of 1.02, 2.24 or 3.46 MHz and at peak negative pressures [P-] ranging from 0.0 to approximately 3.0 MPa in 0.5 MPa increments. The duty factor was 0.01. At each frequency, hemolysis increased with increasing acoustic pressure and depended weakly on pulse duration. At relatively high acoustic pressures, hemolysis depended strongly on ultrasound frequency; at lower pressures, the frequency dependence was weaker. The potential clinical significance of ultrasonic hemolysis is discussed.

Albumins↗

PubMed1997

Laboratory process improvement through point-of-care testing.

BACKGROUND: In the 1992-1996 period Methodist Clinical Laboratory Services of the Methodist Health Group, Indianapolis, was restructuring all work processes. In one initiative, point-of-care testing (POCT) was used to optimize the decision cycle time while reducing the overall cost of providing information. DEVELOPING THE COMPARATIVE MODEL: In a typical month (May 1994) for hospital admissions and laboratory usage, events related to the traditional blood analysis process were observed. In March 1995 the same model that was applied to analyze the traditional blood analysis process was used to evaluate the newly implemented POCT blood analysis process. Comparisons of both processes, cost per test panel, nursing time spent, and overall turnaround time were made between the two methodologies. RESULTS: A restructure of delivery of blood analysis with the POCT system saved the hospital $392, 336 compared to the total annual cost of the traditional approach for delivering blood analysis. The average cost per test panel was $15.33 with the traditional model and $8.03 with the POCT system. Improvements in the overall turnaround time of test results affected the decision cycle time of the caregiver. The POCT system saved four steps on the patient care floor and ten in the laboratory. DISCUSSION: It is critical to establish a POCT committee, including the most vocal critics of POCT1-to look at how a program of this nature will affect the organization. CONCLUSIONS: POCT became more than just an isolated change-it became a core strategy of moving laboratory testing out of the traditional laboratory setting to where it could become immediately accessible to caregivers as information.

Blood Chemical Analysis↗

PubMed1997

Incorporating sonographic cheek-to-cheek diameter, biparietal diameter and abdominal circumference improves weight estimation in the macrosomic fetus.

The objective of this study was to improve the accuracy of sonographic fetal weight estimation in macrosomic (> 4000 g) fetuses by combining the cheek-to-cheek diameter (CCD), an indicator of subcutaneous tissue mass, with the biparietal diameter (BPD) and abdominal circumference (AC) in generating a new weight formula. Three hundred well-dated, uncomplicated singleton pregnancies > 32 weeks' gestational age (GA) were analyzed. Sonographic fetal measurements obtained in every case included BPD, head circumference, AC, femur length and CCD. Sonographic estimation of fetal weight (EFW) was derived by using BPD and AC. Actual birth weights (BW) of fetuses delivered within 7 days of the last sonographic examination and weighing over 1500 g (n = 123) were compared to EFW. A formula was derived by correlating BPD, AC and CCD with BW in these 123 fetuses using multiple regression analysis. A second formula was derived from the data of 39 macrosomic fetuses. The two formulae were then tested for accuracy of prediction of fetal weight in 157 other fetuses delivered within 7 days and grouped by birth weight, 44 of them weighing > 4000 g. The new formula for macrosomic fetuses was: EFW (g) = 1065 + 84.5 BPD (cm) + 41.29 AC (cm) + 111.0 CCD (cm). In the macrosomic fetuses, a difference of < 10% between EFW and BW was demonstrated in 72.7% by the BPD-AC formula and 95.5% when incorporating CCD. In this group, the mean percentage error was significantly smaller: 4.14 vs. 7.97% (p = 0.0005). In the regression analysis, the contributions of BPD, AC and CCD to the variance in BW were 5.5%, 16%, and 18.3%, respectively (p = 0.008). In the non-macrosomic fetuses, CCD improved prediction of BW, but the trend did not reach statistical significance. Our results demonstrate that, in the macrosomic fetus, CCD explains more of the variance in BW than other parameters and incorporating it in the sonographic weight estimation greatly improves its accuracy.

Abdomen↗

PubMed1997

Remote electronic blood release system.

BACKGROUND: The Hunter Area Pathology Service provides transfusion services to 4 metropolitan and 11 rural hospitals in Australia. To improve blood availability, conserve blood stocks, and reduce crossmatch-to-transfusion ratios, a networked electronic blood release system (EBRS) has been developed for computer cross-matching within the laboratory and at sites remote from the transfusion laboratory. It is innovative, in that non-laboratory staffs have been trained to release computer-matched blood at remote hospitals without transfusion laboratories. STUDY DESIGN AND METHODS: The EBRS software was tested and validated according to the Australian software standards AS 3563.1 and 3563.2 (1991). Over 7000 units were released by the EBRS in a laboratory trial conducted in conjunction with the conventional immediate-spin crossmatch. A further, 12-month study was conducted within the laboratory before the staged implementation of the EBRS at the remote hospitals. RESULTS: The EBRS has resulted in 1) a 25-percent reduction in the number of units requested by the medical staff, resulting from the reduction in time needed to provide compatible blood due to the elimination of the serologic crossmatch; 2) better blood stock management (reducing outdated red cell units by 30%); and 3) significant savings in laboratory workload (savings of approximately 100 hours/month). In addition, the rapid availability of computer-crossmatched red cells in emergency situations has enhanced patient safety. CONCLUSION: The EBRS is a safe and efficient means of providing red cells within the laboratory and at remote hospitals without laboratory services.

Blood Banks↗

PubMed1997

Fluorescein as a marker for subretinal transplantation of human fetal neural retina.

