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Biomedical subjects

R Hankin

Publications and source records attributed to R Hankin.

At least 19 recordsLinked to original sources

Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma.

BACKGROUND: The relationship between the clinical pattern of asthma and airway inflammation in childhood asthma is poorly characterised, yet underpins the treatment recommendations in current asthma guidelines. A study was undertaken to examine the relationship between airway inflammation and clinical asthma in children. METHODS: Children with asthma (n=146) and healthy controls (C, n=37) were recruited from primary and specialist clinics. Sputum induction and hypertonic saline challenge were performed. RESULTS: As the frequency of asthma episodes in the past 12 months increased, there were significant increases in sputum eosinophils (median; infrequent episodic (IE) 1.5%, frequent episodic (FE) 2.3%, persistent (P) 3.8%, control (C) 1.0%; p=0.002), sputum eosinophil cationic protein (ECP) (IE 113 ng/ml, FE 220, P 375, C 139; p=0.003), and desquamated bronchial epithelial cells (IE 2.0%, FE 6.0%, P 5.0%, C 2.5%; p=0.04). Treatment intensity was also associated with increased sputum eosinophils (p=0.005). The relationships between other severity markers (current symptoms, lung function) were less strong. CONCLUSION: Children with more frequent episodes of clinical asthma exhibit increasing airway inflammation that is characterised by sputum eosinophilia and bronchial epithelial desquamation. The results support clinical assessment by frequency of wheezing episodes over the past 12 months when determining anti-inflammatory treatment requirements, and indicate that current symptoms are determined by mechanisms in addition to sputum eosinophilia.

Adolescent↗

The tolerability, safety, and success of sputum induction and combined hypertonic saline challenge in children.

Induced sputum using hypertonic saline (HS) is a useful research tool to study airway inflammation (AI). HS provocation testing can also be used to measure airway hyperresponsiveness (AHR). A combined HS challenge and sputum induction procedure has been developed to permit assessment of AI and AHR in a single test. The aim of this study is to report the success and tolerability of sputum induction alone, and in combination with a HS bronchial provocation challenge. Sputum induction alone was performed with beta2-agonist pretreatment. In the combined challenge, no beta2-agonist pretreatment was used. A high-output ultrasonic nebulizer with valve box and tubing were used to deliver 4.5% saline in doubling time periods from 0.5 s to 4 min. Outcomes assessed were completion of the test protocol, adequacy of sputum samples, decrease in FEV1, and adverse effects during the procedure. Fifty-three children who underwent a sputum induction alone, and 182 children who underwent a combined sputum induction and bronchial provocation using HS. Sputum induction alone was well tolerated, with 98% of children completing the procedure and only 4% experiencing a significant (> 15%) fall in FEV1. An adequate sample of sputum was obtained in 92% of children. The combined challenge was completed by 90% of children. A distressing cough occurred in 13% of children and irritation of the mucosa in 1% of children. In the combined challenge an adequate sample of sputum was obtained in significantly fewer children than with sputum induction alone (70% versus 92%, p < 0.05). Sputum cellular changes reflected the shorter nebulization time with sputum induction alone. We conclude that induction of sputum using HS after pretreatment with bronchodilator is well tolerated with a high success rate in children. Combining the HS challenge with sputum induction provides additional information and is a useful means of comparing AHR and AI simultaneously, but at the expense of having a reduced success rate in obtaining an adequate sample of sputum, as well as increased side effects.

Adolescent↗

Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores.

Patients with chronic viral hepatitis and cirrhosis often have elevated serum alpha-fetoprotein (AFP) values, the causes of which are unclear. We studied 81 patients with chronic hepatitis C and the relationships of serum AFP and alanine aminotransferase (ALT) values, hepatic histologic features, and hepatocyte proliferation activity scores. Twenty-two patients had nil to mild fibrosis, 34 had moderate fibrosis, and 25 had marked fibrosis-cirrhosis. The mean serum AFP value was significantly greater in patients with more fibrosis. Serum ALT values were slightly greater in the marked fibrosis-cirrhosis patient group. The differences in the HAI and in hepatocyte MIB-1 scores were not significant. Among all patients, increasing serum AFP values significantly correlated with increasing ALT values. However, there were no significant correlations with serum ALT or HAI and serum AFP values. There was no association between serum AFP values and immunohistochemical staining for AFP within hepatocytes. These results suggest that elevated serum AFP values are the result of altered hepatocyte-hepatocyte interaction and loss of normal architectural arrangements. The presence of marked fibrosis or cirrhosis, a state of significant altered hepatocyte architecture, may be the underlying cause of increased serum AFP, rather than necrosis or active regeneration.

