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Biomedical subjects

N Kerr

Publications and source records attributed to N Kerr.

At least 19 recordsLinked to original sources
PubMed1999

Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation.

Relaxation of IGF2 imprinting occurs in Wilms tumours and many other cancers, but the mechanism of loss of imprinting (LOI) remains unknown. To investigate the role of altered DNA methylation in LOI, we examined the pattern of methylation of the human insulin-IGF2 region in Wilms tumours and the normal kidney. The analysis included regions homologous to three 'differentially methylated regions' of the mouse Igf2 gene (dmrs 0, 1 and 2). In tumours displaying normal IGF2 imprinting, and in the normal kidney, maternal allele-specific DNA methylation was identified spanning exons 2 and 3. This region is homologous to dmr 0, a site of maternal-specific differential methylation in the mouse. In Wilms tumours with relaxed imprinting or 11p15.5 LOH this region was unmethylated. No other differential methylation was identified. In particular, two sites of paternal methylation in the mouse (dmrs 1 and 2), and all three imprinted IGF2 promoters were not methylated in the kidney or in Wilms tumours. We postulate that LOI in Wilms tumours is associated with loss of maternal allele-specific methylation from a region located upstream of the imprinted IGF2 promoters. This region may contain cis acting sequences that coordinately influence imprinting.

Animals↗
PubMed1999

A two-compartment model for zinc in humans.

The oral absorption of zinc, from a test meal of minced beef, mashed potatoes and peas, have been measured in 19 healthy adults using the radiotracer 65Zn. The oral absorption, expressed as a percentage of the administered dose, was 20 +/- 5% (mean +/- 1 SD) in good agreement with previous results. In a subset of 9 subjects, tracer retention in whole body and whole blood was followed out to one year. The data were fitted to a simple two compartment model yielding total body zinc (TBZn), the zinc content in each of the 2 compartments and zinc turnover. The TBZn values ranged from 15.5 to 35.9 mmol while zinc turnover ranged from 0.043 to 0.073 mmol/d in keeping with results reported for significantly more complicated compartmental models applied to more comprehensive 65Zn tracer data sets. Additionally, TBZn correlated well with total body potassium, a measure of lean body mass, measured by whole body counting of the naturally-occurring potassium radioisotope, 40K. The zinc content of the more rapidly turning over compartment ranged from 3.2 to 5.6 mmol in reasonable agreement with exchangeable zinc pool estimations reported for short term studies using stable zinc isotopes. Therefore, the simple dataset and model employed in the present study yielded information on the short- and long-term behaviour of zinc compatible with both more complex radiotracer studies and analytically more demanding stable isotope studies.

Administration, Oral↗
PubMed1997

Clothing as protection from ultraviolet radiation: which fabric is most effective?

BACKGROUND: With increasing levels of solar ultraviolet radiation (UVR) in the earth's near environment and evidence that exposure to UVR contributes to skin cancer, cataracts, and photoaging, protection of the skin is imperative during exposure to the sun. The purpose of this study was to examine the effectiveness of various fabrics in screening UVR and to determine if specific characteristics of fabric are directly related to the amount of protection provided. METHODS: Transmission of UVR was measured using spectrophotometric techniques. This transmission, as a function of wavelength over the range 250-400 nm, was weighted with solar and biological spectral data to determine a "sun protection factor" (SPF) for each fabric. RESULTS: The transmission of UVR through fabric depends on the wavelength and varies with factors such as type of fiber, fabric mass, cover, and color. CONCLUSIONS: Of 28 white fabrics tested, 19 offered less protection than a sunscreen with SPF 15. Polyester fabrics offered increased protection over cotton. The presence of dyes increased protection considerably.

Animals↗
PubMed1997

Prevalence of retinal hemorrhages in pediatric patients after in-hospital cardiopulmonary resuscitation: a prospective study.

