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Biomedical subjects

C L Robertson

Publications and source records attributed to C L Robertson.

At least 19 recordsLinked to original sources
PubMed2003

Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release.

Bax mediates cytochrome c release and apoptosis during neurodevelopment. Brain mitochondria that were isolated from 8-day, 17-day, and adult rats displayed decreasing levels of mitochondrial Bax. The amount of cytochrome c released from brain mitochondria by a peptide containing the BH3 cell death domain decreased with increasing age. However, approximately 60% of cytochrome c in adult brain mitochondria could be released by the BH3 peptide in the presence of exogenous human recombinant Bax. Mitochondrial Bax was downregulated in PC12S neural cells differentiated with nerve growth factor, and mitochondria isolated from these cells demonstrated decreased sensitivity to BH3-peptide-induced cytochrome c release. These results demonstrate that immature brain mitochondria and mitochondria from undifferentiated neural cells are particularly sensitive to cytochrome c release mediated by endogenous Bax and a BH3 death domain peptide. Postnatal developmental changes in mitochondrial Bax levels may contribute to the increased susceptibility of neurons to pathological apoptosis in immature animals.

Animals↗
PubMed2001

Assessment of the effect of 2-chloroadenosine in normal rat brain using spin-labeled MRI measurement of perfusion.

Adenosine analogs such as 2-chloroadenosine are potent cerebrovasodilators. Spin-labeled MRI was used to investigate the spatial distribution, dose-response, and timing of the effect of 2-chloroadenosine on cerebral blood flow (CBF) after intraparenchymal injection into rat brain. Sprague-Dawley rats (N = 10) were injected with 2-chloroadenosine at doses of 0.3, 6.0, or 12 nmoles, or saline vehicle (2-4 microL). CBF was serially quantified in a slice through the injection site in a circular (3.6 mm diameter) region of interest (ROI) around the injection and in ipsilateral hemispheric ROIs at approximately 90 min and approximately 180 min. Marked 3.77- and 3.93-fold increases in CBF (vs. vehicle) were seen in the circular ROI at approximately 90 min and approximately 180 min after 12-nmol injection, respectively. Similarly, 2.92- and 2.78-fold increases in hemispheric CBF were observed at approximately 90 min and approximately 180 min, respectively, after injection of 12 nmoles. Linear dose-response relationships were observed at both times after injection in both ROIs (all P < 0.01). Spin-labeling MRI assessment revealed that parenchymal injection of 2-chloroadenosine produces potent, dose-dependent, and sustained vasodilation over large areas of brain. This treatment and imaging paradigm should facilitate investigation of the effect of CBF promotion in models of traumatic and ischemic brain injury.

2-Chloroadenosine↗
PubMed2001

Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in infants and children.

Adrenomedullin is a recently discovered 52-amino acid peptide that is a potent vasodilator and is produced in the brain in experimental models of cerebral ischemia. Infusion of adrenomedullin increases regional cerebral blood flow and reduces infarct volume after vascular occlusion in rats, and thus may represent an endogenous neuroprotectant. Disturbances in cerebral blood flow (CBF), including hypoperfusion and hyperemia, frequently occur after severe traumatic brain injury (TBI) in infants and children. We hypothesized that cerebrospinal fluid (CSF) adrenomedullin concentration would be increased after severe TBI in infants and children, and that increases in adrenomedullin would be associated with alterations in CBF. We also investigated whether posttraumatic CSF adrenomedullin concentration was associated with relevant clinical variables (CBF, age, Glasgow Coma Scale [GCS] score, mechanism of injury, and outcome). Total adrenomedullin concentration was measured using a radioimmunometric assay. Sixty-six samples of ventricular CSF from 21 pediatric patients were collected during the first 10 days after severe TBI (GCS score < 8). Control CSF was obtained from children (n = 10) undergoing lumbar puncture without TBI or meningitis. Patients received standard neurointensive care, including CSF drainage. CBF was measured using Xenon computed tomography (CT) in 11 of 21 patients. Adrenomedullin concentration was markedly increased in CSF of infants and children after severe TBI vs control (median 4.5 versus 1.0 fmol/mL, p < 0.05). Sixty-two of 66 CSF samples (93.9%) from head-injured infants and children had a total adrenomedullin concentration that was greater than the median value for controls. Increases in CSF adrenomedullin were most commonly observed early after TBI. CBF was positively correlated with CSF adrenomedullin concentration (p < 0.001), but this relationship was not significant when controlling for the effect of time. CSF adrenomedullin was not significantly associated with other selected clinical variables. We conclude adrenomedullin is markedly increased in the CSF of infants and children early after severe TBI. We speculate that adrenomedullin participates in the regulation of CBF after severe TBI.

