bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurochemical Features of Frontotemporal Dementia
Authors: Procter A.W. , Qurne M. , Francis P.T.
Published: April 2003

This study examines neurochemical measures of cholinergic, serotonergic and glutamatergic innervation in frontal temporal and parietal cerebral cortex from 16 subjects with frontotemporal dementia (FTD) including 10 subjects with Pick pathology and 6 with dementia of frontal lobe type (DFT) together with 9 subjects with Alzheimer’s disease, and 28 matched controls. In both forms of FTD there was not evidence of any cholinergic abnormality, unlike the situation in AD. Serotonin receptors were lost from frontal and temporal cortex in FTD and from temporal and parietal cortex in AD. In FTD there was no loss of kainate receptors but loss of AMPA receptors from both temporal and frontal lobes. Loss of AMPA receptors differentiated Pick-type FTD from DFT. These results are interpreted to indicate selective losses of subpopulations of cortical pyramidal neurones.
Reduced Expression of Amyloid Precursor Protein, Presenilin-1 and rab3a in Cortical Brain Regions in Alzheimer’s Disease
Authors: Davidsson Pia , Bogdanovic Nenad , Lannfelt Lars , Blennow Kaj
Published: April 2003

To study the role of amyloid precursor protein (APP) in the pathogenesis of Alzheimer’s disease (AD), the level of APP was analysed by quantitative immunoblotting in 6 AD patients and 6 age-matched controls in 9 brain regions. These were associative cortices (orbital frontal cortex, inferior temporal cortex, inferior parietal cortex), primary cortex (occipital cortex), limbic structures (anterior cingulate gyrus, hippocampus), subcortical structures (putamen, thalamus) and cerebellum. To assess a potential relationship between APP and presenilin-1 (PS-1) and/or synaptic proteins, the levels of PS-1 and rab3a, a specific synaptic vesicle protein, were also determined in the same tissue samples. The level of APP was almost the same in the association cortical regions, primary cortex, and limbic structures and in the subcortical structures, while the lowest level was found in the cerebellum. There were more marked differences in the level of PS-1 and rab3a between different brain regions. The highest levels of PS-1 and rab3a were found in the association cortical areas, while intermediate levels were found in primary cortex, limbic structures and subcortical structures. As for APP, the lowest level was found in cerebellum. We found significantly reduced levels of all three proteins in the association cortices and in hippocampus in AD. Our data show that the protein levels are reduced in specific areas, restricted to neuronal populations that are known to degenerate in AD. Due to the similarity of the expression of APP, PS-1 and rab3a, it is tempting to speculate whether there is a functional relationship between these proteins.
Frontal Dysfunction and Frontal Cortical Synapse Loss in Alcoholism –The Main Cause of Alcohol Dementia?
Authors: Brun Arne , Andersson Jessica
Published: April 2003

Alcoholics often develop personality and behavioural changes, social and personal neglect, confabulation, lack of insight, empathy and emotional control. Such symptoms would increase the risk of engagement in and exposure to acts of violence and criminal activities carrying a risk of physical damage including head trauma and violent death. This was the case in at least 4 of the studied cases. A structural basis for such frontal lobe symptoms was looked for in a forensic material of 18 alcoholics, compared with an age-matched control group with regard to liver disease, brain changes of the Wernicke-Korsakoff type and cortical, especially frontal cortical changes. The salient finding was a consistent pattern of synapse loss in the superior laminae of the frontal cortical area 10 of Brodman in heavy drinkers, not related to liver disease or possible previous mental disease. The synapse loss is more likely related to alcohol, possibly mediated through vitamin B deficiency. Brain stem lesions as a source of additional symptoms cannot be dismissed. This pattern of synapse loss in alcoholism has not been described previously. The cortical changes are closely similar to those found in frontotemporal dementia, and seem to be a plausible main cause of the alcoholic frontal symptomatology and alcoholic dementia.
What Are Natural Retinoids?
Authors: Vahlquist A.
Published: April 2003

Vitamin A (retinol) is the prototype of all other natural retinoids. It is composed of a nonaromatic ring structure, a polyprenoid side chain and a carbonyl end group. These features make it liable to metabolic interconversion and protein interactions but also cause detergent-like properties and a sensitivity to UV irradiation and oxidation. Natural retinoids are present in all living organisms, either as preformed vitamin A or as carotenoids, and are required for a vast number of biological processes, e.g. vision, cellular growth and differentiation and reproduction. Although retinol is the most omnipotent compound, natural retinoids like all-trans-, 9-cis- and didehydroretinoic acid (RA) are clearly more potent outside the retina and trigger gene expression via binding to nucelar retinoid receptors. Retinaldehyde takes an intermediate position in this respect, with ability to convert to both retinol and RA. Over the years, many natural retinoids have been tried therapeutically against skin disorders with the best effects achieved with retinol, retinaldehyde, 13-cis-RA and all-trans-RA. The latter compound was the prototype when new, synthetic derivatives of vitamin A were sought, hoping for a better therapeutic index and a higher functional specificity. Inevitably, treatment with such drugs will influence the effects of coexisting natural retinoids. An understanding of the basic principles of these interactions may have major impact on patient outcome.
Manometric Components of the Lower Esophageal Double Hump
Authors: Klaus Alexander , Raiser Frank , Swain James , Hinder Ronald
Published: April 2003

