Presentation of laryngeal papilloma in childhood: the Leeds experience.

INTRODUCTION: The human papilloma virus (HPV) can cause laryngeal papillomatosis in childhood. The aetiology is thought to be vertical transmission. Clinically these children are usually asymptomatic for the first 6 months of life. As the papillomas develop locally, symptoms begin to develop. The symptoms range from voice change to frank hoarseness, and 'noisy' breathing, most commonly inspiratory stridor. METHOD: Clinical images from microlaryngoscopy and bronchoscopy over a 12-year period were assessed for laryngeal papilloma. RESULTS: In Leeds seven cases presented to the specialist centre over the past 12 years, the average age at presentation was 6.8 years and duration of onset of symptoms to specialist review was 21 months. Five of the children had been treated for asthma and two presented in extremis. CONCLUSION: The take home message for clinicians is hoarse voice associated with shortness of breath needs specialist referral.

The use of ice-lollies for pain relief post-paediatric tonsillectomy. A single-blinded, randomised, controlled trial.

OBJECTIVES: To assess whether the use of ice-lollies after tonsillectomy with or without adenoidectomy in children aged 2-12 reduces pain in the immediate postoperative period. DESIGN: A prospective, randomised, single-blinded study design consisting of two groups with an intention to treat analysis. SETTING: Tertiary referral centre. PARTICIPANTS: Children aged 2-12 undergoing tonsillectomy with or without adenoidectomy. MAIN OUTCOME MEASURES: Pain assessment by nursing staff in the form of the validated modified Children's Hospital of Eastern Ontario Pain Scale at 15, 30 and 60 min and 4 h. RESULTS: Ninety-two patients were recruited into the study with 46 allocated to receive an ice-lolly and 41 not to receive an ice-lolly after exclusion of those with incomplete data. The two groups were comparable for number, age, sex and diagnosis. The pain score at every time interval was lower in the group that had received the ice-lolly compared with the group that had not. This was statistically significant at 30 (P = 0.008) and 60 min (P = 0.049). CONCLUSION: Our data suggest that ice-lollies are a cheap, effective and safe method of reducing postoperative pain up to one hour following paediatric tonsillectomy.

Diode laser for paediatric airway procedures: a useful tool.

OBJECTIVE: A wide range of lasers have been used in the larynx. Diode laser is a portable and relatively inexpensive laser which is delivered via a glass fibre hand-held probe. The objective of this study was to report our experience with the use of diode laser in a variety of paediatric airway pathologies. METHODS: In this study, 90 diode laser laryngeal procedures were performed on 31 patients in the age range of 1 month to 16 years at the time of the operation. The follow up after the procedure has been in the range of 6 months to 3 years. RESULTS: As per our records 19/31 (61.3%) patients have been cured of their initial pathologies and were not under further review, 3/31 (9.6%) were having repeated laser treatments. The remaining 9/31 (29.0%) had to undergo further treatment. There was no laser-related intra-operative or postoperative complications. CONCLUSIONS: Diode laser is a good tool for several paediatric laryngeal pathologies. The ability to guide the laser light using the flexible glass fibre directly onto the area requiring vapourisation enables very precise treatment.

Blood coagulation factor XIa binds specifically to a site on activated human platelets distinct from that for factor XI.

Binding of 125I-Factor XIa to platelets required the presence of high molecular weight kininogen, was enhanced when platelets were stimulated with thrombin, and reached a plateau after 4-6 min of incubation at 37 degrees C. Factor XIa binding was specific: 50- to 100-fold molar excesses of unlabeled Factor XIa prevented binding, whereas Factor XI, prekallikrein, Factor XIIa, and prothrombin did not. When washed erythrocytes, added at concentrations calculated to provide an equivalent surface area to platelets, were incubated with Factor XIa, only a low level of nonspecific, nonsaturable binding was detected. Factor XIa binding to platelets was partially reversible and was saturable at concentrations of added Factor XIa of 0.2-0.4 microgram/ml (1.25-2.5 microM). The number of Factor XIa binding sites on activated platelets was estimated to be 225 per platelet (range, 110-450). We conclude that specific, high affinity, saturable binding sites for Factor XIa are present on activated platelets, are distinct from those previously demonstrated for Factor XI, and require the presence of high molecular weight kininogen.