Adrenomedullin↗
PubMed2001

Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitotoxicity.

OBJECTIVES: To measure adenosine concentration in the cerebrospinal fluid of infants and children after severe traumatic brain injury and to evaluate the contribution of patient age, Glasgow Coma Scale score, mechanism of injury, Glasgow Outcome Score, and time after injury to cerebrospinal fluid adenosine concentrations. To evaluate the relationship between cerebrospinal fluid adenosine and glutamate concentrations in this population. DESIGN: Prospective survey. SETTING: Pediatric intensive care unit in a university-based children's hospital. PATIENTS: Twenty-seven critically ill infants and children who had severe traumatic brain injury (Glasgow Coma Scale < 8), who required placement of an intraventricular catheter and drainage of cerebrospinal fluid as part of their neurointensive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 months to 14 yrs. Cerebrospinal fluid samples (n = 304) were collected from 27 patients during the first 7 days after traumatic brain injury. Control cerebrospinal fluid samples were obtained from lumbar puncture on 21 infants and children without traumatic brain injury or meningitis. Adenosine concentration was measured by using high-pressure liquid chromatography. Adenosine concentration was increased markedly in cerebrospinal fluid of children after traumatic brain injury vs. controls (p < .001). The increase in cerebrospinal fluid adenosine was independently associated with Glasgow Coma Scale < or = 4 vs. > 4 and time after injury (both p < .005). Cerebrospinal fluid adenosine concentration was not independently associated with either age (< or = 4 vs. > 4 yrs), mechanism of injury (abuse vs. other), or Glasgow Outcome Score (good/moderately disabled vs. severely disabled, vegetative, or dead). Of the 27 patients studied, 18 had cerebrospinal fluid glutamate concentration previously quantified by high-pressure liquid chromatography. There was a strong association between increases in cerebrospinal fluid adenosine and glutamate concentrations (p < .005) after injury. CONCLUSIONS: Cerebrospinal fluid adenosine concentration is increased in a time- and severity-dependent manner in infants and children after severe head injury. The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury.

Adenosine↗
PubMed2000

Assessment of 2-chloroadenosine treatment after experimental traumatic brain injury in the rat using arterial spin-labeled MRI: a preliminary report.

Adenosine is a putative endogenous neuroprotectant. Its action at A1 receptors mitigates excitotoxicity while action at A2 receptors increases cerebral blood flow (CBF). We hypothesized that cerebral injection of the adenosine analog, 2-chloroadenosine, would decrease swelling and increase CBF early after experimental traumatic brain injury (TBI). To test this hypothesis, rats were anesthetized and subjected to TBI using a controlled cortical impact (CCI) model (n = 5/group). Immediately after injury, 2-chloroadenosine (0.3 nmole in 2 microliters) or an equal volume of vehicle were stereotactically injected lateral to the area of contusion. Using magnetic resonance imaging (MRI), in vivo spin-lattice relaxation time of tissue water (Tlobs) and CBF (arterial spin labeling) were measured in a 2-mm thick slice in the injured and non-injured hemispheres at 3-4 h after CCI. In a separate, preliminary experiment, the effect of 2-chloroadenosine injection in normal rat brain was studied. Rats (n = 2) were anesthetized and a burr hole was made for injection of 2-chloroadenosine into the same site as in the TBI model. One rat received the standard dose of 0.3 nmole and one rat received a 6 nmole injection. Tlobs and CBF studies were obtained 1.5-3.5 h after injection, using the same MRI methods as in the TBI study. In rats subjected to TBI, treatment with 2-chloroadenosine attenuated the increase in Tlobs after injury (p < 0.05 for treatment vs vehicle) in both hippocampus and cortex ipsilateral to injury. However, treatment with 2-chloroadenosine did not improve post-traumatic hypoperfusion. In normal rats, injection of 0.3 nmole of 2-chloroadenosine did not increase CBF, but the higher dosage of 6 nmole dramatically increased hemispheric CBF by 1.5-2.0-fold. The effect of local injection of 2-chloroadenosine at a dose of 0.3 nmole after experimental TBI on Tlobs presumably represents a reduction in post-traumatic edema. This reduction in edema, along with the augmentation of CBF seen in normal rats at higher dosage (6 nmole), supports a role for adenosine in neuroprotection following TBI.

