bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Use of an ELISA Test to Detect IgE Antibody to Cry9c following Possible Exposure to Bioengineered Corn
Authors: Raybourne Richard B. , Williams Kristina M. , Vogt Robert , Reissman Dori B. , Winterton Brad S. , Rubin Carol
Published: January 2004

Background: StarlinkTM, a variety of corn genetically engineered to contain the insecticidal protein Cry9c, had not been approved for human consumption because it possessed some characteristics associated with allergenic proteins. However, in the fall of 2000 cry9c DNA was detected in several corn-containing products, suggesting that Starlink corn had entered the human food supply. Subsequently, consumers, following consumption of corn products, reported a number of adverse health events, possibly consistent with allergic reaction. Methods: To investigate the possibility of allergic reactions due to Cry9c in these consumers an ELISA test was developed for the purpose of detecting IgE antibodies to Cry9c and blood samples were taken from a total of 18 people who self-reported allergic reactions. Sera collected prior to the 1996 development of Starlink were used as negative controls. Results: None of the adverse event sera were found to be reactive with recombinant Cry9c antigen, based on comparison with normal controls. Although a known human positive control serum containing IgE specific for Cry9c was not available, other controls were incorporated into the ELISA protocol, including the use of sera from subjects allergic to other allergens and their homologous antigens (cat, grass, peanut) to validate the IgE detection reagents. Conclusions: While the results do not support the likely occurrence of allergic reactions to Cry9c, such reactions cannot be ruled out, nor can the possibility that sera might react with unique glycosylated epitopes of Cry9c that may be expressed in the corn plant/seed.
Protein Fv Produced during Viral Hepatitis Is an Endogenous Immunoglobulin Superantigen Activating Human Heart Mast Cells
Authors: Genovese Arturo , Borgia Guglielmo , Bouvet Jean-Pierre , Detoraki Aikaterini , de Paulis Amato , Piazza Marcello , Marone Gianni
Published: January 2004

Protein Fv, an endogenous protein produced in the liver, is released in biological fluids during viral hepatitis. Acute and chronic viral hepatitis can be associated with cardiovascular derangements. Protein Fv induced the release of histamine, tryptase and the de novo synthesis of prostaglandin D2 and cysteinyl leukotriene C4 from mast cells isolated from human heart tissue (HHMC). Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion. The maximal percent histamine secretion induced by protein Fv correlated (rs = 0.60; p < 0.05) with that induced by anti-IgE, whereas there was no correlation between the release caused by proteins Fv and C5a. Preincubation of HHMC with protein Fv or anti-IgE caused complete cross-desensitization to subsequent challenge with heterologous stimulus. HHMC from which IgE had been dissociated no longer released histamine in response to anti-IgE and protein Fv. A human monoclonal IgE blocked both anti-IgE- and protein Fv-induced release. Three human monoclonal IgM VH3+ inhibited protein-Fv-induced secretion of histamine from HHMC, whereas monoclonal IgM VH6+ did not inhibit the release induced by protein Fv. Protein Fv acts as an endogenous immunoglobulin superantigen by interacting with the VH3 domain of IgE to induce the release of mediators from HHMC.
Gene Expression Analysis of Atopic Dermatitis-Like Skin Lesions Induced in NC/Nga Mice by Mite Antigen Stimulation under Specific Pathogen-Free Conditions
Authors: Heishi Masayuki , Imai Yukiho , Katayama Hiroko , Hashida Ryoichi , Ito Mikito , Shinagawa Akira , Sugita Yuji
Published: January 2004

Background: Atopic dermatitis (AD) is a chronic relapsing inflammation characterized by pruritic and eczematous skin lesions usually observed in patients with a familial history of atopic diseases, but its exact etiology is unclear. An animal model is indispensable for the analysis of the pathogenesis and the development of new drugs to treat this disease. Here, we compare changes in gene expression profiles in the AD-like skin lesions of NC/Nga or BALB/c mice stimulated intradermally by mite antigen under specific pathogen-free (SPF) conditions. Methods: Mite Extract-Dp was injected intradermally into the right and left pinnae and into the skin of the back of NC/Nga or BALB/c mice in 2 places once per 3 days, and the clinical symptoms and the ear thickness were measured. On day 14 or day 28 after starting mite extract injection, we collected plasma and pinnae from NC/Nga or BALB/c mice. The amount of total immunoglobulin E (IgE) in plasma was assayed. We analyzed mRNA transcripts in pinnae using real-time quantitative PCR for the murine counterparts of several known allergy-related genes. Moreover, genome-wide gene expression in pinnae from NC/Nga mice was analyzed using high-density oligonucleotide arrays (GeneChip, Affymetrix). Results: From 2 weeks after stimulation, marked skin inflammation was induced in the pinnae of NC/Nga but not BALB/c mice. However, IgE levels in sera rose equally in both strains. Quantitative PCR analysis and comprehensive GeneChip analysis of the AD-like pinna skin lesions revealed that their development was accompanied by changes in expression of more than 1,000 genes. These included cytokines, cytokine receptors, proteases, and adhesion molecules. Furthermore, genes thus far not reported in association with AD were also affected. Conclusion: From these results, the NC/Nga mouse model using mite sensitization under SPF conditions could be useful for elucidating the mechanisms of AD pathogenesis and developing more effective therapy for AD.
Allergen Skin Test Reaction Patterns in Children (≤10 Years Old) from Atopic Families Suggest Age-Dependent Changes in Allergen-IgE Binding in Early Life
Authors: Jackola Duaine R. , Pierson-Mullany Lisa , Blumenthal Malcolm N. , Rosenberg Andreas
Published: January 2004

