Black holes and high levels of neurofilaments in glial fibrillary acidic protein - astrocytopathy: a case report.

BACKGROUND AND PURPOSE: Glial fibrillary acidic protein (GFAP) is an intracellular protein of the astrocytic cytoskeleton. Recently, autoantibodies to GFAP detected by cell-based assay in cerebrospinal fluid (CSF) or serum have been implicated in cerebral astrocytopathy, presenting predominantly with autoimmune meningoencephalomyelitis. However, the phenotypic spectrum, prognosis and therapeutics of this new entity remain to be elucidated. METHODS: Herein, we report radiological, CSF and serological findings during disease exacerbation and remission, from a patient with autoimmune GFAP astrocytopathy, presenting as an immunotherapy responsive GFAP IgG-associated meningoencephalomyelitis. RESULTS: Brain and spine magnetic resonance imaging revealed meningeal enhancement, T2 hyperintensities, black holes, significant sulci widening and spinal atrophy. In addition, high levels of neurofilaments (NfL) and GFAP were also identified during disease exacerbation, consistent with the appearance of the black holes. CONCLUSIONS: To date, black holes and atrophy have never been reported before in autoimmune GFAP astrocytopathy. These findings, combined with the high levels of GFAP and NfL, suggest the existence of an underlying neurodegenerative mechanism in addition to the known inflammatory response. Further studies are needed to elucidate the pathomechanism of GFAP-astrocytopathies.

Dermoscopic features of melanocytic skin lesions in Greek children and adolescents and their association with environmental factors and skin types.

BACKGROUND: Acquired naevi often present in childhood and increase in number and size during early and middle life. As naevi represent potential mimickers of melanoma, the knowledge of their epidemiologic and morphologic characteristics is essential. OBJECTIVE: In this study, we intend to determine the prevalence of dermoscopic patterns of naevi, as well their association with environmental and constitutional factors. METHODS: Cross-sectional data derived from a population-based cohort of children and adolescents aged 6-18 years, from 12 different schools in Thessaloniki, Greece. For each participant, a consent form and a questionnaire were completed, which included data on age, sex, phototype, sun sensitivity, sun exposure, sunscreen use and previous sunburn history. All naevi, their body distribution, and their dermoscopic patterns were recorded. RESULTS: Two thousand and five hundred and five (2505) subjects were enrolled into the study (47.8% males and 52.2% females). The mean number of MN counted in a single person was 29.11 (SD = ±23.863). TNC increased continuously with higher age. Males were found to have a significantly increased number on the trunk (11.7 ± 11.2 and 10.0 ± 8.7, respectively, P < 0.001) and face and neck (6.2 ± 5.3 and 5.1 ± 4.3, respectively, P < 0.001) while females on the upper (10.3 ± 10.1 and 9.3 ± 9.4, respectively, P = 0.008) and lower extremities (2.8 ± 3.4 and 2.5 ± 3.2, respectively, P = 0.008). Globular pattern was the most frequent dominant pattern in lower age groups, and its percentage fell as age increased. On the contrary, the reticular pattern was more often documented in individuals in adolescence. CONCLUSION: This first study of MN in our young population aims to be the basis of further investigation for the MM preventive policy of our state.

CARDIOCARE: An integrated platform for the management of elderly multimorbid patients with breast cancer therapy induced cardiac toxicity.

Breast cancer (BC) remains the most diagnosed cancer in women, accounting for 12% of new annual cancer cases in Europe and worldwide. Advances in surgery, radiotherapy and systemic treatment have resulted in improved clinical outcomes and increased survival rates in recent years. However, BC therapy-related cardiotoxicity, may severely impact short- and long-term quality of life and survival. This study presents the CARDIOCARE platform and its main components, which by integrating patient-specific data from different categories, data from patient-oriented eHealth applications and wearable devices, and by employing advanced data mining and machine learning approaches, provides the healthcare professionals with a valuable tool for effectively managing BC patients and preventing or alleviating treatment induced cardiotoxicity.Clinical Relevance- Through the adoption of CARDIOCARE platform healthcare professionals are able to stratify patients for their risk for cardiotoxicity and timely apply adequate interventions to prevent its onset.

Rates of lipid fluxes in adipose tissue in vivo after a mixed meal in morbid obesity.

