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Biomedical subjects

L C Knight

Publications and source records attributed to L C Knight.

At least 19 recordsLinked to original sources

Stenting for bilateral congenital choanal atresia--a new technique.

We describe a new nasal stent for the treatment of bilateral congenital choanal atresia. The stent is made up of reinforced endotracheal tube mounted on a portex carrier tube. It potentially causes less internal crusting and stent blockage and is secured without sutures. It remains patent for at least 4 weeks. We have used the stent successfully in six patients between 1998 and 2004 at Leeds General Infirmary and present the data collected retrospectively. The current practice in the UK for treatment and stenting for congenital choanal atresia was investigated by a prospective internet based questionnaire sent to 18 consultant paediatric otolaryngologists of whom 12 (67%) responded. Their experience and results are reported. The literature has been reviewed.

Choanal Atresia↗

Laryngeal inflammatory pseudotumour: an unusual cause of airway obstruction.

We report a rare case of a laryngeal pseudotumour in a child presenting with stridor, which was treated by endoscopic laryngeal resection, without the need for a tracheostomy. A short review of the literature is also presented. Although rare, laryngeal pseudotumour should be considered as part of the differential diagnosis of stridor and upper airway obstruction in children.

Airway Obstruction↗

Non-oncologic applications of radiolabeled peptides in nuclear medicine.

Radiolabeled peptides have been investigated for diagnostic imaging in a variety of non-oncologic diseases. For imaging thromboembolic disease, peptides which bind to various components of thrombi have been tested. For targeting the fibrin component of thrombi, peptide analogues of fibrin or fragments of fibronectin which have a distinct binding domain for fibrin have been studied. For targeting activated platelets within thrombi, linear and cyclic peptide antagonists of the glycoprotein IIb/IIIa receptor on platelets have been studied, as well as naturally occurring antagonists of this receptor which are found in venoms. Analogues of laminin and thrombospondin which bind to other receptors on platelets have also been tested. There is an approach which uses a peptide to target thrombin which is sequestered within a fibrin clot. Another area of investigation has been to develop an improved radiopharmaceutical for imaging sites of infection and/or inflammation. Peptides which would bind to leukocytes in vivo, such as antagonists to the tuftsin receptor, chemotactic peptides, interleukin-8, or a platelet factor 4 analogue, have been radiolabeled for this purpose. These agents would enable imaging of both infection and inflammation. Development of a radiopharmaceutical for specifically imaging infection has focused on antimicrobial peptides such as human neutrophil defensin, ubiquicidin, human lactoferrin and alafosfalin, which are expected to bind selectively to microorganisms and not to leukocytes. Radiolabeled peptides are also being explored as agents for assessing unstable atherosclerotic plaque (endothelin), amyloid deposits (amyloid beta peptides), and the consequences of diabetes mellitus (human C-peptide).

Alzheimer Disease↗

Tonsillectomy by guillotine is less painful than by dissection.

Most tonsillectomies are carried out by dissection. Only a small minority of otolaryngologists still routinely perform guillotine tonsillectomy. We carried out a prospective study on 86 children undergoing tonsillectomy utilising a standard anaesthetic and analgesic regimen to compare post-operative pain after dissection tonsillectomy and guillotine tonsillectomy using a Popper's hemostatic guillotine. Guillotine tonsillectomy was significantly less painful (P<0.001) than dissection tonsillectomy. The relative risk of experiencing moderately severe to severe pain was 0.36 (95% CI, 0.18-0.72) in the guillotine group. A significant proportion of children experience moderately severe to severe pain despite a comprehensive analgesic regimen confirming that post operative pain remains an important issue after this operation. On the basis of our findings we advocate tonsillectomy by guillotine in children. The less pain that arises within the first 24 h may be particularly important if performing tonsillectomy as a day-case procedure.

Adolescent↗

Imaging pulmonary emboli and deep venous thrombi with 99mTc-bitistatin, a platelet-binding polypeptide from viper venom.