Background/Aims: The lower esophageal sphincter manometry of patients with hiatal hernia often displays a double hump configuration. It seems that this is due to gastric herniation above the high-pressure zone of the crura. This study examines this manometric phenomenon in patients with hiatal hernia and relates it to the lower esophageal antireflux barrier. Methods: Manometric and 24-hour pH studies of 68 consecutive patients with suspected gastroesophageal reflux disease were analyzed to obtain information regarding the double hump and acid reflux. Results: The findings of a manometric double hump correlated well with the presence of a hiatal hernia of >5 cm. The overall length of the sphincter complex was greater in patients with a double hump, but the length below the respiratory inversion point was constant. Resting pressures at the respiratory inversion point were significantly lower than those measured at either high-pressure zone. The location of the respiratory inversion point was seen most commonly at the superior margin of the distal high-pressure zone. Double hump patients with a negative acid reflux score were found to have higher pressures in the distal high-pressure zone than those patients with acid reflux. Conclusions: The two high-pressure zones comprising the manometric double hump represent the crural and muscular components of the lower esophageal sphincter. Descriptive information regarding the double hump phenomenon is given, and the importance of the crural component of the lower esophageal sphincter in preventing acid reflux is stressed.
Reduction of Acid Exposure and Regression of Barrett’s Esophagus
Authors: Sampliner Richard E.
Published: April 2003

The goals of treatment of Barrett’s esophagus (BE) include relieving reflux symptoms, healing inflammatory lesions, and preventing esophageal adenocarcinoma. Reduction of acid reflux is believed to prevent progression of BE. A critical question is whether or not regression of BE occurs in response to therapy with proton pump inhibitors. The natural history of BE is altered both by the use of medications (over-the-counter or prescribed) and by endoscopic surveillance with periodic biopsies. Regression occurs when the length and surface area of BE decreases, along with the emergence of islands of squamous epithelium in the BE segment. However, the extent of regression is difficult to assess because intestinal metaplasia may underlie the islands of squamous epithelial regrowth. Sampling by endoscopic biopsy is useful in ruling out progression of BE to dysplasia or adenocarcinoma; however, complete regression of the lesion cannot be definitively proven by this technique. To date, published clinical trials of proton pump inhibitor therapy in patients with BE provide evidence of increases in squamous islands in the BE segment, but do not provide convincing data in support of complete regression of BE. In a review of prospective studies of the treatment of BE with proton pump inhibitors (PPIs) (with or without surgery), only 3 of 123 patients had apparent complete reversal of BE. This article reviews the current understanding of regression in BE following treatment with PPIs.
What Is the Optimal Medical Therapy for Barrett’s Esophagus?
Authors: DeVault Kenneth R.
Published: April 2003

The development of Barrett’s esophagus (BE) in patients with gastroesophageal reflux disease (GERD) is troubling because of its known association with esophageal cancer. When evaluated clinically, patients with BE have the severest form of GERD and require aggressive therapy to control esophageal acid exposure. Both hypotension of the lower esophageal sphincter and the extent of esophageal acid exposure are major contributors to severe GERD and its complications. It is hypothesized that better control of acid will improve outcomes for BE patients. While it is clear that therapy (medical or surgical) for reflux rarely if ever results in total regression of BE, there are some limited data to support improvement in BE with control of reflux. Current medical choices include prokinetic agents, histamine type-2 receptor antagonists, and proton pump inhibitors. In the future, genetic markers may be used in identifying BE patients at the greatest risk for histologic progression, and chemoprevention with cyclooxygenase-2 inhibitors may be a therapeutic option. This paper will review the rationale for and results of medical antireflux therapy in patients with BE.
Pathogenesis of Bleeding in Portal Hypertension
Authors: Escorsell Angels , Bosch Jaume
Published: April 2003

Hemorrhage from ruptured gastroesophageal varices is the main complication of portal hypertension, and represents a major cause of death and of liver transplantation in patients with cirrhosis [1]. Variceal bleeding is the last step of a chain which is initiated by the increase in portal pressure, followed by the formation and progressive dilatation of the varices until these finally rupture and bleed. Approximately 10% of patients having varices will develop variceal hemorrhage per year [2].
Pharmacological Treatment of Acute Variceal Bleeding
Authors: Burroughs A.K.
Published: April 2003

A review of the progress in pharmacological treatment of portal hypertension is best considered in the clinical setting of the acute variceal bleeding episode, the primary prophylaxis of variceal bleeding, and prevention of rebleeding from varices and portal hypertensive gastropathy. The data from randomized trials has been evaluated using meta-analysis when possible, and a conclusion made regarding the optimal drug or other therapy in the particular clinical setting. A recent meta-analytic review has been published [1].
Endoscopic Treatment of Portal Hypertension
Authors: Kleber Gerhard , Steudel Norbert , Fleig Wolfgang
Published: April 2003

Portal hypertension frequently is complicated by development of varices in the esophagus, stomach or other sites of the gastrointestinal tract. Portal hypertensive gastropathy and on rare occasions gastric antral vascular ectasia as well as portal hypertensive colopathy are also possible. This paper mainly deals with the most common problem, i.e. endoscopic treatment of esophageal varices.
Antibiotic Prophylaxis for the Prevention of Bacterial Infections in Cirrhotic Patients with Ascites: A Meta-Analysis
Authors: Bernard Brigite , Grangé Jean , Khac Eric Nguyen , Amiot Xavier , Opolon Pierre , Poynard Thierry
Published: April 2003