OBJECTIVE: Although insulin resistance in obesity is established, information on insulin action on lipid fluxes, in morbid obesity, is limited. This study was undertaken in morbidly obese women to investigate insulin action on triacylglycerol fluxes and lipolysis across adipose tissue. SUBJECTS AND DESIGN: A meal was given to 26 obese (age 35+/-1 years, body mass index 46+/-1 kg m(-2)) and 11 non-obese women (age 38+/-2 years, body mass index 24+/-1 kg m(-2)). Plasma samples for glucose, insulin, triglycerides and non-esterified fatty acids (NEFAs) were taken for 360 min from a vein draining the abdominal subcutaneous adipose tissue and from the radial artery. Adipose tissue blood flow was measured with (133)Xe. RESULTS: In obese vs non-obese: (1) Arterial glucose was similar, but insulin was increased (P=0.0001). (2) Adipose tissue blood flow was decreased (P=0.0001). (3) Arterial triglycerides (P=0.0001) and NEFAs (P=0.01) were increased. (4) Lipoprotein lipase was decreased (P=0.0009), although the arteriovenous triglyceride differences were similar. (5) Veno-arterial NEFA differences across the adipose tissue were similar. (6) NEFA fluxes and hormone-sensitive lipase-derived glycerol output from 100 g adipose tissue were not different. (7) Total adipose tissue NEFA release was increased (P=0.02). CONCLUSIONS: In morbid obesity: (a) hypertriglycerinemia could be attributed to a defect in the postprandial dynamic adjustment of triglyceride clearance across the adipose tissue, partly caused by blunted BF; and (b) postprandially, there is an impairment of adipose tissue to buffer NEFA excess, despite hyperinsulinemia.

Approaches to management of cardiovascular morbidity in adult cancer patients - cross-sectional survey among cardio-oncology experts.

BACKGROUND: In cardio-oncology, a range of clinical dilemmas can be identified where high-quality evidence for management is still lacking. The aim of this project was to study clinical practices and expert approaches to several clinical cardio-oncological dilemmas regarding prediction, prevention and treatment of cardiovascular disease in adult cancer patients. METHODS: A cross-sectional online survey was sent out to internationally renowned experts in the field of cardio-oncology. Participants were selected based on being first or last authors of papers in the field of cardio-oncology, or principal investigators to trials in this field. RESULTS: Topics discussed include, among others, the use of biomarkers for subclinical cardiovascular toxicity, approaches towards primary prevention and follow-up with medication and life-style recommendations, and management of fluoropyrimidine-vasospasm, QTc-prolongation and asymptomatic declines in left ventricular ejection fraction. CONCLUSION: The answers provided in this survey have shed light on expert-based practices in cardio-oncologic dilemmas. Attitudes towards, as well as discrepancies in those dilemmas are presented. Existing discrepancies clearly indicate the need for generation of high-quality data that allows for more evidence-based recommendations in the future.

Intestinal neurofibromatosis and small-bowel adenocarcinoma: a single case study.

OBJECTIVE: Patients with Von Recklinghausen's disease (neurofibromatosis type 1) are at increased risk of developing various tumours. However, the coexistence of neurofibromatosis with small-bowel adenocarcinoma is exceedingly rare. We present an uncommon case of neurofibromatosis type 1, involving the small bowel in a 73-year-old man, who was admitted to our department with signs of acute abdomen. At laparotomy, multiple mesenteric and intramural nodules were seen in the distal ileum. These nodules obstructed ileal lumen, while the intestine wall was perforated in one point. A wide resection of the affected ileum together with all visible nodules in the adjacent mesentery was performed. Histology revealed neurofibromatosis type 1 with malignant transformation to small-bowel adenocarcinoma. The patient had no additional therapy. In a follow-up of 2 years, the patient is very well and there was no recurrence of the disease. We suggest that adenocarcinoma of small bowel should be considered in the evaluation of acute abdominal pain in neurofibromatosis patients.

Psychological condition and quality of life in patients with morbid obesity before and after surgical weight loss.