UNLABELLED: An imaging test that could locate both pulmonary emboli (PE) and their source, active deep venous thrombi (DVT), would be valuable in patient management. Bitistatin, an 83-amino-acid polypeptide isolated from Bitis arietans venom, binds avidly to the glycoprotein IIb/IIIa receptor on platelets. The goal of this study was to label bitistatin with 99mTc and assess its potential for imaging thrombi and emboli in vivo. METHODS: Molecular modeling of bitistatin indicated that its primary amines are located on the opposite side of the molecule from the receptor-binding domain. The primary amines were reacted with succinimidyl-4-hydrazino nicotinate hydrochloride to place 2.4 hydrazino nicotinate (Hn) chelating groups per peptide molecule. Hn-bitistatin was labeled by incubation with 99mTc-glucoheptonate to 96 TBq/mmol and then tested for binding to platelets in vitro and for imaging of 24-h-old DVT and PE in a canine model used previously for other thrombus tracers. RESULTS: 99mTc-Hn-bitistatin bound to stimulated platelets with a dissociation constant (Kd) = 32 nmol/L, similar to that of 125I-bitistatin (Kd = 41 nmol/L). In vivo, focal uptake was observed in planar images as early as 30 min (DVT) and 60 min (PE) after injection. Lesion uptake of 99mTc-Hn-bitistatin at 4 h after injection was calculated in terms of percentage injected dose per gram (%ID/g) of tissue and averaged 0.89 %ID/g PE and 0.79 %ID/g DVT. Lesion-to-background ratios averaged 34:1 (PE-to-lung), 18:1 (DVT-to-blood), and 284:1 (DVT-to-muscle). These values were not significantly different from iodinated bitistatin, but uptakes were higher than other tracers tested in the same model. CONCLUSION: 99mTc-Hn-bitistatin retains the functional activity of the iodinated peptide, has higher DVT and PE uptakes than other thrombus tracers in this standardized model, and has target-to-background characteristics suitable for imaging both PE and DVT in a single test.

Animals↗

Nasal pH measurement: a reliable and repeatable parameter.

The nasal mucosal pH is approximately 5.5-6.5, and increases in rhinitis to 7.2-8.3. This knowledge has not led to the widespread measurement of the nasal mucosal pH as an objective clinical parameter. The purpose of this study was to assess whether repeatable measures of nasal mucosal pH could be obtained in the clinical setting. Fifty-four adults without nasal symptoms were prospectively recruited. Using a semi-disposable antimony pH catheter, the nasal mucosal pH was measured in four specific areas of the nose and each reading repeated three times. The patients' age, sex, smoking habits, nasal anatomical variation and clearest nostril at the time of measurement were also recorded. The data shows that it is possible to obtain reliable and repeatable values for the pH of the nasal mucosa (Spearman-Brown R = 0.84). Analysis shows there is no significant difference between septal and turbinate mucosal pH. Subset analysis implies that nasal mucosal pH is higher in men then women (P < 0.05). The other variables did not affect the nasal mucosal pH significantly.

Adult↗

Cholinergic effects on human gastric motility.

BACKGROUND: Cholinergic regulation of chronotropic (frequency) and inotropic (force) aspects of antral contractility and how these impact on gastric emptying are not well delineated. AIMS: To determine the effects of cholinergic stimulation and inhibition on myoelectric, contractile, and emptying parameters of gastric motility. METHODS: Ten normal subjects underwent three studies each, using simultaneous electrogastrography (EGG), antroduodenal manometry, and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of baseline fasting manometry and EGG, subjects received saline intravenously, atropine (0.6 mg then 0.25 mg/hour intravenously), or bethanechol (5 mg subcutaneously). This was followed by another 30 minutes' recording and by three hours of postprandial recording after ingestion of a technetium-99m labelled solid meal. RESULTS: During fasting, atropine decreased, whereas bethanechol increased, the antral manometric motility index and EGG power. Postprandially, atropine decreased the amplitude of antral contractions by DAS, decreased the postprandial antral manometric motility index, and slowed gastric emptying. Atropine caused a slight increase in postprandial frequency of antral contractions by DAS and gastric myoelectrical activity by EGG. Bethanechol slightly increased the amplitude, but slightly decreased the frequency of antral contractions by DAS and decreased the frequency of gastric myoelectrical activity by EGG, with no significant increase in the motility index or gastric emptying. CONCLUSIONS: Cholinergic antagonism with atropine reduces antral contractility and slows gastric emptying. Cholinergic stimulation with bethanechol increases antral contractility, but decreases the frequency of antral contractions, without altering the antral motility index or gastric emptying.