Background: Genetic studies of atopy rely upon evidence of abnormal IgE production, usually elevated total IgE or skin prick test (SPT) reactions. However, these measures may change with subject age. Methods: We screened 1,099 members of atopic families (aged 6–87 years) by serum total IgE and SPT for 14 allergens. For those SPT negative, we screened for Amb a 1- and Der p 1-specific IgE. Der p 1 IgE-Der p 1 allergen binding affinities were done on randomly selected subjects. Results: There were significantly fewer atopics ≤10 years old (69.1%) compared to those >10 years old (75.8%) based upon any SPT-positive result. Children ≤10 years had fewer SPT-positive reactions and smaller SPT wheal reaction areas. Yet, mean total IgE values were comparable to those of the older group. Screens for specific IgE showed no differences in proportions of atopics (≤10 years old = 83.1% and >10 years old = 82.3%). Among those SPT-positive for house dust mite extract, there was a positive correlation between Der p 1 binding affinity and the wheal area of the house dust mite extract. There was a positive correlation between the number of SPT-positive reactions and total IgE for both age groups. However, there was only a significant relationship between SPT-positive wheal area and total IgE for those >10 years old and no apparent relationship between wheal area and total IgE for those ≤10 years old. Conclusion: These results suggest that atopy-specific physiological mechanisms, primarily those involving allergen-IgE binding, change during the earliest years of life.
Suckling Reduces Allergic Skin Responses and Plasma Levels of Neuropeptide and Neurotrophin in Lactating Women with Atopic Eczema/Dermatitis Syndrome
Authors: Kimata Hajime
Published: January 2004

Background: Lactation is associated with an inhibited hypothalamic-pituitary-adrenal axis response to physical and psychological stress in women and female rats. However, suckling also improved mood and calmness in nonatopic lactating women. Relaxation by humor reduced allergen-induced skin wheal responses, while various forms of stress enhanced those responses in allergic patients. Moreover, enhancement and reduction in allergen-induced skin wheal responses are associated with up- and down-regulation of plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP), respectively. In addition, plasma levels of SP, VIP and nerve growth factor (NGF), but not neurotrophin-3 (NT-3), are elevated in allergic patients. Therefore, the effects of suckling on allergic responses and plasma levels of neuropeptides and neurotrophins were studied in lactating women with atopic eczema/dermatitis syndrome (AEDS). Methods: Before and after suckling, allergic skin responses to allergens were studied by skin prick test; simultaneously plasma levels of substance P, vasoactive intestinal peptide, nerve growth factor and neurotrophin-3 were measured in lactating women with atopic eczema/dermatitis syndrome. Results: Suckling reduces allergen-induced, but not histamine-induced, skin wheal responses, while holding infants without suckling failed to do so. Suckling also reduced plasma levels of SP, VIP and NGF, but not NT-3 in these patients, while holding infants without suckling failed to do so. Conclusions: These results indicate that suckling reduces allergic responses with a concomitant reduction in plasma levels of SP, VIP and NGF. Collectively, suckling may have some implication in the study of maternal allergy in atopic patients.
Cardiac Disease in Chronic Kidney Disease: Current Understandings and Opportunities for Change
Authors: Levin A.
Published: January 2004

Cardiovascular disease (CVD) is prevalent in patients with kidney disease: in populations prior to dialysis, on dialysis and after transplantation. Publications over the last decade have focused on this, and more recently, patients with cardiac disease are now recognized as being at increased risk in the presence of even mild kidney dysfunction. The presence of both traditional and non-traditional risk factors contributes to this overwhelming burden of cardiovascular disease in patients with chronic kidney disease (CKD). Recent studies have focused on the impact of anemia and disorders of mineral metabolism on CVD outcomes, in the context of inflammation and evidence of cytokine activation. Cross-sectional and prospective observational studies have led to improved understanding, and generated novel hypotheses. To date, no clinical trial has determined the positive impact of interventions targeted at these novel risk factors. This overview describes the current state of knowledge and emphasizes the interplay between CVD and CKD as two aspects of a set of pathophysiological processes, which impact on patient outcomes.
Volume Control in Peritoneal Dialysis Patients: Role of New Dialysis Solutions
Authors: Lameire Norbert
Published: January 2004

This paper reviews the most recent clinical data on the volume status of long-term peritoneal dialysis (PD) patients. It appears that many PD patients are volume overloaded, associated with a high prevalence of hypertension and left ventricular hypertrophy. In the presence of the poor results in patients with peritoneal ultrafiltration, the introduction of the polyglucose solution, icodextrin, has ameliorated volume control in some of these patients. In a second part of the review, some of the structural and functional alterations in the peritoneal membrane and the role of glucose degradation products (GDP) in the commonly used dialysates as well as the resulting formation of advanced glycation end products are described. The introduction of low GDP-containing solutions at normal pH has at least in experimental models of PD attenuated the hemodynamic changes observed with the classical solutions. The solutions at normal pH containing either bicarbonate or a mixture of bicarbonate/lactate were clinically associated with less inflow pain.
Role of Sodium and Volume in the Pathogenesis of Hypertension in Dialysis Patients
Authors: Kooman Jeroen P. , van der Sande Frank M. , Leunissen Karel M.L.
Published: January 2004

