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Biomedical subjects

N Kerr

Publications and source records attributed to N Kerr.

17 recordsLinked to original sources

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

The casualties of war.

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Attitude of Health Personnel

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

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

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

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

The stroke patient.

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Cerebrovascular Disorders

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