Adult↗

Effect of gastric acid suppressants on human gastric motility.

BACKGROUND: The effect of histamine H2 receptor antagonists on gastric emptying is controversial. AIMS: To determine the effects of ranitidine, famotidine, and omeprazole on gastric motility and emptying. PATIENTS AND METHODS: Fifteen normal subjects underwent simultaneous antroduodenal manometry, electrogastrography (EGG), and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of fasting manometry and EGG recording, subjects received either intravenous saline, ranitidine, or famotidine, followed by another 30 minutes recording and then three hours of postprandial recording after ingestion of a radiolabelled meal. Images were obtained every 10-15 minutes for three hours to measure gastric emptying and assess antral contractility. Similar testing was performed after omeprazole 20 mg daily for one week. RESULTS: Fasting antral phase III migrating motor complexes (MMCs) were more common after ranitidine (9/15 subjects, 60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%) compared with placebo (4/14, 29%; p < 0.05). Postprandially, ranitidine, famotidine, and omeprazole slowed gastric emptying, increased the amplitude of DAS contractions, increased the EGG power, and increased the antral manometric motility index. CONCLUSIONS: Suppression of gastric acid secretion with therapeutic doses of gastric acid suppressants is associated with delayed gastric emptying but increased antral motility.

Adolescent↗

Effects of in vitro versus in vivo red cell labeling on image quality in gastrointestinal bleeding studies.

OBJECTIVE: Both in vivo and in vitro red cell labeling methods are available for performing gastrointestinal bleeding studies. While in vitro labeling has been shown to result in higher binding efficiency, no comparison of clinical image quality has been reported between those techniques. This study compares in vivo and in vitro methods using both subjective and objective measurements of image quality. METHODS: A consecutive series of gastrointestinal bleeding studies performed on 23 patients using in vivo labeling was compared to a series of 23 studies using in vitro labeling. Images at 30 min postinjection were randomized and analyzed by two observers. Subjective evaluation of image quality, as well as renal activity, was based on a comparison of femoral vein and inferior vena cava activity to adjacent background using numerical scores with a scale of 0-3. Image quality using the subjective scores was further classified as acceptable and poor. Target-to-background measurements of femoral vein to adjacent soft tissue in the thigh and inferior vena cava to adjacent abdominal background also were made. RESULTS: In vitro label subjective image quality was acceptable in 87% and 91% of cases for vascular and renal activity, respectively, but only 35% and 52% for in vivo labeling. In vitro label target-to-background ratios were significantly better than in vivo label for the femoral vein and inferior vena cava, as well as for the subjective assessment of vascular image quality, but not for renal activity. CONCLUSION: In vitro red cell labeling improves clinical image quality as compared with in vivo labeling. Both subjective and objective measurements of image quality are useful for comparing the results of labeling methods.

Abdomen↗

In vitro platelet binding compared with in vivo thrombus imaging using alpha(IIb)beta3-targeted radioligands.