The incidence of spontaneous bacterial peritonitis (SBP) in hospitalized patients with cirrhosis ranges from 7 to 25% [1, 2], with an in-hospital mortality rate ranging from 20 to 50% [1, 3–5]. Prospective studies have shown that the 1-year mortality rate in these patients ranges from 65 to 93% [5]. Recurrence of SBP is common (69% at 1 year) [5]. The most accepted pathogenic mechanism for SBP is the passage of intestinal bacteria into the general circulation and then into the ascitic fluid [6].
Surgical Therapy of Hepatocellular Carcinoma
Authors: Rogiers X. , Brunken C. , Malagó M. , Knoefel W.T. , Broelsch C.E.
Published: April 2003

The only potential curative therapy modality of the hepatocellular carcinoma (HCC) is the complete radical resection. The indication of liver resection becomes problematic in the coincidence of HCC with liver cirrhosis. Only in 1 of 5 patients is the HCC small enough and the liver function good enough to perform a safe curative resection, this means with a safety margin and a sufficient remaining liver function [1].
Gene Therapy of Liver Tumors: Principles and Applications
Authors: Ruiz Juan , Qian Cheng , Prieto Jesús
Published: April 2003

The introduction in the last two decades of molecular biology techniques into medical research has produced an explosion in our understanding of the human genetics at the molecular level. It has also contributed to increase our knowledge of the pathophysiology of diseases and opened up new therapeutic possibilities such as the emergence of gene therapy.
A Novel Diamino-Pyridine Derivative Prevents Excessive Leukocyte Infiltration in Aggravation of Acute Necrotizing Pancreatitis
Authors: Yamauchi Jun-ichiro , Sunamura Makoto , Shibuya Kazuhiko , Takeda Kazunori , Kobari Masao , Matsuno Seiki
Published: April 2003

Leukocyte infiltration in the pancreas is involved in the aggravation of acute pancreatitis from edematous phase into necrotic change, and mild disease into severe disease; however, the mechanism responsible for leukocyte accumulation is not fully understood. This study was designed to clarify the mechanism underlying leukocyte accumulation into the pancreas and to elucidate the therapeutic efficacy of a novel diamino-pyridine derivative, IS-741 on leukocyte-endothelial cell interaction using rat necrotizing pancreatitis model. The number of adherent leukocytes to pancreatic collecting venules assessed by in vivo fluorescence microscopy increased significantly in necrotizing pancreatitis animals in a time-dependent manner. The expression of CD11b on circulating neutrophils determined by flow cytometric analysis was enhanced to approximately 500% after 2 h. IS-741 attenuated the leukocyte adherence significantly, accompanied by a lower up-regulation of CD11b. These findings were further supported by the histological examination that the accumulation of leukocytes in the pancreas was remarkably inhibited by IS-741. These results suggest that the leukocyte accumulation in the early phase of acute necrotizing pancreatitis may be mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. IS-741 attenuated the leukocyte endothelial cell interaction as a consequence of its inhibitory effect on CD11b upregulation.
Mechanism of Cholecystokinin-A- Receptor Antagonist on Human Pancreatic Exocrine Secretion
Authors: Funakoshi Akihiro , Fukamizu Yuji , Miyasaka Kyoko
Published: April 2003

Expressions of the cholecystokinin (CCK)-A and -B receptor genes in human duodenum, pancreas and gallbladder were examined by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization. The autoradiographic study of CCK-A and -B receptors in the human duodenum and pancreas was examined in vitro. To determine the subtypes to CCK receptors in the pancreas or duodenum, we studied the abilities of CCK-A and -B receptor agonists (CCK-8 and gastrin) and antagonists (loxiglumide, L-364,718 and L-365,260) to inhibit binding of 125I-CCK-8. CCK-A receptor mRNA was not expressed in the human pancreas, but was expressed in the gallbladder and duodenum, although it was expressed in the pancreas by RT-PCR. CCK-B receptor mRNA was expressed in the pancreas, but not in gallbladder and duodenum. Using autoradiography, high concentrations of CCK-A receptors were detected in the duodenal mucosa, although in the pancreas only CCK-B receptors were detected by this method. These results suggest that localization of CCK-A receptor in human duodenum provides a biochemical and morphological basis for some physiological functions of CCK.
Assessment of Exocrine Pancreatic Dysfunction in Chronic Pancreatitis
Authors: Kataoka Keisho , Hosoda Masanori , Yasuda Hiroaki , Sakagami Junichi , Kato Masato , Kashima Kei
Published: April 2003

The clinical diagnosis of chronic pancreatitis is usually based on imaging studies, pancreatic function tests, and the presence of characteristic clinical features. In Japan, diagnostic criteria for chronic pancreatitis were established in 1995. The secretin test (a duodenal intubation test) and the combination of noninvasive tests, N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) and fecal chymotrypsin (FCT), have been recommended for evaluating exocrine pancreatic function in patients with chronic pancreatitis. In the present study, the diagnostic value of these two noninvasive tests was compared to the secretin test. Although noninvasive tests are less sensitive and specific for determining exocrine pancreatic dysfunction than the secretin test, greater reliability for diagnosing chronic pancreatitis can be obtained by performing the BT-PABA and FCT simultaneously. Assessment of exocrine pancreatic function is important not only to diagnose chronic pancreatitis but also to decide a treatment method with pancreatic enzyme preparation.
Extended Pancreatectomy and Liver Perfusion Chemotherapy for Resectable Adenocarcinoma of the Pancreas
Authors: Ishikawa Osamu , Ohhigashi Hiroaki , Sasaki Yo , Furukawa Hiroshi , Imaoka Shingi
Published: April 2003