Volume and sodium excess is the predominant factor in the pathogenesis of hypertension in dialysis patients. However, except for anephric patients, the relationship between volume status, blood pressure, and hemodynamics is not straightforward, but may vary between subgroups of patients. In general, the sensitivity of blood pressure to changes in the volume/sodium status appears to be increased in patients with end-stage renal disease. The blood pressure response to changes in the sodium/volume status may be influenced by disturbances in the activity of and response to various neurohumoral mechanisms, such as the renin-angiotensin and sympathetic nervous systems, Na-K-ATP-ase inhibitors, and the nitric oxide system. Regarding these aspects, there might be a parallel with salt-sensitive (essential) hypertension. Preliminary data showed a beneficial effect of sodium removal beyond changes in the volume status. Also of interest is the fact that prolonging dialysis time may improve blood pressure control without clear changes in the fluid status. It is hypothesized that a reduction in exchangeable sodium, by increased diffusive transport of sodium, in combination with increased removal of vasopressor substances, might be partly responsible for the observed blood pressure changes during long dialysis times. In conclusion, sodium and volume overload and neurohumoral factors coincide in the pathogenesis of hypertension in dialysis patients. Nevertheless, their exact relationship has not yet been elucidated and deserves further study.
Sorbents in Acute Renal Failure and End-Stage Renal Disease: Middle Molecule and Cytokine Removal
Authors: Winchester James F. , Silberzweig Jeffrey , Ronco Claudio , Kuntsevich Viktoria , Levine Daniel , Parker Tom , Kellum John A. , Salsberg Jamie A. , Quartararo Peter , Levin Nathan W.
Published: January 2004

Renal replacement therapy in acute renal failure (ARF) and chronic renal failure (end-stage renal disease; ESRD) has been based on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle-molecular-weight toxins, consisting of low-molecular-weight proteins and peptides (LMWP) and cytokines involved in inflammation. High-flux dialyzers are not efficient at removing LMWP, and for this reason, sorbents have been studied to augment or replace dialysis. Removal of LMWP such as β2-microglobulin, leptin, complement factor D, angiogenin and cytokines such as interleukin (IL)-1, IL-6, IL-10, IL-18 and tumor necrosis factor-α has been established in animal models of sepsis and in ESRD patients using sorbents. Sorbent devices added to hemodialysis, or the use of such devices alone in inflammatory states, including sepsis, ARF, cardiopulmonary bypass, pre-explantation of donor organs and ESRD, are being studied.
Mathematical Model of the Effect of Affinity Hemodialysis on the T-Cell Depletion Leading to AIDS
Authors: Tullis Richard H.
Published: January 2004

HIV-derived envelope proteins appear to be intimately involved in the destruction of uninfected T cells that leads to AIDS in a process known as the ‘bystander effect’. Affinity hemodialysis has been proposed as an effective means of reducing these viral toxins. Using deterministic mathematical models based on the well-known Perelson formulations, the effectiveness of affinity hemodialysis in reducing the levels of viral gp120 was analyzed. Incorporating experimental data on the function of the affinity dialysis system and data from published analyses of HIV viral dynamics, two different models of HIV and AIDS were analyzed. Both models predict a rapid and sustained reduction in gp120 levels. In the model incorporating stem cell dynamics, affinity hemodialysis treatment under several different scenarios was associated with a significant increase in T-cell levels independent of any release from lymphatic tissues. The calculations support the contention that affinity hemodialysis is a potentially useful adjunctive therapy, which can be employed to treat HIV-infected patients in conjunction with drug therapy. For those patients resistant to anti-retroviral drugs or those unable to take the drugs due to the side effects of those medications, affinity hemodialysis treatment may become a viable option.
Iron Requirements in Hemodialysis
Authors: Sargent John A. , Acchiardo Sergio R.
Published: January 2004

The correction of anemia in dialysis patients with erythropoietin (EPO) can be frustrated by insufficient iron. To address this effect, we preloaded candidate EPO patients with intravenous iron in the early 1990s. Preloading with 900–1,525 mg of iron yielded the following results: 70% of patients had increasing hematocrits (HCTs) without EPO, and 40% of patients had HCTs greater than 30%. Apparent lack of iron led to blood loss studies. Routes evaluated were blood sampling, dialyzer clotting, blood in the dialyzer circuit and postdialysis bleeding. Projected annual losses were between 2,516 and 5,126 ml, depending on circuit and posttreatment losses. In terms of red cell loss, the results are comparable to those in the early days of dialysis before the introduction of current technology. Extension of these studies to daily dialysis predicts possible losses with this 6 times a week therapy of between 4,663 and 9,884 ml per year.
Hemoadsorption to Improve Organ Recovery from Brain-Dead Organ Donors: A Novel Therapy for a Novel Indication?
Authors: Venkataraman Ramesh , Song Mingchen , Lynas Rachel , Kellum John A.
Published: January 2004

