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Biomedical subjects

J A Jordan

Publications and source records attributed to J A Jordan.

At least 37 records · Page 2Linked to original sources

Techniques for improving ear definition in microtia reconstruction.

Surgeons involved in microtia repair recognize the difficulty in creating a natural appearing ear. One key to successful reconstruction is to provide sufficient relief between the helix, scaphoid fossa and antihelix to create the illusion of thin skin overlying thin cartilage. Problems such as thick skin, hair-bearing skin and poor-quality cartilage serve to frustrate the surgeons attempt to achieve the desired result. Surgical techniques to improve cartilaginous framework definition in microtia repair are discussed.

Cartilage↗

Regulation of acute lung inflammatory injury by endogenous IL-13.

Using IgG immune complex deposition to trigger acute lung inflammation in rats, we have previously shown that exogenously administered IL-13 suppresses the acute inflammatory response. In the same model, expression of both mRNA and protein for IL-13 has now been detected. Treatment of rats with Ab to IL-13 accentuated the inflammatory response, with significant increases in lung vascular permeability and in the number of neutrophils in bronchoalveolar lavage fluids. In the presence of anti-IL-13, activation of the transcription factor, NF-kappaB, was significantly increased in lung. In addition, anti-IL-13 caused significant increases in bronchoalveolar lavage levels of TNF-alpha, macrophage inflammatory protein-2, and cytokine-inducible neutrophil chemoattractant but no changes in lung vascular ICAM-1. These data suggest that during lung inflammation endogenous IL-13 regulates NF-kappaB activation and related cytokine/chemokine generation, all of which determines the intensity of the lung inflammatory response.

Acute Disease↗

Inhibition of NF-kappaB activation and augmentation of IkappaBbeta by secretory leukocyte protease inhibitor during lung inflammation.

In earlier experiments, exogenous administration of secretory leukocyte protease inhibitor (SLPI) suppressed acute lung injury induced by deposition of IgG immune complexes. In the current studies we examined the mechanism of the protective effects of SLPI in this model. The presence of SLPI in the IgG immune complex-model of lung injury reduced the increase in extravascular leakage of 125I-albumin, the intensity of up-regulation of lung vascular intercellular adhesion molecule-1, and the numbers of neutrophils accumulating in the lung. The presence of SLPI caused greatly reduced activation (ie, nuclear translocation) of the transcription nuclear factor-kappaB (NF-kappaB) in lung cells but did not suppress activation of lung mitogen-activated protein kinase. SLPI did not alter NF-kappaB activation in alveolar macrophages harvested 30 minutes after initiation of lung inflammation. In the presence of SLPI, content of tumor necrosis factor-alpha, CXC chemokines, and C5a in bronchoalveolar fluids was unaffected. In the inflamed lungs, inhibition of NF-kappaB activation by SLPI was associated with elevated levels of lung IkappaBbeta (but not IkappaBalpha) protein in the absence of elevated mRNA for IkappaBbeta. When instilled into normal lung, SLPI also caused similar changes (increases) in lung IkappaBbeta. Finally, in the lung inflammatory model used, the presence of anti-SLPI caused accentuated activation of NF-kappaB. These data confirm the anti-inflammatory effect of SLPI in lung and point to a mechanism of anti-inflammatory effects of SLPI. SLPI appears to function as an endogenous regulator of lung inflammation.

Animals↗

Eotaxin expression in Sephadex-induced lung injury in rats.

The CC chemokine eotaxin is a potent and specific eosinophil chemoattractant. Eosinophil-dependent tissue injury has been shown to contribute to airway inflammation such as that in asthma. In the present study, We investigated eotaxin expression in a rat model of pulmonary inflammation (featuring accumulation of eosinophils) induced by intratracheal instillation of cross-linked dextran beads (Sephadex G200). Intratracheal instillation of 5 mg/kg Sephadex caused a time-dependent eosinophil infiltration into the lung, reaching a peak at 24 hours. Eotaxin mRNA in the lung paralleled the eosinophil influx. Eotaxin protein in bronchoalveolar (BAL) fluids and lung homogenates was shown by Western blot and immunostaining to be maximally expressed by 24 hours. Sephadex-induced lung injury, as measured by (125)I-labeled albumin leakage from the pulmonary vasculature, developed in a time-dependent manner. Intravenous injection of blocking antibody to eotaxin significantly decreased eosinophil infiltration and lung permeability. These data suggest that, in the Sephadex model of lung inflammation, eotaxin up-regulation mediates intrapulmonary accumulation of eosinophils and the development of lung injury.

Animals↗

Upregulation of lung chemokines associated with hemorrhage is reversed with a small molecule multiple selectin inhibitor.

