Acute mastoiditis in infants aged six months or younger.

OBJECTIVE: Bibliographic data for the management of acute mastoiditis in infants aged six months or less are very limited. This study investigated the presenting symptomatology, diagnostic and treatment options, and final outcomes in this age group. METHOD: A retrospective review was conducted of all infants aged six months or less suffering from acute mastoiditis, admitted to our department between 2007 and 2017. RESULTS: Eleven infants were identified. All of them developed the typical symptomatology of acute mastoiditis, while a higher rate of subperiosteal abscess formation was observed. Imaging was necessary in three cases only. Parenteral antibiotics and myringotomy were applied in all infants. A drainage procedure was also included in the infants with a subperiosteal abscess. Antrotomy was reserved for non-responsive cases. No intracranial complications were observed. All infants were cured without further complications or sequelae. CONCLUSION: Acute mastoiditis in infants aged six months or less can be safely diagnosed and treated using a standardised algorithmic approach, similar to that used for older children.

Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent 25-kDa protein mainly secreted by neutrophils. In inflammatory bowel disease (IBD), overexpression of NGAL in colon epithelium has been previously shown. This is the first study analyzing serum and urinary NGAL levels in IBD patients, with regard to specific characteristics of patients and disease. METHODS: Serum and urinary NGAL levels were determined in 181 patients with IBD, 93 with ulcerative colitis (UC), and 88 with Crohn's disease (CD), 82 healthy controls (HC), and 41 patients with irritable bowel syndrome (IBS). RESULTS: Serum NGAL levels were elevated in IBD patients (88.19 ± 40.75 ng/mL) compared with either HC (60.06 ± 24.18 ng/mL) or IBS patients (60.80 ± 20.30 ng/mL), P < 0.0001. No significant difference was shown between UC (86.62 ± 35.40 ng/mL) and CD (89.92 ± 46.05 ng/mL). Significantly higher levels of serum NGAL were observed in patients with active (120.1 ± 38.46) versus inactive IBD (61.58 ± 15.98), P < 0.0001. Serum NGAL displayed a strong ability to distinguish active IBD from inactive disease, healthy controls, or IBS patients with a sensitivity of 100, 95, and 95% and a specificity of 68, 83, and 79%, respectively, performing better than erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in both UC and CD. Urinary NGAL levels showed neither significant difference among patients and controls nor correlation with disease activity. CONCLUSIONS: Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.

TLR4 gene polymorphisms: evidence for protection against type 2 diabetes but not for diabetes-associated ischaemic heart disease.

OBJECTIVE: Several factors either predisposing or protecting from the onset of diabetes mellitus type 2 (DM2) have been proposed. Two specific polymorphisms of toll-like receptor 4 (TLR4; Asp299Gly and Thr399Ile) have recently been identified either as candidate protector genes against DM2 and associated neuropathy or risk alleles for the manifestation of diabetic retinopathy. The impact of these alleles on the risk for ischaemic heart disease (IHD) is controversial while their role in diabetes-associated IHD has never been studied. DESIGN AND METHODS: In order to clarify the potential impact of TLR4 polymorphisms on the predisposition for DM2 as well as on diabetes-related IHD vulnerability, the distribution of the mutant TLR4 Asp299Gly and Thr399Ile alleles in 286 DM2 patients and 413 non-DM2 controls with or without IHD, was examined. RESULTS: Mutant alleles were predominantly detected in 79/413 non-diabetic individuals versus 15/286 DM2 patients (P<0.0001). The rates of positivity for mutant alleles were similar among diabetic patients with or without IHD (7/142 vs 8/144, P>0.1), whereas they proved different among non-diabetic individuals with or without IHD (39/145 vs 40/268, P=0.004). Following multivariate analysis, the difference between diabetic and non-diabetic subjects, with regard to TLR4 mutations alone, remained significant (P=0.04). CONCLUSIONS: Mutant TLR4 alleles confer protection against DM2. However, their presence does not seem to play any role, protective or aggravating, in the manifestation of IHD either in diabetic or in non-diabetic individuals.

Acute upper gastrointestinal bleeding in central Greece: the role of clinical and endoscopic variables in bleeding outcome.