BACKGROUND: Bariatric surgery results in significant weight loss, improvement or cure of accompanying illnesses, and may lead to important changes in psychological conditions. The aim of this paper is to study the changes in the psychological and emotional lives of patients as well as quality of life during the first 2 years after vertical banded gastroplasty (VBG). METHODS: The study population comprised 59 patients, 45 women (76.3%) and 14 men, between 18 and 64 years old. Patients were asked to complete an SCL-90R questionnaire before VBG. 2 years after VBG, patients were again asked to complete an SCL-90R as well as a BAROS questionnaire. Comparisons were made between loss of weight, alteration in the psychological condition and quality of life postoperatively, within the parameters of sex, age, marital status, level of education, duration of obesity and family history of obesity. RESULTS: Women had a greater degree of depression from obesity than their male counterparts before the procedure (P=0.001), while their postoperative emotional improvement was more marked (P=0.008). The General Mental Health Index was higher in female than male patients (P=0.008). At 2 years after VBG, BMI was significantly reduced (P<0.001). Oversensitivity in personal relationships and anxiety affected patients more both pre- and postoperatively. The averages of all the indexes of the subgroups of the SCL-90R, which relates to psychological condition of patients, showed a statistically significant reduction at 2 years following VBG, indicative of the improvement of the patients' psychosomatic condition. The more weight patients lost, the more their quality of life improved, as evaluated by the BAROS (P<0.001). CONCLUSIONS: The bariatric surgery most satisfactorily improved the patients' psychosomatic condition, as well as their quality of life, during the first 2 years after VBG.

Gastrointestinal complications after vertical banded gastroplasty.

BACKGROUND: Gastric surgical procedures for morbid obesity may have occasional serious complications. The vertical banded gastroplasty according to Mason's technique (VBG) is a common procedure for morbid obesity. The aim of this study is to present the complications in the gastrointestinal (GI) tract after VBG and to discuss their treatment. METHODS: In this study 260 morbidly obese patients (62 males and 198 females) underwent VBG. RESULTS: Complications in the GI tract were encountered as follows: narrowing of the communicating lumen of the two parts of the stomach in four patients, dehiscence of the vertical stomach staple line in three patients, cholelithiasis in 12 patients, gastric perforation in four patients, postoperative fistulas in three patients, serious hepatic failure in one patient, significant gastritis and esophagitis in 32 patients, intestinal obstruction in five patients and frequent prolonged vomiting in 23 patients. The authors attempted to treat all these complications conservatively. In 22 patients, however, a new procedure was necessary. In some cases a partial gastrectomy was necessary. CONCLUSION: VBG is considered to be a satisfactory procedure for weight loss in morbid obesity, but has occasional complications from the GI tract, besides the complications from the other systems. Thus, this procedure should be performed only when absolute indications exist.

Pre- and postoperative psychological characteristics in morbidly obese patients.

BACKGROUND: Quality of life is poor in morbidly obese patients, because of impaired physical and psychosocial functioning. Surgical treatment offers long-term weight reduction and amelioration of most associated comorbidities. Studies of the effect of weight loss on patients' mental well-being are required, because discrimination and psychopathologic consequences represent a heavy burden. PATIENTS AND METHODS: 53 patients were interviewed 48 hours before vertical banded gastroplasty (VBG) by the psychiatric team and completed the self-administered SCL-90-R questionnaire. Correlations of patients' age, educational level, employment, duration of obesity and family conditions were investigated and compared with the degree of obesity 10-12 months postoperatively. 35 patients returned to psychiatric follow-up and completed the same questionnaire, and the various psychopathologic characteristics were compared to the preoperative ones. RESULTS: Females had statistically significant higher scores in all psychopathologic parameters studied; more obvious differences were seen in depression (P < 0.001), paranoid ideation (P < 0.001) and interpersonal sensitivity (P < 0.001). Correlations of several demographic characteristics with the patients' preoperative BMI were negative. 10-12 months following VBG, statistically significant improvement in the parameters of phobic anxiety, obsessions-compulsions, paranoid ideation and interpersonal sensitivity (P < 0.05) were found. CONCLUSION: Pre-existing psychopathology was more obvious among females, and improved significantly following successful weight loss 1 year postoperatively.

Bleeding from the upper gastrointestinal tract after Mason's vertical banded gastroplasty.