In order to increase the long-term survival after resection of pancreatic adenocarcinoma, it is essential to eradicate both locoregional recurrence and hepatic metastasis. We have added a wide range of lymphatic and connective tissue clearance to conventional pancreatectomy (extended pancreatectomy) and succeeded in improving the 5-year survival rate from 8 to 25% via decreasing the incidence of local failure. Among many procedures which together compose an extended pancreatectomy, connective tissue clearance seems to have played a more important role on patients’ prognosis rather than wide range lymphadenectomy. Concomitant resection of the portal vein is recommended for selected patients, and it is important not to overlook a minute invasion even though it appears macroscopically intact. With regard to adjuvant therapy in combination with our extended pancreatectomy, the addition of preoperative irradiation failed to further improve the long-term survival rate because the cause of cancer deaths shifted from local recurrence to hepatic metastasis. When liver perfusion chemotherapy was added to this operation (without radiation), the 5-year survival rate was improved to 39% by decreasing the incidence of hepatic metastasis. In the future, a combination of extended pancreatectomy with chemoradiation plus liver perfusion chemotherapy is one of the promising approaches for this cancer.
Treatment of Acute Nonvariceal Upper Gastrointestinal Hemorrhage
Authors: Meier R. , Wettstein A.R.
Published: April 2003

Hospitalization for nonvariceal upper gastrointestinal hemorrhage (UGIH) is still common with an incidence of 100/100,000 adults/year. Mortality rates range between 8 and 14%. The most common etiologies of acute UGIH are gastric and duodenal ulcers which are associated with older age, Helicobacter pylori gastritis and nonsteroidal anti-inflammatory drugs. Approximately 70% of UGIH stop spontaneously, 10% bleed continuously and about 20% rebleed in the first 24–72 h. Mortality and the probability of rebleeding have been related to the ulcers’ stigmata (Forrest) and to a variety of clinical findings (hematemesis, low initial hemoglobin, signs of shock, coagulopathy and liver disease). It is well established that only patients with continued bleeding or with a risk of rebleeding benefit from endoscopic or medical treatment. Endoscopic treatment (including heater probe, bipolar electrocoagulation, laser and injection therapy) control active bleeding in up to 90% and reduce significantly the rates of further bleeding, the need for blood transfusions, hospital costs and emergency surgery. Medical treatment is still controversial although positive results for somatostatin and octreotide have been found. A meta-analysis including 1,829 patients from 14 randomized trials showed the relative risk for continued bleeding or rebleeding of 0.53 (95% CI, 0.43–0.63) in favor of somatostatin and octreotide. Interventional endoscopy is the first line of treatment for UGIH. Somatostatin and its analogue octreotide may be a useful adjunct to endoscopic management or alternative when endoscopy is unsuccessful, contraindicated or unavailable.
Role of Octreotide and Somatostatin in the Treatment of Intestinal Fistulae
Authors: Dorta G.
Published: April 2003

Intestinal fistulae usually arise as a complication of abdominal surgery. Its treatment is complex and intestinal fistula-related morbidity and mortality is high. Fistula closure rates under conservative medical treatment vary between 24 and 72%. Octreotide and somatostatin reduce gastrointestinal, biliary and pancreatic secretion and increase intestinal water and electrolyte absorption. In recent years, octreotide and somatostatin have been associated with conservative medical treatment for patients with intestinal fistulae. Four placebo-controlled studies have been published within the past 6 years. The interpretation of their results is difficult because patient collectives were small and heterogeneous. In one study, somatostatin decreased fistula-related complications when compared to placebo, and in another study, octreotide decreased the healing time of intestinal fistulae and the time patients required total parenteral nutrition when compared to placebo. In contrast, the fistula closure rate, hospitalization time and mortality were not influenced by the use of octreotide or somatostatin in conservative medical treatment. In conclusion, octreotide and somatostatin actually cannot be recommended in the treatment of intestinal fistulae in settings outside of controlled trials.
Theophylline Alters Neutrophil Function in Preterm Infants
Authors: Mehta Rajeev , Weinberger Barry , Usmani Shaista S. , Wapnir Raul A. , Harper Rita G.
Published: April 2003

Theophylline (1,3-dimethylxanthine), which is often prescribed to premature infants to treat apnea, acts, in part, by altering the metabolism of cyclic AMP. This second messenger plays a role in signal transduction mediating neutrophil functions, including respiratory burst, chemotaxis, and motility. We hypothesize that theophylline causes reduced respiratory burst activity, chemotaxis, and random motility in neutrophils. In these studies, we aim at determining the effects of theophylline on neutrophil function in vitro in cells from preterm and full-term infants and adults as well as on neutrophils obtained from premature infants receiving theophylline treatment. Neutrophils were obtained from 20 preterm infants, 16 full-term infants, and 14 adults. Chemiluminescence, chemotaxis, and random motility were measured after exposure of these cells to theophylline in vitro (0– 84 µmol/l or 0–15 µg/ml). In addition, these neutrophil activities were correlated with serum theophylline levels in 13 preterm infants receiving theophylline treatment for 72 h. Neutrophils from premature infants, term infants, and adults all displayed reduced chemiluminescence, chemotaxis, and random motility at 84 µmol/l (15 µg/ml) of theophylline in vitro. The relative reductions were greatest in cells from premature infants (p < 0.01). A level-dependent reduction in these activities was also noted in neutrophils from preterm infants with serum theophylline levels >46 µmol/l (8.2 µg/ml; p < 0.001). In contrast, lower theophylline concentrations (about 28 µmol/l or 5 µg/ml), either in vitro or in vivo, caused significant increases in neutrophil activities. Theophylline concentrations in the high therapeutic range (84 µmol/l or 15 µg/ml) cause dose-dependent reductions in neutrophil chemiluminescence, chemotaxis, and random motility. Cells from preterm infants are particularly sensitive to this effect. In contrast, theophylline concentrations in the low therapeutic range (28 µmol/l or 5 µg/ml) cause increased neutrophil activities. Altered neutrophil activity in newborns related to theophylline treatment may affect the infants’ response to infection as well as the incidence of inflammatory diseases.
Unilesional Mycosis fungoides
Authors: Hodak E. , Phenig E. , Amichai B. , Feinmesser M. , Kuten A. , Maron L. , Sahar D. , Bergman R. , David M.
Published: April 2003