The objectives of this work were to portray the incidence of upper gastrointestinal bleeding in central Greece and to define subsets at higher risk of poor outcome or death. Two hundred and sixty-four cases were recorded. The incidence was 116 per 100,000 per year (95% CI: 102-130). Re-bleeding was noted in 7.9% of patients. The case fatality was 7.2% and population mortality 8 per 100,000 per year (95% CI: 4-12). Independently significant risk factors for re-bleeding were stigmata of bleeding at endoscopy (OR: 3.11; 95% CI: 1.06-9.13, P = 0.04), smoking (OR: 3.39; 95% CI: 1.08-10.62, P = 0.03), and the use of anti-coagulant drugs (OR: 2.64; 95% CI: 1.00-7.13, P = 0.05), while the independently significant risk factor for death was re-bleeding (OR: 5.74; 95% CI: 1.40-23.52, P = 0.03). We conclude that patients with stigmata of bleeding at endoscopy and on anti-coagulant therapy should be under close surveillance because of the higher risk of re-bleeding. Smoking also increases the risk of re-bleeding. Patients with re-bleeding episodes must be managed intensively because of the higher risk of death.

Malakoplakia of the colon associated with colonic adenocarcinoma diagnosed in colonic biopsies.

Malakoplakia, typically involving the urinary tract, is an uncommon form of chronic inflammation caused by chronic infections and characterized by accumulation of macrophages. It has also been found in many other sites such as the gastrointestinal tract, pancreas, liver, lymph nodes, skin, respiratory tract, adrenal gland, vagina and brain. We present a case of a 64-year-old man referred to our hospital with cachexia and radiologic evidence of metastatic tumor of the liver. Colonoscopy revealed a large malignant - appearing polypoid mass of the ascending colon and multiple distinct polyps throughout the rest of the colon. Biopsies of the ascending colon mass confirmed the diagnosis of adenocarcinoma. Histological examination of two of the other polyps revealed malakoplakia which was characterized by aggregates of granular histiocytes with Michaelis - Gutmann bodies and histochemically confirmed with periodic acid-Schiff and von Kossa stains. This is a rare case diagnosed on endoscopic samples. The majority of reported cases were found in surgical specimens. In addition, the endoscopic appearance of multiple polyps is unusual in malakoplakia.

A bioequivalence study of levothyroxine tablets versus an oral levothyroxine solution in healthy volunteers.

Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent, quality control is an essential factor. Due to the unreliability of Levothyroxine-based commercial products, in the present study we decided to follow the Food and Drug Administration (FDA) guidelines*, and use a Levothyroxine solution as reference product. The bioavailability of the Levothyroxine sodium tablet formulation THYROHORMONE/Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3 mg/100 ml) under fasting conditions were compared in an open, randomized, single-dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=15/9, mean age=32.9+/-7.4yr) participated in the study. Bioavailability was assessed by pharmacokinetic parameters such as the area under plasma concentration-time curve from time zero up to the measurable last time point (AUC(last)) and the maximum plasma concentration (Cmax). Heparinized venous blood samples were collected pre-dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples was assayed by a validated electrochemiluninescent immunoassay technique. Statistical analysis showed that the post-dose thyrotropin-stimulating hormone (TSH) levels decreased significantly (p<0.05). Regarding Levothyroxine (T4), the point estimate of the test formulation to the reference formulation ratios (T/R) for AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93 with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L-thyronine (T3), the point estimate for the T/R ratios of AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits (0.92, 0.95), respectively. The 90% confidence limits for the pharmacokinetic parameters AUC(last) and Cmax lie within the acceptance limits for bioequivalence (0.80, 1.25), for both T3 and T4.

Labeling of monoclonal antibodies with 153Sm for potential use in radioimmunotherapy.

The labeling of a monoclonal (anti-CEA) and a polyclonal (IgG) antibody with 153Sm has been investigated, using the bicyclic anhydride of DTPA (cDTPAa) as the chelating agent. The radiochemical study was performed using a combination of radioanalytical techniques (gel filtration, HPLC, ITLC-SG and SDS-PAGE). Optimization of factors affecting labeling (pH, Ab, Ab-DTPA concentration, etc.) leads to a labeling yield higher than 90%. Biodistribution studies in normal mice showed slow blood clearance and high uptake into the liver, kidney and lungs.

Diminutive polyps of large bowel should be an early target for endoscopic treatment.

