Thalidomide for the Management of Gastrointestinal Bleeding in a Palliative Care Setting.

BACKGROUND: Palliative care patients frequently present with clinically significant gastrointestinal bleeding. Due to the existence of confounding comorbidities and a remarkably reduced state of general health in many cases, the management of gastrointestinal bleeding in this population is often challenging. SUMMARY: This review summarizes and discusses the role of thalidomide in gastrointestinal bleeding with a special focus on palliative care patients. In addition, an illustrative case report is presented. Thalidomide may be beneficial in gastrointestinal bleeding by exerting antiangiogenic effects. The drug has an acceptable safety profile. Side effects like neurotoxicity may limit its use but can be monitored safely. Due to thalidomide's thrombin generation potential, patients managed with thalidomide-containing regimes should be closely monitored for deep venous thrombosis. Given its teratogenicity, thalidomide should not be administered to women of childbearing potential who are not using adequate contraception. KEY MESSAGE: Physicians caring for patients in a palliative care setting should be aware of thalidomide as an effective therapeutic option when endoscopy fails to find a bleeding source or for those patients who cannot or refuse to undergo endoscopy but present with recurrent or obscure gastrointestinal bleeding.

Pseudoachalasia as First Manifestation of a Malignancy.

Pseudoachalasia is a condition in which symptoms, radiologic, endoscopic, and manometric findings mimick idiopathic achalasia. About 4% of patients with a typical constellation for idiopathic achalasia will turn out to have pseudoachalasia, posing a major diagnostic challenge. A large spectrum of underlying causes of pseudoachalasia has been described. However, in about 70% of affected patients, this condition is caused by a malignancy (mostly adenocarcinoma of the esophagogastric junction or cardia). We describe a 16-year-old high school student referred for management of achalasia who turned out to have pseudoachalasia due to adenocarcinoma of the cardia. He was cured with preoperative chemotherapy followed by radical surgery. Therapy of pseudoachalasia secondary to neoplasia is directed against the tumor or may be palliative to keep the lumen open. Other causes of pseudoachalasia include esophageal motility disturbances as a paraneoplastic phenomenon (e.g., with small cell lung cancer), post fundoplication or post bariatric surgery, in association with a thoracic aortic aneurysm, or with sarcoidosis or amyloidosis. Therapy is directed accordingly to eliminate or correct the underlying cause.

D-lactic acidosis - case report and review of the literature.

D-lactic acidosis is a rare complication that occurs mainly in patients with malabsorption due to a surgically altered gastrointestinal tract anatomy, namely in short bowel syndrome or after bariatric surgery. It is characterized by rapid development of neurological symptoms and severe metabolic acidosis, often with a high serum anion gap. Malabsorbed carbohydrates can be fermented by colonic microbiota capable of producing D-lactic acid. Routine clinical assessment of serum lactate covers only L-lactic acid; when clinical suspicion for D-lactic acidosis is high, special assays for D-lactic acid are called for. A serum level of more than 3 mmol/L of D-lactate confirms the diagnosis. Management includes correction of metabolic acidosis by intravenous bicarbonate, restriction of carbohydrates or fasting, and antibiotics to eliminate intestinal bacteria that produce D-lactic acid. We report a case of D-lactic acidosis in a patient with short bowel syndrome and review the pathophysiology of D-lactic acidosis with its biochemical and clinical features. D-lactic acidosis should be considered when patients with short bowel syndrome or other malabsorption syndromes due to an altered gastrointestinal tract anatomy present with metabolic acidosis and neurological symptoms that cannot be attributed to other causes. With the growing popularity of bariatric surgery, this metabolic derangement may be seen more frequently in the future.

Age-related modification of antioxidant enzyme activities in relation to cardiovascular risk factors.