Background: Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL), characterized by a solitary lesion clinically and by histopathological features indistinguishable from those of MF, and typically having a benign course. Objective: To describe the clinicopathological features of a series of patients with unilesional MF. Methods: The records of cases of unilesional MF identified during a 10-year period in two medical departments were reviewed. Results: There were 7 patients: 6 males, 1 female; mean age at the time of diagnosis: 32 years; age range: 12–58 years; 3 were below the age of 18 years. The mean pretherapy follow-up period was 9 years (range: 2–20 years). In 5 patients, the eruption consisted of a characteristic patch or plaque of MF located on the trunk or upper extremity; in 2 it was atypical – in 1, a hypopigmented patch, and in 1, a plaque indistinguishable from MF-associated follicular mucinosis. Histopathologically all the lesions exhibited features characteristic of MF, with CD3+ lymphoid cells. In 6 cases (with available fresh frozen tissue) there was a predominance of CD3+ CD4+ cells; in 1 of 5 there was deletion of CD7, and in 3 of 5 there was an overexpression of IL-2 receptor. T-cell receptor γ gene rearrangement was found in 1 of 4 cutaneous lesions tested; in 2 cases it was found in the blood but not in the skin. Treatment modalities included localized electron beam, excision, topical nitrogen mustard or topical steroids and sunbathing, resulting in all cases in a sustained complete clinical response. In 1 patient, however, there were 2 local recurrences and in yet another patient there was distant cutaneous spread 3.5 years after therapy. Conclusions: Unilesional MF is a rare variant of CTCL, has heterogeneous clinical manifestations and can affect any age group, including children. The histopathological and immunophenotypical features are in general indistinguishable from those observed in multilesional MF. Although it is a unifocal event, there may occasionally be cutaneous spread with the appearance of noncontiguous lesions, even a long time after therapy. Whether all cases represent minimal-stage IA MF or whether some are actually T-cell pseudolymphoma remains to be clarified.
Increased Plasma Adrenomedullin Levels in Patients with Behçet’s Disease
Authors: Evereklioglu Cem , Yurekli Muhittin , Er Hamdi , Ozbek Emin , Hazneci Ersoy , Cekmen Mustafa , Inaloz H. Serhat
Published: April 2003

Background: Behçet’s disease (BD) is a chronic systemic inflammatory disorder affecting multiple organs with a generalized vasculitis of arteries and veins. Endothelial dysfunction is one of the prominent features of BD. Adrenomedullin (AM) is a peptide produced not only in normal adrenal medulla but also in the vascular smooth muscle cells and endothelial cells, and its role in the course of BD has not been previously described. Objective: To detect changes of plasma AM concentrations in patients with BD compared with age- and sex-matched healthy subjects by using high-performance liquid chromatography (HPCL). We also investigated if disease activity or the duration of BD correlates with AM levels. Methods: Forty-two consecutive patients with BD (38.5 ± 11.1 years, 19 male and 23 female) and 20 healthy age- and sex-matched control subjects (39.5 ± 10.9 years, 8 male and 12 female) were included in this study. We measured plasma AM levels by HPCL, and acute-phase reactants including α1-antitrypsin and α2-macroglobulin, neutrophil count and the erythrocyte sedimentation rate. Results: Mean ± SD plasma AM levels in patients with BD (73.22 ± 25.55 pmol/l) were significantly higher (p < 0.001) than in healthy control volunteers (21.35 ± 12.37 pmol/l). Patients with active BD had similar plasma AM concentrations (79.32 ± 21.89 pmol/l) with patients with inactive disease (67.44 ± 29.92 pmol/l). On the other hand, patients with longer duration of the disease (mean duration, 13.9 ± 3.8 years) had significantly higher plasma AM levels (83.99 ± 19.71 pmol/l; p = 0.005) than patients (62.45 ± 26.57 pmol/l) with shorter duration of the disease (mean duration, 5.5 ± 2.3 years). All acute-phase reaction parameters were found to be significantly increased in the active disease. Conclusion: Considering its endothelial cell implications, AM may be involved in reparatory vessel endothelium mechanisms, especially in the chronic disease.
The Effect of a New Tissue-Adhesive Wound Dressing on the Healing of Traumatic Abrasions
Authors: Quinn James , Lowe Laurie , Mertz Michelle
Published: April 2003