BACKGROUND AND AIMS: Aim of the present study is to ascertain the importance of diminutive colorectal polyps and define the need for removal according to their characteristics and malignant potential. PATIENTS AND METHODS: A total of 4,723 patients who underwent colonoscopy were evaluated and 624 patients with 826 polyps were recorded. There were 352 patients with 443 diminutive polyps, studied according to their distribution. Of these, 371 were removed, histologically examined and correlated to patient characteristics and occurrence of synchronous neoplasms. RESULTS: Of the right colon polyps, 81/115 were diminutive, versus 362/711 of the left colon (p<0.0001). Adenomas were more common in patients over 50 years of age, (p<0.0001). In all colonic segments, diminutive adenomas prevailed over hyperplastic polyps, whereas the proportion of diminutive adenomas predominated in the right colon (p=0.0015). Adenomas were classified as tubular 39%, tubulovillous 55.7% and villous 5.3%. The degree of dysplasia was mild in 45.5%, moderate in 51% and severe in 3.5%. The prevalence of synchronous neoplasms was 37.4%. They were more frequently found in males over 50 years of age and in patients with diminutive adenomas compared to those with diminutive hyperplastic polyps (p=0.0078). CONCLUSIONS: The majority of right colon polyps are diminutive. The proportion of diminutive adenomas is higher in patients over 50 years and in the right vs left colon. Diminutive polyps should be removed taking into account the high prevalence of adenomas with a villous component and their significant degree of dysplasia.

Mean platelet volume: a useful marker of inflammatory bowel disease activity.

OBJECTIVES: We investigated whether the mean platelet volume would be a useful marker in the evaluation of inflammatory bowel disease activity. METHODS: Complete blood count, C-reactive protein, erythrocyte sedimentation rate, serum thrombopoietin and erythropoietin, plasma beta-thromboglobulin, and platelet factor 4 were measured in 93 patients with ulcerative colitis, 66 patients with Crohn's disease, and 38 healthy blood donors. Disease activity was assessed by the Clinical Colitis Activity Index in patients with ulcerative colitis and by the Crohn's Disease Activity Index in patients with Crohn's disease. RESULTS: Mean platelet count was increased in patients with active compared to inactive ulcerative colitis (p < 0.05), and in patients with active compared to inactive Crohn's disease (p = 0.0002) or healthy controls (p < 0.0001). On the other hand, mean platelet volume was significantly decreased in patients with active compared to inactive ulcerative colitis (p = 0.02) or healthy controls (p < 0.0001), and in patients with active compared to inactive Crohn's disease (p = 0.0005) or healthy controls (p < 0.0001). Mean platelet volume was inversely correlated with the white blood cell count (r = -0.17, p = 0.02), C-reactive protein (r = -0.46, p = 0.009) and erythrocyte sedimentation rate (r = -0.28, p = 0.008). No significant correlations were found between mean platelet volume and serum thrombopoietin or erythropoietin levels; however, a strong negative correlation between mean platelet volume and beta-thromboglobulin (r = -0.34, p < 0.0001) and platelet factor 4 (r = -0.30, p = 0.0002) was observed. CONCLUSIONS: Mean platelet volume is significantly reduced in active inflammatory bowel disease and is negatively correlated with the known inflammatory bowel disease activity markers and the platelet activation products. We propose that mean platelet volume provides a useful marker of activity in inflammatory bowel disease.

Idiopathic fibrosing pancreatitis and Crohn's disease: an interesting association.

Idiopathic fibrosing pancreatitis is an uncommon condition in children and adolescents of unknown aetiology. This syndrome has been reported in 36 cases so far. To our knowledge none of these cases was definitively associated with Crohn's disease. In this report we describe a young female patient who developed Crohn's disease of the colon 5 years after having been diagnosed with idiopathic fibrosing pancreatitis. The differential diagnosis between this syndrome associated with Crohn's disease and pancreatic Crohn's disease or fibrosing colonopathy, an entity related to pancreatic enzyme therapy, is discussed.

Radioimmunoscintigraphy and radioimmunotherapy in cancer: principles and application.

Radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) are recent approaches in the diagnosis and treatment of cancer. They take advantage of the antibody specificity of tumor surface antigens and of the emitted radiation from suitable radioisotopes, as a means of imaging (RIS) or therapy (RIT). Research into RIS and RIT radiolabelled agents remains an ongoing process. Principles governing the choice of radionuclides, labelling protocols, antibody suitability, and optimization of "tumor to normal tissue ratios" are the same for both RIS and RIT. The investigational stages of the labelled product, prior to clinical application, are also the same. These stages include radiochemical and radiobiological evaluation as well as determination of immunoreactivity. Furthermore, RIS may be considered as the first stage in development, before progressing on to RIT. Differences between RIS and RIT are associated with the application of each technique, that is, the type of radiation emitted by the isotope, dosage regimens, haematopoetic toxicity and the appearance of human antimurine antibody response (HAMA). RIS has found widespread clinical application, detecting a variety of tumors. However, its potential lies in patient management and in detecting metastases. On the other hand RIT is still in its infancy. It appears promising, and for the moment is used as a complementary technique to surgery and/or chemotherapy in clinical trials on cancer treatment. Finally, incorporation of these basic principles arising from past experiences, into the design of RIT trials improve responses.

Elevated thrombopoietin serum levels in patients with inflammatory bowel disease.