BACKGROUND: Since oxidative stress might cause and promote cardiovascular risk factors such as oxidized low-density lipoproteins (oxLDL), apolipoprotein(a) [apo(a)], asymmetric dimethylarginine (ADMA) and fetuin A, we investigated antioxidant enzyme activities in relation to the vascular redox balance and these risk factors in elderly people. MATERIALS AND METHODS: For this observational study, a total of 102 subjects were recruited and divided into three groups: A (70-74 years/n = 48), B (75-79 years/n = 35) and C (≥ 80 years/n = 19). Activities of the erythrocyte antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined photometrically oxLDL, apo(a), ADMA and fetuin A by ELISA. Plasma concentrations of the lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were analysed with HPLC. RESULTS: There were no significant age-associated alterations in apo(a) levels, but there was a significant age-related decrease in activities of SOD (A>C, B>C: P < 0·01), CAT (A>C: P < 0·05) and GSH-Px (A>C: P < 0·05), accompanied by a significant increase in oxLDL (AC: P < 0·01; B>C: P < 0·05). Consequently, all groups showed significant negative age-associated correlations between CAT and MDA (A, B, C: P < 0·05), GSH-Px and CD (A, C: P < 0·01; B: P < 0·05), SOD and oxLDL (A, B: P < 0·05; C: P < 0·01), and fetuin A and MDA (A: P < 0·01; B, C: P < 0·05), and a significant positive correlation between oxLDL and ADMA (A, B: P < 0·05; C: P < 0·01). CONCLUSIONS: This study indicates a significant age-related decrease in antioxidant enzyme activities accompanied by significantly increased systemic oxidative stress, which promotes the cardiovascular risk factors oxLDL, ADMA and fetuin A in elderly people.

Expression of CD98hc in Pancreatic Cancer and Its Role in Cancer Cell Behavior.

Background: Cluster of differentiation 98 heavy chain (CD98hc) is a transmembrane protein, which functions both as a coreceptor of ß-integrins, enhancing intracellular integrin-dependent downstream signaling, and as a transporter of branched-chain and aromatic amino acids. As such, it is pivotal in cell cycle regulation and protection of oxidative, nutritional and DNA replication stress. Overexpression of CD98hc occurs widely in cancer cells and is associated with poor clinical prognosis. The role of CD98hc in pancreatic cancer remains to be elucidated. The aim of this study was to determine the expression of CD98hc in pancreatic ductal adenocarcinoma and to define its potential functional role in cancer cell biology. Methods: Immunohistochemical staining for CD98hc was performed on 222 tissue samples of patients with pancreatic ductal adenocarcinoma. The pancreatic cancer cell lines PANC-1 and BxPC-3 were used to determine the effect of CD98hc expression on cancer cell behavior using cell adhesion, cell trans-migration and cell spreading assays. Flow cytometry was performed to study the rate of apoptosis after detachment or serum starvation. shRNA-lentiviral constructs were used to knock down or reconstitute full length or mutated CD98hc. Results: Up to 20% of pancreatic ductal adenocarcinomas express CD98hc in the acinar cells (13%) and islet cells (20%) embedded in tumor tissue. Although expression of CD98hc in tumor tissue was not associated with a particular tumor stage or grade, our data show a trend towards longer overall survival of pancreatic cancer patients without CD98hc expression as compared to those with immunohistochemical positivity. In vitro downregulation of CD98hc in the pancreatic cancer cell lines PANC-1 and BxPC-3 significantly inhibits cell proliferation (p<0.05), self-renewal (p<0.05) and anchorage-independent growth (p<0.05). Conclusion: CD98hc is expressed in a remarkable percentage of pancreatic ductal adenocarcinomas. Due to its important role in cell behavior and malignant cell transformation, it may be a promising molecular target for potential new therapeutic approaches in pancreatic cancer in the future.

Activities of antioxidant enzymes in relation to oxidative and nitrosative challenges in childhood asthma.