High molecular weight kininogen binds to unstimulated platelets.

Studies were performed to determine if the unstimulated platelet membrane has a site for high molecular weight kininogen (HMWK) binding. 125I-HMWK bound to unstimulated platelets. Zn++ was required for 125I-HMWK binding to unstimulated platelets and binding was maximal at 50 microM Zn++. Neither Mg++ nor Ca++ substituted for Zn++ in supporting 125I-HMWK binding to unstimulated platelets, and neither ion potentiated binding in the presence of 50 microM zinc. 125I-HMWK competed with equal affinity with HMWK for binding, and excess HMWK inhibited 125I-HMWK-platelet binding. Only HMWK, not prekallikrein, Factor XII, Factor XI, Factor V, fibrinogen, or fibronectin inhibited 125I-HMWK-platelet binding. 125I-HMWK binding to unstimulated platelets was 89% reversible within 10 min with a 50-fold molar excess of HMWK. Unstimulated platelets contained a single set of saturable, high affinity binding sites for 125I-HMWK with an apparent dissociation constant of 0.99 nM +/- 0.35 and 3,313 molecules/platelet +/- 843. These studies indicate that the unstimulated external platelet membrane has a binding site for HMWK that could serve as a surface to modulate contact phase activation.

Specific uptake of radioiodinated fragment E1 by venous thrombi in pigs.

Fragment E1, a product of plasmic digestion of cross-linked fibrin, binds specifically in vitro to polymerized fibrin but not to fibrinogen. Purified human Fragment E1 was radiolabeled with 125I or 131I by the Iodogen technique. The uptake of radioiodinated Fragment E1 in vitro into forming or preformed clots was demonstrated. Animal biodistribution studies of radioiodinated Fragment E1 showed its rapid removal from the circulation; radioactive catabolites did not reside long in any organ and were excreted in the urine. The uptake in vivo was evaluated in pigs with preexisting venous thrombi of various ages from 1 h up to 5 d at the time of intravenous systemic injection of the tracer. Radioiodinated fibrinogen was also injected into the same animals to compare the uptake of the two tracers. Thrombus-to-blood ratios for Fragment E1 averaged 43:1 (range 10-108) and 29:1 (range 8-107) in thrombi 1-6 h and 1-5 d old, respectively. In contrast, mean thrombus-to-blood ratios for fibrinogen were, in the same time intervals, 26:1 (range 17-41) and 2:1 (range 0.5-3.9), respectively. It is concluded that radioiodinated Fragment E1 is a specific marker of thrombi in vivo: its uptake by fresh thrombi is better than that of labeled fibrinogen and, in contrast to radioiodinated fibrinogen, this fragment is incorporated into old thrombi as well.

Aryepiglottoplasty for laryngomalacia: results and recommendations following a case series of 84.

OBJECTIVES: To examine one consultant's experience of aryepiglottoplasty at Leeds General Infirmary. To identify risk factors for post-operative complications. Comparing the outcomes of surgery with the published literature on aryepiglottoplasty. DESIGN: A retrospective case series of consecutive patients undergoing aryepiglottoplasty identified from theatre records. SETTING: The Otolaryngology Department, Leeds General Infirmary. This is part of Leeds Teaching Hospitals NHS Trust and is a tertiary referral centre with regional paediatric intensive care unit (PICU) and specialises in managing paediatric airway pathology. PARTICIPANTS: Ninety-one consecutive cases of aryepiglottoplasties, between 1997 and 2005. The medical records for 84 cases were reviewed. MAIN OUTCOME MEASURES: Unplanned admissions to PICU, complication rate, length of post-operative hospital stay, and successful resolution of symptoms amongst our patient group. RESULTS: The primary indication for surgery was found to be severe stridor. There was a low rate (3.6%) of unplanned admissions to the PICU. 7.1% of patients suffered a post-operative aspiration pneumonia. The majority (66.7%) of patients were able to return home after just one night in hospital. 11.9% of patients continued to have some stridor at follow-up. CONCLUSIONS: The majority of patients undergoing aryepiglottoplasty for isolated laryngomalacia can be monitored overnight on a paediatric surgical ward and return home the following day (85%). Furthermore, they should expect improvement of their stridor with a single procedure (90%). Aryepiglottoplasty at an experienced unit is a low-risk procedure with a high success rate.