OBJECTIVES: Elevated platelet count is a well recognized marker of inflammatory bowel disease (IBD) activity. Thrombopoietin (TPO) is a critical cytokine in the physiological regulation of thrombopoiesis. The aim of this study was to investigate the serum levels of endogenous TPO in patients with IBD, the relationship between platelet counts and TPO levels, and the correlation of TPO with the clinical characteristics of the patients. METHODS: TPO levels in 40 patients with Crohn's disease (CD), 63 patients with ulcerative colitis (UC), and in 42 healthy blood donors were assessed by ELISA. Platelet and white blood cell counts as well as C-reactive protein, and erythrocyte sedimentation rate were measured. RESULTS: TPO levels were significantly elevated in patients with CD (mean 124.3 +/- SD 58.0 pg/ml, p < 0.0001) and in patients with UC (mean 152.2 +/- SD 142.3 pg/ml, p < 0.0001), compared to controls (mean 53.4 +/- SD 45.7 pg/ml). TPO levels remained significantly elevated in remission (mean 144.7 +/- SD 131.1 pg/ml, p < 0.0001 compared to controls). Platelets were significantly elevated only in active CD, being normal in inactive disease as well as in all patients with UC. There was no significant correlation between TPO levels and various clinical characteristics of patients with IBD. No significant correlation was found between TPO levels and either platelet counts or white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSIONS: TPO levels are increased in IBD, irrespective of disease activity, platelet counts, and clinical characteristics of the patients. These observations indicate that TPO, apart from being a platelet producer, might have additional functions, probably related to the procoagulant state of IBD.

Oral administration of recombinant human granulocyte macrophage colony-stimulating factor in the management of radiotherapy-induced esophagitis.

Radiation-induced esophagitis often results in treatment interruption, which may severely affect the probability of control of the local disease in patients undergoing chest radiotherapy (RT). No effective regimen that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of oral mucosal healing using topical recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) has been reported, the mechanism of such an interaction remains obscure. Effective topical application of rhGM-CSF for the treatment of radiation-induced esophagitis has never been reported in the past. In pharmacological studies, we observed that glycerol exerts a remarkable stabilizing effect on rhGM-CSF immunoreactivity. After studying the kinetics of esophageal emptying with nuclear imaging, we proposed a rhGM-CSF regimen that could be applied for topical treatment of esophagitis during RT. The regimen was applied for 5 consecutive days in a cohort of 36 patients undergoing chest RT, immediately after the documentation of grade 3 esophagitis. RT was not interrupted. Mucosal biopsies were performed endoscopically and examined immunohistochemically. Regression of dysphagia to grade 0/1 was observed in 19 of 36 (52%) patients, whereas grade 2 dysphagia persisted in 12 of 36 (33%) patients. Progression of dysphagia was seen in 5 of 36 (14%) patients. Recurrence of severe esophagitis within 5-8 days after rhGM-CSF therapy was observed in 7 of 31 (22%) patients with initial response to rhGM-CSF. Four of these patients presented significant improvement of symptomatology after additional rhGM-CSF medication. In immunohistochemical studies, active intraepithelial neovascularization and thymidine phosphorylase and vascular endothelial growth factor overexpression were observed in the damaged epithelium, which was not accompanied by macrophage or neutrophil infiltration. We conclude that rhGM-CSF topical therapy (p.o. administration) exerts a significant therapeutic effect against RT-induced esophagitis. The rhGM-CSF mucosa healing effect is probably due to its direct angiogenic activity and/or to the potentiation of the activity of other angiogenic factors released by the damaged epithelium.

Carcinoma of the ampulla of Vater in Crete. A clinical and ERCP registry over eight years.

BACKGROUND: Carcinoma of the ampulla of Vater is an infrequent tumor that can be diagnosed, early. PATIENTS AND METHODS: Twenty-four patients with histologically proven carcinoma of the ampulla of Vater were retrospectively studied and their data were analyzed. RESULTS: Most common presenting symptoms were jaundice (67%), weight loss (58%), fever and pain (54%). Endoscopic biopsies which were taken in 19 patients revealed carcinoma or dysplasia in 15 patients and were normal for in the rest. Twelve patients were treated with a Whipple's resection, 5 with local resection, 2 with palliative surgery and 2 received a stent endoscopically. During a mean follow-up period of 25 months, (range 1-82) 12 deaths were noted, and one patient was lost during follow-up. CONCLUSIONS: Presenting symptoms, endoscopic and histological findings were similar as in other series. The contribution of duodenoscopy, ERCP and endoscopic biopsy is essential for diagnosis but endoscopic biopsies may be misleading.