BACKGROUND: This study aimed to investigate the relationship between antioxidant enzyme activities, extent of airway inflammation, and systemic oxidative stress in children suffering from atopic asthma. METHODS: A total of 35 asthmatic (AG) and 21 healthy children (CG) participated in this study. The volume of fractionated exhaled NO (Fe(no)) was measured with the NIOX test system. The activities of the erythrocyte antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the total antioxidant capacity (TAC) were determined photometrically. Plasma interleukin (IL)-6 was measured using ELISA; malondialdehyde (MDA) levels were analyzed using HPLC. RESULTS: Compared to healthy controls, asthmatic children exhaled a significantly (p < .001) higher mean volume of Fe(no), had significantly reduced plasma concentrations of TAC (p = .006), and significantly enhanced levels of MDA (p < .001) and IL-6 (p = .012). SOD (p = .027), CAT (p < .001), and GSH-Px (p = .005) were significantly less active in the asthma group and significantly negatively associated with Fe(no) (SOD/Fe(no): p = .017; CAT/Fe(no): p = .008; GSH-Px/Fe(no): p = .001); the oxidative stress marker MDA showed such correlations in both investigated groups (SOD/MDA: AG: p = .001, CG: p = .381; CAT/MDA: AG: p = .003, CG: p = .020; GSH-Px/MDA: AG: p = .006, CG: p = .011). Furthermore, there was a significant (p< .01) positive correlation between MDA/Fe(no) and MDA/IL-6 observed in both groups. CONCLUSIONS: These results indicate that inflammation of the bronchial tree, reflected by increased NO formation in the airways and enhanced systemic oxidative stress, is related to an alteration of antioxidant enzyme activities in childhood asthma. Modulating the activity of antioxidant enzymes may therefore have beneficial effects on pulmonary and systemic antioxidant defense mechanisms and could reduce airway inflammation and oxidative stress in asthmatics.

Use of complementary and alternative medicine supplements in patients with diabetes mellitus.

BACKGROUND/AIMS: This study was conducted to evaluate the current use of biologically-based complementary and alternative medicine (CAM) therapies in diabetics, considering health awareness, motivation, and expectations for CAM use. Moreover, patients' attitudes toward cinnamon preparations and the need for appropriate information from health care professionals were determined. METHODS: A total of 200 patients (59% men and 41% women) with type 1 (16%) or type 2 diabetes (84%) were interviewed using a standardized, validated questionnaire; the results from 198 respondents were analyzed. RESULTS: A third of type 1 and type 2 diabetics (women > men; p < 0.01) reported current use of biologically-based CAM supplements, and intake was significantly (r = 0.203; p < 0.05) correlated to the degree of health awareness/interest in self-care in type 2 diabetics. The use of nutritional supplements (vitamins/multivitamins and minerals), herbal medicine, and cinnamon was reported most frequently. Prevention (36%) and improved well-being/quality of life (13%) but not the positive modulation of diabetes management (4%) were given as main motivations. Eighty-three percent of type 1 diabetics (women > men; p < 0.05) and 70% of type 2 diabetics already knew about the postulated positive effect of cinnamon on blood glucose. Up to 85% reported a willingness or a probable willingness to test the effect of cinnamon on blood glucose. Among patients with type 2 diabetes the subjectively felt disease burden was found to have a significant (r = 0.235; p < 0.01) impact on the willingness to use cinnamon preparations for better diabetes management. CONCLUSION: This study indicates a remarkable interest in CAM remedies in the investigated group of diabetics as a strategy for active engagement in health and disease self-management. Healthcare professionals should be aware of the increasing number of patients using CAM supplements and hence incorporate these aspects into patient care in order to ensure patient satisfaction and optimize health care.

Intake of medication and vitamin status in the elderly.