BACKGROUND: Hemorrhage can modify the leukocyte-endothelial cell response leading to tissue injury. The selectin family of adhesion molecules and chemokines mediate the leukocyte-endothelial cell interaction, resulting in neutrophil sequestration and activation. This work studies whether a small molecule inhibitor of selectins can ameliorate the effect of hemorrhage on chemokine expression and neutrophil infiltration in the lung. We also aimed to assess the regulatory effect of this small molecule inhibitor of selectins in the lung functional and structural response of animals subjected to hemorrhagic shock. STUDY DESIGN: We subjected 36 Sprague-Dawley rats to uncontrolled hemorrhagic shock for a period of 150 minutes. Three groups of animals were included (n = 12 per group)-the sham, control, and treated groups, with the latter receiving a small molecule selectin inhibitor (TBC-1269) at 25 mg/kg, which was given after tail artery transection. The following measurements were evaluated: fluid requirements during resuscitation for 150 minutes; PO2/FIO2 ratio, lung water, and lung histology, lung myeloperoxidase and lung macrophage inflammatory protein-2 (MIP-2) mRNA and cytokine induced neutrophil chemoattractant mRNA at 6 hours. Statistical analysis included Student's t-test and ANOVA. RESULTS: There was significant improvement in lung function as expressed by PO2/FIO2 ratio and wet to dry lung water ratio in the treated group. There were no significant changes in fluid requirements between the three groups. Neutrophil infiltration, measured by tissue myeloperoxidase, was significantly (p < 0.05) decreased in the lungs of the treated animals. Lung histology was considerably improved in the treated group. The small molecule selectin inhibitor had a profound downregulating effect on macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant as expressed in lung tissue. CONCLUSIONS: Our study confirms the key role that selectins play in the pathogenesis of hemorrhagic shock. The multiple selectin blockade allowed for better function and structure of the lung. The mechanism of protection may be secondary to the downregulation of chemokine expression and neutrophil infiltration.

Animals↗

Globoside expression within the human placenta.

This report demonstrates the presence of the neutral glycosphingolipid, globoside, on the villous trophoblast layer of human placenta. Immunoreactivity for globoside which is the receptor used by human parvovirus B19 was strongest in villous trophoblast cells of first trimester placentae, with diminished reactivity in second trimester placentae, and a near lack of staining for the antigen in those of third trimester. This relative reduction in globoside-specific immunoreactivity in placentae of increasing gestational ages was confirmed using thin-layer chromatographic analyses of extracted neutral glycolipids from the syncytiotrophoblast layer and cytotrophoblast cells of first and third trimester placental villi. The presence of globoside on the protective trophoblast layer of the villi provides a potential pathway whereby B19 may be transmitted from an infected mother to the fetus. The virus once across the placental barrier, may gain access to its erythroid precursor target cells within fetal villus capillaries. The observed change found in globoside immunoreactivity correlates well with the observation that fetal outcome is worse when maternal infection occurs during first or second trimester as compared to an infection occurring near term. The reason for this observed difference in fetal outcome may be due not only to the presence of more target cells potentially to infect during the first and second trimesters, but also to the greater number of viral receptors present on the villous trophoblast layer.

Chromatography, Thin Layer↗

Fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum.

OBJECTIVES: This study investigates the effect of fosfomycin on the tumoricidal efficacy of cisplatinum. STUDY DESIGN: Prospective study utilizing the FaDu squamous cell carcinoma cell line and a nude mouse tumor xenograft model. METHODS: Tumor cell growth was assessed in vitro in the presence of cisplatinum and/or fosfomycin utilizing the MTT assay. An optimal cisplatinum dose and dosing schedule was established in a nude mouse tumor xenograft model of squamous cell carcinoma. Using this model, fosfomycin was tested at three dosages and tumor growth monitored over 4 weeks. RESULTS: Mice treated with cisplatinum and fosfomycin had smaller tumors than those treated with cisplatinum alone (P<.01). CONCLUSIONS: This study is the first demonstration that fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum in vivo. This suggests that fosfomycin may be useful in preventing cisplatinum-induced ototoxicity and nephrotoxicity in humans without altering the tumor response rate.

Animals↗

Regulatory effects of interleukin-11 during acute lung inflammatory injury.