OBJECTIVE: Child abuse occurs in 1% of children in the United States every year; 10% of the traumatic injuries suffered by children under 5 years old are nonaccidental, and 5% to 20% of these nonaccidental injuries are lethal. Rapid characterization of the injury as nonaccidental is of considerable benefit to child protection workers and police investigators seeking to safeguard the child care environment and apprehend and prosecute those who have committed the crime of child abuse. Physically abused children present with a variety of well-described injuries that are usually easily identifiable. In some cases, however, particularly those involving children with the shaken baby syndrome, obvious signs of physical injury may not exist. Although external signs of such an injury are infrequent, the rapid acceleration-deceleration forces involved often cause subdural hematomas and retinal hemorrhages, hallmarks of the syndrome. Frequently, retinal hemorrhages may be the only presenting sign that child abuse has occurred. Complicating the interpretation of the finding of retinal hemorrhages is the belief by some physicians that retinal hemorrhages may be the result of chest compressions given during resuscitative efforts. The objective of this study is to determine the prevalence of retinal hemorrhages after inpatient cardiopulmonary resuscitation (CPR) in pediatric patients hospitalized for nontraumatic illnesses in an intensive care unit. DESIGN: Prospective clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Forty-three pediatric patients receiving at least 1 minute of chest compressions as inpatients and surviving long enough for a retinal examination. Patients were excluded if they were admitted with evidence of trauma, documented retinal hemorrhages before the arrest, suspicion of child abuse, or diagnosis of near-drowning or seizures. All of the precipitating events leading to cardiopulmonary arrest occurred in our intensive care unit, eliminating the possibility of physical abuse as an etiology. INTERVENTIONS: None. MEASUREMENTS: Examination of the retina was performed by one of two pediatric ophthalmologists within 96 hours of CPR. The chart was reviewed for pertinent demographic information; the platelet count, prothrombin time, and partial thromboplastin time proximate to the CPR were recorded if they had been determined. RESULTS: A total of 43 pediatric patients hospitalized with nontraumatic illnesses survived 45 episodes of inpatient CPR. The mean age was 23 months (range, 1 month to 15.8 years), and 84% of the patients were under 2 years old. The majority of the patients (44%) were admitted to the intensive care unit after surgery for congenital heart disease, and another 21% were admitted for respiratory failure. The mean duration of chest compressions was 16.4 minutes +/- 17 minutes with 58% lasting between 1 and 10 minutes. Five patients had chest compressions lasting >40 minutes, and two patients had open chest cardiac massage. All patients survived their resuscitative efforts. Ninety-three percent of patients had an elevated prothrombin time and/or partial thromboplastin time while 49% were thrombocytopenic. Sixty-two percent of the patients had low platelet counts and an elevated prothrombin time and/or partial thromboplastin time. Small punctate retinal hemorrhages were found in only one patient. CONCLUSIONS: Retinal hemorrhages are rarely found after chest compressions in pediatric patients with nontraumatic illnesses, and those retinal hemorrhages that are found appear to be different from the hemorrhages found in the shaken baby syndrome. Despite the small number of patients in this prospective study, we believe that these data support the idea that chest compressions do not result in retinal hemorrhages in children with a normal coagulation profile and platelet count. A larger number of patients should be evaluated in a prospective multi-institutional study to achieve statistical significance

Adolescent↗
PubMed1996

Inhibitory action of nociceptin on spinal dorsal horn neurones of the rat, in vivo.

Intrathecally administered nociceptin (5, 50, 225 micrograms) dose-relatedly inhibited the C-fibre evoked wind-up and post-discharge of dorsal horn neurones, but not the baseline C-fibre evoked responses. Spinal naloxone 50 micrograms, but not 10 micrograms, reversed the effects of nociceptin. Thus the antinociceptive role of nociceptin in the spinal cord differs from that of classical opioids.

Animals↗
PubMed1994

Radiologic diagnosis of traumatic occipitovertebral dissociation: 2. Comparison of three methods of detecting occipitovertebral relationships on lateral radiographs of supine subjects.