BACKGROUND/AIMS: An inadequate vitamin status is associated with higher morbidity and frailty in the elderly and might be due to medication. This study aimed to evaluate the status of several vitamins in relation to regular intake of medication in this population. METHODS: A total of 102 non-institutionalized subjects aged 70-90 years were recruited. Plasma levels of vitamins A, D, E, K and C were determined by HPLC. The functional parameters of vitamins B(1), B(2) and B(6), i.e. the activities of the erythrocyte enzymes transketolase, glutathione reductase and glutamic oxaloacetic transaminase were analyzed photometrically; plasma folate and vitamin B(12) were determined by RIA. RESULTS: The status of vitamins A, E and C was generally satisfactory. Eighty-eight percent and 42% of participants were deficient in vitamins D and K, respectively, as were 29% in B(6); up to 10% were deficient in vitamins B(1), B(2), B(12) and folate. A considerable percentage of participants was, however, at risk for vitamin deficiencies (vitamins B(1), B(6), B(12) and folate: 20-30%; vitamin B(2): 60%). Regular intake of maximally 2 drugs per day was not adversely related to the status of several vitamins; intake of ≥ 3 drugs per day was significantly negatively associated with the status of vitamins D, K, B(6) and folate. CONCLUSION: Daily intake of ≥ 3 drugs was found to be adversely associated with the status of some vitamins in the elderly. Hence, the medication schedule and nutritional status of these subjects should be monitored closely to ensure that the daily micronutrient requirement is fulfilled.

Nutritional situation of the elderly in the European Union: data of the European Nutrition and Health Report (2004).

BACKGROUND: The European Nutrition and Health Report contains data about the nutritional situation of elderly of 11 EU countries. METHODS: The assessment of the energy and nutrient intake was performed using different methods: 24-hour recall, (semiquantitative) FFQ, 4/7-day-weighed record, personal interview, HBS. RESULTS: Compared to adults of the same country, the energy intake of elderly was on average lower. In most EU countries, the mean proportion of protein intake was within the recommended range while the share of carbohydrates was considerable low. The mean fat intake was remarkably high, the dietary fatty acid pattern predominantly imbalanced and the intake of cholesterol exceeded 300 mg/day in most European elderly. The average intake of vitamin D and folic acid was clearly below 10 and 400 microg/day, respectively, in elderly of all countries. Sodium intake was quite high in several participating countries, whereas calcium intake remained below 800 mg/d in all investigated states. The supply of vitamin A/C, thiamine, niacin, cobalamin, and the elements: magnesium, iron, zinc, copper, and manganese could generally be regarded as sufficient. Only in some countries the intake of these nutrients had to be assessed as unsaturated. CONCLUSION: Data analysis showed that the proportions of macronutrient intake of European elderly are not balanced. Apart from vitamin D, calcium, folate, iodine, and sodium the mean intake of micronutrients could be regarded as acceptable.

Influence of probiotic and conventional yoghurt on the status of vitamins B1, B2 and B6 in young healthy women.