Radioligands for the alpha(IIb)beta3 integrin on platelets are being studied for their ability to image venous thrombi and pulmonary emboli. One such radioligand, 123I-bitistatin, was previously shown to have higher thrombotic uptake in an animal model than other disintegrins, but the reason for this difference was not clear. The purpose of this study was to evaluate three labeled disintegrins, bitistatin, kistrin and barbourin, to look for in vitro differences in platelet binding which could explain the in vivo behavior. Disintegrins labeled with 121I were compared in vitro for extent of binding to platelets and rates of binding and dissociation. These findings were related to organ distribution and image quality for imaging thrombotic lesions, following administration of 123I-disintegrins in an animal model. Fibrinogen at 8.8 micromol/l was able to displace 125I-barbourin and 125I-kistrin more rapidly from ADP-stimulated platelets, with half-times of 3.5 and 10.7 min, compared with 125I-bitistatin (31.6 min). At equivalent concentrations in whole blood, a higher percentage of bitistatin bound to platelets compared with the other two. In vivo, kistrin and barbourin had significantly lower thrombus:muscle and pulmonary embolus:lung ratios in images compared with bitistatin. There was evidence of more metabolic deiodination of labeled kistrin and barbourin in vivo compared with bitistatin. A surprising finding was that conventional in vitro platelet binding studies did not predict the relative in vivo behavior of labeled disintegrins. The results suggest that labeled bitistatin has improved targeting of thrombi because it is less easily displaced from stimulated platelets, permitting longer lesion retention. It also appears to have a greater association with resting platelets in the blood, which may increase bioavailability and delay metabolic breakdown.

Animal Testing Alternatives↗

Comparison of scintigraphy and lactulose breath hydrogen test for assessment of orocecal transit: lactulose accelerates small bowel transit.

UNLABELLED: The lactulose breath test (LBT) and gastroenterocolonic scintigraphy (GECS) can both be used to measure orocecal transit time (OCTT). The aims of this study were (1) to measure OCTT by LBT and GECS and (2) to determine whether lactulose alters orocecal transit. METHODS: Eight normal subjects underwent simultaneous breath hydrogen testing, GECS, and duodenal manometry while receiving either 10 g lactulose or placebo with a radiolabeled solid/liquid test meal during two studies. There was a good correlation between OCTT by LBT and GECS when performed simultaneously (r = 0.95; P < 0.001). OCTT by GECS with lactulose was significantly faster (P = 0.004) than by GECS without lactulose, despite no change in gastric emptying of liquids and slowing of gastric emptying of solids (P = 0.02). The postprandial duodenal motility index was greater with lactulose than with placebo (P = 0.031). This study demonstrates that LBT and GECS (without lactulose) are not equivalent measures of OCTT. The standard LBT accelerates OCTT and slows gastric emptying. Therefore, lactulose has a direct accelerating effect on small intestinal transit.

Adult↗

Streptococcal tonsillitis and its association with psoriasis: a review.

Lancefield group A streptococcal upper respiratory tract infections are well known to be precursors of a number of disease processes. That they frequently herald a first attack of guttate psoriasis or a reactivation of chronic plaque psoriasis is well recognized, though this is perhaps more true among dermatologists than otolaryngologists. This paper briefly summarizes the historical background, recent research into, and current understanding of the connection between the two pathological phenomena.

Humans↗

Electrogastrography and gastric emptying scintigraphy are complementary for assessment of dyspepsia.

We have tried to correlate abnormalities in electrogastrography (EGG) and gastric emptying (GE) with symptom severity in patients with functional dyspepsia. Seventy-two patients with functional dyspepsia underwent EGG, GE, and symptom severity quantitation. EGGs were assessed for dominant frequency (DF), percentage of time of DF in the 2 to 4 cpm range, and postprandial-fasting DF power ratio. Solid-phase GE scintigraphy was assessed for 2-hour percentage retention. Symptoms of upper abdominal discomfort, early satiety, postprandial abdominal distension, nausea, vomiting, and anorexia were graded as none (0), mild (1), moderate (2), and severe (3); the sum represented a total symptom score. The EGG was abnormal in 11 of 22 (50%) patients with delayed GE compared with 11 of 50 (22%) with normal GE (p < 0.025). The total symptom scores were higher in patients with both delayed GE and abnormal EGG compared with patients with normal GE and EGG, normal GE and abnormal EGG, and delayed GE and normal EGG. We conclude that EGG abnormalities are more common in dyspeptic patients with delayed GE. Patients with both delayed GE and abnormal EGG have more severe symptoms. Our results suggest that EGG and GE complement each other in correlating symptoms to gastric dysmotility.