Alanine Transaminase↗

Chemotherapy for malignancy induces a remission in asthma symptoms and airway inflammation but not airway hyperresponsiveness.

Inflammation with infiltrations of eosinophils and mast cells into the walls of airways is considered to increase airway hyperresponsiveness (AHR), which in turn characterizes asthma. We present a child with AHR in whom the clinical course of asthma was related to eosinophilic bronchitis. Our patient was admitted at age 6 months with bronchiolitis and at age 4 years with asthma. Inhaled corticosteroids were begun at age 7 years. At age 8 he developed a meningeal sarcoma. While on chemotherapy, his asthma symptoms resolved and he no longer required prophylactic asthma treatment. After 14 months off all chemotherapy, he again had mild episodic asthma. While receiving chemotherapy for malignancy, he had an admission with a coagulase negative staphylococcal bacteremia. During sputum induction with 4.5% saline, he developed cough, wheeze, and a 20% reduction in peak expiratory flow (220 to 180 L/min) that reversed after treatment with salbutamol. The sputum cell count was 1.7 x 10(6)/ml with 1.1 x 10(6) being neutrophils. Two weeks later and prior to the induction of the second sputum, a 21% increase in FEV1 was recorded after bronchodilator inhalation (82% to 99% of predicted). The second sputum contained 2.7 x 10(6)/ml cells with 1.6 x 10(6)/ml neutrophils. Neither eosinophils nor mast cells were identified in the sputum. A third sputum obtained 14 months after the cessation of chemotherapy showed a sputum cell count of 16 x 10(6)/ml, with 11.6 x 10(6) neutrophils and 0.4 x 10(6) eosinophils; no mast cells were detected. A reversible 15% reduction in FEV1 was detected on hypertonic saline challenge testing. This boy had persistent airway hyperreactivity and reversible airways obstruction on three occasions during and following chemotherapy. When he developed asthma symptoms, his sputum contained neutrophils and eosinophils; while on chemotherapy his sputum did not contain eosinophils and he was symptom-free and off all asthma therapy. One can speculate that chemotherapy for malignancy can induce a remission in asthma symptoms but not AHR, and remission in symptoms is associated with a lack of eosinophilic or mast cell infiltrates in the sputum.

Asthma↗

Augmentation of autograft using rhBMP-2 and different carrier media in the canine spinal fusion model.

This study evaluated the use of recombinant human bone morphogenetic protein (rhBMP-2) with various types of carrier media, and the effect of rhBMP-2 as an adjunct to autogenous iliac crest bone graft in the canine spinal fusion model. BMP induces mesenchymal cells to differentiate into cartilage and bone. The recent availability of rhBMP-2 has created the opportunity to evaluate this material's properties in augmenting autogenous bone graft in spinal fusion. Currently, the most appropriate type of carrier media for rhBMP-2 is undetermined. Bilateral intertransverse spinal fusions were performed on six canine lumbar spines at L1-L2, L3-L4, and L5-L6, using autogenous posterior iliac crest bone graft at each level, creating a total of 18 segmental fusion sites. All 18 sites were then randomly assigned to one of six fusion methods: autogenous bone graft (ABG) alone, ABG + rhBMP-2, ABG + collagen (Helistat) "sandwich" + rhBMP-2, ABG + collagen (Helistat) morsels + rhBMP-2, ABG + polylactic/glycolic acid sponge (PLGA) sandwich + rhBMP-2, and ABG + open-pore polylactic acid morsels + rhBMP-2. Each material was evaluated for ease of handling and application at the index surgery. The animals underwent computed tomography (CT) scanning of the lumbar fusion sites after 8 weeks. Volumetric measurements of total fusion mass at each level were performed using two-dimensional CT scan slices and a volumetric program supplied by the Siemens Medical System. The animals were killed after imaging studies. The lumbar spine fusion sites were evaluated for integrity of the fusion mass, both visually and with manual mechanical stressing. Crossover of the fusion mass to adjoining levels was also evaluated. Histologic evaluation of all fusion sites was performed. The addition of rhBMP-2 significantly increased bone graft volume as noted on CT scan. Carrier that could be mixed with morselized bone graft offered easier handling and application and all spine segments fused. Polylactic/glycolic acid (PLGA) sites were associated with a greater incidence of voids within the fusion mass. No significant difference in carrier media for rhBMP-2 could be determined. However, PLGA was associated with a higher rate of fusion mass void formation. rhBMP-2, when added to autograft, significantly increased the volume and the maturity of the resulting fusion mass.