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.

Sites of direct and indirect halogenation of albumin.

The sites of radiohalogenation in proteins vary with the labeling method and the pH of the labeling reaciton. We have directly halogenated albumin with carrier-free radioiodide by three methods (pH range 2.2--9.3), and with carrier-free radiobromide by the chloroperoxidase method (pH range 2.2--4.6). Albumin was also indirectly halogenated by attaching a radioiodinated acylating agent, N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP). The labeled proteins were proteolyzed enzymatically at neutral pH and the labeled amino acids produced were analyzed by liquid chromatography. Iodination at pH 7 yielded predominantly monoiodotyrosine, but at lower pH, fewer tyrosyl residues are labeled and a greater number of unstable sulfur-iodine bonds are formed at cysteinyl residues. Bromination with chloroperoxidase resulted in a high degree of labeling of cysteinyl residues at pH 2.8, the condition for optimum activity of this halogenating enzyme. Indirect halogenation with SHPP resulted in labeling of mid-chain lysyl, histidyl and tyrosyl residues.

Differences in the sites of iodination of proteins following four methods of radioiodination.

The rate of deiodination of radioiodinated proteins varies with the method of iodination. To elucidate differences in the iodinated protein labeled by various methods, we have hydrolyzed fibrinogen and several small peptides iodinated by the iodine monochloride, chloramine-T, electrolytic and enzymatic methods. Under conditions of either acidic or basic proteolysis, extensive deiodination occurred and the major product was I-. When a protease of Streptomyces griseus was used, radio-iodinated fibrinogen and other polypeptides were degraded to single iodinated amino acid residues and only a small yield of I-. The iodinated amino acids resulting from proteolysis were separated by ion-exchange chromatography. The iodine monochloride and enzymatic methods yielded largely iodotyrosine with small amounts of other iodinated amino acids. The chloramine-T product spectrum varied with the chloramine-T:protein ratio, whereas the electrolytic method yield was a complex function of the reaction conditions. The different methods of iodination lead to some differences in the site of iodination which correlate with stability of the protein-iodine bond.

Binding properties of 111In-diethylenetriaminepentaacetic acid (DTPA)-fragment E1,2, a fibrin-specific probe, are dependent on use of protecting complex during attachment of DTPA groups.

Fragments E1 and E2, plasmic degradation products of crosslinked fibrin, bind specifically to polymers of fibrin. A mixture of these fragments, denoted as fragment E1,2, was radiolabeled with 111In after covalently attaching metal chelating groups (diethylenetriaminepentaacetic acid, DTPA) to the fragment, using two approaches. In the first approach, DTPA groups were attached directly to purified fragment E1,2. In the second approach, attachment sites of DTPA groups were directed away from the active region of the molecule by having fragment E1,2 bound in complex, with its active sites protected during the derivatization. Direct attachment of DTPA groups to fragment E1,2 resulted in complete loss of binding to fibrin in vitro. When derivatized in complex, 111In-DTPA-fragment E1,2 retained a higher degree of binding to human fragment DD and human plasma clots in vitro than did radioiodinated fragment E1, even when up to eight DTPA groups were attached per molecule of fragment E1,2.

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.

Long-term effects of dietary fiber on glucose tolerance and gastric emptying in noninsulin-dependent diabetic patients.