Background: Octylcyanoacrylate is a new medical-grade adhesive with antimicrobial properties. It forms a thin, flexible, occlusive bandage. Objective: To determine the gross and histological effects of the spray bandage when treating abrasions. Methods: Abrasions were produced on the flanks of 18 albino guinea pigs and randomized to treatment with a control (Biobrane) or octylcyanoacrylate dressing. The wounds were assessed with digital photography using a previously validated method. Histopathological analysis was done on day 14. Results: There were no differences in the mean wound-healing ratios on days 1 (1.25 vs. 1.23, p = 0.61), 7 (1.15 vs. 1.13, p = 0.14) and 14 (1.03 vs. 1.02, p = 0.63) for tissue adhesive and Biobrane, respectively. There were no differences found on histopathological analysis either. Conclusions: This external spray bandage was well tolerated and did not show any signs of histotoxicity or adverse wound healing.
Analysis of p53, p21Waf1/Cip1 and TGF-β3 Immunohistochemical Staining in Bowen’s Disease
Authors: Kawakami Tamihiro , Soma Yoshinao , Mizoguchi Masako , Saito Ryuzo
Published: April 2003

Background: The p53 gene is one of a family of tumor suppressor genes that have been implicated in the genesis of a wide variety of malignant neoplasms including Bowen’s disease. Its role in oncogenesis and tumor progression is thought to be of importance. Transforming growth factor β (TGF-β) is the most potent known inhibitor of the progression of normal epithelial cells through the cell cycle. p21Waf1/Cip1 is thought to mediate p53 signaling induced by DNA-damaging agents to arrest the cell cycle. Objective: The present study evaluates the expression of p53, p21Waf1/Cip1 and TGF-β3 protein and speculates on their role in Bowen’s disease. Methods: Sixteen patients seen at our clinic between 1993 and 2000 were examined. We analyzed p21Waf1/Cip1, p53 and TGF-β3 immunohistochemical staining in all specimens. Results: In 7 of the Bowen’s disease patients, overexpression of p53-positive cells was present in the middle and basal layers, and intense staining of p21Waf1/Cip1 was observed in the upper spinous layers. In the other 9 Bowen’s disease patients, we found positively stained cells for p21Waf1/Cip1 but negative p53 immunostaining in the upper epidermal layer. Downregulated TGF-β3 expression was detected in all layers except the upper spinous layers. Conclusion: These observations suggest different roles for p21Waf1/Cip1 and p53 within abnormal cells in Bowen’s disease. p21Waf1/Cip1 may induce terminal differentiation to the superficial layer in Bowen’s disease via either a p53-independent or -dependent pathway. Moreover, downregualtion of TGF-β3 immunostaining provides relevant information concerning the pathogenesis of Bowen’s disease.
The Number and Distribution of Merkel Cells in Rudimentary Polydactyly
Authors: Ban Masanori , Kitajima Yasuo
Published: April 2003

Background: Rudimentary polydactyly histologically reveals a marked neural proliferation in the dermis and a large number of Meissner corpuscles in the dermal papillae. Objective: Our study was performed to determine whether this neural proliferation is related to Merkel cells. Method: Using an antibody to cytokeratin 20, we examined the number and distribution of Merkel cells in 5 cases of rudimentary polydactyly, including an immature case without Meissner corpuscles. Results: Only the case without Meissner corpuscles had a markedly large number of Merkel cells and some dermal Merkel cells. Conclusion: The normal number of Merkel cells in the mature cases suggests that abundant Merkel cells may appear at first and disappear after the development of neural proliferation. Merkel cells may be associated with the generation of cutaneous nerve plexus and nerve endings in the upper dermis, and possibly with the development of Meissner corpuscles, at the early stage of rudimentary polydactyly.
The Successful Treatment of Prurigo pigmentosa with Macrolide Antibiotics
Authors: Yazawa Norihito , Ihn Hironobu , Yamane Kenichi , Etoh Takafumi , Tamaki Kunihiko
Published: April 2003

Recent studies have demonstrated that macrolide antibiotics have anti-inflammatory as well as antibacterial effects. Therefore, macrolide antibiotics have been successfully used to treat patients with various inflammatory diseases. We evaluated the effect of macrolide antibiotics in 4 patients with prurigo pigmentosa who were treated with either 400 mg of clarithromycin or 300 mg of roxythromycin daily. Eruption and pruritus disappeared within a week in all the patients while those symptoms were unresponsive to other drugs. Although the mechanism of this effect remains unclear in patients with prurigo pigmentosa, macrolide antibiotics can be considered as an alternative treatment for prurigo pigmentosa.
Granzyme-B-Containing Lymphocyte Involvement in Epidermal Injury in Graft-versus-Host Disease
Authors: Higaki Yuko , Yamada Osamu , Okamura Takamitsu , Mizoguchi Hideaki , Kawashima Makoto
Published: April 2003

Background: Skin lesions from graft-versus-host disease (GVHD) show histological features of epidermal cell death with lymphocyte infiltration. Perforin and granzyme B are involved in the process of apoptosis induced by cytotoxic T lymphocytes (CTL). Objective: To elucidate the role of CTL in the mechanism of epidermal injury in GVHD. Methods: We studied immunohistochemical staining for granzyme B and perforin in the skin lesions of 8 patients who developed GVHD after bone marrow transplantation. Results: Granzyme-B-positive lymphocytes were CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it was negative. Perforin-positive lymphocytes were observed in the epidermis of the specimens from 1 acute and 1 chronic GVHD. Conclusions: Granzyme B derived from CTL may be involved in the mechanisms of epidermal injury in GVHD.
Paraneoplastic Pemphigus in a Patient with a Thymoma
Authors: Leyn J. , Degreef H.
Published: April 2003

