Role of cytological and ultrasonographic features in predicting the risk of malignancy in thyroid nodules with indeterminate cytology.

AIM: The aim of this paper was to examine the diagnostic value of several cytological and ultrasonographic features in predicting malignancy in thyroid follicular neoplasms. METHODS: The sample of the study consisted of 145 patients, who have had the diagnosis of follicular neoplasm on US guided fine-needle aspiration (FNA), and had undergone thyroidectomy. The cytological slides and the ultrasonographic images were reviewed, and several ultrasonographic and cytological features were evaluated and correlated with final histology. RESULTS: Histological diagnosis of malignancy was obtained in 14.5% of the patients, papillary carcinoma being the most frequent (66% of malignancies). The cytological and ultrasonographic features that have been associated with malignancy were: micro-fragments (P<0.00001), overlapping (P<0.005), hypercellularity (P<0.009), micronucleoli (P<0.013), atypical features (P<0.027), nodule size larger than 2 cm (P<0.029) and micro-calcifications (P<0.0002). Using the features that were statistically independent ones, which included two cytological features: micro-fragments and micronuclei, and one ultrasonographic feature: micro-calcifications, a statistical model for predicting malignancy was constructed. According to this model, it was found that the risk for malignancy is 2.65% in the absence of the three parameters, and amounts to 93.93% in the presence of all three of them. CONCLUSION: In a thyroid follicular neoplasm, the cytological and ultrasonographic features that were associated with malignancy were: micro-fragments, overlapping, hypercellularity, micronucleoli, atypical features, nodule size larger than 2 cm and micro-calcifications. In an attempt to predict malignancy, we proposed a simple statistical model using only three features derived from cytological and ultrasonographic tests.

B cell-activating factor enhances interleukin-6 and interleukin-10 production by ODN-activated human B cells.

We aim to investigate the additive value of B cell-activating factor (BAFF) when added to oligodeoxynucleotides (ODN)-activated B cells with respect to TLR-9, CD69, MHC-II expression, IL-6 and IL-10 secretion and B cell cycling. Therefore, B cells from healthy individuals were incubated under the following conditions: (1) B cells with medium, (2) B cells with ODN 0.5 µm, (3) B cells with BAFF 20 µm and (4) B cells with both ODN 0.5 µm and BAFF 20 µm. We found that addition of BAFF did not enhance the expression of TLR-9, CD69 and MHC-II in ODN-activated B cells. Incubation of B cells with BAFF and ODN together leads to a marked elevation of IL-6 and IL-10 levels compared to ODN alone. Synthesis and mitosis were higher in B cells stimulated by BAFF than in B cells stimulated by ODN. These findings suggest that both BAFF and TLR-9 contribute independently to B cell function.

Normal fetal salivary glands at 14-16 weeks of gestation as observed by transvaginal ultrasound imaging.

OBJECTIVES: Absence or congenital anomalies of the parotid glands are associated with significant long-term morbidity. To date there are no published data on ultrasonographic detection of these defects in early pregnancy. We set out to demonstrate and measure the fetal parotid and submandibular salivary glands at 14-16 weeks using transvaginal ultrasound imaging. METHODS: During a routine fetal anomaly detection scan in 30 consecutive patients, an attempt was made to examine the fetal parotid and submandibular glands. The fetal head was scanned in transverse sections just below the fetal ears, and the area of the parotid and submandibular glands was inspected. The examination time was not prolonged for the purpose of measuring the salivary glands. The fetal biparietal diameter and the femur length were also documented. RESULTS: The median gestational age was 15.4 (range, 14.4-16.5) weeks. In all 30 patients examined, at least one pair of parotid and submandibular glands was clearly visualized and measured. In seven patients the parotid and submandibular glands were visualized on both sides. The median length of the parotid gland was 7.5 (range, 5.5-11.5) mm and that of the submandibular gland was 5.4 (range, 3.7-8.5) mm. CONCLUSIONS: The fetal salivary glands can be demonstrated by transvaginal ultrasound imaging at 14-16 weeks of gestation. This is the first reported study presenting the normal values of salivary gland measurements, which may be important in detecting fetuses with congenital absence or other malformations of the glands.