2-Chloroadenosine↗
PubMed2000

Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in children: a preliminary report.

Adrenomedullin is a recently discovered 52-amino-acid peptide that is a potent vasodilator. Infusion of adrenomedullin increases regional cerebral blood flow and reduces infarct volume after vascular occlusion in rats. Adrenomedullin may represent an endogenous neuroprotectant since it is increased after focal brain ischemia. Cerebral hypoperfusion is present after traumatic brain injury (TBI) in children. We hypothesized that adrenomedullin levels would be increased in children with severe TBI. Total adrenomedullin concentrations were measured using a radioimmunometric assay. Thirty-six samples of ventricular cerebrospinal fluid (CSF) from 10 pediatric patients were collected during the first 10 days after severe TBI (GCS < 8). Control CSF was obtained from 5 children undergoing lumbar puncture, who had normal CSF parameters and no evidence of central nervous system infection. Patients underwent standard neuro-intensive care, including cerebrospinal fluid drainage. Data were analyzed using a univariate regression model. Adrenomedullin concentration was markedly elevated in CSF of children following TBI versus control (mean level 10.65 vs 1.51 fmol/ml, p = 0.006). All 36 case samples had an adrenomedullin concentration above the median value for the controls (1.52 fmol/ml). We conclude adrenomedullin is elevated in the CSF of children following severe TBI. We speculate that it participates in the endogenous response to cerebral hypoperfusion after TBI.

Adrenomedullin↗
PubMed2000

No long-term benefit from hypothermia after severe traumatic brain injury with secondary insult in rats.

OBJECTIVES: To evaluate the effect of application of transient, moderate hypothermia on outcome after experimental traumatic brain injury (TBI) with a secondary hypoxemic insult. DESIGN: Prospective, randomized study. SETTING: University-based animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: All rats were subjected to severe TBI followed by 30 mins of moderate hypoxemia, associated with mild hypotension. Rats were randomized to three groups: a) normothermia (37 degrees C + 0.5 degrees C); b) immediate hypothermia (32 degrees C +/- 0.5 degrees C initiated after trauma, before hypoxemia); and c) delayed hypothermia (32 degrees C +/- 0.5 degrees C after hypoxemia). The brain temperature was controlled for 4 hrs after TBI and hypoxemia. MEASUREMENTS AND MAIN RESULTS: Animals were evaluated after TBI for motor and cognitive performance using beam balance (days 1-5 after TBI), beam walking (days 1-5 after TBI), and Morris Water Maze (days 14-18 after TBI) assessments. On day 21 after TBI, rats were perfused with paraformaldehyde and brains were histologically evaluated for lesion volume and hippocampal neuron counts. All three groups showed marked deficits in beam balance, beam walking, and Morris Water Maze performance. However, these deficits did not differ between groups. There was no difference in lesion volume between groups. All animals had significant hippocampal neuronal loss on the side ipsilateral to injury, but this loss was similar between groups. CONCLUSIONS: In this rat model of severe TBI with secondary insult, moderate hypothermia for 4 hrs posttrauma failed to improve motor function, cognitive function, lesion volume or hippocampal neuronal survival. Combination therapies may be necessary in this difficult setting.