A 76-year-old woman, with a history of thymoma, presented with a painful extensive stomatitis, painful paronychia, lichenoid papules on the hands and superficial erosions on the neck and the trunk. Histological examination showed lichenoid changes, acantholytic blister formation and apoptotic keratinocytes. Direct immunofluorescence was positive for IgG both in the epidermal intercellular spaces and along the basement membrane zone. Indirect immunofluorescence was similarly positive in a pemphigus vulgaris pattern. There was only a partial response to intravenous corticoids. These findings allowed the diagnosis of paraneoplastic pemphigus. The diagnostic characteristics, histopathology and the differential diagnosis of this disease are discussed.
Superficial Granulomatous Pyoderma gangrenosum of the Face, Successfully Treated by Ciclosporine: A Long-Term Follow-Up
Authors: Lachapelle Jean-Marie , Marot Liliane , Jablonska Stefania
Published: April 2003

We report a case of the superficial granulomatous (vegetating) form of pyoderma gangrenosum, involving the forehead and the left temporal area in a 44-year-old woman. No association with other pathologies could be found. Lesions responded dramatically to systemic ciclosporine (5 mg/kg/day), and complete healing was reached after 6 months. Doses were tapered progressively. Treatment was discontinued after 4.5 years. Discontinuation was not followed by recurrence of the disease. Healing is maintained after another 4.5 years of follow-up.
Autologous Cellular Suspensions and Sheets in the Treatment of Achromic Disorders: The Need for Future Controlled Studies
Authors: Ongenae K. , van Geel N. , Naeyaert J.M.
Published: April 2003

Transplantation techniques using cultured and noncultured keratinocyte and/or melanocyte suspensions or sheets have been reported as successful in inducing repigmentation in achromic epidermal diseases such as vitiligo and piebaldism. However, the role of a lot of variable factors in the transplantation procedure remains unclear. Occasionally control sites are included in the reported patient series. We point out the need for future controlled studies when performing transplantations of cellular suspensions and sheets. This approach will help to understand how these techniques induce repigmentation and may eventually indicate the essential requirements for successful results.
Dual Presentation of Extranodal Marginal B-Cell Lymphoma Involving the Skin, Viscera and Bones
Authors: Uhoda I. , Piérard-Franchimont C. , Arrese J.E. , Piérard G.E.
Published: April 2003

A 65-year-old man presented with an erythematous indurated plaque on the scalp and forehead. A low-grade marginal-zone B-cell lymphoma with small cells and ĸ-chain monoclonality was diagnosed. Radiotherapy was initiated. He soon developed abdominal pain and hematemesis. A high-grade marginal-zone B-cell lymphoma with large cells and λ-chain predominance was disclosed infiltrating the stomach and lungs. Bone localizations were also found. There was no evidence for lymph node and bone marrow involvement. The distinct cytological and immunophenotypic presentations in the skin and viscera are a puzzling finding.
Epidermal Growth Factor Receptor Overexpression and Genetic Aberrations in Metastatic Squamous-Cell Carcinoma of the Skin
Authors: Shimizu T. , Izumi H. , Oga A. , Furumoto H. , Murakami T. , Ofuji R. , Muto M. , Sasaki K.
Published: April 2003

Background: Cutaneous squamous-cell carcinoma (SCC) sometimes causes lymph node metastasis and results in poor prognosis. However, little is known about cytogenetic alterations underlying tumor progression or metastasis. The aim of the present study was to investigate the genetic aberrations and expression of epidermal growth factor receptor (EGFR) in metastatic SCC of the skin. Methods: We undertook comparative genomic hybridization (CGH) analysis of 4 specimens which were obtained from a case of cutaneous SCC, including the primary lesion and 3 lymph nodes of the metastatic lesion. Results: Only one amplified locus (7p12–13) was detected in any metastatic lymph node, in which the EGFR gene is located. Therefore, we applied immunohistochemistry for EGFR to 5 cases of metastatic SCC including the case analyzed using CGH and 4 other cases (5 primary and 5 metastatic lesions). EGFR was expressed in 4 of 5 cases (both primary and metastatic lesions, including the case analyzed using CGH), and the staining patterns of primary and metastatic lesions were different. The primary tumors were focally weakly positive for immunostaining (+), whereas the 4 metastases were diffusely and strongly positive (+++). Conclusions: Our findings suggest that the clone with EGFR expression might selectively metastasize in some cutaneous SCCs. The existence of an EGFR-negative case reveals that EGFR expression is not always required for skin carcinogenesis, but expression of EGFR might confer metastatic potential of cutaneous SCCs.
Zosteriform Metastatic Skin Cancer: Report of Three Cases and Review of the Literature
Authors: Kikuchi Y. , Matsuyama A. , Nomura K.
Published: April 2003