While brain-dead organ donors represent the majority of the organ donor pool, it appears that graft survival is adversely affected by brain death itself. Brain death has been shown to cause severe disturbances in the hormonal, hemodynamic and immunological homeostasis, which could in part be responsible for the inferior outcome of organs originating from brain-dead donors compared to living donors. Hemodynamic effects of brain death lead to a wide fluctuation in mean perfusion pressures, blood flow to the organs and systemic oxygen consumption, altering regional perfusion. In addition, a wide array of immunological changes has been shown to occur after brain death contributing to organ injury and hemodynamic instability. Recent studies have shown that brain death upregulates multiple lymphocyte- and macrophage-derived cytokines and the injured brain itself may be the source of proinflammatory factors such as S100B. This increased inflammatory response seen during and immediately after brain death has also been associated with poor allograft function. Furthermore, there is evidence to suggest that the massive inflammatory response seen in brain-dead donors could also lead to increased immunogenicity and accelerated allograft rejection after transplantation. Hence, we hypothesize that nonspecific downregulation of this inflammatory response by hemoadsorption could potentially lead to improved donor organ and allograft function. As a ‘proof of concept’ we tested the ability of a novel hemoadsorbent to remove S100B in vitro using two human glioblastoma cell lines. Our results indicate a >80% reduction in S100B after 2 h of circulation with the sorbent.
Extracorporeal Therapies in Non-Renal Disease: Treatment of Sepsis and the Peak Concentration Hypothesis
Authors: Ronco Claudio , Bonello Monica , Bordoni Valeria , Ricci Zaccaria , D’Intini Vincenzo , Bellomo Rinaldo , Levin Nathan W.
Published: January 2004

In the setting of intensive care, patients with acute renal failure often present a clinical picture of the systemic inflammatory response syndrome (SIRS). SIRS can be caused by bacterial stimuli or by non-microbiological stimuli that induce a significant inflammatory response. When this response is exaggerated, the patient experiences multiple organ system failure and a condition of sepsis also defined as a systemic malignant inflammation. This is mostly characterized by an invasion of cytokines and other pro-inflammatory mediators into the systemic circulation where major biological effects take place, including vasopermeabilization, hypotension and shock. At the same time, the monocyte of the septic patient seems to be hyporesponsive to inflammatory stimuli to a certain extent. In this condition, the patient faces a situation of hyperinflammation but at the same time of immunodepression expressing a clinical entity defined as counter anti-inflammatory response syndrome. The general picture of the clinical disorder is therefore better characterized by an immunodysregulation than by a simple pro- or anti-inflammatory disorder. Due to the short half-life of cytokines and other mediators spilled over into the circulation, it is extremely difficult to approach the problem at the right moment with the right pharmacological agent. For these reasons, the peak concentration hypothesis suggests that continuous renal replacement therapies, due to their continuity and unspecific capacity of removal, might be beneficial in cutting the peaks of the concentrations of both pro- and anti-inflammatory mediators, restoring a situation of immunohomeostasis. Thus the patient may benefit from a lesser degree of immunodysregulation and he/she may restore a close-to-normal capacity of response to exogenous stimuli.
Development of Lymphoid Tissues of the Stripe-Faced Dunnart (Sminthopsis macroura)
Authors: Old J.M. , Selwood L. , Deane E.M.
Published: January 2004

The development of the lymphoid tissues of a model marsupial, the stripe-faced dunnart, has been described from birth to weaning, a period of 2.5 months. At birth the lymphoid tissues, including the thymus, lymph nodes and mucosa-associated lymphoid tissues, were undeveloped. A thoracic thymus consisting primarily of stromal tissue was observed by day 4 after birth but by day 12, lymphocytes were observed in the thymus and some cortico-medullary differentiation was apparent. Lymph nodes were histologically mature by day 31, the earliest day investigated for this tissue. In gut tissue, lymphoid follicles were first observed by day 57 post-partum. No bronchus-associated lymphoid tissue was observed in any lung samples. The thymus, lymph nodes and gut-associated lymphoid tissues were all distinguishable before weaning (day 70) but not all were histologically mature. The sequence of development of the lymphoid tissues in the stripe-faced dunnart was similar to those observed in other marsupial species.
The Ramifications and Terminals of Optic Fibres in Layers 2 and 3 of the Avian Optic Tectum: A Golgi and Light and Electron Microscopic Anterograde Tracer Study
Authors: Tömböl T. , Eyre M. , Zayats N. , Németh A.
Published: January 2004

The ramification patterns and terminals of optic fibres in layers 2 and 3 of the optic tectum were studied in Golgi-stained and immunolabelled preparations made from the brains of chicks and pigeons. The different neuronal structures of layers 2 and 3 were also examined. In Golgi preparations, two types of optic fibre were found both in chick and pigeon tectum according to their thickness and terminal branching patterns. The same types of optic fibres were also found to be present in the anterograde tracer experiments after iontophoresis of biotinylated dextran amine into the optic nerve. The varicose terminals of thin fibres mostly terminated on terminal dendritic sections of radiate and pyramidal-like neurons, contacting them on their apical dendrites. The medium-thick fibre terminals in layer 2 mainly established synapses with horizontally extending dendrites, which may therefore be contacts with inhibitory local circuit neurons. The medium-thick optic fibre bushy-like arborisation in layer 3 established synapses with larger dendrites and also stem dendrites. Their terminals formed groups with different dendritic profiles, some of which were partly covered by glial processes, and/or were located among converging dendrites. The presence of these glomerular-like synapses in layer 3 proves that the optic terminals in layer 3 also take part in the transmission of optic impulses to the nucleus rotundus.
Group A Beta-Haemolytic Streptococcal Necrotising Fasciitis: Early Diagnosis and Clinical Features
Authors: Simonart T.
Published: January 2004