Animals↗
PubMed1993

A private breast imaging practice: medical audit of 25,788 screening and 1,077 diagnostic examinations.

During 1989 and 1990, 25,788 screening and 1,077 diagnostic breast imaging examinations were performed. Audit was performed in 6-month intervals to allow comparison of performance over time. Sensitivity, positive predictive value, and stage of disease were determined for each radiologist, for patients over and those under 50 years of age, and for patients with and for those without a suspect palpable breast abnormality. In the screening portion of the study, 1,539 of 25,788 (5.9%) patients were asked to return for diagnostic breast imaging, 119 of 188 (63%) cancers were stage 0 or stage 1 disease, and a sensitivity of 91% and a positive predictive value of 11% were found. If patients with a palpable breast abnormality were eliminated, 103 of 138 (75%) patients had disease that was less than stage 2. In the diagnostic portion of the study, 296 of 1,077 (27%) patients were referred for biopsy and 53 of 71 (75%) cancers were stage 0 or stage 1 disease. A sensitivity of 97% and a positive predictive value of 24% were found. If patients with a palpable breast abnormality were eliminated, 51 of 63 (81%) patients had disease that was less than stage 2.

Breast Neoplasms↗
PubMed1989

Communication problems after mammographic screening.

The authors prospectively assessed the effectiveness of requests for immediate additional evaluation or biopsy made on the basis of the interpretation of abnormal findings on screening mammograms. In 1,125 screening mammograms obtained in asymptomatic women referred by physicians, the findings in 63 (6%) were interpreted as requiring additional imaging or biopsy. Written reports were sent, and in all cases the office of the referring physician was notified directly by phone. Physicians were periodically contacted if no follow-up had been performed to resolve the questioned abnormality. In the first 2.5 months, no action had been taken in 40 of 63 (63%) of the recommendations. After additional calls, this diminished to 10 of 63 (16%) at 3.5 months, but at 4.5 months four of 63 (6%) patients had not undergone the recommended additional studies. These results suggest the need for development of systems to ensure prompt action in patients with abnormal findings at mammographic screening.

Communication↗
PubMed1989

Improved control of image optical density with low-dose digital and conventional radiography in bedside imaging.

The technical and diagnostic performance of simultaneously acquired low-dose (44% of standard dose) storage-phosphor digital radiographs (system resolution = 0.2 mm, 10 bits) were compared with those of standard-dose conventional bedside radiographs of the chest in 32 patients. The mean optical density (OD) of the lungs (800 measurements) was closer to the ideal density with digital radiography (1.45 OD +/- 0.20 [standard deviation] vs 1.75 OD +/- 0.53) and was less often outside the usable range (2.5% vs 42.5%). Receiver operating characteristic analysis for detection of simulated nodules and monitoring devices (nine readers, 4,608 observations) showed that digital radiography was superior to conventional radiography (P less than .05) for four of the nine readers and equivalent to conventional radiography for five readers. The authors concluded that digital radiography produces more consistent and ideal image density and performs at least as well as conventional radiography under phantom test conditions.

Absorptiometry, Photon↗
PubMed1989

Nonpalpable lesions in the augmented breast: preoperative localization.

Special compression views of the breast were used to detect suspect lesions in eight women who had undergone augmentation mammoplasty. Hook-wire localization with the use of these views proved safe and accurate for preoperative localization in these women, one of whom had a very small cancer.

Breast↗
PubMed1988

Why isn't every woman over 40 in a breast cancer detection program?