Adult↗

Regional differences in gastric acidity and antacid distribution: is a single pH electrode sufficient?

UNLABELLED: Accurate measurement of intragastric acidity has both clinical and investigational importance in studying gastric pathophysiology. OBJECTIVES: The aims of this study were fourfold: (1) to investigate whether regional differences in intragastric acidity exist; (2) to determine intragastric acidity after a standard antacid was administered in both the fasting and fed states; (3) to monitor gastric emptying of and anatomic distribution of radiolabeled antacid during fasting and postprandial periods; and (4) to determine whether the regional effects of ingested antacid correlated with the anatomic distribution of the antacid. METHODS: Eight normal male volunteers were studied after fluoroscopically guided nasogastric placement of a tube assembly containing four pH electrodes, with one electrode in each quartile of the stomach. Simultaneous pH readings were made from the four electrodes while fasting, after administration of fasting antacid (30 ml, 79 mEq buffering capacity), postprandially, and after postprandial antacid ingestion. All subjects repeated the protocol on a separate day, five of them using radiolabeled antacid. Gastric emptying and gastric distribution over time of radiolabeled antacid were determined for comparison to regional intragastric acidity. RESULTS: Intragastric acidity varied regionally over time in response to meals and to fasting and postprandial antacid. In the fasting state, intragastric acidity returned to baseline after antacid ingestion in a proximal to distal (cardia to antrum) sequence, while postprandial antacid resulted in a return to baseline acidity in a distal to proximal (antrum to cardia) sequence. Radiolabeled antacid distribution paralleled intragastric pH and hydrogen ion concentration in the fasting state, with 82% of the antacid localizing in the distal half of the stomach within the first minute after antacid ingestion. Postprandially, the greatest initial and most prolonged antacid buffering effect occurred proximally, correlating with the presence of radiolabeled antacid. Postprandial antacid remained in the stomach for a longer time (T1/2 = 93.1 +/- 23.4 min) compared with fasting antacid (T1/2 = 23.6 +/- 11.1 min). CONCLUSIONS: Measurement of acidity in the four quartiles of the stomach demonstrated regional variation in response to both food and a standard antacid. A single pH electrode does not detect regional intragastric pH differences.

Adult↗

Delayed gastric emptying and decreased antral contractility in normal premenopausal women compared with men.

OBJECTIVES: The effects of gender on gastric emptying have not been fully elucidated. The aims of this study were to determine how gender affects gastric emptying and to see whether any of the observed differences in gastric emptying correlate with alterations in antral motility as measured by dynamic antral scintigraphy (DAS), cutaneous electrogastrography (EGG), and antroduodenal manometry (ADM). METHODS: Nine normal women [age 27.9 +/- 2.2 (mean +/- SEM) yr] in the first 10 days of the menstrual cycle and 13 normal men (age 27.5 +/- 1.7 yr) underwent simultaneous gastric emptying scintigraphy, DAS, EGG, and ADM. After an overnight fast and placement of an ADM catheter and EGG electrodes, a 60-min fasting recording was obtained, followed by ingestion of a 99m Tc-labeled solid meal. Measurements for all modalities were acquired every 10-15 min for 180 min. RESULTS: The gastric T1/2 was longer in women than in men [102 +/- 18 min vs. 71 +/- 4 (mean +/- SEM) min, p < 0.05]. A comparison of the gastric emptying pattern in women with that in men revealed no difference in proximal gastric emptying and lag phase, but in women the terminal slope of emptying was decreased compared with that in men (p < 0.05). The contractility measured in mid-antrum by DAS was significantly lower for women (p < 0.05). A decrease was also seen in the strength of contractions as measured by ADM. CONCLUSIONS: These data demonstrate that gastric emptying of solid food in normal young, premenopausal women is slower than in age-matched men, even during the first 10 days of the menstrual cycle. The findings suggest that the delay is due primarily to altered distal gastric motor function. This hypothesis was corroborated by finding decreased antral contractility as recorded by both dynamic antral scintigraphy and ADM. This study demonstrates the need to use appropriate control values to evaluate symptomatic female patients.