Necrotising fasciitis (NF) due to group A β-haemolytic streptococci (GAS) is a rare but still life-threatening soft-tissue infection characterised by rapidly spreading inflammation and subsequent necrosis of the muscle fascia and of the surrounding tissues. Previous studies have emphasised that the outcome of patients with NF depends essentially on early diagnosis and treatment, consisting of extensive surgical debridement, along with appropriate antibiotic therapy. However, one of the striking features of the published series of GAS NF is that there was a delay in diagnosis in several cases, which underscores the difficulty of the early diagnosis of the condition. The goal of this article was to review the clinical features and diagnostic tools that could facilitate the early recognition of GAS NF.
Clinical Criteria for the Diagnosis of Bullous Pemphigoid: A Reevaluation according to Immunoblot Analysis of Patient Sera
Authors: Joly P. , Courville Ph. , Lok C. , Bernard Ph. , Saiag Ph. , Dreno B. , Delaporte E. , Bedane C. , Picard C. , Sassolas B. , Plantin P. , D’Incan M. , Chosidow O. , Pauwels C. , Lambert D. , Loche F. , Prost C. , Tancrede-Bohin E. , Guillaume J.C. , Roujeau J.C. , Gilbert D. , Tron F. , Vaillant L.
Published: January 2004

Background: We previously proposed a set of 4 clinical criteria for the diagnosis of bullous pemphigoid (BP) that consisted of age greater than 70 years, absence of atrophic scars, absence of mucosal involvement and absence of predominant bullous lesions on the neck and head. These results have been challenged because direct immunoelectron microscopy (IEM), which was used as the standard diagnostic criterion in our initial study, does not identify the different antigens of the basement membrane zone. Objective: To reassess the validity of these clinical criteria for the diagnosis of BP using immunoblot analysis of patient sera as the main diagnostic criterion, in order to precisely identify the antigens recognized by patient sera. Methods: One hundred and eighty-nine sera from patients with various subepidermal autoimmune blistering diseases (AIBDs) were tested by immunoblotting using dermal and epidermal extracts. IEM was used as a complementary diagnostic procedure in a few patients whose serum recognized BPAG2 exclusively or was negative in immunoblotting. Results: 142 patients (75%) had at least 3 of the 4 clinical diagnostic criteria. Sera from patients who lacked the set of BP clinical criteria were more frequently immunoblot negative (34%) than sera from patients who had the criteria (18%; p = 0.025). BPAG1 was more frequently recognized by sera from patients with the set of BP clinical criteria (78%) than by sera from patients without the criteria (45%; p = 5·10–4). In contrast, BPAG2 was recognized by a great number of sera from patients who lacked the criteria of BP (71%), which was in accordance with the presence of numerous patients with cicatricial pemphigoid in this group. Among patients with various subepidermal AIBDs, the diagnosis of BP could be made with a sensitivity of 86%, a specificity of 90% and an excellent prognostic positive value over 95%, if 3 of these clinical criteria were present. Conclusion: These results confirm the interest of this set of clinical criteria for the rapid diagnosis of BP.
A Prospective Study of Cutaneous Adverse Events Induced by Low-Dose Alpha-Interferon Treatment for Malignant Melanoma
Authors: Guillot B. , Blazquez L. , Bessis D. , Dereure O. , Guilhou J.J.
Published: January 2004

Introduction: α-Interferon is associated with numerous cutaneous side effects, but the accurate incidence of these complications is not clearly known. Objectives: A prospective study was designed to evaluate the incidence and clinical pattern of cutaneous side effects in a cohort of patients receiving adjuvant therapy with low-dose interferon for malignant melanoma. Material and Methods: A cohort of 33 patients with stage IIA and IIB melanoma treated with low-dose α-interferon (3 MIU 3 times a week for 18 months) were prospectively enrolled in a single-center study. The patients responded to a questionnaire on their medical history and were systematically examined for any cutaneous lesions before treatment and every 3 months afterwards. Results: 29/33 patients (87%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 16 cases (48.4%). Hair discoloration was noted in 6 cases (18%). Eczematous reactions at injection sites or at remote sites were observed in 13 patients (39%). Pruritus occurred in 10 cases (30%). Xerostomia, Raynaud’s phenomenon or livedo reticularis were observed in 10 patients, associated with an increase in circulating autoantibody titer in 2 cases. Some rare side effects were observed: urticaria (1 case) or angioedema (1 case), worsening of preexisting seborrheic dermatitis (3 cases), herpetic recurrence (2 cases), pityriasis versicolor (1 case), worsening of recurrent buccal aphthous ulcer (1 case) and vitiligo (1 case). Conclusion: Cutaneous adverse events during adjuvant immunotherapy of melanoma with low-dose α-interferon seem to be frequent but do not result in treatment discontinuation. A good awareness of these side effects may be useful for a more accurate survey and clinical management of patients receiving this treatment.
Single-Dose Fluconazole versus Itraconazole in Pityriasis versicolor
Authors: Partap R. , Kaur I. , Chakrabarti A. , Kumar B.
Published: January 2004