Effects of long-term (2 months) supplementation of diet with 20 g of guar gum and 10 g of wheat bran on metabolic control was studied in 12 obese, poorly controlled noninsulin-dependent diabetic patients. Addition of fiber reduced urinary excretion of glucose from 30.5 +/- 6 to 8.3 +/- 2 g/24 h, (p less than 0.025), fasting plasma glucose concentration from 301 +/- 24 to 184 +/- 15 mg/dl (p less than 0.025), and plasma cholesterol concentration from 277 +/- 24 to 193 +/- 9 mg/dl (p less than 0.025). No significant changes were observed in the patients weight and serum concentrations of triglycerides, high-density lipoproteins, free fatty acids, and insulin. Addition of fiber also delayed gastric emptying of liquids and solids. This effect became statistically significant 60 and 90 min after intake of a test meal for liquids and solids, respectively. We conclude that addition of guar and bran to the diet resulted in long-term improvement of metabolic control in these patients and that delayed gastric emptying may be one of the mechanisms responsible for this beneficial effect.

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.

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.

In vitro stability and in vivo clearance of fibrinogen or serum albumin labeled with 77Br, 131I, or 125I by direct or indirect synthetic methods.

Conventional protein iodination involves the addition of an oxidizing agent to the protein solution. Through the use of the acylating agent N-succinimidyl-3(4-hydroxyphenyl)propionate, labeling can be accomplished without subjecting the protein to oxidizing conditions. Fibrinogen and serum albumin labeled with 131I and 77Br by this technique were compared with each other and with 125I-protein prepared by direct iodination using the ICI, chloramine-T, and lactoperoxidase methods. Iodinated proteins have two drawbacks: the high radiation dose accompanying 125I and 131I, and the ease of hydrolysis of the weak carbon-iodine bond. These drawbacks can be overcome by using 56-hr 77Br.

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.

Evaluation of indium-111-labeled anti-fibrin antibody for imaging vascular thrombi.

Monoclonal antibody 59D8 developed by Hui et al., binds to fibrin but not fibrinogen. An 111In-labeled Fab fragment of 59D8 was studied in vitro and in animal models to evaluate its potential for imaging thrombi and emboli in man. Rabbits and dogs were used as models for studying thrombus uptake in vivo. Thrombi and emboli up to 4 days old were successfully visualized at 4-24 hr postinjection in five of eight rabbits. In dogs, 0.5-hr-old and 24-hr-old thrombi were successfully imaged at 24 hr in six of eight animals, and 3/6 of these were positive at 3-4 hr postinjection. Thrombus-to-blood ratios in the dogs averaged 7.1 +/- 1.3. The findings suggest this antibody may be useful for imaging thrombi in man.

Evaluation of three imaging instruments in dogs with liver hemotomas: concise communication.

Single-gamma emission computerized tomography (ECT) was compared with transmission computerized tomography (TCT) and scintillation-camera imaging (SC) in eight dogs with acute, solitary hematomas in the left liver lobe. The superior performance of TCT was attributed to its inherently better spatial resolution than those of ECT or SC, and to the fact that studies with TCT could be performed during apnea. ECT was more sensitive than SC to small changes in the spatial distribution of radionuclides. In addition, the ECT, by virtue of its sectioning capability, was more sensitive than is SC to differences in radionuclide concentrations at same depth in an organ.

Comparison of In-111-labeled platelets and iodinated fibrinogen for the detection of deep vein thrombosis.

Indium-111-labeled platelets and I-125 fibrinogen were administered to dogs with experimentally induced deep-vein thrombosis. The thrombus uptake of both labeled compounds was studied as a function of thrombus age. In thrombi less than 24 hr old, thrombus-to-blood ratios for In-111 platelets were about twice as great as those obtained for I-125 fibrinogen. Excellent scintiphotos were obtained with In-111 platelets. In thrombi older than 24 hr, uptake of both agents was low, but good images were still obtained with In-111 platelets. The images in this case are not of thrombi, but rather of damaged vessel wall. Indium-111-labeled platelets are superior to iodinated fibrinogen for imaging fresh thrombi, but offer no advantage for thrombi over 24 hr old.