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Biomedical subjects

L C Knight

Publications and source records attributed to L C Knight.

At least 37 records · Page 2Linked to original sources
PubMed1996

Thrombus imaging with a technetium-99m-labeled activated platelet receptor-binding peptide.

UNLABELLED: The objective of this work was the preclinical evaluation of 99mTc-P280, a 99mTc-labeled peptide having high affinity and specificity for the GPIIb/IIIa receptor expressed on activated platelets, for use as a thrombus imaging agent. METHODS: The affinity and specificity of P280 peptide for the GPIIb/IIIa receptor was assessed by the inhibition of ADP-stimulated human platelet aggregation, the inhibition of the binding of fibrinogen to the GPIIb/IIIa receptor and the inhibition of the binding of vitronectin to the vitronectin receptor. P280 peptide was radiolabeled with 99mTc by ligand exchange using 99mTc-glucoheptonate. The ability of 99mTc-P280to detect thrombi in vivo was assessed using a canine venous thrombosis model and the biodistribution of 99mTc-P280 was determined in rats and rabbits. RESULTS: P280 peptide had an IC50 of 79 nM for the inhibition of aggregation of human platelets in platelet rich plasma, an IC50 of 6.8 nM for the inhibition of fibrinogen binding to the GPIIb/IIIa receptor and an IC50 of 13 microM for the inhibition of vitronectin binding to the vitronectin receptor, showing the high in vitro receptor binding affinity and specificity of the peptide. 99mTc-P280 was readily prepared in > or = 90% radiochemical and yield purity and provided images of femoral vein thrombin in the canine model by 1 hr postinjection (thrombus-to-blood ratio of 4.4 and thrombus-to-muscle ratio of 11 at 4 hr). Dog, rat and rabbit studies all showed rapid clearance of the radiotracer from the blood and rapid renal excretion. CONCLUSION: The combination of high in vitro receptor-binding affinity and specificity, in vivo thrombus imaging and fast clearance support the evaluation of 99mTc-280 as a clinical imaging agent.

Animals↗
PubMed1996

Opioid and opioid-like drug effects on whole-gut transit measured by scintigraphy.

UNLABELLED: We studied the effects of several drugs on gastrointestinal transit (tramadol HCl, acetaminophen with codeine and placebo) in a randomized, double-blind, crossover study. METHODS: Combined gastric emptying, small bowel and colonic transit scintigraphy was performed in 12 normal subjects. Each subject received a standardized diet and study drug on Days 1-5. On Day three, subjects received a radiolabeled solid and liquid phase meal. RESULTS: No significant difference in the gastric T1/2 (mean +/- s.e.m.) of solids for placebo (69 +/- 7 min), APAP/C (74 +/- 15 min) or tramadol (686 +/- 8 min) (p = 0.86) were seen. Similarly there was no significant difference in the T1/2 of liquids for placebo (31 +/- 4 min), APAP/C (41 +/- 6 min) (p = 0.29). Orocecal transit times were not significantly different for placebo (237 +/- 20 min), APAP/C (311 +/- 26 min) or tramadol (311 +/- 10 min) (p = 0.12). Colon geometric centers (GC) for placebo at 24, 48 and 72 hr were 4.6 +/- 0.35, 6.0 +/- 0.28 and 6.8 +/- 0.08. The GC for tramadol and APAP/C were all significantly lower at 72 hr, 6.4 +/- 0.17 and 6.2 +/- 0.17, respectively compared to the placebo. The GC of tramadol at 24 and 48 hr (3.8 +/- 0.4, 5.4 +/- 0.26) were not significantly different from placebo. In contrast, the GC for APAP/C at 24 and 48 hr (3.3 +/- 0.31, 5.0 +/- 0.26) were significantly delayed. All subjects recorded a significant increase in constipation on drugs compared to placebo (p = 0.04). CONCLUSION: Tramadol and APAP/C had no effect on gastric emptying or small bowel transit. At equianalgesic doses, tramadol caused less delay in colonic transit than APAP/C for 48 hr and delay in the GC agreed with the subjective complaints of constipation on both drugs.