Background: The new antifungal triazoles itraconazole and fluconazole have revolutionized the treatment of pityriasis versicolor. Both drugs have shown promising results in different dose schedules. Objective: To compare the efficacy and safety of single oral dose treatment with fluconazole versus itraconazole in patients with pityriasis versicolor. Methods: A total of 40 patients with pityriasis versicolor were allocated randomly to group A and group B. A single dose of fluconazole (400 mg) or itraconazole (400 mg) was given orally to group A or group B patients, respectively. Patients were assessed mycologically by KOH and culture. Culture was done from lesional and perilesional skin to quantify growth and to observe the effect of these drugs and the persistence/reappearance of the fungus in relation to relapse at 2 and 8 weeks. Relapse was defined as reappearance or worsening of clinical signs and symptoms or positive KOH/culture after initial improvement. Results: Thirteen (65%) patients in the fluconazole group and 4 (20%) patients in the itraconazole group became culture negative at the end of 8 weeks. Relapse was found to be higher in the itraconazole group compared to the fluconazole group (60 vs. 35%). A direct correlation was found between the relapse rate and positivity of perilesional skin for Malassezia furfur.Conclusion: In the same dosing, fluconazole was found to be more effective than itraconazole; however, both drugs were found to be safe.
Possibility of Treating Basal Cell Carcinomas of Nevoid Basal Cell Carcinoma Syndrome with Superficial X-Ray Therapy
Authors: Caccialanza Massimo , Percivalle Serena , Piccinno Roberta
Published: January 2004

Background: The nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin-Goltz syndrome, is a rare dermatological disease inherited according to an autosomal dominant pattern. From the dermatological point of view, the most evident characteristic of the syndrome is the early onset of multiple basal cell carcinomas (BCCs). An ideal treatment of BCCs of the NBCCS does not exist. Objective: To evaluate if in particular cases (e.g. poor general health conditions, previous multiple surgical excisions) radiotherapy may be useful, under the condition that it does not promote the onset of new BCCs and that the healing of irradiated lesions is normal. Methods: A study on 3 patients with 17 BCCs treated with superficial radiotherapy is here reported. Results: Complete remission without carcinogenic effects was reached in all treated lesions, with a mean follow-up of 30.35 months. Conclusion: In our opinion, such results suggest the possibility of a cautious application of superficial radiotherapy in selected cases of NBCCS.
Coexistence of HLA-B*08 and HLA-B*18 in Four Siblings with Lichen sclerosus
Authors: Şentürk Nilgün , Aydın Fatma , Birinci Asuman , Yildiz Levent , Cantürk Tayyar , Durupınar Belma , Turanlı Ahmet Yaşar
Published: January 2004

Background: Lichen sclerosus (LS), is characterized by localized patches of atrophy and whitening of the skin. The cause of LS remains unknown, but genetic, hormonal, immunologic factors and autoimmune mechanisms have been incriminated. There are conflicting data regarding the association between LS and human leukocyte antigens (HLA). Methods: We have analyzed the HLA alleles of a family, in which 4 of 5 children have lichen sclerosus. Results: HLA-B*08 and HLA-B*18 alleles were detected in children with LS, but not in a healthy sister. None of the patients had autoimmune disease. Conclusion: In our opinion, coexistence of these two alleles may play a role in the development of LS.
Eruptive Vellus Hair Cyst in Patients with Chronic Renal Failure
Authors: Mieno Hideki , Fujimoto Norihiro , Tajima Shingo
Published: January 2004

Two cases of eruptive vellus hair cysts associated with chronic renal failure are reported. Histologically the lesions of both cases showed cystic structures in the dermis lined by squamous epithelium which contained varying amounts of vellus hair shafts. Immunohistochemical studies using monoclonal anti-AGE (advanced glycation end product) antibody demonstrated that keratinous materials within the cystic structures were immunoreactive to the antibody, whereas those of cystic lesions (epidermal cyst, eruptive vellus hair cyst, steatocystoma multiplex, trichofolliculoma and trichilemmal cyst) seen in otherwise healthy individuals were negative. Because it has been reported that plasma and skin levels of AGE are elevated in renal failure patients, AGE-modified keratinous materials may be associated with the formation of cystic structures by stimulating the occlusion of the epithelium.
Myoepithelioma Possibly Originating from the Accessory Parotid Gland
Authors: Isogai Rieko , Kawada Akira , Ueno Kengo , Aragane Yoshinori , Tezuka Tadashi
Published: January 2004

Myoepithelioma originates almost exclusively from myoepithelial cells of the salivary, prostate and mammary glands. The skin is a very rare site where myoepithelioma occurs. We describe a patient with a myoepithelioma on the right cheek seen as a subcutaneous nodule that was separated from the parotid gland at surgical resection. Histopathological findings were consistent with those of a myoepithelioma that had originated from the parotid gland, suggesting that this tumor may have developed from the accessory parotid gland.
Lung Retrieval from Non-Heart-Beating Donors: First Experience with an Innovative Preservation Strategy in a Pig Lung Transplantation Model
Authors: Wittwer T. , Franke U.F.W. , Fehrenbach Antonia , Sandhaus T. , Pfeifer F. , Dreyer N. , Mueller T. , Schubert H. , Petrow P. , Richter J. , Wahlers T.
Published: January 2004