Liver transplantation exceeding UCSF criteria: case report of a late recurrence treated by surgery and review of the literature.

INTRODUCTION: Treatment of a recurrence of hepatocellular carcinoma (HCC) after liver transplantation. Surgery has seldom been considered in such a situation because HCC recurrences are generally considered as a systemic disease. PATIENT AND METHODS: We describe a 47-year-old male patient who underwent liver transplantation in October 1999 for HCC exceeding the Milan and University of California, San Francisco (UCSF), criteria. RESULTS: In 2007 (8 years after liver transplantation), the patient developed a cervical bone metastasis treated by surgery. In April 2008, HCC had disseminated to hepatic pedicle lymph nodes. An extended hepatic pedicle lymphadenectomy was then performed. Today, our patient is doing well, without signs of recurrence. DISCUSSION: The risk of developing a tumor recurrence is the main argument against expanding the UCSF criteria. In case of an HCC recurrence, various treatments ranging from a change in the immunosuppression regimen to chemotherapy have been proposed. Surgical treatment has rarely been envisaged in the treatment of HCC recurrences because of the technical difficulties and the frequent dissemination of cancer.

Acute abdomen from chylous peritonitis: a surgical diagnosis. Case report and literature review.

Acute accumulation of chyle in the peritoneal cavity is a rare event (less than 100 cases are described in the literature) and is to be distinguished from chylous ascites, which is characteristically chronic. It is frequently idiopathic, and diagnosis is usually made at laparotomy, whenever signs of acute peritonitis impose it. Peritoneal toilette and drainage are the only treatment required, and the prognosis is excellent. We describe the case of a 69-year-old man who underwent emergency surgery for acute peritonitis. Approximately 0.5 liters of chyle were found free in the peritoneal cavity at laparoscopic exploration, without any important underlying pathological condition apart from a blood vessel congestion in the bowel resembling angiomatosis. Laparotomic conversion, peritoneal toilette and drainage, with postoperative low-fat diet, were the pursued treatments. Two years after discharge, chemistry and clinics are normal, without evidence of associated disease or recurrence.

Experiences of engineering Grid-based medical software.

OBJECTIVES: Grid-based technologies are emerging as potential solutions for managing and collaborating distributed resources in the biomedical domain. Few examples exist, however, of successful implementations of Grid-enabled medical systems and even fewer have been deployed for evaluation in practice. The objective of this paper is to evaluate the use in clinical practice of a Grid-based imaging prototype and to establish directions for engineering future medical Grid developments and their subsequent deployment. METHOD: The MammoGrid project has deployed a prototype system for clinicians using the Grid as its information infrastructure. To assist in the specification of the system requirements (and for the first time in healthgrid applications), use-case modelling has been carried out in close collaboration with clinicians and radiologists who had no prior experience of this modelling technique. A critical qualitative and, where possible, quantitative analysis of the MammoGrid prototype is presented leading to a set of recommendations from the delivery of the first deployed Grid-based medical imaging application. RESULTS: We report critically on the application of software engineering techniques in the specification and implementation of the MammoGrid project and show that use-case modelling is a suitable vehicle for representing medical requirements and for communicating effectively with the clinical community. This paper also discusses the practical advantages and limitations of applying the Grid to real-life clinical applications and presents the consequent lessons learned. CONCLUSIONS: The work presented in this paper demonstrates that given suitable commitment from collaborating radiologists it is practical to deploy in practice medical imaging analysis applications using the Grid but that standardization in and stability of the Grid software is a necessary pre-requisite for successful healthgrids. The MammoGrid prototype has therefore paved the way for further advanced Grid-based deployments in the medical and biomedical domains.

Effect of positional changes of anatomic structures on upper airway dilating muscle shortening during electro- and chemostimulation.