OBJECTIVE: The purpose of this study was to describe a method for recognizing acute traumatic occipitoatlantal dissociation that uses the basion-axial interval and basion-dental interval and to compare the accuracy of this method with the accuracies of two other methods: the Powers ratio and the x-line method. MATERIALS AND METHODS: Lateral radiographs of the cervical spine of 37 patients in whom the diagnosis of occipitoatlantal dissociation had been made on the basis of the relationship of the basion to the tip of the dens, the Powers ratio, and/or the x-line method were reviewed. Retrospectively, the occipitoatlantal junction of each was reassessed by using the the Powers ratio, the x-line, and the basion-axial interval-basion-dental interval methods. Independently, the neurologic findings at admission and the final neurologic diagnosis at discharge were obtained from the hospital records and were compared with the radiologic findings to determine the degree of radiologic-clinical correlation. RESULTS: Three groups of patients were identified by analyzing the basion-axial and basion-dental intervals of the occipitovertebral junction and related clinical findings. Twenty-three patients (group 1) had frank occipitoatlantal dislocation. Eight patients (group 2) had incomplete occipitoatlantal dissociation, which was defined as occipitoatlantal subluxation. The remaining six patients (group 3) had normal radiologic and clinical findings. Four patterns of occipitovertebral dissociation were identified: purely anterior (4/31, 13%), purely distracted (6/31, 19%), concomitantly anterior and distracted (20/31, 65%), and purely posterior (1/31, 3%). Regardless of the magnitude or direction of occipitoatlantal dissociation, the basion-axial interval-basion-dental interval method correctly identified the abnormality and the type of each. Positive clinical correlation was found in 13 (57%) of the 23 patients in group 1 and in 100% of the eight and six patients in groups 2 and 3, respectively. Neither the Powers ratio nor the x-line method could be applied in 17 (46%) of 37 cases, either because the opisthion could not be detected on the radiographs or because fusion of the posterior arch of C1 had not occurred. In the remaining 20 patients in whom the Powers ratio and the x-line method were applicable, the type of occipitoatlantal dissociation was correctly identified by the Powers ratio in 12 (60%) and by the x-line method in four (20%). Neither the Powers ratio nor the x-line method was applicable in three (50%) of the six patients in whom analysis by the basion-axial interval-basion-dental interval method and clinical findings showed no occipitoatlantal abnormality. Normal occipitovertebral anatomy was correctly identified by the Powers ratio in the remaining three patients (50%) and by the x-line method in two (33%). CONCLUSION: Direct measurement of occipitovertebral skeletal relationships altered by occipitoatlantal dissociation using the basion-axial and basion-dental intervals provides the most accurate radiologic assessment of this injury.

Atlanto-Occipital Joint↗
PubMed1993

The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival.

Increased expression of epidermal growth factor receptor (EGFr) has been reported in non small cell lung cancers (NSCLC) when compared to normal lung. We have examined post-operative survival in 19 surgically treated patients with NSCLC who had full characterisation of EGFr on primary tumour membrane preparations from resection specimens. There were ten squamous, seven adeno and two large cell carcinomas. The median concentration of high affinity sites was 31 fmol per mg of protein (4-1532) and the median dissociation constant (Kd) of these high affinity sites was 2.3 x 10(-10) per mol (1.2-30 x 10(-10)). Seven patients survived over 5 years. Twelve patients died between 8.5 and 55 months from the time of surgery. When > 5 year survivors were compared to non-survivors there was no difference as regards tumour size or stage, or as regards age or sex. The survivors had a median concentration of high affinity EGFr sites of 16.1 fmol mg-1 protein compared to a median concentration of 68.6 fmol mg-1 protein in the non-survivors (P = 0.01 Wilcoxon test). No long term survivor had > 35 fmol mg-1 protein of receptor. Thus EGFr quantitation may give independent prognostic information in NSCLC and help to select patients for adjuvant therapy after surgery. These results need confirmation in a larger prospective study.

Adenocarcinoma↗
PubMed1992

Bacterial keratitis associated with vernal keratoconjunctivitis.

We cared for two patients with longstanding vernal keratoconjunctivitis who had bacterial corneal ulcers in each eye. Both patients were young, black, and had histories of atopy. The patients came for treatment with acute symptoms of pain, redness, and reduced vision in the affected eye. On examination in each case we found an epithelial defect associated with dense stromal infiltration, a calcific plaque in the bed of the ulcer, and a severe anterior chamber reaction, including a hypopyon in two cases. Cultures of corneal scrapings from all four eyes were positive for Staphylococcus aureus, and three of the four infections were polymicrobial. All four eyes responded rapidly to intensive topical antibiotic therapy, debridement of the calcific plaque, and subsequent treatment with topical corticosteroids and/or cromolyn sodium. Bacterial keratitis can occur in patients with vernal keratoconjunctivitis, especially those with vernal corneal ulcers. The abnormalities of ocular immune mechanisms found in patients with vernal keratoconjunctivitis may predispose them to bacterial keratitis.