The role of interleukin-11 (IL-11) was evaluated in the IgG immune complex model of acute lung injury in rats. IL-11 mRNA and protein were both up-regulated during the course of this inflammatory response. Exogenously administered IL-11 substantially reduced, in a dose-dependent manner, the intrapulmonary accumulation of neutrophils and the lung vascular leak of albumin. These in vivo anti-inflammatory effects of IL-11 were associated with reduced NF-kappaB activation in lung, reduced levels of tumor necrosis factor alpha (TNF-alpha) in bronchoalveolar lavage (BAL) fluids, and diminished up-regulation of lung vascular ICAM-1. It is interesting that IL-11 did not affect BAL fluid content of the CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-inducible neutrophil chemoattractant (CINC); the presence of IL-11 did not affect these chemokines. However, BAL content of C5a was reduced by IL-11. These data indicate that IL-11 is a regulatory cytokine in the lung and that, like other members of this family, its anti-inflammatory properties appear to be linked to its suppression of NF-kappaB activation, diminished production of TNF-alpha, and reduced up-regulation of lung vascular ICAM-1.

Animals↗

Endoscopic cauterization for treatment of fourth branchial cleft sinuses.

Fourth branchial cleft sinuses are rare, and the nature of their origin is controversial. Clinical presentation is varied because they may present as asymptomatic neck masses, recurrent neck abscesses, or suppurative thyroiditis. We describe herein 7 children who presented with abscesses on the left side of their necks, 3 of whom had abscesses that involved the thyroid gland. Direct laryngoscopy revealed that all 7 children had a sinus tract opening into the apex of the piriform sinus. Endoscopic obliteration of this tract was achieved using an insulated electrocautery probe either when the abscess was initially incised and drained or 4 to 6 weeks later. All 7 children recovered uneventfully. Four of the 7 children were followed up for more than 18 months without recurrence.

Abscess↗

Calcium pyrophosphate deposition disease of the temporal bone.

Massive calcium pyrophosphate crystal deposition is a rare disorder that may affect the temporomandibular joint and temporal bone. The diagnosis is difficult, and misdiagnosis as malignancy, particularly chondrosarcoma, is frequent. This can lead to unnecessarily aggressive management. The clinical, radiographic, and pathologic features of this entity are reviewed, and treatment options are discussed.

Aged↗

Geriatric rhinitis: what it is, and how to treat it.

In the nose, normal physiologic changes of aging include loss of nasal tip support, atrophy of mucus-producing mucosal glands, and decreased olfaction. These changes contribute to geriatric rhinitis, the symptoms of which are often attributed by the older patient to "allergies" or "sinus trouble." An understanding of these anatomic changes, linked with a thorough history and physical examination, allows the physician to properly manage geriatric rhinitis. Medical management most often involves liquifying--not drying--nasal secretions with oral and topical preparations. Conservative surgical treatment is occasionally indicated.

Aged↗

Transient erythroblastopenia of childhood associated with human herpesvirus type 6, variant B.

Transient erythroblastopenia of childhood (TEC) is a disorder of young children ages 3 months to 4 years that is characterized by anemia associated with reticulOcytopenia and decreased red blood cell precursors in the bone marrow aspirate (BMA). A viral cause has been suspected for TEC. Bone marrow aspirate-derived DNA from 14 children with anemia or another hematologic disorder, including two children with TEC, were analyzed by polymerase chain reaction for human herpesvirus type 6 (HHV-6) DNA and human parvovirus B19 DNA. Testing revealed an HHV-6 variant B DNA in both children with TEC but not in the children who did not have TEC. The BMAs from these two children contained large pronormoblasts and an extensive lymphoid infiltrate. We proposed that HHV-6 may be a causative agent of TEC in immunocompetent children. This hypothesis is based on the demonstrated ability of HHV-6 to suppress the formation of burst-forming units-erythroid (BFU-E) and granulocyte macrophage-colony-forming units (GM-CFU) in vitro, and in vivo in HHV-6-infected patients who undergo bone marrow transplantation.

Adolescent↗

Pediatric respiratory papillomatosis: prognostic role of viral typing and cofactors.

Children with recurrent respiratory papillomatosis vary greatly in their clinical disease course. Many have mild disease with eventual remission while others present with an early aggressive airway obstructive course. This study consisted of 24 pediatric patients whose specimens underwent polymerase chain reaction analysis for cytomegalovirus (CMV), herpes simplex virus (HSV), and human papillomavirus (HPV) type. Nineteen of 24 specimens contained enough DNA for this study. None of the specimens were found to contain DNA from HPV-16, -18, -31, -33; CMV; or HSV, which contrasts with our previous findings in adults. Ten patients were infected by HPV-11 and seven of these underwent tracheotomy because of an aggressive tumorigenic clinical course. Nine patients were infected by HPV-6 alone of whom only two required a tracheotomy (P = 0.05, Fisher's Exact Test). The early airway obstructive course associated with HPV-11, however, had no bearing on achieving eventual disease remission, with decannulation achieved in eight of nine children.