Positional changes of anatomic structures surrounding the upper airway are known to affect pharyngeal mechanics and collapsibility. We hypothesized that these alterations also affect the ability of the upper airway dilator muscles to enlarge the pharynx by altering their ability to shorten when activated. Using sonomicrometry, we evaluated in seven anesthetized dogs the effects of changes in tracheal and head position on the length of the genioglossus (GG) and the geniohyoid (GH) and the effects of these positional changes on the magnitude of shortening of the two muscles in response to electro- (ES) and chemostimulation (CS). Caudal traction of the trachea lengthened the GG and GH in all dogs, whereas cranial displacement of the trachea and flexion of the head to a vertical position shortened the muscles. Compared with the magnitude of ES-induced shortening in the neutral position, ES-induced shortening of the GG was 144.7 +/- 14.6, 49.3 +/- 4.3, and 33.5 +/- 11.6% during caudal and cranial displacement of the trachea and during head flexion, respectively. Similar effects of the positional changes were found for the GH, as well as for both muscles during respiratory stimulation with P(CO2) of 90 Torr at the end of CO(2) rebreathing, although inspiratory muscle shortening during CS reached only one-quarter to one-third of the magnitude observed during ES. We conclude that positional alterations of anatomic structures in the neck have a dramatic effect on the magnitude of shortening of the activated GG and GH, which may reduce substantially their ability to protect pharyngeal patency.

Correlation between levels of tumour necrosis factor-alpha and levels of pH, glucose, and lactate dehydrogenase in parapneumonic effusions.

OBJECTIVES: This study was undertaken to investigate the correlation, which has not been previously investigated, between levels of tumour necrosis factor-alpha (TNF) and levels of pH, glucose, and lactate dehydrogenase (LDH) in pleural fluid of patients with uncomplicated parapneumonic effusion (UCPPE), and patients with complicated parapneumonic effusion (CPPE). METHODS: Using a commercially-available high sensitivity ELISA kit, levels of TNF were measured in pleural fluid of patients with UCPPE (n = 23), and CPPE (n = 15), and were compared with levels of pH, glucose, and LDH in these two groups. RESULTS: The mean +/- SD values of pleural fluid TNF, pH, glucose, and LDH in the UCPPE group were 11.05 +/- 7.65 pg/ml, 7.41 +/- 0.08, 125 +/- 48 mg/dl, and 306 +/- 182 IU/l, respectively. In the CPPE group the values were 56.07 +/- 28.5 pg/ml, 6.82 +/- 0.25, 42 +/- 36 mg/dl, and 2096 +/- 1916 IU/l, respectively. The only significant correlation, which was negative, was found between levels of TNF and pH in the CPPE group (r = -0.62, P = 0.01). Levels of pleural fluid TNF and LDH were significantly higher, and levels of glucose were significantly lower in the CPPE group than in the UCPPE group (P < 0.0001). CONCLUSIONS: This study demonstrates, for the first time that TNF levels correlate inversely with levels of pH in pleural fluid of patients with CPPE but not of patients with UCPPE. This correlation may, in part, explain the pathophysiology of the pleural complications which occur in the presence of CPPE.

Resolving clinicians' queries across a Grid's infrastructure.

OBJECTIVES: The past decade has witnessed order of magnitude increases in computing power, data storage capacity and network speed, giving birth to applications which may handle large data volumes of increased complexity, distributed over the internet. METHODS: Medical image analysis is one of the areas for which this unique opportunity likely brings revolutionary advances both for the scientist's research study and the clinician's everyday work. Grids [1] computing promises to resolve many of the difficulties in facilitating medical image analysis to allow radiologists to collaborate without having to co-locate. RESULTS: The EU-funded MammoGrid project [2] aims to investigate the feasibility of developing a Grid-enabled European database of mammograms and provide an information infrastructure which federates multiple mammogram databases. This will enable clinicians to develop new common, collaborative and co-operative approaches to the analysis of mammographic data. CONCLUSION: This paper focuses on one of the key requirements for large-scale distributed mammogram analysis: resolving queries across a grid-connected federation of images.

Hyponatremia during therapy with amiodarone.

We describe an elderly woman who presented with significant hyponatremia caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during therapy with amiodarone. The hyponatremia resolved after discontinuation of the drug and did not recur during a follow-up period of 6 months. Such an association has previously been reported only once in the medical literature. Since severe hyponatremia can produce significant neurologic damage and is associated with a high mortality rate, clinicians should be aware that this complication may occur during amiodarone therapy.