BACKGROUND: Gastric bleeding is a rare complication after a vertical banded gastroplasty (VBG). Only a few cases of gastric bleeding after a VBG have been reported, and there is discussion about its etiology. We present two cases of gastric bleeding after a VBG, and discuss the etiology, diagnostic approach and management. METHODS: During the period 1989-98, we treated two cases of gastric bleeding out of 328 morbidly obese patients that underwent a VBG. The first patient was a 36-year-old woman with body mass index (BMI) 61.5. Gastric bleeding occurred on the 7th postoperative day, due possibly to the increased dose of Low Weight Molecular Heparin (LWMH) which was administrated as prophylactic anticoagulation. The second case concerns a 27-year-old man with 54.0 BMI. Gastric bleeding occurred on the 16th postoperative day and was attributed to a stress ulcer. RESULTS: Both patients were treated conservatively successfully. In the first patient, bleeding was stopped when LWMH was discontinued. In the second patient, bleeding was stopped by gastroscopic epinephrine injection in the bleeding spot. CONCLUSIONS: From our cases and review of the literature, gastric bleeding after a VBG is rare, may be treated easily with conservative measures. Tension of the mesh that surrounds the canal between the two compartments, gastric mucosal irritation from the nasogastric tube and postoperative stress ulcer formation are the most frequent causes of this complication.

Ulcerative colitis and acute stroke: two rare complications after Mason's vertical banded gastroplasty for treatment of morbid obesity.

The authors present a very rare case of ulcerative colitis and acute stroke appearing as complications after Mason's vertical banded gastroplasty for treatment of morbid obesity in a 46-year-old man. On the basis of recent studies, the authors attempt to find the correlation of these three diseases and the possible effect of each disease on the appearance of the others. The dilemmas in the treatment of this patient are also described.

Chronic spondyloarthropathy mimicking abdominal disease.

Chronic spondyloarthopathy is a very common disease in the elderly. Its more common symptoms are pain in the waist, sluggishness and stiffness. Sometimes, however, it presents with the symptoms of abdominal disease. In a six year period, we observed 4,172 patients with several surgical diseases. Attentive clinical and laboratory studies of these showed that 112, who presented with abdominal symptoms, in fact, had chronic spondyloarthropathy. These cases are reported here with a brief discussion of the treatment and results.

Skeletal muscle insulin resistance in morbid obesity: the role of interleukin-6 and leptin.

BACKGROUND: Although insulin resistance in obesity is established, the link between excess body fat and skeletal muscle insulin resistance is obscure. The aim of this study was to investigate whether cytokines secreted from the subcutaneous adipose tissue are related to the sensitivity of glucose metabolism to insulin in skeletal muscle. METHODS: A meal was given to 14 obese and 10 non-obese women. Plasma samples were taken for 360 min from a forearm vein and from the radial artery for glucose and insulin measurements. Interleukin-6, leptin, TNFα, resistin and adiponectin were measured preprandially from the radial artery and from the superficial epigastric vein. Forearm blood flow was measured with plethysmography. RESULTS: (1) In obese vs non-obese: (a) Glucose uptake by skeletal muscle was decreased (AUC (0-360)369 ± 55 vs. 877 ± 146 µmol/100 g tissue, p=0.001) (b) arterial interleukin-6 (2.5 ± 0.5 vs. 1 ± 0.1 pg/ml, p=0.013) and subcutaneous venous interleukin-6 (5 ± 0.5 vs. 3.4 ± 0.5 pg/ml, p=0.027) were increased (c) arterial leptin (63 ± 7 vs. 5 ± 0.6 ng/ml, p<0.0001) and subcutaneous venous leptin 80 ± 8 vs. 6.5 ± 0.7 ng/ml, p<0.0001) were increased. (2) Arterial interleukin-6 (p=0.002) and subcutaneous venous interleukin-6 (p=0.014) were negatively associated with forearm glucose uptake in obese. (3) No association was found between leptin and forearm glucose uptake, after correcting with fat mass. CONCLUSIONS: In morbid obesity: (1) Subcutaneous adipose tissue releases interleukin-6 which could then mediate insulin resistance in skeletal muscle. (2) Although there is increased secretion of leptin by the subcutaneous adipose tissue, leptin levels are not correlated to the sensitivity of glucose metabolism to insulin in muscle.

Survival of shigellae in soil.

The survival of four Shigella strains in soil (Sh. sonnei, Sh. boydii, Sh. flexneri and Sh. dysenteriae) was studied under various conditions. Their survival period was tested in two different types of sterile soil at 18-20 degrees C and in one type of soil at 4 and 37 degrees C. This latter type of soil, after enrichment with casaminoacids or (NH4)2HPO4 was also used for testing again the survival of the strains at 18-20 degrees C. Though the initial number of the inoculated microorganisms was quite high (10(7) to 10(8) micr. per g of soil) the survival periods were generally short (6 to 39 days). It was found that their viability depended mainly on the bacterial species and not so much on the type of soil, enriched or not, and the temperature. Thus the survival period in soil was always longer for Sh. sonnei and Sh. boydii and shorter for Sh. flexneri and Sh. dysenteriae. The incubations at 4 degrees C or in enriched soil increased and in 37 degrees C decreased the longevity of the strains but for a few days.