Adolescent↗

Hearing aids and glue ear.

This study was designed to determine the acceptance and effectiveness of a hearing aid in the management of children with persistent hearing loss due to glue ear (otitis media with effusion [OME]). Forty-eight children with OME, in whom the main symptom was deafness, were treated with a hearing aid instead of surgery and reviewed at 3-monthly intervals over 6-12 months. Seventy-one per cent reported unequivocal satisfaction with the aid. Sixty-five per cent used the aid continuously throughout the day whilst 35% used it only at specific times of need. Ninety-eight per cent noticed a definite improvement in their hearing whilst using the aid and this was confirmed audiometrically in 100%. Disability was considered in terms of speech development and educational achievement. In 66% there had been a subjective decline in these parameters prior to aid prescription. In all but one child significant improvement was made sufficient to alleviate parental and teachers' concern. No children reported significant symptoms due to OME other than deafness and there were no complications of hearing aid usage. At follow-up, however, 13% of children continued to use a hearing aid in an ear in which the OME had resolved. This study has shown that in this preselected group of children with persistent OME and the predominant symptom of deafness, a hearing aid was an effective treatment for their deafness with high acceptance and compliance.

Audiometry, Pure-Tone↗

Comparison of iodine-123-disintegrins for imaging thrombi and emboli in a canine model.

UNLABELLED: Disintegrins are peptides found in viper venoms which bind to platelets through the glycoprotein IIb-IIIa receptor. The purpose of this work was to evaluate the ability of disintegrins to image thrombi and emboli in vivo. METHODS: Eight disintegrins (bitistatin, albolabrin, echistatin, eristostatin, kistrin, mambin, halysin and barbourin) were purified from snake venom. After radiolabeling with 123I, disintegrins were tested for their ability to image 24-hr-old experimental deep vein thrombi (DVT) and pulmonary emboli in a canine model. Labeled fibrinogen and platelets were used as controls. Gamma camera imaging was performed during the first 4 hr, after which tissue samples were collected for counting. RESULTS: Of the disintegrins tested, 123I-bitistatin had higher uptake in DVT (0.21 +/- .06% ID/g) than any other disintegrin (0.009-0.036%/g, p < 0.05). Bitistatin had higher DVT-to-blood ratios (9.8 +/- 2.5) than all other disintegrins, 125I-fibrinogen or 99mTc-HMPAO-platelets (p < 0.05). Images of DVT obtained with 123I-bitistatin were focally positive within 1 hr and improved by 4 hr. In pulmonary emboli, the absolute uptake of 123I-bitistatin (0.64 +/- 0.17% ID/g) was higher than all other compounds (p < 0.05), although barbourin had moderate uptake (0.23 +/- 0.11% ID/g) and may also be useful for imaging pulmonary embolism (PE). The uptake of bitistatin in PE was superior to both 125I-fibrinogen (0.18 +/- 0.02% ID/g) (p < 0.05) and 99mTc-HMPAO-platelets (0.14 +/- 0.02% ID/g, p < 0.05). Iodine-123-bitistatin had embolus-to-blood ratios averaging 27 +/- 7, which was higher than platelets, fibrinogen, echistatin, mambin or halysin (p < 0.05). Iodine-123-bitistatin background in lungs, liver and heart were low, which permitted visualization of all pulmonary emboli by 2-4 hr after injection. CONCLUSION: Labeled bitistatin should be investigated further as an agent which may permit rapid imaging of both thrombi and emboli.

Amino Acid Sequence↗