Assessment of hyperacute rejection in a rat-to-primate cardiac xenograft model.

We studied a rat-to-cynomolgous monkey model for xenotransplantation of vascularized organs and found that a rat heart was rejected in 5.5 +/- 1.4 min (n = 10). This hyperacute rejection (HAR) was consistent with kinetic experiments in vitro that showed damage to rat endothelial cells (ECs) after 3 min of incubation with primate serum. Histopathology and ultrastructural analysis of rejected hearts showed marked EC damage and early adherence of platelets and polymorphonuclear leukocytes to the endothelium. Immunohistochemical analysis revealed deposition along endothelial surfaces of IgG, IgM, and complement (C) components of the classical but not the alternative pathway, suggesting that, as in the pig-to-primate model, HAR is mediated by the binding of recipient xenogeneic natural antibodies and C activation. The effect of C depletion on xenograft survival was evaluated in two recipients that were treated with cobra venom factor (CVF). CVF caused complete C inactivation, demonstrated by lack of serum hemolytic activity and C-dependent EC cytotoxicity at engraftment and until the animals died. The rat cardiac transplants survived for at least 9 hr and 77 hr. Histology showed massive interstitial hemorrhage, edema, and cellular infiltration with scanty fibrin deposits. These results in CVF-treated recipient monkeys indicate that C activation mediates the development of HAR in this rat-to-primate model. We suggest that the model may be of interest as an alternative to the more expensive and time-consuming pig-to-primate model for testing the efficacy of transgenic modification of donor organs to prolong xenograft survival and for studying mechanisms of discordant xenograft rejection.

Age-related changes in upper airway muscles morphological and oxidative properties.

Obstructive sleep apnea (OSA) is a common disorder of the middle aged and elderly. It results from the decrease in upper airway muscle (UAM) tone that occurs during sleep. It is unclear whether age-related changes in UAM could constitute a contributory mechanism to the increased prevalence of OSA with increasing age, and previous papers evaluating the effects of aging on UAM in rats reported conflicting results. In the present study, we compared, in four age groups of Wistar rats (6-24 months), fiber-type distribution, mean cross-sectional fiber area and succinate dehydrogenase optical density of dilating and non-dilating UAM, and the diaphragm. Succinate dehydrogenase optical density, a marker of oxidative capacity, decreased significantly after the age of 6 months in all muscles (except for the sternohyoid), particularly in the genioglossus, the main tongue protrudor. In this muscle, we also found a significant decrease in type IIa and an increase in IIb fibers after the age of 18 months. Age-related changes in fiber-type distribution in other muscles were mostly insignificant. Dilating UAM could not be distinguished from their non-dilating neighboring muscles by their histochemical properties or aging-related changes. The aging-related changes observed in the present study may decrease UAM endurance, particularly that of the main tongue protrudor, the genioglossus.

Localized Wegener's granulomatosis relapsing as diffuse massive intra-alveolar hemorrhage.

In a 75-year-old patient presenting with a solitary pulmonary mass, a localized form of Wegener's granulomatosis was diagnosed after lobectomy. In the absence of extrapulmonary manifestations and after a benign postoperative course, the patients was discharged without medical treatment. Three months later, diffuse alveolar hemorrhage developed abruptly, necessitating mechanical ventilation, and was followed by cardiac complications and a fatal outcome. This case and another previously reported strongly suggest the need for medical treatment in patients with a localized form of pulmonary Wegener's granulomatosis, even when complete remission after surgical resection of the lung lesion seems to have been achieved.

Tumour necrosis factor alpha in the diagnostic assessment of pleural effusion.