Oral ganciclovir treatment in chronic hepatitis B virus infection: a pilot study.

BACKGROUND/AIMS: Ganciclovir is a nucleoside analogue with an excellent safety record; it is effective against cytomegalovirus infection in both its intravenous and its oral form. Intravenous administration of ganciclovir is active against hepatitis B virus but the efficacy of oral ganciclovir is unknown. The aim of this study was to evaluate the tolerability and primary efficacy in reducing HBV DNA levels and liver enzymes of 2 dosing schedules of oral ganciclovir in HBeAg-positive and -negative patients with chronic hepatitis B. METHODS: Oral ganciclovir was administered to 15 consecutive patients with active chronic hepatitis B (age 43+/-12 years; 73% males; seven HBeAg-positive and eight negative; no cirrhosis) in a pilot, phase I, open-label study. Before treatment, all patients were screened for 8 weeks to ascertain the persistence of biochemical and virological activity, and then randomized to receive 3 g (eight patients), or 6 g (seven patients) of oral ganciclovir daily for 8 weeks; following therapy, they were closely observed for 8 more weeks. RESULTS: Baseline HBV DNA declined by 99% or 2 log10 at the end of treatment (405.0 vs 3.9 MEq/ml, respectively) and in four patients serum HBV DNA became undetectable by the Monitor assay. Oral ganciclovir suppressed HBV equally well in HBeAg-positive and -negative patients, and the 3- and 6-g daily dose regimens were equally effective. The pre-treatment viral load, however, was a determinant of response, with patients in the lowest quartile of baseline HBV DNA levels responding significantly better than those in the upper quartile (3.0 vs 0.6 log10 respectively, p=0.002). Serum alanine aminotransferase levels became normal or declined in most patients. Oral ganciclovir was very well tolerated. Within 8 weeks after stopping medication, a relapse in serum HBV DNA levels occurred in nine of the 15 patients (60%). CONCLUSIONS: These findings suggest that ganciclovir administered orally at a dose of 3 g can achieve sufficient suppression of HBV replication. This dose, and even higher doses, are well tolerated and could be used as an alternative or in combination with other antivirals for the treatment of chronic hepatitis B.

Interferon treatment with or without oral ganciclovir in HBeAg-negative chronic hepatitis B: a randomized study.

The treatment of HBeAg-negative chronic hepatitis B with alpha interferon alone is unsatisfactory. We evaluated the efficacy of combined administration of interferon-a2a (IFN) with oral ganciclovir, a nucleoside analogue. Forty patients with hepatitis B virus (HBV)-DNA-positive/HBeAg-negative chronic hepatitis B, were randomized to receive 4.5 MU IFN thrice weekly, subcutaneously, alone or in combination with 3 g ganciclovir per os daily for 26 weeks and followed for 12 months after treatment. Mean serum HBV-DNA levels decreased by 4.0 log10 in the combination group (from 5 x 106 to 4.8 x 102 copies/ml) and by 2.2 log10 in the interferon group (from 8 x 106 to 4.8 x 104 copies/ml) by quantitative polymerase chain reaction (PCR). HBV-DNA became undetectable in 11 of 20 (55%) and in three of 20 (15%) patients in the two groups, respectively (P=0.02). The alanine aminotransferase levels became normal in all patients receiving combination therapy, compared to 75% of those in the interferon group. After cessation of therapy, HBV-DNA increased or reappeared in all patients with 85% also relapsing biochemically. One year after treatment, three patients in each group (15%) remained in sustained biochemical remission with very low serum HBV-DNA levels (median 15 700 copies/ml). We conclude that, in HBeAg-negative chronic hepatitis B, 6-month combination therapy with oral ganciclovir and IFN is associated with complete biochemical remission in all treated patients and a 4 log10 decrease in serum HBV-DNA levels. The end of treatment efficacy of this combination scheme is far super- ior to that of IFN monotherapy but sustained responses are few. Further studies are warranted to evaluate the efficacy of prolonged combination schemes with nucleoside analogues and IFN, compared to IFN monotherapy.