Adult↗

Observer variability among colposcopists from the West Midlands region.

OBJECTIVE: To assess variation in diagnoses and management decisions among colposcopists when presented with cervical images; to see the impact of the referral cytology report on diagnostic accuracy. DESIGN: A two-part video questionnaire study. PARTICIPANTS: Colposcopists from West Midlands Region. METHODS: Twenty cervical images displaying a range of transformation zones from normal through varying abnormalities up to cervical intraepithelial neoplasia (CIN) grade 3 were shown on video tape together with basic patient information. Two sets of videos were made, the second being identical to the first other than including the referral cytology. Participants recorded their diagnoses and management decisions on prepared questionnaires. The two sets of videos were viewed several weeks apart. RESULTS: Completed questionnaires to both videos were received from 30 colposcopists. Diagnostic accuracy improved with knowledge of the cervical cytology result in cases of CIN 2/3 (chi 2 = 19.45, P < 0.0001) but not where the histology was CIN 1 or less (chi 2 = 2.64, P = 0.10). Overall interobserver agreement improved slightly from kappa = 0.169 to kappa = 0.212 when the cytology was revealed. While only 2.6% of cases of CIN 2/3 would have been under-managed after the second questionnaire, 37.5% cases where the abnormality did not amount to CIN would have been overtreated. CONCLUSION: There is considerable inter-observer variability and variation in diagnostic accuracy in scoring cervical images particularly at the lower end of the spectrum of abnormality which has the potential to lead to over-treatment. We rely considerably on the cervical cytology result in forming a diagnosis. We recommend that a see-and-treat approach be abandoned when the referral smear shows minor abnormalities. The study has implications for both training and audit in colposcopy.

Colposcopy↗

Randomised trial of immediate versus deferred treatment strategies for the management of minor cervical cytological abnormalities.

OBJECTIVE: To compare immediate and deferred treatment in women with cervical smears showing borderline nuclear abnormalities or mild dyskaryosis. DESIGN: Prospective randomised trial. SETTING: Colposcopy clinics at Birmingham and Midland Hospital for Women and the City Hospital NHS Trust, Dudley Road, Birmingham. PARTICIPANTS: Four hundred and thirty-five women with minor cytological abnormality younger than 35 years of age, of whom 353 were randomised to immediate treatment or deferred treatment. MAIN OUTCOME MEASURES: Comparison of histologies in the subsequent two years in the immediate and deferred treatment groups. RESULTS: Thirty-six women (21%) defaulted from follow up. The percentage of high grade abnormalities (CIN II and III) in the deferred treatment arm at two years is similar to that in the immediate treated arm at first colposcopy (25% vs 24%). Cytology failed to pick up two cases of CIN III and there was one case of early invasive carcinoma at the six month follow up. If treatment is deferred, the proportion with CIN I is almost halved (25% vs 13%); the proportion with koilocytic atypia is slightly reduced (51% vs 42%) and the proportion with no abnormality is substantially increased (0.6% vs 20%). CONCLUSION: Immediate referral and a select-and-treat management strategy of all women with any degree of dyskaryosis is recommended based on the case of invasive cervical cancer, high default rate and the failure of cytology to pick up two cases of CIN III.

Adolescent↗

Competition and performance on a computer-based complex perceptual-motor task.

Employees of temporary agencies practiced Space Fortress, a complex video game task, for 10 sessions, each consisting of 8 practice and 2 test games of 3 min each. Trainees practiced individually, in dyads, or in tetrads, and they were classified as having high or low aptitude based on computer attitude scores and baseline performance. Competition for monetary prizes was introduced early in training, late in training, or not at all. Competition facilitated high-aptitude trainees but not low-aptitude trainees. Group size and the timing of competition instructions had no main effects or interactions. The results are discussed in terms of social facilitation theory, according to which competition facilitates dominant responses, which helps high-skill trainees but not low-skill trainees.

Adolescent↗

Congenital syringocystadenoma papilliferum of the ear and neck treated with the CO2 laser.

Syringocystadenoma papilliferum (SCAP) is a rare benign skin tumor which clinically resembles papilloma. It is characterized by extensive papillary epithelial elements growing into the dermis. SCAP often presents at birth and most commonly in the head and neck. We present a case of a newborn with SCAP of the right ear and neck, treated with CO2 laser excision because the lesion was poorly amenable to excision and closure or grafting. Two CO2 laser procedures have produced a good result and reasonable cosmesis. CO2 laser excision of SCAP of the head and neck is a clinical treatment option in anatomic areas unfavorable to excision and grafting.

Adenoma, Sweat Gland↗