Animals↗

The future European system for the free circulation of veterinary vaccines in Europe.

Although Community legislation has only recently been extended to cover veterinary biologicals, these products are fully covered by the recent Commission proposals for the free movement of medicinal products after 1992. The proposals are based on more than 25 years of harmonization of national regulations and more than 10 years' experience of coordinating national decisions on individual medicinal products. The proposals envisage the establishment of two new Community authorization procedures: a centralized procedure based on a single scientific evaluation of the highest possible quality to be undertaken within a new European Medicines Evaluation Agency, leading to a binding EEC-wide decision, with the possibility of limited exceptions to take account of differences in disease status in the Member States; a decentralized procedure based on the concept of mutual recognition of national decisions, with binding Community arbitration in the event of a dispute. To provide the Community institutions with the scientific and technical resources necessary to operate these new procedures, the proposals also provide for the establishment of a European Medicines Evaluation Agency.

Animals↗

Clear cell sarcoma presenting as an interdigital neuroma.

The incidence of malignant soft-tissue sarcomas in the general population is approximately 1.4 per 100,000. Approximately 2% of all cancer deaths are attributable to these tumors. Presented is a case history of a soft-tissue malignant neoplasm that was originally thought to be an interdigital neuroma and that eventually required a modified Chopart's amputation. A review of the literature is presented on other soft-tissue malignant tumors that have an affinity for the foot and ankle. The intention of presenting this case is to caution physicians that malignant lesions can simulate a benign process and should always be considered in the differential diagnosis of any foot mass.

Adolescent↗

Carotid plaque morphology: correlation of duplex sonography with histology.

This study attempted to determine whether images obtained during preoperative duplex scanning correlated with histologic studies of carotid endarterectomy plaque and, therefore, might be useful in subsequent studies of the importance of plaque morphology and intraplaque hemorrhage. Forty-six endarterectomy specimens from 44 patients with satisfactory preoperative images were evaluated. The plaques were marked for orientation at the time of removal, and each plaque was imaged by duplex scanning in a saline bath. Magnification radiographs were made. Specimens were embedded in paraffin and slices 6 mu thick were made for staining with hematoxylin and eosin, Masson's trichrome, a modified Verhoeff-vanGieson stain, and von Kossa's stain. Overall, correlation between the preoperative images and the histologic specimens were good to excellent in 42 of 46 specimens. Scanning did not identify three cases of extensive recent intraplaque hemorrhage, however, and one instance of plaque calcification was missed. We conclude that duplex images correlate well with histologic studies except in some cases of recent intraplaque hemorrhage. Duplex imaging is valuable in the correlation of plaque morphology with symptoms for long-term studies. The accuracy of the technique may be improved by using post-processing on static images and in vitro scanning of endarterectomy specimens.

Aged↗

Rules governing pharmaceuticals in the European Community.

In the interest of public health, the European community has progressively established common scientific criteria for the evaluation of human and veterinary medicines and harmonized the national authorization procedures. One major consequence of this has been that neither the tests and trials carried out to obtain authorization nor batch controls need be repeated within the European community. Henceforth the pharmaceutical industry may benefit from two types of procedures intended to facilitate the registration of their medicinal products in the member states. One, reserved for biotechnology/high technology medicinal products, involves community coordination prior to any national decision together with special protection against copies for ten years, irrespective of the position under patent law. The other enables firms to request the recognition by the other member states of an authorization previously granted by one member state. The experience gained from these two procedures will lead to the choice of the most appropriate European registration procedure for the next decade. In the interests of the European consumer, cooperation between the 12 member states and the Commission of the European Communities has progressively increased within the Committee for Proprietary Medicinal Products (adverse effects of medicines/pharmacovigilance) and the Committee for Veterinary Medicinal Products (residues). In association with these committees, several working groups of experts attempt to approximate and codify practices in the evaluation of the quality, safety, and efficacy of medicinal products (guidelines).(ABSTRACT TRUNCATED AT 250 WORDS)

Commerce↗