Objective: Lung transplantation is limited by the scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. Methods: Heparinized asystolic pigs (n = 5, 30–35 kg) were ventilated for 90 min. The lungs were retrogradely preserved with Perfadex solution and stored inflated at 4°C for 3 h. Left lung transplantation in the recipient was followed by exclusion of the right lung. Results were compared to sham-operated animals. Oxygenation, hemodynamics and dynamic compliance were monitored for 4 h. Infiltration of polymorphonuclear cells (PMNs) and stereological quantification of alveolar edema was performed. Statistical analysis comprised Kruskal-Wallis and Mann-Whitney tests and ANOVA analysis with repeated measures. Results: No mortality was observed. During preservation, continuous elimination of blood clots via the pulmonary artery venting site was observed. Oxygenation and compliance were similar between groups, but sham controls showed significantly lower pulmonary vascular resistance. Stereological quantification revealed higher volume fractions of intra-alveolar edema in NHBD grafts, while PMN infiltration was comparable to sham controls. Conclusions: Use of NHBD lungs results in excellent outcome after 90 min of warm ischemia followed by retrograde preservation with Perfadex solution. This novel approach can optimize lung preservation by eliminating clots from the pulmonary circulation and might clinically be considered in brain-dead organ donors who become hemodynamically unstable prior to organ harvest. Further trials with longer warm and cold ischemic periods are necessary to further elucidate this promising approach to donor pool expansion.
Effect of Mg2SO4 Usage on Spinal Cord Ischemia-Reperfusion Injury: Electron Microscopic and Functional Evaluation
Authors: Kaplan Sadi , Ulus A. Tulga , Tütün Ufuk , Aksöyek Ayşen , Özgencil Eser , Saritaş Zülfikar , Apaydin Nusret , Pamuk Kamuran , Can Zeynep , Sürücü Selçuk , Katircioğlu S. Fehmi
Published: January 2004

Objectives: To evaluate the effects of intravenous magnesium sulfate (Mg2SO4) administration on ischemia-reperfusion injury of the spinal cord. Material and Methods: Sixteen rabbits were randomly assigned to the control (group I, 8 rabbits) and the study group (group II, 8 rabbits). The abdominal aorta was clamped for a period of 30 min followed by a reperfusion period of 60 min. The animals in group II received 0.25 ml/kg/h Mg2SO4 intravenous infusion (15% Mg2SO4) throughout this procedure. The animals were then observed for 24 h after which their neurological states were evaluated and tissue samples obtained from the spinal cord were examined with electron microscopy. Results: Aortic pressure distal to the cross-clamp during the occlusion period was 9 ± 3 mm Hg in group I and 19 ± 6 mm Hg in group II. All animals in group I were paraplegic at the end of the study. In group II the neurological outcome of 1 animal was poor while the other 7 animals were neurologically in a good condition. Electron microscopic examinations of the spinal cord tissues of group I revealed severe injury but the ultrastructure was well preserved in group II. Conclusions: Intravenous Mg2SO4 administration may have protective effects on the ischemia-reperfusion injury of the spinal cord. We propose that Mg2SO4 may be an additional protective pharmacological agent in thoracal and thoracoabdominal aortic surgery.
Effect of Different Enteral Nutrients on Bacterial Translocation in Experimental Obstructive Jaundice
Authors: Kuru B. , Dinc S. , Altınok Gulcin , Aksoz T. , Camlibel M. , Gulcelik M.A. , Alagol H.
Published: January 2004

Obstructive jaundice leads to bacterial translocation (BT) by disruption of the gut barrier, intestinal microecology, and impaired host immune defence. The objective of the present study is to investigate the effects of different enteral nutrients on BT that is induced by obstructive jaundice in rats. Eighty male Wistar-Albino rats were randomly assigned into 4 groups. Group 1: 20 rats underwent laparotomy, common bile duct (CBD) was not actually ligated and transected, but sham ligation of CBD was performed. Groups 2–4: 60 rats underwent laparotomy, CBD ligation and transection. Group 1 and 2 rats were given rat chow, group 3 rats were fed a glutamine and arginine supplemented enteral diet, and group 4 rats were fed an arginine, m-RNA and ω-3 supplemented enteral diet, an immunonutrient. Rats in groups 3 and 4 had significantly less BT to mesenteric lymph nodes compared to rats in group 2 (p = 0.001). These findings suggest that oral administration of an arginine and glutamine supplemented diet and immunonutrition reduce BT in rats with obstructive jaundice.
Effectiveness of Coagulation Factor XIII Concentrate for Reversing Loss of Tensile Strength of Rat Intestinal Anastomoses
Authors: Hasegawa H. , Eguchi Y. , Endoh K. , Yoshida T. , Okabe H. , Tani T.
Published: January 2004