BACKGROUND: In vitro studies indicate that yoghurt bacteria are able to generate several water-soluble vitamins and therefore yoghurt could be a good source of these micronutrients. However, whether lactobacilli or other viable bacteria release the synthesized vitamins or utilize vitamins from their surroundings is a matter of debate. This study was carried out to investigate whether probiotic and traditional yoghurt bacteria are able to influence the status of different B vitamins (B(1), B(2), B(6)) in young healthy women. METHODS: In this investigation, female volunteers consumed 100 g/day of probiotic (n = 17) or conventional yoghurt (n = 16) for 2 weeks (T1-T2) and 200 g/day for another 2 weeks (T2-T3). A wash-out phase lasting 2 weeks followed. Plasma and urine concentrations of thiamine (vitamin B(1)), riboflavin (B(2)) and pyridoxine (B(6)) were analyzed using HPLC. The functional parameters, i.e. the erythrocyte transketolase (alpha-ETK) expressed as TPP (thiamine pyrophosphate) effect, erythrocyte glutathione reductase (alpha-EGR) and glutamic oxaloacetic transaminase (alpha-EGOT) were determined photometrically. RESULTS: The plasma levels of vitamin B(1) increased significantly in both the probiotic (p < 0.001) and the control group (p < 0.01) when consuming 200 g yoghurt/day (T2-T3) and decreased to the baseline levels after the wash-out phase (T3-T4). Urinary excretion of thiamine and the TPP effect did not significantly change in either the probiotic or the control group during the period of daily yoghurt consumption (T1-T3). The plasma concentration of flavin adenine dinucleotide (FAD) decreased significantly (p < 0.001) after consuming 100 g yoghurt/day (T1-T2) while plasma concentrations of flavin mononucleotide (FMN) (probiotic: p < 0.01, control: p < 0.001) and free riboflavin increased significantly (probiotic: p < 0.01, control: p < 0.001). Afterwards, the levels of these parameters remained unchanged to the end of the study in both tested groups. The urinary excretion of riboflavin and alpha-EGR remained unaffected throughout the study in both the probiotic and the control group. The average status of vitamin B(6), evaluated by its plasma level, urinary excretion and alpha-EGOT was unaffected by daily intake of 100 g (T1-T2) and 200 g yoghurt (T2-T3), respectively, for 4 weeks (T1-T3). CONCLUSION: The results of the present study indicate that daily consumption of 200 g of both, probiotic and conventional yoghurt for 2 weeks can contribute to the total intake of vitamin B(1) and B(2) reflected by increased levels of plasma thiamine and free riboflavin in healthy women. The diminished plasma FAD and increased FMN concentrations, observed during the period of daily yoghurt consumption in both groups, may be the result of enhanced immune function and an oxidant/antioxidant imbalance, caused by the daily intake of lactic acid bacteria. Since the long term status parameters of all three investigated vitamins (B(1), B(2), B(6)) remained unaffected during the investigation the changes in plasma concentrations seem more likely the result of regular yoghurt consumption as a fermented dairy product, rather than of the specific intake of probiotic bacteria.

The effect of daily consumption of probiotic and conventional yoghurt on oxidant and anti-oxidant parameters in plasma of young healthy women.

In recent years there has been increasing interest in the potential beneficial effects of probiotic bacteria, particularly concerning their immune-modulating effects. Considering the involvement of free radicals in immunological processes, we tried to verify and compare the effects of probiotic (Lactobacillus casei) and conventional yoghurt on antioxidant and oxidant parameters in plasma of humans. In this study female volunteers consumed 100 g/day of probiotic (n = 17) or conventional yoghurt (n = 16) for two weeks (T1-T2) and 200 g/day for another two weeks (T2-T3). A wash-out phase lasting two weeks followed. Total antioxidant capacity (TAC), albumin, and bilirubin were determined photometrically, uric acid was determined by enzymatic methods, and vitamin E, carotenoids, malondialdehyde (MDA), and conjugated dienes (CD) were measured using high-performance liquid chromatography (HPLC). In the period of continuous yoghurt intake (T1-T3), mean concentrations of the antioxidants vitamin E, lycopene, and zeaxanthin decreased significantly (p < 0.01) in the probiotic and in the control group. The average concentrations of lutein, beta-carotene, albumin, uric acid, and bilirubin decreased significantly (p < 0.05) in the probiotic group, only. These alterations led to a significant (p < 0.001) decrease of the average TAC values during the period T1-T3 in both tested groups. In the interval of daily yoghurt consumption (T1-T3) the mean plasma levels of oxidant parameters MDA and CD increased significantly in the probiotic (MDA: p < 0.01; CD: p < 0.001) and the control group (CD: p < 0.01). The average activity of the antioxidant enzyme superoxide dismutase (SOD) was quite constant throughout the study in both groups. The mean activities of GSH-Px and catalase decreased significantly (p < 0.001) in the probiotic group, only after consuming yoghurt daily for four weeks (T1-T3). Although several parameters changed significantly during the study, no significant differences were observed between both investigated groups. Therefore, the results indicate a possible influence of both probiotic and conventional yoghurt on the plasma levels of antioxidant and oxidant parameters.