Background: Metastatic skin cancer is a rare complication of internal malignancies. Patients who do develop skin metastases seldom present with a zosteriform distribution. Objective: To elucidate the characteristics of zosteriform metastatic skin cancer, 15 cases from the medical literature and 3 cases seen in our clinic were reviewed clinically and histopathologically. Methods: The age and sex of each patient, site of the primary tumor, pathology of primary and metastatic lesions, location of the skin cancer and presence of pain were determined for the 18 cases of zosteriform skin cancer. Results: The most frequent site of the primary tumor was the breast (4 cases), ovary or lung (3 cases each), prostate, bladder or stomach (2 cases each) and uterus or colon (1 case each). The most common site of the skin metastases was the chest wall (8 cases) and abdominal wall (7 cases). The histology of the primary lesion was compatible with adenocarcinoma (10 cases), transitional cell carcinoma or serous papillary cystadenocarcinoma (2 cases each) and ductal carcinoma (1 case). Eleven cases developed on the nearest covering skin and/or on the same side as the primary tumor. Eleven patients complained of pain. Seven cases were treated as herpes zoster with antiviral agents. Conclusion: Approximately 50% of cases of metastatic skin cancer developed on the nearest skin covering and on the same side as the primary tumor. This evidence may be useful when trying to pinpoint the location of the primary tumor. One third of patients with skin metastases were misdiagnosed and their lesions were treated initially as herpes zoster. When a band-like eruption is seen in patients with internal malignancies, the possibility of metastatic skin lesions should be considered. A skin biopsy is necessary to confirm the diagnosis.
Acne Resolution Rates: Results of a Single-Blind, Randomized, Controlled, Parallel Phase III Trial with EE/CMA (Belara®) and EE/LNG (Microgynon®)
Authors: Worret I. , Arp W. , Zahradnik H.-P. , Andreas J.-O. , Binder N.
Published: April 2003

Background and Objective: Acne in women can often be successfully treated by the intake of oral contraceptives containing gestagens with anti-androgenic properties. This study aimed to evaluate the efficacy of the monophasic oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA; Belara®) for the treatment of mild to moderate papulopustular acne of the face and acne-related disorders in comparison to EE/levonorgestrel (LNG; Microgynon®). Methods: 199 female acne patients were enrolled in a single-blind, randomized, multicentre phase III study and divided into two groups who received either EE/CMA or EE/LNG. The primary end point was fulfilled if the number of papules/pustules per half of the face present on admission had decreased by at least 50% in the 12th medication cycle. Results: 59.4% of the women under EE/CMA and 45.9% under EE/LNG were responders. The relative frequency of women with complete resolution was 16.5% under EE/CMA and 4.3% under EE/LNG at cycle 12.Conclusion: EE/CMAis an efficient treatment for women with mild and moderate papulopustular acne of the face and related disorders, reflecting the well-known anti-androgenic properties of the progestogen CMA.
Acute Generalized Exanthematous Pustulosis Associated with STI571 in a Patient with Chronic Myeloid Leukemia
Authors: Brouard M.C. , Prins C. , Mach-Pascual S. , Saurat J.-H.
Published: April 2003

The tyrosine kinase inhibitor STI571 is a novel promising class of anticancer drugs. We report a case of cutaneous adverse reactions to STI571 in a young woman with blast crisis of chronic myeloid leukemia. She had first typical acute generalized exanthematous pustulosis mimicking mercury rash and then urticarial eruption. We suggest that cell pathways mediated by some tyrosine kinases might be involved in the pathogenesis of these skin eruptions.
Marginal Papular Acrokeratodermas: No Racial Limitations for a Clinical Spectrum That Responds to Acitretin
Authors: Lambiris A.G. , Newman P.L.
Published: April 2003

Marginal papular acrokeratoderma (MPA) encompasses a group of disorders that share crateriform, keratotic papules along the margins of the hands and feet. We report a unique case of a Philippino woman, with focal acral hyperkeratosis (FAH) associated with sensorineural hearing loss. The clinical phenotype of FAH (hereditary MPA without elastorrhexis) is expanded and the hypothesis of a racially limited disorder is weakened. Effective treatment of this embarrassing condition with acitretin is demonstrated.
Swiss Guidelines for the Treatment and Follow-Up of Cutaneous Melanoma
Authors: Dummer R. , Bösch U. , Panizzon R. , Bloch P.H. , Burg G.
Published: April 2003

Melanoma is the most common lethal cutaneous neoplasm. There is major controversy over the best management of this malignancy. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated. They have been approved by all Swiss medical societies involved in the care of melanoma patients.
Primary Hyperparathyroidism and Cutaneous T-Cell Lymphoma: Fortuitous Association?
Authors: Albès B. , Bazex J. , Bayle-Lebey P. , Bennet A. , Lamant L.
Published: April 2003

This is the third report of an association between T-cell cutaneous lymphoma (mycosis fungoides) and primary hyperparathyroidism (adenoma). Some studies support the concept that hyperparathyroidism may have promotional activity for the development of certain malignant tumors. A high risk for successive or concurrent neoplasms has been reported in patients with parathyroid adenomas. Primary hyperparathyroidism in a neoplastic context may be underreported. Patients with tumor-associated hypercalcemia should be evaluated for the possibility of primary hyperparathyroidism.
A Case of Subungual Reactive Eccrine Syringofibroadenoma
Authors: Theunis Anne , Andre Josette , Forton Fabienne , Wanet Josette , Song Micheline
Published: April 2003

Eccrine syringofibroadenoma (ESFA) is a rare eccrine tumor. We report the case of a 70-year-old woman who had presented a pincer nail deformity on the toes for 55 years and a left painless subungual tumor for 2 years. Histologic examination revealed branching anastomosing strands of epithelial cells with ductal structures in a fibrovascular stroma. The luminal cells showed positive staining for carcinoembryonic antigen, as in acrosyringeal cells and cells of dermal ducts. To our knowledge, our case is the first with a subungual location. In the context of chronic trauma due to a pincer nail, it may be classified in the reactive subtype recently described.