Background: Blood coagulation factor XIII (F-XIII) promotes cross-linking of fibrin during blood coagulation. Impaired clot stabilization in patients with genetic deficiencies of F-XIII is associated with marked pathologies of wound healing. Methods: 60 rats given carbon tetrachloride underwent ileal anastomosis after which they received albumin (Alb animals) or F-XIII concentrate (F-XIII animals) immediately after surgery and daily thereafter until day 2 or 4 and were euthanized on day 3 or 5, respectively, or until day 5 and were euthanized on day 7, 10, or 21. We measured the plasma F-XIII activity and anastomotic tensile strength, followed by immunohistochemical localization of F-XIII subunit A within anastomoses. Results: On day 3, there were no significant differences between Alb and F-XIII animals for plasma F-XIII activity and tensile strength, and both groups of animals showed little immunostaining for F-XIII on anastomoses. Plasma F-XIII activities did not differ between Alb and F-XIII animals on day 5 (115.8 ± 16.8 vs. 137.3 ± 14.9%). Although the tensile strength in both groups was increased compared with that of day 3, that in F-XIII animals (129.8 ± 3.3 gf) was significantly higher than that in Alb animals (100.8 ± 5.3 gf, p = 0.014). F-XIII animals showed de novo collagen fibers and intense immunoreactivity of F-XIII in the extracellular matrix around the anastomoses. Similar differences occurred on day 7 but not days 10 and 21. Conclusions: F-XIII concentrate may accelerate the early healing process of intestinal anastomosis because of the protein’s accumulation in situ.
Effects of Locally Applied Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor on Ischemic Bowel Anastomoses in Rat
Authors: Dinc S. , Gulcelik M.A. , Kuru B. , Ergeneci Deniz , Camlibel M. , Caydere M. , Alagol H.
Published: January 2004

Background: Ischemia is one of the most common causes of anastomosis disruption. In the present study we investigated the effect of locally injected recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on ischemic bowel anastomosis in rats. Methods: 144 male Sprague-Dawley rats were randomized into four groups: in group 1, colon anastomoses were performed; in group 2, anastomoses were performed then 50 µg rhGM-CSF was injected subserosally into the perianastomotic area; in group 3, anastomoses were performed on ischemic colon segments, and in group 4, colon anastomoses were performed on ischemic segments and then 50 µg rhGM-CSF was injected subserosally into the perianastomotic area. On the 3rd and 7th post-operative days, the rats were sacrificed and anastomotic bursting pressures were measured. Hydroxyproline contents were studied on the tissues from the anastomotic line. Three anastomotic segments were saved from each group for histopathological studies before bursting pressure measurement. Results: The bursting pressure in group 3 was significantly weaker than in the other groups. There were no significant differences between the bursting pressures in groups 1 and 4. The levels of hydroxyproline content in group 4 were significantly greater than in group 3. Conclusions: These data suggest that the local injection of rhGM-CSF improves the healing of ischemic and even normal colon anastomoses.
Experimental Heterotopic Heart Transplantation: An Easier Technique
Authors: Roda J.R. , Alvarez Lourdes , Téllez G. , Cañas A. , Castedo E. , Ugarte J. , Castillo-Olivares J.L.
Published: January 2004

Aim: The use of heterotopic heart transplantation (HHT) in experimental surgery is an extended method to evaluate cardiac graft viability. To study endothelial injury after ischemia-reperfusion, the technique described by Matsui et al. in 1988 for HHT was chosen. A modification, which consists of replacing the atrium-to-atrium anastomosis for the tip of a 30-Fr venous cannula, was developed with the purpose of using this technique in small pigs. Both techniques were compared. Methods: Twenty-seven consecutive HHTs in 17- to 20-kg pigs using Matsui’s original technique and the modified technique were performed. Ischemia time, bleeding volume, mean gradient and anastomosis complications were measured to compare both techniques. Results: Statistically significant decreases in ischemia time, bleeding volume and mean gradient with the modified technique were found. Furthermore, there were two cases of suture dehiscence with the original technique. Conclusions: The replacement of the atrium-to-atrium anastomosis for the venous cannula is a modification that statistically decreases the ischemia time, blood loss and avoids suture complications. This modification makes Matsui’s technique easier, faster and safer in small pigs and it may be used in bigger animals and in any kind of non-permanent anastomosis.
Clinical Relevance of Inter-Method Differences in Fat-Free Mass Estimation in Chronic Obstructive Pulmonary Disease
Authors: Kilduff Liam P. , Fuld Jonathan P. , Neder J. Alberto , Pitsiladis Yannis P. , Carter Roger , Stevenson Robin , Ward Susan A.
Published: January 2004

Background: Evaluation of fat-free mass (FFM) is becoming recognised as an important component in the assessment of clinical status and formulation of prognosis in patients with chronic obstructive pulmonary disease (COPD). Objective: The aim of this study was to determine whether potential differences in FFM estimation performed by air displacement plethysmography (ADP), bioelectrical impedance (BIE) and anthropometry (ANTHRO) would assume clinical significance. Methods: Twenty-eight patients with moderate-to-severe COPD were submitted to FFM estimation by ADP, BIE and ANTHRO. FFM was then allometrically related to peak oxygen uptake (peak v̇O2) as determined by symptom-limited incremental cycle ergometry. Results: We found that ANTHRO classified fewer patients as ‘FFM-depleted’ than the other two techniques (p < 0.05). Although mean biases of the BIE-ADP differences were close to zero, their 95% confidence limits extended as high as 5.9 kg (16%). The ANTHRO-based allometric exponents for peak v̇O2 correction of FFM, therefore, were typically higher than those obtained by the other two methods in both depleted and non-depleted patients (ANTHRO: 1.45–1.41, BIE: 0.97–1.18, ADP: 1.08–1.14, respectively). Conclusion: We conclude that between-method differences in FFM estimation can be sufficiently large to have practical implications in patients with moderate-to-severe COPD. A single method of body composition assessment, therefore, should be used for FFM estimation in these patients.