Acetaminophen↗
PubMed1995

Insulin receptors on the endolymphatic sac: an autoradiographic study.

Light microscopic autoradiographs were prepared of isolated guinea pig endolymphatic sac (ES) tissue incubated with iodine (I)-125-labeled insulin (insulin I 125). These demonstrated specific binding of the insulin I 125 to receptors in the ES. Receptor-mediated endocytosis of the insulin-receptor complex is postulated to occur, and the relevance of insulin receptors in the ES is discussed, with particular emphasis on the previously observed synthesis of hyaluronan from glucose by the ES.

Animals↗
PubMed1994

Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct measurement by transvesical absorption of 99mtechnetium-diethylenetriaminepentaacetic acid.

Bladder permeability was directly measured with the radionuclide used clinically for detecting vesicoureteral reflux (99mtechnetium-diethylenetriaminepentaacetic acid, 99mTc-DTPA) in 10 interstitial cystitis patients diagnosed according to National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criterion and compared to 9 sex matched, symptom-free, normal volunteers. After functional bladder capacity was determined (capacity at which the patient demands fluid inflow to stop), the bladder was emptied and 5 mCi. 99mTc-DTPA in 10 ml. of saline were infused followed by normal saline to 80% of functional capacity. This was done to normalize the patients to the same low bladder pressure, since previous studies of rabbits indicated that bladder permeability is low and not significantly different at 20% and 60% of anesthetized bladder capacity (defined as the volume producing an intravesical pressure of 20 cm. water). Radioactivity of 1 ml. serum specimens taken at 0, 2, 15 and 30 minutes after radionuclide infusion was determined in a gamma counter, corrected for radioactive decay and converted to per cent of instilled dose per whole body based on blood volume estimated from body weight for each individual. There was considerable interindividual variability in the absorption between the patients and the volunteers. Analysis of variance of these data showed no statistically significant difference between the patients and controls at any time sampled. These results indicate that while some interstitial cystitis patients have a more permeable bladder than others, the same is true for normal, symptom-free volunteers. Thus, the concept of increased bladder permeability in interstitial cystitis is not supported by this direct measurement of bladder permeability.

Adult↗
PubMed1994

Thrombus imaging with technetium-99m synthetic peptides based upon the binding domain of a monoclonal antibody to activated platelets.

UNLABELLED: Monoclonal antibodies which recognize fibrin or platelets have enabled imaging of vascular thrombi, however, early imaging has been difficult because of the slow blood disappearance of even small antibody fragments. It was theorized that it might be possible to synthesize peptides which possess the same thrombus affinity as monoclonal antibodies, but which would leave the blood pool much more rapidly. METHODS: In this study, peptides were synthesized with amino acid sequences based on the primary binding region of the platelet glycoprotein IIb/IIIa-directed monoclonal antibody PAC1. Both termini of the peptides were blocked to prevent rapid proteolysis and a metallothionein-derived sequence was incorporated as a chelating agent for reduced technetium. RESULTS: Technetium-99m-labeled peptides produced images of fresh clots in the jugular veins of rabbits and day-old thrombi in the femoral veins of dogs within 2 hr after injection. In control experiments, a 99mTc-labeled nonspecific peptide failed to produce focal images of thrombus. Another control compound, 99mTc-glucoheptonate, did produce images of fresh clots in rabbits but failed to produce focal images of day-old thrombi. As was hoped, blood clearance of the 99mTc peptides was rapid, with excretion through the kidneys, however, none of the peptides studied had better thrombus-to-blood ratios than iodinated fibrinogen and all had significantly lower deposition in the thrombus. CONCLUSION: Using labeled synthetic peptides appears to be technically feasible but the absolute binding to thrombus is not yet sufficient for reliable imaging of pre-existing thrombi.

Amino Acid Sequence↗
PubMed1993

The effects of grommet insertion on Eustachian tube function.

A prospective study on the effect of grommet insertion on the passive Eustachian tube opening pressure was undertaken in children's ears with otitis media with effusion. After an initial immediate improvement following aspiration of the middle ear no further change in Eustachian tube function occurred over 4 subsequent weeks. Grommet insertion probably has no effect on Eustachian tube function.