Mortality from breast cancer may be reduced by more than 10,000 deaths per year in this country if the recommendations for screening all asymptomatic women older than 40 years for breast cancer, issued in 1982 by the American Cancer Society and the American College of Radiology, are followed. Compliance with those recommendations six years later is poor, even in well-to-do, medically served populations, primarily because of poor compliance by physicians. Radiation risk is an often-cited concern, although it has been shown to be an insignificant factor in breast cancer screening. High cost, also cited as a concern, is less of a problem-the charges for mammography having declined steeply in the past few years. At the current price levels, it makes financial and humanitarian sense to provide screening rather than terminal care for metastatic breast cancer. The third concern cited by physicians, that of diagnostic accuracy, must be addressed by a careful and accurate statistical description of the results of each screening program. Sensitivity of more than 80% with positive predictive values of about a third can be achieved.

Adult↗
PubMed1986

Factors relating to the sensory acuity of limbs with peripheral vascular insufficiency.

We examined several possible causes for the high incidence of poor sensory acuity in the limbs of 176 patients with moderate to severe peripheral vascular insufficiency. We investigated the relationships of diabetes, alcoholism, and smoking, as well as the severity of peripheral vascular disease, to the integrity of basic sensory modalities such as two-point discrimination and perception of light touch. The presence or absence of diabetes exerted the strongest effect on peripheral sensation. In patients who did not have diabetes, sensation in the limbs was most strongly affected by whether the patient was an alcoholic. Smoking did not have a significant effect on limb sensation. Among nondiabetic, nonalcoholic patients, there was a weak residual effect related to the severity of the peripheral vascular insufficiency. Even among these patients, however, systemic factors predominated in determining the loss of sensation. We also examined the extent to which loss of sensation might be related to the development of ulcers. Among patients who were not diabetic, there was a highly significant relationship between loss of sensation and the presence of limb ulceration. Surprisingly, however, there was no discernable relationship between the presence of ulcers in diabetic patients and the degree of loss of peripheral sensation. This result suggests that a large percentage of ulcers seen in diabetic patients are not of neurogenic origin.

Adult↗
PubMed1985

Water-soluble radiocontrast material in the treatment of postoperative ileus.

Reviewed was a series of 47 obstetric, gynecologic, and general surgical patients with apparent postoperative ileus who had received an oral administration of water-soluble radiocontrast material. Forty of these patients were found to have an ileus, and seven to have a mechanical small bowel obstruction. In the 40 patients with ileus, prompt resolution of the ileus was obtained, no complications were noted, and the method provided rapid differentiation between ileus and obstruction. This modality of therapy offers an excellent alternative both therapeutically and diagnostically to the traditional treatment of ileus with intravenous fluid, nasogastric suction, and gastrointestinal rest.

Administration, Oral↗
PubMed1984

The relationship of transcutaneous PO2 and laser Doppler measurements in a human model of local arterial insufficiency.

Transcutaneous PO2 and laser Doppler measurements were made over areas of unheated and heated skin of the feet of normal volunteers. Stepwise elevation of the foot above the level of the heart systematically reduced the local arterial pressure and, thus, the local arteriovenous gradient in these areas. Results indicated that transcutaneous PO2 and laser Doppler measurements reflect changes in local arteriovenous gradient when made over areas of warmed skin, but not unwarmed skin. Comparison of skin surface and subcutaneous temperatures obtained with two heater types revealed the importance of heater configuration. Results confirm a previously hypothesized nonlinear relationship between transcutaneous PO2 and local cutaneous blood flow and indicate that a transcutaneous PO2 reading of zero may be obtained in the presence of significant local cutaneous blood flow.

Arterial Occlusive Diseases↗
PubMed1984

The effect of exercise upon cutaneous oxygen delivery in the extremities of patients with claudication and in a human laboratory model of claudication.

Transcutaneous PO2 measurements have been shown previously to reflect local cutaneous oxygen delivery in patients with severe peripheral arterial insufficiency. In the present studies, transcutaneous PO2 measurements indicated that exercise of the involved extremity lowered cutaneous oxygen delivery in patients with moderate peripheral arterial insufficiency (claudication). These exercise-related changes in transcutaneous PO2 were reproduced in a human laboratory model of claudication. The pattern of change in transcutaneous PO2 observed in this model during and after exercise correlated closely with the pattern of change in mean systemic blood pressure during the same time period.

Ankle↗