Adolescent↗
PubMed1991

The casualties of war.

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Attitude of Health Personnel↗
PubMed1989

Characterization of epidermal growth factor receptor in primary human non-small cell lung cancer.

Membrane preparations from 36 human non-small cell lung cancers were examined for the expression of epidermal growth factor (EGF) receptors, and comparisons were made between tumor types and stage. Eight normal lung membrane preparations were also examined. The concentrations of EGF receptors were assessed by ligand binding studies using 125I-radiolabeled EGF. In two point saturation experiments using 0.3 nM 125I-EGF incubated with membranes from 35 primary lung tumors, a median of 18 fmol/mg of protein (range, 1.1 to 530) was found. This was significantly greater than binding to eight lung membranes: median, 6.1 fmol/mg of protein (range, 1.0 to 14.5) (P less than 0.02). Scatchard binding curves obtained in 21 of the 36 tumors and seven of eight of the normal lung preparations showed high and low affinity sites for EGF receptors on all but two tumor membranes. The dissociation constant of the high affinity sites was similar on tumor and normal lung membranes: range, 0.75 to 30 x 10(-10) M/liter. However, the tumors had a significantly higher concentration of these receptor sites: median, 30.4 fmol/mg of protein versus a median of 6.2 fmol/mg of protein on normal lung membranes (P less than 0.01). Likewise, there were significantly more low affinity sites on tumors: median, 237 fmol/mg compared to 60.2 fmol/mg on normal lung (P less than 0.01). No differences were found in this analysis between tumors of different histological subtypes or clinical stage. It is possible that the high level of expression of high affinity sites on lung tumors could be used as a target for ligand-complexed drugs.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Dose-dependent systemic and regional hemodynamic effects of calcitonin gene-related peptide.

The dose-response effects of infused calcitonin gene-related peptide (CGRP), a potent vasodilator, on systemic and regional hemodynamics in the conscious rat remain incompletely defined. The radioactive microsphere technique provided these determinations before and after the intravenous administration of vehicle or 22, 65, 220, and 2200 pmol of CGRP. Neither vehicle nor 22 pmol of CGRP significantly changed any systemic or regional hemodynamic parameter. Starting at the 65-pmol dose, CGRP significantly decreased mean blood pressure and total peripheral resistance, while increasing heart rate without changing cardiac output. CGRP produced selective regional vasodilatory effects, with the coronary circulation being unusually sensitive. In contrast, CGRP caused significant increases in blood flow to the mesenteric and cutaneous circulations only at the two highest doses. CGRP increased plasma norepinephrine, epinephrine, and renin activity significantly at only the 2200-pmol dose. In conclusion, CGRP decreases blood pressure by peripheral vasodilation, with a threshold dose occurring between 22 and 65 pmol. In addition, the coronary circulation appears to be particularly sensitive to the vasodilatory properties of CGRP.

Animals↗
PubMed1989

Comparative evaluation of urographic contrast media, inulin, and 99mTc-DTPA clearance methods for determination of glomerular filtration rate in clinical transplantation.