Child↗
PubMed1993

The relationship between nasal airway resistance and middle ear pressure in subjects with acute upper respiratory tract infection.

Middle ear pressure and nasal airway resistance were measured over 7 1/2h in 8 subjects (age 18-32) with symptomatic acute upper respiratory tract infection. The mean middle ear pressure was -13 +/- 1.5 daPa (s.e.m.) with a range between 65 to -140 daPa. The mean total nasal resistance was 0.4 +/- 0.02 Pa/cm3/s (s.e.m.) with a range between 0.20 to 1.28 Pa/cm3/s. Unilateral nasal airway resistance exhibited reciprocal fluctuations with a range between 0.18-3.60 Pa/cm3/s. The mean difference between the highest and lowest unilateral nasal resistance values for each subject was 1.48 +/- 0.22 Pa/cm3/s (n = 16). No correlation was found between unilateral nasal airway resistance and middle ear pressure. Total nasal airway resistance had an inverse correlation with middle ear pressure r = 0.32, r2 = 0.11, n = 176 (p < 0.001). The results indicate that the generation of a negative middle ear pressure in acute upper respiratory tract infection occurred in a manner consistent with intermittent obstruction of the Eustachian tube and gradual middle ear gas absorption. Rapid increases in middle ear pressure and the generation of a positive middle ear pressure were associated with nose blowing. No evidence was found to support the hypothesis that negative middle ear pressures are associated with sniffing.

Adult↗
PubMed1993

Scintigraphic methods for detecting vascular thrombus.

Vascular thrombosis is a common and potentially life-threatening condition, but objective diagnosis is highly desirable before anticoagulant therapy is instituted. Existing nonscintigraphic modalities such as contrast venography and ultrasonography can image venous morphology but cannot reliably indicate the hematologic state of thrombi. Radiopharmaceuticals that bind specifically to fibrin or platelets afford the ability to determine whether a thrombus is hematologically active and therefore likely to propagate and/or embolize. Ideally, the test should produce a diagnostic result within a few hours and be capable of imaging thrombi that are several days old. A number of radiolabeled materials have been tested for their ability to bind to and permit scintigraphic detection of thrombi. These have included labeled fibrinogen, autologous platelets, monoclonal antibodies, fibrin fragment E1, plasminogen activators and synthetic peptides that mimic the molecular recognition units of antibodies. The current status of investigation of each of these radiopharmaceuticals is reviewed in this article.

Antibodies, Monoclonal↗
PubMed1992

Seasonal allergic rhinitis and its effects on eustachian tube function and middle ear pressure.

Middle ear pressure was recorded from 396 ears and aural symptoms inquired of 198 adult subjects with seasonal allergic rhinitis. Evidence of eustachian tube dysfunction was found in 24% of subjects. Increased duration of exposure to pollen over a further 2 weeks increased the incidence of eustachian tube dysfunction to 48%. The development of eustachian tube dysfunction did not correlate with the severity of nasal symptoms.

Adolescent↗
PubMed1992

Effect of ethyl alcohol on motor function in canine stomach.

The aim of this study was to elucidate the effects of ethanol on gastric emptying and the trituration of solid food. With the use of a noninvasive physiological imaging technique, gastric processing of a radiolabeled solid meal was evaluated in unanesthetized dogs which ingested 6-8% ethanol solutions or received intravenous alcohol before the meal. Oral alcohol (resulting in blood levels up to 174 mg/dl) decreased the amplitude of antral contractions or completely abolished them. Alcohol did not significantly affect the fundamental frequency of contractions except at high doses, at which contractions were abolished. Alcohol lengthened the mean time to 50% of gastric emptying in a dose-dependent manner, from 132 +/- 3 min without alcohol to 160 +/- 10 min with oral alcohol at blood levels of 80-120 mg/dl (P less than 0.05). This was manifested by a lengthening of the lag phase, but there was no effect on the terminal slope of emptying (emptying rate) of the processed meal. At equal blood levels up to 120 mg/dl, orally administered alcohol had a more pronounced effect than intravenous alcohol. These data suggest that even low doses of dilute alcohol affect the ability of the antrum to process solid food and thereby contribute to impairment of gastric emptying.