PURPOSE: To investigate the effect of fluorescein on human fetal neural retina and adult rat retina; and to use fluorescein to map the area of subretinal transplantation. METHODS: In vitro: Human fetal neural retina (8 to 14 weeks gestational age) was incubated in 0.03% fluorescein in Dulbecco's Modified Eagles Medium (DMEM) or DMEM alone for 30 min. Viability was determined using the trypan blue exclusion test, and results were compared. Effects of the fluorescein on cell morphology were assessed by observation of primary cultures for 1 week. In vivo: Human fetal neural retina was mechanically dissociated in 0.03% fluorescein in DMEM and transplanted to the subretinal space of immunosuppressed rats. To control for the effect of fluorescein on the grafted tissue, transplants were also performed in DMEM only. After transplantation, indirect ophthalmoscopy and true color fundus photography were performed to document the area covered by the transplant. One month after transplantation, the appearance of grafts exposed to fluorescein was compared to those that were not, at the light microscopic level. RESULTS: In vitro: Exposure of human fetal neural retina to fluorescein had no effect on viability. Similarly, in tissue culture, the fluorescein-exposed cells exhibited the same phenotype as the controls. In vivo: Immediately after transplantation the graft site was clearly outlined within the subretinal area and fluoresced intensely. There were no traces of the dye 2 h after transplantation. Cells that were transplanted with fluorescein survived transplantation, and one month after transplantation could be seen forming subretinal grafts. No differences were noted between these and control grafts. CONCLUSIONS: Fluorescein is an effective dye for immediate and transient localization of trans-scleral transplants to the subretinal space. It allows mapping of the area covered by the injection without interfering with the viability and differentiation of the transplanted cells. It allows unequivocal photo- and video-documentation in both the albino and pigmented fundi. It is already FDA approved for many other extra- and intraocular studies and now has directly been shown to be non-toxic to both human fetal neural retina and adult rodent retina.

Animals↗

PubMed1997

Findings from a statewide program of respite care: a comparison of service users, stoppers, and nonusers.

This study compared respite users with stoppers and nonusers in the Health Resources and Services Administration-funded Alzheimer's disease demonstration grant in the State of Maryland. Of those accepted into the program, only 54% participated for at least 6 months. The primary reasons for stopping were the death or institutionalization of the relative, while those not using respite services felt they didn't really need them. Determinants of program use included the poorer cognitive status of the relative and less anxiety and greater burden among the caregivers. After 6 months, users reported fewer hours of informal assistance, less burden, and that the relative had fewer behavioral problems although cognitive status and activities of daily living (ADLs) had deteriorated.

Aged↗

PubMed1997

Hydroxyurea-related ankle ulcers in patients with myeloproliferative disorders: a case report and review of the literature.

The association of ankle ulcer development with hydroxyurea therapy in patients with myeloproliferative disorders has been reported in two small case series and two patient reports. It is thought that hydroxyurea, an antineoplastic agent with selective cytotoxicity for cells that divide most actively (such as those of the skin), causes these ulcerations through impairment of normal wound healing in areas of common trauma. Treatment modalities reported include discontinuation of medication, debridement, and topical antibiotics. We report the successful split-thickness skin grafting of a hydroxyurea-related ankle ulceration after preoperative discontinuation of hydroxyurea treatment in a patient with chronic myelogenous leukemia who had previously failed grafting while taking this medication. It is hoped that heightened awareness of the link between hydroxyurea and chronic, debilitating ankle ulcerations in patients with myeloproliferative disorders, as well as familiarity with reported treatments, will promote early diagnosis and aggressive management of these unique and relatively uncommon lesions.

Ankle↗

PubMed1997

Propofol 2% in critically ill patients: effect on lipids.

OBJECTIVE: To investigate the concentrations of triglyceride, cholesterol, and high-density lipoprotein during a 50-hr infusion of 2% propofol, starting within 24 hrs of admission to the intensive care unit (ICU). DESIGN: Prospective, clinical study. SETTING: ICU, university hospital. PATIENTS: Thirty adult patients, who were ventilated and expected to be sedated for >2 days, were studied for 50 hrs, beginning at 1800 hrs on the first day of ICU admission. MEASUREMENTS AND MAIN RESULTS: Triglyceride, cholesterol, and high-density lipoprotein were measured at 2000, 0400, and 0800 hrs. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C-reactive protein were measured at 2000 hrs. Median cholesterol and high-density lipoprotein concentrations were at the low end of the normal range. In seven patients, peak triglyceride concentrations were >3 mmol/L up to a maximum of 4.83 mmol/L. Although there was no statistical difference in lipid concentrations between days 1 and 2, there was an apparent pattern of increasing triglyceride concentrations. There was a correlation between peak triglyceride concentration and total propofol consumption, but there was no correlation between lipids and age, gender, or Acute Physiology and Chronic Health Evaluation II scores. There was a direct correlation between triglyceride and C-reactive protein concentrations, and an inverse correlation between cholesterol and C-reactive protein. Twenty-two patients had evidence of TNF and 11 patients had an IL-6 of >1000 pg/mL, but there was no relationship between concentrations of cytokines and triglycerides in plasma. CONCLUSIONS: Infusion of 2% propofol to critically ill patients over a 50-hr period does not result in a significant increase in triglyceride concentrations. Mean cholesterol and high-density lipoprotein concentrations were low throughout the study period. There was a significant direct correlation between triglyceride and C-reactive protein and an inverse correlation between cholesterol and C-reactive protein, suggesting that the changes in lipids in critically ill patients may be partly attributable to the acute-phase response.

APACHE↗