Plasma clearance of inulin (Cin), 99mTc-DTPA (CDTPA), and urographic contrast media (CCM) were determined simultaneously in 31 patients with varying levels of renal function evaluated in the setting of affiliated cardiac and renal transplantation programs. Cin and CDTPA were calculated from the ratio of simultaneously measured plasma concentration and urine excretion rate of these test agents (UxV/P). CCM was derived from x-ray fluorescence measurement of plasma iodine (PI) content following intravenous injection of 50 ml of nonionic, low-osmolar contrast media (180 mg I/ml). Urine collections were not required for CCM determinations. No adverse reactions attributable to CM occurred in any patient, and follow-up serum-creatinine values did not differ significantly from prestudy levels. CCM determined from the rate of decline in PI between 3 hr and 4 hr following administration of contrast media ("slope-intercept" technique) [Ccm-SI] correlated closely with corresponding levels of Cin (r = .86, P less than 0.0001). and CDTPA (r = 0.89, P less than 0.0001). Mean CCM-SI/Cin and CCM-SI/CDTPA ratios for the entire study cohort were 1.09 +/- 0.06 and 1.08 +/- 0.06, respectively. CCM-SI determinations also correlated well with CCM levels derived from a single measurement of PI ("single sample" technique) made at 3 hr following injection of contrast media (r = 0.94, P less than 0.0001). Both CCM-SI and CCM determined by the "single sample" method (CCM-3 degrees SS) tended to overestimate Cin and CDTPA, however, when the latter were less than 20 ml/min/1.73 m2 (mean CCM-SI/Cin and Ccm-3 degrees SS/Cin ratios 1.36 +/- 0.14 and 1.95 +/- 1.0, respectively. Reproducibility was evaluated by paired comparison of 3-hr vs. 4-hr "single sample" CCM determinations (r = 0.99, P less than 0.0001). In addition, analysis of the variation in iodine content between duplicate specimens obtained at each of these time intervals revealed a mean ratio of 1.0 +/- 0.01 (P = NS vs. identity). Contrast clearance determination utilizing the slope-intercept method is accurate, safe, pragmatic, and more precise than serum-creatinine and endogenous-creatinine clearance for measurement of renal function in clinical transplantation.

Contrast Media↗
PubMed1988

Phase 1 study of high-dose hydroxyurea in lung cancer.

The in vitro chemosensitivity of a human lung cancer cell line to hydroxyurea (HU) was measured, and concentrations of 1 mM HU effected 99% inhibition of cell growth. Therefore, infusions designed to achieve serum levels of over 1 mM HU were assessed by escalating doses of hydroxyurea (HU) administered by continuous i.v. infusion at 3-weekly intervals in 18 patients with lung cancer. Dose increments from 24 g in 24 h to 48 g in 48 h were achieved. The dose-limiting toxicity at 48 g in 48 h was myelosuppression. Oral administration of HU did not result in sustained levels comparable to those achieved with continuous infusion. Two patients showed evidence of radiological response after three courses of treatment. Serum HU profiles were monitored after administration i.v. in 26 courses and after administration p.o. in 5 courses of treatment. A mean serum level of greater than 1 mM was achieved by 6 h and then maintained during treatment. The standard error of the mean area under the curve showed an overall 5% variation. HU can be given in doses up to 48 g in 48 h 3-weekly with manageable tissue and bone marrow toxicity, and the in vivo blood levels attained are equal to those necessary for effective cell inhibition in an appropriate in vitro model. This schedule provides a basis for combination studies with other cytotoxics or for use of HU as a DNA repair inhibitor.

Aged↗
PubMed1988

The stroke patient.

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Cerebrovascular Disorders↗
PubMed1987

Systemic and regional hemodynamic effects of calcitonin gene-related peptide.

Calcitonin gene-related peptide, a 37-amino-acid neuropeptide, has been shown to be widely distributed in periadventitial nerves throughout the cardiovascular system, particularly in association with coronary arteries. In vivo and in vitro studies have demonstrated that calcitonin gene-related peptide possesses potent vasodilator properties. Circulating calcitonin gene-related peptide is derived primarily from periadventitial nerves, though its systemic and regional hemodynamic effects are unknown. In this study, systemic and regional hemodynamics were determined by the radioactive microsphere technique prior to and following the intravenous administration of 65-pmol and 2.2-nmol doses of calcitonin gene-related peptide and vehicle to three groups of conscious, unrestrained rats. Vehicle administration did not change any systemic or regional organ hemodynamic parameter determined. In contrast, 65 pmol and 2.2 nmol of calcitonin gene-related peptide significantly decreased mean blood pressure and total peripheral resistance and increased heart rate in a dose-dependent manner, while only slightly increasing cardiac output. Both 65-pmol and 2.2-nmol doses of calcitonin gene-related peptide significantly increased blood flow (percentage of cardiac output) to the heart. There was no difference in blood flow to the heart between the two doses. In addition, the 2.2-nmol dose of calcitonin gene-related peptide significantly increased blood flow to the stomach, liver, and skin and decreased it to the brain, kidneys, and spleen. In conclusion, calcitonin gene-related peptide infusion decreases blood pressure in a dose-dependent manner primarily by peripheral vasodilation. In addition, calcitonin gene-related peptide selectively changes regional organ blood flow, particularly to cause coronary vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