Administration, Oral↗
PubMed1992

Extra cranial arteriovenous malformations presenting as pulsatile tinnitus.

We present two cases of extra cranial arteriovenous malformations, which presented as pulsatile tinnitus. They were originally diagnosed by clinical examination and both lesions were subsequently confirmed by angiography and their feeding vessels defined. One case was managed by surgical excision, which produced relief of symptoms. The diagnosis and management of arteriovenous malformations is discussed.

Adult↗
PubMed1992

Preparation and preliminary evaluation of technetium-99m-labeled fragment E1 for thrombus imaging.

Fragment E1 labeled with 123I has been previously shown to permit imaging of thrombi in patients within as little as 20 min after injection. Because of the relatively rapid localization and blood disappearance of this protein, 99mTc would be the most clinically acceptable radionuclide for labeling Fragment E1. In this study, human fragment E1 was derivatized with a hydrazino nicotinate function to permit radiolabeling with reduced technetium. The modification reaction was carried out while the fragment E1 was protected in a complex, so that the modification occurred in nonfunctional regions of the fragment E1 molecule. After radiolabeling with 99mTc, the modified fragment E1 retained its functional activity, as judged by its binding to fragment DD in vitro. The ability of 99mTc-fragment E1 to produce images of venous thrombi was demonstrated in animal models. Images were focally positive within 20 min to 1 hr after injection. Thrombus-to-blood ratios exceeded those from 125I-fibrinogen in the same animals. This method of labeling appears to provide an alternative radiolabel to 123I without compromising the function of fragment E1.

Animals↗
PubMed1991

Temporal changes in unilateral middle ear pressure under basal conditions.

Spontaneous changes in middle ear pressure were measured tympanometrically in 15 healthy adults over 7.5 h under basal conditions. Despite fluctuation of middle ear pressure no temporal pattern existed and there was no evidence of reciprocal changes in pressure between sides. When awake but at rest the middle ear pressure fluctuates around ambient pressure. Recordings of positive pressure may represent supportive evidence in favour of a net basal tendency to produce a positive middle ear pressure.

Acoustic Impedance Tests↗
PubMed1991

The effect of postural change and upper respiratory tract infection on middle ear pressure.

The effect of a change in posture from sitting erect to lying supine and horizontal on middle ear pressure was investigated in 5 healthy adults and 5 adults with symptoms of an acute upper respiratory tract infection (URTI). The change in posture had no significant effect on middle ear pressure in the healthy subjects (p greater than 0.05). In those with URTI mean middle ear pressure increased from -39.5 daPa (erect) to -16.9 daPa (supine) (p = 0.026, n = 10). In the supine posture the middle ear pressure in subjects with URTI was raised. The cause of the increase in middle ear pressure is discussed in terms that the postural change may alter middle ear physiology such that in the supine posture there is a net production of middle ear gas as opposed to a net reabsorption in the erect posture. This may indicate that an increase in jugular venous pressure causes a net positive production of middle ear gas.

Acoustic Impedance Tests↗
PubMed1991

Cyclical changes in nasal airway resistance and middle ear pressures.

The relationship between unilateral changes in nasal airway resistance and the ipsilateral middle ear pressure were investigated in 8 otologically and rhinologically normal adults over the course of 7 1/2 h under laboratory conditions. Despite mean changes in unilateral nasal resistance of 0.75 Pa/cm3/s associated with the nasal cycle, no correlation existed with changes in ipsilateral Eustachian tube function, as judged by serial middle ear pressure recordings (r = 0.06, r2 = 0.00, p = 0.461). Middle ear pressure in healthy adults in a controlled environment remained very constant (mean = -6.71 +/- 0.52 daPa). 69% of middle ear pressures were equal to or above 0 daPa, which represents evidence in favour of a net positive production of middle ear gas.

Adult↗