We investigated the role of tumour necrosis factor-alpha (TNF) in the evaluation of pleural effusion aetiology. Using a commercially-available ELISA kit, concentrations of TNF were measured in the serum and pleural fluid of patients with malignant effusions (n=19), uncomplicated parapneumonic effusions (n=13), and exudative (n=13) and transudative (n=13) effusions due to congestive heart failure (CHFex and CHFtr, respectively). Serum TNF did not differ significantly between the four groups (p>0.05). In the group with malignancy, pleural fluid TNF was significantly higher than in the other groups (p<0.001), which were not significant different from each other (p>0.05). However, a considerable overlap between all four groups was found. Pleural fluid TNF was significantly higher than serum TNF in the malignant and the uncomplicated parapneumonic groups (p<0.001), and there was a significant positive correlation between serum TNF and pleural fluid TNF in the group with uncomplicated parapneumonic effusion (r=0.7, p<0.005), in the group with CHFex (r=0.54, p<0.01), and in the group with CHFtr (r=0. 8, p<0.005), but not in the group with malignancy. Pleural fluid TNF:serum TNF (TNF ratio) was significantly higher in the malignancy group than in the other groups (p<0.001); no significant difference was found between the other three groups (p>0.05). At an optimal cut-off point of 2.0 for TNF ratio, determined by ROC analysis for discrimination between malignant and non-malignant groups, sensitivity was 84%, specificity 90%, and total accuracy 88% (p<0. 0001). TNF ratio might be helpful in the diagnostic assessment of exudative pleural effusion.

Coma and seizures due to severe hyponatremia and water intoxication in an adult with intranasal desmopressin therapy for nocturnal enuresis.

Desmopressin, a synthetic analogue of the antidiuretic hormone, is an effective medication for primary nocturnal enuresis for both children and adults. Its safety is well established. Although it has a favorable side effect profile, because of its pharmacological effect, intranasal desmopressin can rarely induce water intoxication with profound hyponatremia if given without adequate restriction of water intake. The authors describe an adult patient with water intoxication and severe hyponatremia accompanied by loss of consciousness and seizures after 2-day intranasal administration of desmopressin. The present and the previously reported cases emphasize the need for greater awareness of the development of this serious and potentiallyfatal complication. In addition, to adjust the drug to the lowest required dosage, adequate restriction of water intake is recommended, and serum levels of sodium should be measured periodically to allow for early detection of water intoxication and hyponatremia.

Severe life-threatening hyponatremia during paroxetine therapy.

Hyponatremia secondary to the syndrome of inappropriate secretion of antiduretic hormone (SIADH) is an uncommon complication of treatment with the antidepressants the selective serotonin reuptake inhibitors (SSRIs). These effective anti-depressant agents are becoming widely used because of their favorable side effect profile and their safety in overdose. Although most reports have implicated fluoxetine in causing hyponatremia, there have also been a few reports of hyponatremia associated with paroxetine. We describe an elderly patient with severe life-threatening hyponatremia in association with paroxetine therapy. The present case and the others previously reported emphasize the need for greater awareness of the development of this serious and potentially fatal complication, and suggest that serum sodium concentration should be measured periodically in elderly patients soon after they start taking any agent of the SSRIs, especially during the first 2 to 4 weeks of treatment.

Role of cytokines in rheumatoid arthritis.

Cytokines have emerged as crucial players in mediating synovial inflammation in the rheumatoid joint, where the local and systemic production of cytokines appears to account for most of the pathologic and clinical manifestations of rheumatoid arthritis. Among the cytokines, tumor necrosis factor-alpha and interleukin-1 are considered to be of great importance in the pathogenesis of the disease. Other pro-inflammatory cytokines in rheumatoid arthritis are interleukin-6, interleukin-8, leukemia inhibitory factor, granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta The potent antiinflammatory cytokines interleukin-4 and interleukin-10, which are powerful inhibitors of most of these mediators, seem to be promising agents and candidates for an optimal approach to treatment.

Bowel perforation due to gastrointestinal autonomic nerve tumour associated with neurofibromatosis type 1.

Gastrointestinal autonomic nerve (GAN) tumours form a distinct subcategory of gastrointestinal stromal tumours, and are thought to originate from the enteric autonomic plexus. To date, a total of 45 cases have been documented in the literature; a few of these cases were associated with neurofibromatosis type 1 (NF-1). Bowel perforation due to other gastrointestinal stromal tumours has been reported only twice, but never in association with a GAN tumour. We describe a 40-year-old woman with NF-1 who had bowel perforation due to a GAN tumour. The patient underwent radical surgical resection and remained tumour free for at least 4 years, which may indicate a good prognosis.